JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
On-line capillary isoelectric focusing hyphenated to native electrospray ionization mass spectrometry for the characterization of interferon-? and variants.
Analyst
PUBLISHED: 11-20-2014
Show Abstract
Hide Abstract
The on-line hyphenation of Capillary IsoElectric Focusing (CIEF) with ElectroSpray Ionization Mass Spectrometry (ESI/MS) has been carried out in a non-denaturing detection mode at the CIEF-MS interface. This CIEF-MS coupling methodology relied on the use of 40% glycerol-water medium as anti-convective agent in the CE capillary and the addition of 10 mM ammonium acetate buffer, pH 5, as a volatile aqueous sheath liquid. These CIEF-MS coupling conditions allowed the characterization of the highly basic cytokine human interferon-gamma (IFN-?) and its detection as a non-covalent homodimer (33?814.3 g mol(-1)) corresponding to the active form of this immune-regulatory protein. An experimental pI value of 9.95 was determined for the human IFN-? homodimer in these conditions. The CIEF-MS analysis of several variants bearing punctual or deletion mutations within the two D1 and D2 basic clusters at the C-terminal end of IFN-? revealed the different contribution of these domains to the charge properties of this heparan sulfate-binding protein.
Related JoVE Video
ATL response to arsenic/interferon therapy is triggered by SUMO/PML/RNF4-dependent Tax degradation.
Blood
PUBLISHED: 11-15-2014
Show Abstract
Hide Abstract
The HTLV-1 Tax transactivator initiates transformation in adult T-cell leukemia/lymphoma (ATL), a highly aggressive chemotherapy-resistant malignancy. The arsenic/interferon combination, which triggers degradation of the Tax oncoprotein, selectively induces apoptosis of ATL cell lines and has significant clinical activity in Tax-driven murine ATL or patients. Yet, the role of Tax loss in ATL response is disputed and the molecular mechanisms driving degradation remain elusive. Here we demonstrate that ATL-derived or HTLV-1-transformed cells are addicted to continuous Tax expression, suggesting that Tax degradation underlies clinical responses to the arsenic/interferon combination. The latter enforces PML nuclear body (NB) formation and partner protein recruitment. In arsenic/interferon-treated HTLV-1-transformed cells, Tax is recruited onto NBs, undergoes PML-dependent hyper-sumoylation by SUMO2/3, but not SUMO1, ubiquitination by RNF4 and proteasome-dependent degradation. Thus, the arsenic/interferon combination clears ATL through degradation of its Tax driver and this regimen could have broader therapeutic value by promoting degradation of other pathogenic sumoylated proteins.
Related JoVE Video
A quartz crystal microbalance method to study the terminal functionalization of glycosaminoglycans.
Chem. Commun. (Camb.)
PUBLISHED: 10-24-2014
Show Abstract
Hide Abstract
We demonstrate the quartz crystal microbalance as a novel method to quantify the reaction yields and stability of the terminal conjugation of chemically complex molecules. Oxime ligation is identified as a facile, broadly applicable method for the reducing-end conjugation of glycosaminoglycans that overcomes the limited stability and yield of popular hydrazone ligation.
Related JoVE Video
Profiling sulfation/epimerization pattern of full-length heparan sulfate by NMR following cell culture 13C-glucose metabolic labeling.
Glycobiology
PUBLISHED: 10-21-2014
Show Abstract
Hide Abstract
Through its ability to interact with proteins, heparan sulfate (HS) fulfills a large variety of functions. Protein binding depends on the level of HS sulfation and epimerization which are cell specific and dynamically regulated. Characterization of this molecule, however, has been restricted to oligosaccharide fragments available in large amount for structural investigation or to sulfate distribution through compositional analysis. Here we developed a (1)H-(13)C 2D NMR-based approach, directly performed on HS isolated from (13)C-labeled cell. By integrating the peak volumes measured at different chemical shifts, this non-destructive analysis enables to determine both the sulfation and the iduronic/glucuronic profiles of the polysaccharide. Applied to wild-type and N-deacetylase/N-sulfotransferase-deficient fibroblasts as well as to epithelial cells differentiation, it also gives insights into the functional relationships existing between HS biosynthetic enzymes. This approach should be of large interest to better understand HS changes that occur through physiologic regulations or during pathological development.
Related JoVE Video
Electronic tongue generating continuous recognition patterns for protein analysis.
J Vis Exp
PUBLISHED: 10-07-2014
Show Abstract
Hide Abstract
In current protocol, a combinatorial approach has been developed to simplify the design and production of sensing materials for the construction of electronic tongues (eT) for protein analysis. By mixing a small number of simple and easily accessible molecules with different physicochemical properties, used as building blocks (BBs), in varying and controlled proportions and allowing the mixtures to self-assemble on the gold surface of a prism, an array of combinatorial surfaces featuring appropriate properties for protein sensing was created. In this way, a great number of cross-reactive receptors can be rapidly and efficiently obtained. By combining such an array of combinatorial cross-reactive receptors (CoCRRs) with an optical detection system such as surface plasmon resonance imaging (SPRi), the obtained eT can monitor the binding events in real-time and generate continuous recognition patterns including 2D continuous evolution profile (CEP) and 3D continuous evolution landscape (CEL) for samples in liquid. Such an eT system is efficient for discrimination of common purified proteins.
Related JoVE Video
The course and the anatomo-functional relationships of the optic radiation: a combined study with 'post mortem' dissections and 'in vivo' direct electrical mapping.
J. Anat.
PUBLISHED: 10-04-2014
Show Abstract
Hide Abstract
Even if different dissection, tractographic and connectivity studies provided pure anatomical evidences about the optic radiations (ORs), descriptions of both the anatomical structure and the anatomo-functional relationships of the ORs with the adjacent bundles were not reported. We propose a detailed anatomical and functional study with 'post mortem' dissections and 'in vivo' direct electrical stimulation (DES) of the OR, demonstrating also the relationships with the adjacent eloquent bundles in a neurosurgical 'connectomic' perspective. Six human hemispheres (three left, three right) were dissected after a modified Klingler's preparation. The anatomy of the white matter was analysed according to systematic and topographical surgical perspectives. The anatomical results were correlated to the functional responses collected during three resections of tumours guided by cortico-subcortical DES during awake procedures. We identified two groups of fibres forming the OR. The superior component runs along the lateral wall of the occipital horn, the trigone and the supero-medial wall of the temporal horn. The inferior component covers inferiorly the occipital horn and the trigone, the lateral wall of the temporal horn and arches antero-medially to form the Meyer's Loop. The inferior fronto-occipital fascicle (IFOF) covers completely the superior OR along its entire course, as confirmed by the subcortical DES. The inferior longitudinal fascicle runs in a postero-anterior and inferior direction, covering the superior OR posteriorly and the inferior OR anteriorly. The IFOF identification allows the preservation of the superior OR in the anterior temporal resection, avoiding post-operative complete hemianopia. The identification of the superior OR during the posterior temporal, inferior parietal and occipital resections leads to the preservation of the IFOF and of the eloquent functions it subserves. The accurate knowledge of the OR course and the relationships with the adjacent bundles is crucial to optimize quality of resection and functional outcome.
Related JoVE Video
Clearance of PML/RARA-bound promoters suffice to initiate APL differentiation.
Blood
PUBLISHED: 09-27-2014
Show Abstract
Hide Abstract
PML/RARA, a potent transcriptional inhibitor of nuclear receptor signaling, represses myeloid differentiation genes and drives acute promyelocytic leukemia (APL). Association of the RXRA co-receptor to PML/RARA is required for transformation, RXRA promoting its efficient DNA-binding. APL is exquisitely sensitive to retinoic acid (RA) and arsenic trioxide (arsenic), which both trigger cell differentiation in vivo. While RA elicits transcriptional activation of PML/RARA targets, how arsenic triggers differentiation remains unclear. Here we demonstrate that extinction of PML/RARA triggers terminal differentiation in vivo. Similarly, ablation of RXRs loosens PML/RARA DNA-binding, inducing terminal differentiation of APL cells ex vivo or in vivo. RXRA sumoylation also directly contributes to PML/RARA-dependent transformation ex vivo, presumably by enhancing transcriptional repression. Thus, APL differentiation is a default program triggered by clearance of PML/RARA-bound promoters, rather than obligatory active transcriptional activation, explaining how arsenic elicits APL maturation through PML/RARA degradation.
Related JoVE Video
Asymmetric interhemispheric excitability evidenced by event-related potential amplitude patterns after "wide-awake surgery" of brain tumours.
Exp Brain Res
PUBLISHED: 08-27-2014
Show Abstract
Hide Abstract
Slow-growing, infiltrative brain tumours may modify the electrophysiological balance between the two hemispheres. To determine whether and how asymmetry in interhemispheric excitability might occur following "wide-awake surgery" for this type of tumour, we recorded electroencephalograms during a simple visuo-manual reaction time paradigm performed by five patients between 3 and 12 months after surgery. Interhemispheric excitability asymmetries were computed by comparing the amplitudes of event-related potentials (ERPs) in the injured hemisphere to those in the healthy hemisphere. For the two patients with the smallest lesions (7.1 and 11.5 cm(3), respectively), increased excitability within the ipsilesional hemisphere was evidenced by characteristics increases in the ERP amplitude at several sites, with few occurrences in the contralesional hemisphere. For smaller lesions (and under certain experimental conditions), cortical excitability in the injured hemisphere may increase in order to maintain local compensation. In addition, we observed and increased excitability in the contralesional frontal homologue for one patient who underwent an extensive resection. Post-operative monitoring of interhemispheric asymmetries in ERP amplitudes is of value for determining task constraints inducing electrophysiological imbalance and guiding rehabilitation.
Related JoVE Video
Significant heterogeneity in the geographical distribution of diffuse grade II/III gliomas in France.
J. Neurooncol.
PUBLISHED: 08-24-2014
Show Abstract
Hide Abstract
Diffuse WHO grade II and III gliomas (DGII/IIIG) are rare tumors, with few specific epidemiological studies. We aimed at describing the geographical distribution of a homogeneous series of histologically confirmed DGII/IIIG, over a four-year period (2006-2009), at a national level. The methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase and data collected directly from every neuropathology department. Personal home addresses were collected for confirmed cases. For each region, the incidence of DGII/IIIG was analyzed and standardized on the age and sex distribution of the French population. The number of patients with newly diagnosed, histologically confirmed DGII/IIIG was 4,790. The overall crude rate was 19.4/10(6). To enable international comparisons, standardized rates were calculated as follows: 19.8/10(6), 18.8/10(6) and 16.0/10(6) (reference population, Europe, US and world, respectively). The geographical distribution by region showed significant differences, with higher incidence rates in Northeast and central parts of France. This work is the first studying the geographical distribution of a pure series of DGII/IIIG at a national level. It demonstrates significant heterogeneity in the distribution, and raises the question of the role of environmental and/or genetic risk(s) factor(s) for DGII/IIIG.
Related JoVE Video
Retinoic acid signaling in cancer: The parable of acute promyelocytic leukemia.
Int. J. Cancer
PUBLISHED: 08-14-2014
Show Abstract
Hide Abstract
Inevitably fatal some 40 years, acute promyelocytic leukemia (APL) can now be cured in more than 95% of cases. This clinical success story is tightly linked to tremendous progress in our understanding of retinoic acid (RA) signaling. The discovery of retinoic acid receptor alpha (RARA) was followed by the cloning of the chromosomal translocations driving APL, all of which involve RARA. Since then, new findings on the biology of nuclear receptors have progressively enlightened the basis for the clinical efficacy of RA in APL. Reciprocally, the disease offered a range of angles to approach the cellular and molecular mechanisms of RA action. This virtuous circle contributed to make APL one of the best-understood cancers from both clinical and biological standpoints. Yet, some important questions remain unanswered including how lessons learnt from RA-triggered APL cure can help design new therapies for other malignancies.
Related JoVE Video
New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach.
Neuro-oncology
PUBLISHED: 08-04-2014
Show Abstract
Hide Abstract
Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a "wait and see" policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associated with a longer overall survival (OS) while minimizing morbidity. However, most studies have investigated the role of only one specific treatment (surgery, radiotherapy, chemotherapy) without taking a global view of managing the cumulative time while preserving quality of life (QoL) versus time to anaplastic transformation. Our aim is to switch towards a more holistic concept based upon the anticipation of a personalized and long-term multistage therapeutic approach, with online adaptation of the strategy over the years using feedback from clinical, radiological, and histomolecular monitoring. This dynamic strategy challenges the traditional approach by proposing earlier therapy, by repeating treatments, and by reversing the classical order of therapies (eg, neoadjuvant chemotherapy when maximal resection is impossible, no early radiotherapy) to improve OS and QoL. New individualized management strategies should deal with the interactions between the course of this chronic disease, reaction brain remapping, and oncofunctional modulation elicited by serial treatments. This philosophy supports a personalized, functional, and preventive neuro-oncology.
Related JoVE Video
Importance of the polarity of the glycosaminoglycan chain on the interaction with FGF-1.
Glycobiology
PUBLISHED: 07-11-2014
Show Abstract
Hide Abstract
Heparin-like saccharides play an essential role in binding to the fibroblast growth factor (FGF)-1 and to their membrane receptors fibroblast growth factor receptor forming a ternary complex that is responsible of the internalization of the signal, via the dimerization of the intracellular regions of the receptor. In this study, we report the binding affinities between five synthetic hexasaccharides with human FGF-1 obtained by surface plasmon resonance experiments, and compare with the induced mitogenic activity previously obtained. These five oligosaccharides differ in sulfation pattern and in sequence. We have previously demonstrated that all the five hexasaccharides have similar 3D structure of the backbone. Consequently, the differences in binding affinity should have their origin in the substitution pattern. Subsequently, the different capacity for induction of mitogenic activity can be, at least partially, explained from these binding affinities. Interestingly, one of the oligosaccharides lacking axially symmetry ( 3: ) was biologically inactive, whereas the other ( 2: ) was the most active. The difference between both compounds is the order of the FGF-binding motifs along the chain relative to the carbohydrate polarity. We can conclude that the directionality of the GAG chain is essential for the binding and subsequent activation. The relative biological activity of the compounds with regular substitution pattern can be inferred from their values of IC50. Remarkably, the sulfate in position 6 of d-glucosamine was essential for the mitogenic activity but not for the interaction with FGF-1.
Related JoVE Video
A Nonradiated Grade II Glioma That Underwent Delayed Malignant Transformation to a Gliosarcoma with Meningeal Growth and Dissemination.
J Neurol Surg A Cent Eur Neurosurg
PUBLISHED: 06-27-2014
Show Abstract
Hide Abstract
Background?Secondary gliosarcomas are rare tumors, especially those arising from a World Health Organization (WHO) grade II glioma not irradiated. We report a case with subtotal resection for a WHO grade II oligoastrocytoma, without adjuvant treatment, whose metaplastic transformation into gliosarcoma suddenly occurred 4 years later with meningeal dissemination. We show a favorable outcome after therapeutic management of this rare entity. Patient?A 46 year-old woman underwent surgery for a right premotor WHO grade II oligoastrocytoma discovered incidentally. Because of a subtotal resection with only 1?cc of residue, no complementary therapy was given, and the patient enjoyed a normal life for 4 years. In the meantime, the magnetic resonance images performed every 6 months showed a very low growth rate. Suddenly, the tumor switched toward a gliosarcoma profile with meningeal dissemination. Results?Reoperation, radiotherapy, and chemotherapy were performed, enabling a control of the disease with 15 months of follow-up (i.e., with radiologic shrinkage of the multiple lesions and preservation of quality of life). Conclusion?A delayed sarcomatous transformation can acutely occur with a low proliferation index in a nonirradiated WHO grade II oligoastrocytoma. Furthermore, an aggressive therapeutic strategy can allow control of secondary gliosarcomas, even in cases of leptomeningeal spreading.
Related JoVE Video
Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited.
Brain
PUBLISHED: 06-25-2014
Show Abstract
Hide Abstract
The organization of basic functions of the human brain, particularly in the right hemisphere, remains poorly understood. Recent advances in functional neuroimaging have improved our understanding of cortical organization but do not allow for direct interrogation or determination of essential (versus participatory) cortical regions. Direct cortical stimulation represents a unique opportunity to provide novel insights into the functional distribution of critical epicentres. Direct cortical stimulation (bipolar, 60 Hz, 1-ms pulse) was performed in 165 consecutive patients undergoing awake mapping for resection of low-grade gliomas. Tasks included motor, sensory, counting, and picture naming. Stimulation sites eliciting positive (sensory/motor) or negative (speech arrest, dysarthria, anomia, phonological and semantic paraphasias) findings were recorded and mapped onto a standard Montreal Neurological Institute brain atlas. Montreal Neurological Institute-space functional data were subjected to cluster analysis algorithms (K-means, partition around medioids, hierarchical Ward) to elucidate crucial network epicentres. Sensorimotor function was observed in the pre/post-central gyri as expected. Articulation epicentres were also found within the pre/post-central gyri. However, speech arrest localized to ventral premotor cortex, not the classical Broca's area. Anomia/paraphasia data demonstrated foci not only within classical Wernicke's area but also within the middle and inferior frontal gyri. We report the first bilateral probabilistic map for crucial cortical epicentres of human brain functions in the right and left hemispheres, including sensory, motor, and language (speech, articulation, phonology and semantics). These data challenge classical theories of brain organization (e.g. Broca's area as speech output region) and provide a distributed framework for future studies of neural networks.
Related JoVE Video
A better surgical resectability of WHO grade II gliomas is independent of favorable molecular markers.
J. Neurooncol.
PUBLISHED: 06-13-2014
Show Abstract
Hide Abstract
A higher extent of resection (EOR) in WHO grade II gliomas (GIIG) is correlated with longer survival. However, the molecular markers also feature prognostic relevance. Here, we examined whether maximal EOR was related to the genetic profile. We retrospectively investigated the predictive value of 1p19q, IDH1, 53 expression and Ki67 index for the EOR in 200 consecutive GIIGs (2007-2013). Data were modeled in a linear model. The analysis was performed with two statistical methods (arcsin-sqrt and Beta-regression model with logit link). There was no deletion 1p19q in 118 cases, codeletion 1p19q (57 cases), single deletion 1p (4 cases) or19q (16 cases). 155 patients had a mutation of IDH1. p53 was graded in 4 degrees (0:92 cases, 1:52 cases, 2:31 cases, 3:8 cases). Mean Ki67 index was 5.2 % (range 1-20 %). Mean preoperative tumor volume was 60.8 cm(3) (range 3.3-250 cm(3)) and mean EOR was 0.917 (range 0.574-1). The statistical analysis was significant for a lower EOR in patients with codeletion 1p19q (OR 0.738, p = 0.0463) and with a single deletion 19q (OR 0.641, p = 0.0168). There was no significant correlation between IDH1 or p53 and the EOR. Higher Ki67 was marginally associated with higher EOR (p = 0.0603). The study demonstrates in a large cohort of GIIG that a higher EOR is not attributable to favorable genetic markers. This original result supports maximal surgical resection as an important therapeutic factor per se to optimize prognosis, independently of the molecular pattern.
Related JoVE Video
Role of fronto-striatal tract and frontal aslant tract in movement and speech: an axonal mapping study.
Brain Struct Funct
PUBLISHED: 06-12-2014
Show Abstract
Hide Abstract
Despite a better understanding of their anatomy, the functional role of frontal pathways, i.e., the fronto-striatal tract (FST) and frontal aslant tract (FAT), remains obscure. We studied 19 patients who underwent awake surgery for a frontal glioma (14 left, 5 right) by performing intraoperative electrical mapping of both fascicles during motor and language tasks. Furthermore, we evaluated the relationship between these tracts and the eventual onset of transient postoperative disorders. We also performed post-surgical tract-specific measurements on probabilistic tractography. All patients but one experienced intraoperative inhibition of movement and/or speech during subcortical electrostimulation. On postoperative tractography, the subcortical distribution of stimulated sites corresponded to the spatial course of the FST and/or FAT. Furthermore, we found a significant correlation between postoperative worsening and distances between these tracts and resection cavity. A resection close to the (right or left) FST was correlated with transitory motor initiation disorders (p = 0.026), while a resection close to the left FAT was associated with transient speech initiation disorders (p = 0.003). Moreover, the measurements of average distances between resection cavity and left FAT showed a positive correlation with verbal fluency in both semantic (p = 0.019) and phonemic scores (p = 0.017), while average distances between surgical cavity and left FST showed a positive correlation with verbal fluency scores in both semantic (p = 0.0003) and phonemic modalities (p = 0.037). We suggest that FST and FAT would cooperatively play a role in self-initiated movement and speech, as a part of "negative motor network" involving the pre-supplementary motor area, left inferior frontal gyrus and caudate nucleus.
Related JoVE Video
PML nuclear bodies: regulation, function and therapeutic perspectives.
J. Pathol.
PUBLISHED: 06-11-2014
Show Abstract
Hide Abstract
PML nuclear bodies (NBs) were first described by electron microscopy and rediscovered through their treatment-reversible disruption in a rare leukaemia. They recruit multiple partner proteins and now emerge as interferon- and oxidative stress-responsive sumoylation factories. NBs mediate interferon-induced viral restriction, enhance proteolysis, finely tune metabolism and enforce stress-induced senescence. Apart from being markers of cellular stress, PML NBs could be harnessed pharmacologically in a number of conditions, including cancer, viral infection or neurodegenerative diseases. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Related JoVE Video
The evolution of brain surgery on awake patients.
Acta Neurochir (Wien)
PUBLISHED: 06-05-2014
Show Abstract
Hide Abstract
In the early days of modern neurological surgery, the inconveniences and potential dangers of general anesthesia by chloroform and ether using the so-called "open-drop technique" led to the quest for alternative methods of anesthesia. Besides preventing the feared side effects, the introduction of regional anesthesia revealed another decisive advantage over general anesthesia in neurosurgery: While intraoperative direct cortical stimulation under general anesthesia could only delineate the motor area (by evocation of contralateral muscular contraction), now, the awake patients were able to report sensations elicited by this method. These properties advanced regional anesthesia to the regimen of choice for cranial surgeries in the first half of the 20th century. While technical advances and new drugs led to a progressive return to general anesthesia for neurosurgical procedures, the use of regional anesthesia for epilepsy surgery has only decreased in recent decades. Meanwhile, awake craniotomies regained popularity in oncologically motivated surgeries, especially in craniotomies for diffuse low-grade gliomas. Intraoperative mapping of brain functions using electrical stimulation in awake patients enables not only for increased tumor removal while preserving the functional status of the patients but also opens a window to cognitive neuroscience. Observations during such interventions and their correlation with both pre - and postoperative neuropsychological examinations and functional neuroimaging is progressively leading to new insights into the complex functional anatomy of the human brain. Furthermore, it broadens our knowledge on cerebral network reorganization in the presence of disease-with implications for all disciplines of clinical neuroscience.
Related JoVE Video
Well-defined biomimetic surfaces to characterize glycosaminoglycan-mediated interactions on the molecular, supramolecular and cellular levels.
Biomaterials
PUBLISHED: 05-21-2014
Show Abstract
Hide Abstract
Glycosaminoglycans (GAGs) are ubiquitously present at the cell surface and in extracellular matrix, and crucial for matrix assembly, cell-cell and cell-matrix interactions. The supramolecular presentation of GAG chains, along with other matrix components, is likely to be functionally important but remains challenging to control and to characterize, both in vivo and in vitro. We present a method to create well-defined biomimetic surfaces that display GAGs, either alone or together with other cell ligands, in a background that suppresses non-specific binding. Through the design of the immobilization platform - a streptavidin monolayer serves as a molecular breadboard for the attachment of various biotinylated ligands - and a set of surface-sensitive in situ analysis techniques (including quartz crystal microbalance and spectroscopic ellipsometry), the biomimetic surfaces are tailor made with tight control on biomolecular orientation, surface density and lateral mobility. Analysing the interactions between a selected GAG (heparan sulphate, HS) and the HS-binding chemokine CXCL12? (also called SDF-1?), we demonstrate that these surfaces are versatile for biomolecular and cellular interaction studies. T-lymphocytes are found to adhere specifically to surfaces presenting CXCL12?, both when reversibly bound through HS and when irreversibly immobilized on the inert surface, even in the absence of any bona fide cell adhesion ligand. Moreover, surfaces which present both HS-bound CXCL12? and the intercellular adhesion molecule 1 (ICAM-1) synergistically promote cell adhesion. Our surface biofunctionalization strategy should be broadly applicable for functional studies that require a well-defined supramolecular presentation of GAGs along with other matrix or cell-surface components.
Related JoVE Video
Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas.
Neuro-oncology
PUBLISHED: 05-20-2014
Show Abstract
Hide Abstract
We explored whether spontaneous imaging tumor growth (estimated by the velocity of diametric expansion) and isocitrate dehydrogenase 1 (IDH1) mutation (estimated by IDH1 immunoexpression) were independent predictors of long-term outcomes of diffuse low-grade gliomas in adults.
Related JoVE Video
Notch1 stimulation induces a vascularization switch with pericyte-like cell differentiation of glioblastoma stem cells.
Stem Cells
PUBLISHED: 05-03-2014
Show Abstract
Hide Abstract
Glioblastoma multiforms (GBMs) are highly vascularized brain tumors containing a subpopulation of multipotent cancer stem cells. These cells closely interact with endothelial cells in neurovascular niches. In this study we have uncovered a close link between the Notch1 pathway and the tumoral vascularization process of GBM stem cells. We observed that although the Notch1 receptor was activated, the typical target proteins (HES5, HEY1, HEY2) were not or barely expressed in two explored GBM stem cell cultures. Notch1 signalling activation by expression of the intracellular form (NICD) in these cells was found to reduce their growth rate and migration which was accompanied by the sharp reduction of neural stem cell transcription factor expression (ASCL1, OLIG2, SOX2) while HEY1/2, KLF9, SNAI2 transcription factors were upregulated. Expression of OLIG2 and growth were restored after termination of Notch1 stimulation. Remarkably, NICD expression induced the expression of pericyte cell markers (NG2, PDGFR? and ?-smooth muscle actin (?SMA)) in GBM stem cells. This was paralleled with the induction of several angiogenesis-related factors most notably cytokines (HB-EGF, IL8, PLGF), metalloprotease (MMP9) and adhesion proteins (VCAM-1, ICAM-1, ITGA9). In xenotransplantation experiments, contrasting with the infiltrative and poorly-vascularized tumors obtained with control GBM stem cells, Notch1 stimulation resulted in poorly-disseminating but highly-vascularized grafts containing large vessels with lumen. Notch1-stimulated GBM cells expressed pericyte cell markers and closely associated with endothelial cells. These results reveal an important role for the Notch1 pathway in regulating GBM stem cell plasticity and angiogenic properties. Stem Cells 2014.
Related JoVE Video
Anatomo-functional study of the temporo-parieto-occipital region: dissection, tractographic and brain mapping evidence from a neurosurgical perspective.
J. Anat.
PUBLISHED: 04-28-2014
Show Abstract
Hide Abstract
The temporo-parieto-occipital (TPO) junction is a complex brain territory heavily involved in several high-level neurological functions, such as language, visuo-spatial recognition, writing, reading, symbol processing, calculation, self-processing, working memory, musical memory, and face and object recognition. Recent studies indicate that this area is covered by a thick network of white matter (WM) connections, which provide efficient and multimodal integration of information between both local and distant cortical nodes. It is important for neurosurgeons to have good knowledge of the three-dimensional subcortical organisation of this highly connected region to minimise post-operative permanent deficits. The aim of this dissection study was to highlight the subcortical functional anatomy from a topographical surgical perspective. Eight human hemispheres (four left, four right) obtained from four human cadavers were dissected according to Klingler's technique. Proceeding latero-medially, the authors describe the anatomical courses of and the relationships between the main pathways crossing the TPO. The results obtained from dissection were first integrated with diffusion tensor imaging reconstructions and subsequently with functional data obtained from three surgical cases, all resection of infiltrating glial tumours using direct electrical mapping in awake patients. The subcortical limits for performing safe lesionectomies within the TPO region are as follows: within the parietal region, the anterior horizontal part of the superior longitudinal fasciculus and, more deeply, the arcuate fasciculus; dorsally, the vertical projective thalamo-cortical fibres. For lesions located within the temporal and occipital lobes, the resection should be tailored according to the orientation of the horizontal associative pathways (the inferior fronto-occipital fascicle, inferior longitudinal fascicle and optic radiation). The relationships between the WM tracts and the ventricle system were also examined. These results indicate that a detailed anatomo-functional awareness of the WM architecture within the TPO area is mandatory when approaching intrinsic brain lesions to optimise surgical results and to minimise post-operative morbidity.
Related JoVE Video
Heparan sulphate saccharides modify focal adhesions: Implication in mucopolysaccharidosis neuropathophysiology.
J. Mol. Biol.
PUBLISHED: 04-25-2014
Show Abstract
Hide Abstract
Mucopolysaccharidoses type III (MPSIII, Sanfilippo syndrome) are genetic diseases due to deficient heparan sulphate saccharide digestion by lysosomal exoglycanases. Progressive accumulation of undigested saccharides causes early onset behavioural and cognitive symptoms. The precise role of these saccharides in the pathophysiological cascade is still unclear. We showed that exposure of wild type neural cells to exogenous soluble heparan sulphate fragments of at least eight saccharides activated integrin-based focal adhesions, which attach cells to the extracellular matrix. Focal adhesions were constitutively activated in MPSIII type B astrocytes or neural stem cells unless undigested saccharides were cleared by exogenous supply of the missing exoglycanase. Defective cell polarisation and oriented migration in response to focal extracellular stimuli in affected cells suggest improper sensing of the environment. We consistently observed abnormal organisation of the rostral migratory stream in the brain of adult mice with MPSIII type B. These results suggest that cell polarisation and oriented migration defects participate to the neurological disorders associated with Sanfilippo syndrome.
Related JoVE Video
Interfering with the neural activity of mirror-related frontal areas impairs mentalistic inferences.
Brain Struct Funct
PUBLISHED: 04-11-2014
Show Abstract
Hide Abstract
According to recently proposed interactive dual-process theories, mentalizing abilities emerge from the coherent interaction between two physically distinct neural systems: (1) the mirror network, coding for the low-level embodied representations involved in pre-reflective sociocognitive processes and (2) the mentalizing network per se, which codes for higher level representations subtending the reflective attribution of psychological states. However, although the latest studies have shown that the core areas forming these two neurocognitive systems do indeed maintain effective connectivity during mentalizing, it is unclear whether an intact mirror system (and, more specifically, its anterior node, namely the posterior inferior frontal cortex) is a prerequisite for accurate mentalistic inferences. Intraoperative brain mapping via direct electrical stimulation offers a unique opportunity to address this issue. Electrical stimulation of the brain creates a "virtual" lesion, which provides functional information on well-defined parts of the cerebral cortex. In the present study, five patients were mapped in real time while they performed a mentalizing task. We found six responsive sites: four in the lateral part of the right pars opercularis and two in the dorsal part of the right pars triangularis. On the subcortical level, two additional sites were located within the white matter connectivity of the pars opercularis. Taken as a whole, our results suggest that the right inferior frontal cortex and its underlying axonal connectivity have a key role in mentalizing. Specifically, our findings support the hypothesis whereby transient, functional disruption of the mirror network influences higher order mentalistic inferences.
Related JoVE Video
Functional reorganization of the attentional networks in low-grade glioma patients: A longitudinal study.
Cortex
PUBLISHED: 03-27-2014
Show Abstract
Hide Abstract
Right brain damage often provokes deficits of visuospatial attention. Although the spatial attention networks have been widely investigated in stroke patients as well as in the healthy brain, little is known about the impact of slow growing lesions in the right hemisphere. We here present a longitudinal study of 20 patients who have been undergoing awake brain surgery with per-operative line bisection testing. Our aim was to investigate the impact of tumour presence and of tumour resection on the functional (re)organization of the attention networks. We assessed patients' performance on lateralized target detection, visual exploration and line bisection before surgery, and in the acute and post-acute operative phases after surgery. Clear evidence for transient neglect signs was observed in the acute post-operative phase, although full recovery had invariably occurred in all patients. The resection of the right angular gyrus was associated with transient neglect-like symptoms in all tasks, whereas resection of more anterior regions correlated with transient deficits only in visual exploration or detection (but not in line bisection). The attentional networks showed substantial functional recovery. This impressive pattern of recovery is discussed in terms of involvement of the contralateral left hemisphere and of preservation of long-range white matter pathways within the right hemisphere.
Related JoVE Video
Unravelling the Scent of Vetiver: Identification of Character-Impact Compounds.
Chem. Biodivers.
PUBLISHED: 02-14-2014
Show Abstract
Hide Abstract
Vetiver oil is a highly esteemed basic ingredient of modern perfumery, but the nature of the constituents that really impart its typical and most sought woody-earthy scent has remained controversial. Indeed, vetiver oil is considered as one of the most complex essential oils, being mostly composed of several hundreds of sesquiterpene derivatives with a large structural diversity. Its complexity has hindered the direct identification of its odoriferous components. We thus aimed at using a combination of GC×GC/MS and GC-Olfactometry in order to identify most of its odor-impact constituents. The olfactory analysis of vetiver oil and vetiveryl acetate revealed a huge variety of odors in both products. While khusimone has almost unanimously been recognized as the most characteristic vetiver odorant, we have identified several even more important contributors to the typical vetiver character.
Related JoVE Video
Parietal network underlying movement control: disturbances during subcortical electrostimulation.
Neurosurg Rev
PUBLISHED: 02-14-2014
Show Abstract
Hide Abstract
Our understanding of brain movement control has changed over the last two decades. Recent findings in the monkey and in humans have led to a parallel and interconnected network. Nevertheless, little is known about these networks. Here, we present two cases of patients with a parietal low-grade glioma. They underwent surgery under local anesthesia with cortical and subcortical mapping. For patient 1, subcortical electrostimulation immediately posterior to thalamocortical fibers induced movement disorders, with an inhibition of leg and arm movements medially and, more laterally, an acceleration of arm movement. For patient 2, electrostimulation of white matter immediately posterior to thalamocortical fibers induced an inhibition of both arm movement. It means that the detected fibers in the parietal lobe may be involved in the motor control modulation. They are distributed veil-like immediately posterior to thalamocortical pathways and could correspond to a fronto-parietal movement control subnetwork. These two cases highlight the major role of the subcortical connectivity in movement regulation, involving parietal lobe, thus the necessity to be identified and preserved during brain surgery.
Related JoVE Video
Oncological patterns of care and outcomes for 265 elderly patients with newly diagnosed glioblastoma in France.
Neurosurg Rev
PUBLISHED: 02-14-2014
Show Abstract
Hide Abstract
The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ? 70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n?=?95) or biopsy (B n?=?170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n?=?76), chemotherapy (CT n?=?52), and concomitant radiochemotherapy (CRC n?=?39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B?+?RT and/or CT, RS?±?RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n?=?41, 199[155-280]; B-CRC n?=?21, 318[166-480]; B-RT n?=?37, 149[130-214]; RS-CT n?=?11, 245[211-na]; RS-CRC n?=?18, 372[349-593]; RS-RT n?=?39, 269[218-343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible.
Related JoVE Video
Concurrent tumor segmentation and registration with uncertainty-based sparse non-uniform graphs.
Med Image Anal
PUBLISHED: 02-13-2014
Show Abstract
Hide Abstract
In this paper, we present a graph-based concurrent brain tumor segmentation and atlas to diseased patient registration framework. Both segmentation and registration problems are modeled using a unified pairwise discrete Markov Random Field model on a sparse grid superimposed to the image domain. Segmentation is addressed based on pattern classification techniques, while registration is performed by maximizing the similarity between volumes and is modular with respect to the matching criterion. The two problems are coupled by relaxing the registration term in the tumor area, corresponding to areas of high classification score and high dissimilarity between volumes. In order to overcome the main shortcomings of discrete approaches regarding appropriate sampling of the solution space as well as important memory requirements, content driven samplings of the discrete displacement set and the sparse grid are considered, based on the local segmentation and registration uncertainties recovered by the min marginal energies. State of the art results on a substantial low-grade glioma database demonstrate the potential of our method, while our proposed approach shows maintained performance and strongly reduced complexity of the model.
Related JoVE Video
Inferring a dual-stream model of mentalizing from associative white matter fibres disconnection.
Brain
PUBLISHED: 02-10-2014
Show Abstract
Hide Abstract
In the field of cognitive neuroscience, it is increasingly accepted that mentalizing is subserved by a complex frontotemporoparietal cortical network. Some researchers consider that this network can be divided into two distinct but interacting subsystems (the mirror system and the mentalizing system per se), which respectively process low-level, perceptive-based aspects and high-level, inference-based aspects of this sociocognitive function. However, evidence for this type of functional dissociation in a given neuropsychological population is currently lacking and the structural connectivities of the two mentalizing subnetworks have not been established. Here, we studied mentalizing in a large sample of patients (n = 93; 46 females; age range: 18-65 years) who had been resected for diffuse low-grade glioma-a rare tumour that migrates preferentially along associative white matter pathways. This neurological disorder constitutes an ideal pathophysiological model in which to study the functional anatomy of associative pathways. We mapped the location of each patient's resection cavity and residual lesion infiltration onto the Montreal Neurological Institute template brain and then performed multilevel lesion analyses (including conventional voxel-based lesion-symptom mapping and subtraction lesion analyses). Importantly, we estimated each associative pathway's degree of disconnection (i.e. the degree of lesion infiltration) and built specific hypotheses concerning the connective anatomy of the mentalizing subnetworks. As expected, we found that impairments in mentalizing were mainly related to the disruption of right frontoparietal connectivity. More specifically, low-level and high-level mentalizing accuracy were correlated with the degree of disconnection in the arcuate fasciculus and the cingulum, respectively. To the best of our knowledge, our findings constitute the first experimental data on the structural connectivity of the mentalizing network and suggest the existence of a dual-stream hodological system. Our results may lead to a better understanding of disorders that affect social cognition, especially in neuropathological conditions characterized by atypical/aberrant structural connectivity, such as autism spectrum disorders.
Related JoVE Video
The effect of delivering the chemokine SDF-1? in a matrix-bound manner on myogenesis.
Biomaterials
PUBLISHED: 02-05-2014
Show Abstract
Hide Abstract
Several chemokines are important in muscle myogenesis and in the recruitment of muscle precursors during muscle regeneration. Among these, the SDF-1? chemokine (CXCL12) is a potent chemoattractant known to be involved in muscle repair. SDF-1? was loaded in polyelectrolyte multilayer films made of poly(L-lysine) and hyaluronan to be delivered locally to myoblast cells in a matrix-bound manner. The adsorbed amounts of SDF-1? were tuned over a large range from 100 ng/cm(2) to 5 ?g/cm(2), depending on the initial concentration of SDF-1? in solution, its pH, and on the film crosslinking extent. Matrix-bound SDF-1? induced a striking increase in myoblast spreading, which was revealed when it was delivered from weakly crosslinked films. It also significantly enhanced cell migration in a dose-dependent manner, which again depended on its presentation by the biopolymeric film. The low-crosslinked film was the most efficient in boosting cell migration. Furthermore, matrix-bound SDF-1? also increased the expression of myogenic markers but the fusion index decreased in a dose-dependent manner with the adsorbed amount of SDF-1?. At high adsorbed amounts of SDF-1?, a large number of Troponin T-positive cells had only one nucleus. Overall, this work reveals the importance of the presentation mode of SDF-1? to emphasize its effect on myogenic processes. These films may be further used to provide insight into the role of SDF-1? presented by a biomaterial in physiological or pathological processes.
Related JoVE Video
Awake mapping for low-grade gliomas involving the left sagittal stratum: anatomofunctional and surgical considerations.
J. Neurosurg.
PUBLISHED: 01-31-2014
Show Abstract
Hide Abstract
Preserving function while optimizing the extent of resection is the main goal in surgery for diffuse low-grade glioma (DLGG). This is particularly relevant for DLGG involving the sagittal stratum (SS), where damage can have severe consequences. Indeed, this structure is a major crossroad in which several important fascicles run. Thus, its complex functional anatomy is still poorly understood. Subcortical electrical stimulation during awake surgery provides a unique opportunity to investigate white matter pathways. This study reports the findings on anatomofunctional correlations evoked by stimulation during resection for gliomas involving the left SS. Surgical outcomes are also detailed.
Related JoVE Video
Structure?Odor Relationships of Semisynthetic ?-Santalol Analogs.
Chem. Biodivers.
PUBLISHED: 01-15-2014
Show Abstract
Hide Abstract
A series of eleven ?-santalol analogs, including nine new derivatives, was prepared by semisynthesis from natural (-)-(Z)-?-santalol and studied by gas chromatography-olfactometry (GC-O) to characterize their olfactory properties and potencies. These compounds and 45 others selected in the literature were used to build three olfactophores by molecular modelling. Three models were obtained that gather structural and physicochemical constraints that will be useful for further design of new sandalwood odorants.
Related JoVE Video
Post-Synthetic Regulation of HS Structure: The Yin and Yang of the Sulfs in Cancer.
Front Oncol
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
Heparan sulfate (HS) is a complex polysaccharide that takes part in most major cellular processes, through its ability to bind and modulate a very large array of proteins. These interactions involve saccharide domains of specific sulfation pattern (S-domains), the assembly of which is tightly orchestrated by a highly regulated biosynthesis machinery. Another level of structural control does also take place at the cell surface, where degrading enzymes further modify HS post-synthetically. Amongst them are the Sulfs, a family of extracellular sulfatases (two isoforms in human) that catalyze the specific 6-O-desulfation of HS. By targeting HS functional sulfated domains, Sulfs dramatically alter its ligand binding properties, thereby modulating a broad range of signaling pathways. Consequently, Sulfs play major roles during development, as well as in tissue homeostasis and repair. Sulfs have also been associated with many pathologies including cancer, but despite increasing interest, the role of Sulfs in tumor development still remains unclear. Studies have been hindered by a poor understanding of the Sulf enzymatic activities and conflicting data have shown either anti-oncogenic or tumor-promoting effects of these enzymes, depending on the tumor models analyzed. These opposite effects clearly illustrate the fine tuning of HS functions by the Sulfs, and the need to clarify the mechanisms involved. In this review, we will detail the present knowledge on the structural and functional properties of the Sulfs, with a special focus on their implication during tumor progression. Finally, we will discuss attempts and perspectives of using the Sulfs as a biomarker of cancer prognosis and diagnostic and as a target for anti-cancer therapies.
Related JoVE Video
Disruption of bimanual movement by unilateral subcortical electrostimulation.
Hum Brain Mapp
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
Cortical areas involved in bimanual coordination have been regularly studied by functional neuroimaging and electroencephalography. However, the subcortical connectivity underlying this complex function has received less attention. Here, we used the technique of direct electrostimulation in awake patients who underwent surgery for brain glioma, with the goal to investigate the white matter pathways subserving bimanual coordination.
Related JoVE Video
The persistent crucial role of the left hemisphere for language in left-handers with a left low grade glioma: a stimulation mapping study.
Acta Neurochir (Wien)
PUBLISHED: 01-09-2014
Show Abstract
Hide Abstract
Left-handers have a more bilateral language representation than right-handers. Therefore, in left-handers with a low-grade glioma (LGG) in the left hemisphere (LH), one could hypothesize that the right hemisphere (RH) might allow language compensation, at least partly, with no or only a minor persistent role of the LH in speech. However, although LGG induces language reorganization in right-handed patients, little is known in left-handers. Here, we report the first series of left-handers who underwent awake surgery for a left LGG using intraoperative mapping, in order to investigate whether there was still an involvement of LH in language.
Related JoVE Video
Disrupting posterior cingulate connectivity disconnects consciousness from the external environment.
Neuropsychologia
PUBLISHED: 01-05-2014
Show Abstract
Hide Abstract
Neurophysiological and neuroimaging studies including both patients with disorders of consciousness and healthy subjects with modified states of consciousness suggest a crucial role of the medial posteroparietal cortex in conscious information processing. However no direct neuropsychological evidence supports this hypothesis and studies including patients with restricted lesions of this brain region are almost non-existent. Using direct intraoperative electrostimulations, we showed in a rare patient that disrupting the subcortical connectivity of the left posterior cingulate cortex (PCC) reliably induced a breakdown in conscious experience. This acute phenomenon was mainly characterized by a transient behavioral unresponsiveness with loss of external connectedness. In all cases, when he regained consciousness, the patient described himself as in dream, outside the operating room. This finding suggests that functional integrity of the PPC connectivity is necessary for maintaining consciousness of external environment.
Related JoVE Video
The left inferior fronto-occipital fasciculus subserves language semantics: a multilevel lesion study.
Brain Struct Funct
PUBLISHED: 01-04-2014
Show Abstract
Hide Abstract
Consequential works in cognitive neuroscience have led to the formulation of an interactive dual-stream model of language processing: the dorsal stream may process the phonological aspects of language, whereas the ventral stream may process the semantic aspects of language. While it is well-accepted that the dorsal route is subserved by the arcuate fasciculus, the structural connectivity of the semantic ventral stream is a matter of dispute. Here we designed a longitudinal study to gain new insights into this central but controversial question. Thirty-one patients harboring a left diffuse low-grade glioma-a rare neurological condition that infiltrates preferentially white matter associative pathways-were assessed with a prototypical task of language (i.e. verbal fluency) before and after surgery. All were operated under local anesthesia with a cortical and subcortical brain mapping-enabling to identify and preserve eloquent structures for language. We performed voxel-based lesion-symptom (VLSM) analyses on pre- and postoperative behavioral data. Preoperatively, we found a significant relationship between semantic fluency scores and the white matter fibers shaping the ventro-lateral connectivity (P < 0.05 corrected). The statistical map was found to substantially overlap with the spatial position of the inferior fronto-occipital fasciculus (IFOF) (37.7 %). Furthermore, a negative correlation was observed between semantic fluency scores and the infiltration volumes in this fasciculus (r = -0.4, P = 0.029). Postoperatively, VLSM analyses were inconclusive. Taken as a whole and when combined with the literature data, our findings strengthen the view that the IFOF plays an essential role in semantic processing and may subserve the direct ventral pathway of language.
Related JoVE Video
Understanding entangled cerebral networks: a prerequisite for restoring brain function with brain-computer interfaces.
Front Syst Neurosci
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Historically, cerebral processing has been conceptualized as a framework based on statically localized functions. However, a growing amount of evidence supports a hodotopical (delocalized) and flexible organization. A number of studies have reported absence of a permanent neurological deficit after massive surgical resections of eloquent brain tissue. These results highlight the tremendous plastic potential of the brain. Understanding anatomo-functional correlates underlying this cerebral reorganization is a prerequisite to restore brain functions through brain-computer interfaces (BCIs) in patients with cerebral diseases, or even to potentiate brain functions in healthy individuals. Here, we review current knowledge of neural networks that could be utilized in the BCIs that enable movements and language. To this end, intraoperative electrical stimulation in awake patients provides valuable information on the cerebral functional maps, their connectomics and plasticity. Overall, these studies indicate that the complex cerebral circuitry that underpins interactions between action, cognition and behavior should be throughly investigated before progress in BCI approaches can be achieved.
Related JoVE Video
Epileptic seizures in diffuse low-grade gliomas in adults.
Brain
PUBLISHED: 12-27-2013
Show Abstract
Hide Abstract
Diffuse low-grade gliomas are highly epileptogenic brain tumours. We aimed to explore the natural course of epileptic seizures, their predictors and the prognostic significance of their occurrence in adult patients harbouring a diffuse low-grade glioma. An observational retrospective multicentre study examined 1509 patients with diffuse low-grade gliomas to identify mutual interactions between tumour characteristics, tumour course and epileptic seizures. At diagnosis, 89.9% of patients had epileptic seizures. Male gender (P = 0.003) and tumour location within functional areas (P = 0.001) were independent predictors of a history of epileptic seizures at diagnosis. Tumour volume, growth velocity, cortical location, histopathological subtype or molecular markers did not significantly affect epileptic seizure occurrence probability. Prolonged history of epileptic seizures (P < 0.001), insular location (P = 0.003) and tumour location close to functional areas (P = 0.038) were independent predictors of uncontrolled epileptic seizures at diagnosis. Occurrence of epileptic seizures (P < 0.001), parietal (P = 0.029) and insular (P = 0.002) locations were independent predictors of uncontrolled epileptic seizures after oncological treatment. Patient age (P < 0.001), subtotal (P = 0.007) and total (P < 0.001) resections were independent predictors of total epileptic seizure control after oncological treatment. History of epileptic seizures at diagnosis and total surgical resection were independently associated with increased malignant progression-free (P < 0.001 and P < 0.001) and overall (P < 0.001 and P = 0.016) survivals. Epileptic seizures are independently associated with diffuse low-grade glioma prognosis. Patients diagnosed with epileptic seizures and those with complete and early surgical resections have better oncological outcomes. Early and maximal surgical resection is thus required for diffuse low-grade gliomas, both for oncological and epileptological purposes.
Related JoVE Video
Brain mapping in tumors: Intraoperative or extraoperative?
Epilepsia
PUBLISHED: 12-17-2013
Show Abstract
Hide Abstract
In nontumoral epilepsy surgery, the main goal for all preoperative investigation is to first determine the epileptogenic zone, and then to analyze its relation to eloquent cortex, in order to control seizures while avoiding adverse postoperative neurologic outcome. To this end, in addition to neuropsychological assessment, functional neuroimaging and scalp electroencephalography, extraoperative recording, and electrical mapping, especially using subdural strip- or grid-electrodes, has been reported extensively. Nonetheless, in tumoral epilepsy surgery, the rationale is different. Indeed, the first aim is rather to maximize the extent of tumor resection while minimizing postsurgical morbidity, in order to increase the median survival as well as to preserve quality of life. As a consequence, as frequently seen in infiltrating tumors such as gliomas, where these lesions not only grow but also migrate along white matter tracts, the resection should be performed according to functional boundaries both at cortical and subcortical levels. With this in mind, extraoperative mapping by strips/grids is often not sufficient in tumoral surgery, since in essence, it allows study of the cortex but cannot map subcortical pathways. Therefore, intraoperative electrostimulation mapping, especially in awake patients, is more appropriate in tumor surgery, because this technique allows real-time detection of areas crucial for cerebral functions-eloquent cortex and fibers-throughout the resection. In summary, rather than choosing one or the other of different mapping techniques, methodology should be adapted to each pathology, that is, extraoperative mapping in nontumoral epilepsy surgery and intraoperative mapping in tumoral surgery.
Related JoVE Video
Delayed leptomeningeal and subependymal seeding after multiple surgeries for supratentorial diffuse low-grade gliomas in adults.
J. Neurosurg.
PUBLISHED: 11-29-2013
Show Abstract
Hide Abstract
Object Diffuse WHO Grade II glioma (diffuse low-grade glioma [DLGG]) is an infiltrative brain tumor that usually migrates along the white matter fibers. The delayed CSF dissemination of supratentorial DLGGs is an exceptional complication and is rarely described in adults. Here, the authors report outcomes in a surgical series of 9 patients with DLGGs with subsequent leptomeningeal and/or subependymal seeding (LMSS) following multiple incomplete resections. Methods The authors performed a retrospective review of patients who underwent surgery for histopathologically confirmed WHO Grade II gliomas between 1998 and 2012 and experienced a secondary CSF spread. Information regarding clinical features, surgical procedures, histopathological results, adjuvant treatment, and clinical outcomes was collected and analyzed. Results Nine consecutive patients were included in this study. There were 6 men and 3 women whose mean age was 35.5 years (range 22-59 years) at the time of initial symptom onset. All patients underwent surgery with the aid of intraoperative mapping, with incomplete tumor removal because of invasion of eloquent structures. The neuropathological examination diagnosed a DLGG in all cases (7 oligodendrogliomas, 1 astrocytoma, and 1 oligoastrocytoma). Five patients had a 1p19q codeletion. Because of tumor regrowth, the 9 patients underwent reoperation (2 surgeries in 6 cases and 3 surgeries in 3 cases), again with incomplete resection. There were no surgical complications. Adjuvant therapy (radiotherapy and chemotherapy) was administered in all patients because of progression to a higher grade of malignancy that was histopathologically confirmed in all tumors. The patients suddenly worsened, and the diagnosis of LMSS was made with a mean delay of 77 months (range 27-140 months) after the initial symptom onset. Six patients benefited from salvage chemotherapy while palliative care was chosen in 3 cases. The median survival in the 6 patients who underwent LMSS treatment was significantly longer than that in the 3 patients who did not receive salvage chemotherapy (p = 0.03). Indeed, all patients died, with a mean delay between the diagnosis of LMSS and death of 11 months (range 2-38 months) and with a mean delay between the initial symptom onset and death of 88 months (range 34-144 months). Conclusions Cerebrospinal fluid dissemination of DLGG is a rare but possible event. It can occur throughout the progression of WHO Grade II oligodendrogliomas, oligoastrocytomas, and astrocytomas, regardless of 1p19q status. This complication seems to appear in patients who have undergone multiple incomplete resections. Salvage therapy can be considered in patients with good neurological status. However, LMSS is associated with a decreased overall survival. Therefore, this rare entity deserves further multicenter studies to better understand its pathophysiology and to adapt therapeutic strategies.
Related JoVE Video
Selection of intraoperative tasks for awake mapping based on relationships between tumor location and functional networks.
J. Neurosurg.
PUBLISHED: 09-20-2013
Show Abstract
Hide Abstract
Intraoperative electrical brain mapping is currently the most reliable method to identify eloquent cortical and subcortical structures at the individual level and to optimize the extent of resection of intrinsic brain tumors. The technique allows the preservation of quality of life, not only allowing avoidance of severe neurological deficits but also facilitating preservation of high neurocognitive functions. To accomplish this goal, however, it is crucial to optimize the selection of appropriate intraoperative tasks, given the limited intrasurgical awake time frame. In this review, the authors aim was to propose specific parameters that could be used to build a personalized protocol for each patient. They have focused on lesion location and relationships with functional networks to guide selection of intrasurgical tasks in an effort to increase reproducibility among neurooncological centers.
Related JoVE Video
Surgical management of diffuse low-grade gliomas associated with other intracranial diseases.
Acta Neurochir (Wien)
PUBLISHED: 09-18-2013
Show Abstract
Hide Abstract
The association of diffuse, low-grade glioma (DLGG) with other intracranial pathologies is a rare condition, raising the question of what constitutes its most effective therapeutic management. It is not known whether this is a simple coincidence or whether there is a higher significant risk involved with the co-existence of DLGG and another disease. We report the first consecutive series of nine patients who underwent surgical resection for such a glioma.
Related JoVE Video
The silent phase of diffuse low-grade gliomas. Is it when we missed the action?
Acta Neurochir (Wien)
PUBLISHED: 06-24-2013
Show Abstract
Hide Abstract
It is commonly believed that, before being diagnosed after onset of symptoms, diffuse low-grade glioma evolve silently for a long time. The present study aimed to estimate for the first time the exact duration of this silent phase, during which the glioma is radiologically visible but undiscovered.
Related JoVE Video
The huge plastic potential of adult brain and the role of connectomics: New insights provided by serial mappings in glioma surgery.
Cortex
PUBLISHED: 06-14-2013
Show Abstract
Hide Abstract
While prominent in the traditional literature, the localizationist and static view of brain processing does not explain numerous observations of functional recovery following cerebral damages. Here, the goal is to revisit this classical modular and inflexible model by proposing a dynamic organization of brain circuits, which allows postlesional cerebral adaptative phenomena able to maintain neurological and cognitive functions, even in adults. In this state of mind, recent data provided by serial mappings performed in patients who underwent awake surgery for diffuse glioma infiltrating eloquent structures will be reviewed. Firstly, the use of intraoperative electrical mapping enables the realization of on-line anatomo-functional correlations both at cortical and subcortical levels, supporting a network distribution of the brain, and resulting in the reappraisal of cognitive models - notably regarding language. Secondly, combination of neuropsychological assessments and functional neuroimaging before and after operation demonstrates that it is possible to achieve massive resections of "critical" regions without eliciting permanent sequelae, thanks to reorganization of cerebral circuits. Thirdly, repeated surgeries in cases of tumor relapse show functional remapping in the same patients over time. Taken together, these findings open the window toward a huge plastic potential of human central nervous system (CNS) in adults. However, a better understanding of cerebral connectomics leads to the conclusion that the white matter connectivity constitutes a main limitation of such brain plasticity, explaining the lack of recovery in patients with extensive subcortical damages.
Related JoVE Video
Surgery for low-grade glioma infiltrating the central cerebral region: location as a predictive factor for neurological deficit, epileptological outcome, and quality of life.
J. Neurosurg.
PUBLISHED: 06-14-2013
Show Abstract
Hide Abstract
A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patients functional integrity. This concern is particularly relevant for gliomas in the central region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life.
Related JoVE Video
Insights into the mechanism by which interferon-? basic amino acid clusters mediate protein binding to heparan sulfate.
J. Am. Chem. Soc.
PUBLISHED: 06-13-2013
Show Abstract
Hide Abstract
The extensive functional repertoire of heparin and heparan sulfate, which relies on their ability to interact with a large number of proteins, has recently emerged. To understand the forces that drive such interactions the binding of heparin to interferon-? (IFN?), used as a model system, was investigated. NMR-based titration experiments demonstrated the involvement of two adjacent cationic domains (D1: KTGKRKR and D2: RGRR), both of which are present within the carboxy-terminal sequence of the cytokine. Kinetic analysis showed that these two domains contribute differently to the interaction: D1 is required to form a complex and constitutes the actual binding site, whereas D2, although unable to associate with heparin by itself, increased the association rate of the binding. These data are consistent with the view that D2, through nonspecific electrostatic forces, places the two molecules in favorable orientations for productive binding within the encounter complex. This mechanism was supported by electrostatic potential analysis and thermodynamic investigations. They showed that D1 association to heparin is driven by both favorable enthalpic and entropic contributions, as expected for a binding sequence, but that D2 gives rise to entropic penalty, which opposes binding in a thermodynamic sense. The binding mechanism described herein, by which the D2 domain kinetically drives the interaction, has important functional consequences and gives a structural framework to better understand how specific are the interactions between proteins and heparin.
Related JoVE Video
Mapping the connectivity underlying multimodal (verbal and non-verbal) semantic processing: a brain electrostimulation study.
Neuropsychologia
PUBLISHED: 06-03-2013
Show Abstract
Hide Abstract
Accessing the meaning of words, objects, people and facts is a human ability, made possible thanks to semantic processing. Although studies concerning its cortical organization are proficient, the subcortical connectivity underlying this semantic network received less attention. We used intraoperative direct electrostimulation, which mimics a transient virtual lesion during brain surgery for glioma in eight awaken patients, to map the anatomical white matter substrate subserving the semantic system. Patients performed a picture naming task and a non-verbal semantic association test during the electrical mapping. Direct electrostimulation of the inferior fronto-occipital fascicle, a poorly known ventral association pathway which runs throughout the brain, induced in all cases semantic disturbances. These transient disorders were highly reproducible, and concerned verbal as well as non-verbal output. Our results highlight for the first time the essential role of the left inferior fronto-occipital fascicle in multimodal (and not only in verbal) semantic processing. On the basis of these original findings, and in the lights of phylogenetic considerations regarding this fascicle, we suggest its possible implication in the monitoring of the human level of consciousness related to semantic memory, namely noetic consciousness.
Related JoVE Video
Is the right frontal cortex really crucial in the mentalizing network? A longitudinal study in patients with a slow-growing lesion.
Cortex
PUBLISHED: 05-11-2013
Show Abstract
Hide Abstract
Assessing the subjective experience of others in terms of mental states, a brain function referred to as mentalizing, is achieved in the brain through a set of low-level perceptual and high-level inference-based processes. Because of its recurrent implication in fMRI studies, the right frontal cortex, especially in its inferolateral and dorsomesial parts, is posited to be a "core system" in the sustenance of these neurocognitive mechanisms. In this context, we reasoned that if the right frontal cortex is really crucial for mentalizing, its surgical resection, following diffuse low-grade glioma invasion, should induce irreversible impairments. To test this hypothesis, we designed a longitudinal experimental setup in which ten patients harboring a low-grade glioma in right frontal areas were assessed just before, immediately after and three months after a brain surgery. Two well-validated behavioral tasks, thought to evaluate both aspects of mentalizing, were administered. The results obtained provide evidence that widespread surgical excisions of the right prefrontal cortex do not induce a long-term worsening of both aspects of mentalizing, although some transitory effects are observed immediately after the surgery. They suggest also for the first time in the same sample of patients a possible double functional dissociation between low-level perceptual (posterior inferolateral prefrontal) and high-level inference-based (dorsomesial prefrontal) mentalizing processes. This overall finding challenges the traditional view according to which the right frontal cortex is an "essential cortical node" in the mentalizing network since it might be expected that massive surgical excisions of this brain area would have induced more definitive impairments.
Related JoVE Video
The Role of Left Inferior Fronto-Occipital Fascicle in Verbal Perseveration: A Brain Electrostimulation Mapping Study.
Brain Topogr
PUBLISHED: 04-28-2013
Show Abstract
Hide Abstract
The subcortical connectivity underlying verbal perseveration (VP) remains poorly understood. We have previously reported that intraoperative electrical stimulation of the caudate nucleus during awake surgery resulted in VP. Here, our purpose is to study the white matter pathway underlying VP using subcortical stimulation mapping in a series of patients who underwent glioma resection. Eleven patients with a left hemispheric low grade glioma were operated on while awake. Intraoperative direct electrical stimulation was used both at cortical and subcortical levels while the patients carried out motor and naming tasks during the resection. All patients experienced VP during electrical stimulation performed at the level of different subcortical locations, which corresponded in the 11 cases to different parts of the left inferior fronto-occipital fascicle. Perseveration persisted into the postoperative days, but resolved completely by three months.Our original findings provide further insight into the neuroanatomical basis of VP, by supporting the role of left inferior fronto-occipital fascicle. Such data may have both fundamental and clinical implications.
Related JoVE Video
Tolerance of awake surgery for glioma: a prospective European Low Grade Glioma Network multicenter study.
Acta Neurochir (Wien)
PUBLISHED: 04-18-2013
Show Abstract
Hide Abstract
Gross total removal of glioma is limited by proximity to eloquent brain. Awake surgery allows for intraoperative monitoring to safely identify eloquent regions. However, data on adverse psychological effects induced in these patients is limited.
Related JoVE Video
A re-examination of neural basis of language processing: Proposal of a dynamic hodotopical model from data provided by brain stimulation mapping during picture naming.
Brain Lang
PUBLISHED: 04-15-2013
Show Abstract
Hide Abstract
From recent findings provided by brain stimulation mapping during picture naming, we re-examine the neural basis of language. We studied structural-functional relationships by correlating the types of language disturbances generated by stimulation in awake patients, mimicking a transient virtual lesion both at cortical and subcortical levels (white matter and deep grey nuclei), with the anatomical location of the stimulation probe. We propose a hodotopical (delocalized) and dynamic model of language processing, which challenges the traditional modular and serial view. According to this model, following the visual input, the language network is organized in parallel, segregated (even if interconnected) large-scale cortico-subcortical sub-networks underlying semantic, phonological and syntactic processing. Our model offers several advantages (i) it explains double dissociations during stimulation (comprehension versus naming disorders, semantic versus phonemic paraphasias, syntactic versus naming disturbances, plurimodal judgment versus naming disorders); (ii) it takes into account the cortical and subcortical anatomic constraints; (iii) it explains the possible recovery of aphasia following a lesion within the "classical" language areas; (iv) it establishes links with a model executive functions.
Related JoVE Video
The disulfide bond between cysteine 10 and cysteine 34 is required for CCL18 activity.
Cytokine
PUBLISHED: 04-09-2013
Show Abstract
Hide Abstract
Asthma is a Th2-mediated disease that involves Th2 cell and eosinophil migration into the bronchial mucosa which is dependent upon the expression of a specific set of chemokines within the lung. Among them, CCL18 seems to play a key role because of its preferential expression in the lung, and its up-regulation by Th2 cytokines. Here, we show that the optimal naïve T cell and basophil chemotaxis, and basophil histamine release induced by rhCCL18 occurred at a 100 time lower concentration with CHO-derived rhCCL18 than with E. coli-derived rhCCL18. FT-ICR mass spectrometry of the intact chemokines showed that the rhCCL18 produced by CHO cells contained the 2 disulfide bonds Cys10-Cys34 and Cys11-Cys50, in clear contrast to the rhCCL18 derived from E. coli where the Cys10-Cys34 bond was absent. We found that reduction of the Cys10-Cys34 of the CHO-derived rhCCL18 resulted in a shift of its activity, reaching the same level as the E. coli-derived rhCCL18. These results demonstrate that the Cys10-Cys34 disulfide bond is involved in the function of CCL18.
Related JoVE Video
Evidence of a middle longitudinal fasciculus in the human brain from fiber dissection.
J. Anat.
PUBLISHED: 04-01-2013
Show Abstract
Hide Abstract
A rostrocaudal pathway connecting the temporal and parietal lobes was described in monkeys using autoradiography and was named the middle longitudinal fasciculus (MdLF). Recently, the use of diffusion tensor tractography has allowed it to be depicted in human volunteers. In the present study, a technique of fiber dissection was used in 18 cadaveric human brains to investigate the presence of this fasciculus and to detail its anatomical relationships. On the basis of our findings, fiber dissection provides evidence for a long horizontal bundle medial to the arcuate fasciculus and extending to the superior temporal gyrus. Its fibers occupy the lateral-most layer of the upper portion of the stratum sagittale and partially cover the inferior fronto-occipital fasciculus, which is situated deeper and slightly inferiorly. Whereas MdLF fibers continue on a relatively superficial level to reach the superior temporal gyrus, the inferior fronto-occipital fasciculus penetrates the deep temporal white matter and crosses the insular lobe. Although diffusion tensor imaging suggests that the MdLF terminates in the angular gyrus, this was not confirmed by the present study. These long association fibers continue onward posteriorly into upper portions of the occipital lobe. Further studies are needed to understand the role of the MdLF in brain function.
Related JoVE Video
Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas: a series of 1097 cases: clinical article.
J. Neurosurg.
PUBLISHED: 03-15-2013
Show Abstract
Hide Abstract
The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed.
Related JoVE Video
Surgical management of multicentric diffuse low-grade gliomas: functional and oncological outcomes: clinical article.
J. Neurosurg.
PUBLISHED: 03-15-2013
Show Abstract
Hide Abstract
Multicentric diffuse low-grade gliomas (DLGGs) are defined as widely separated lesions in different lobes or hemispheres where there is no anatomical continuity between lesions. This condition is rare and its clinicopathological characteristics have been scarcely described in the literature. Here, the authors report the first consecutive surgical series of multicentric DLGGs with functional and oncological outcomes.
Related JoVE Video
Neoadjuvant chemotherapy may optimize the extent of resection of World Health Organization grade II gliomas: a case series of 17 patients.
J. Neurooncol.
PUBLISHED: 03-04-2013
Show Abstract
Hide Abstract
The involvement of eloquent brain areas may preclude the total/subtotal surgical resection of diffuse low-grade gliomas (DLGGs). The feasibility and functional tolerance of neoadjuvant chemotherapy have been demonstrated in such cases. The present study assesses the clinical and radiological impact of neoadjuvant chemotherapy on the natural course of DLGG. Seventeen patients without feasible surgical resection (infiltration of functional areas and/or large contralateral extension) were retrospectively selected. Temozolomide based neoadjuvant chemotherapy was initiated, inducing a tumor volume decrease and allowing a functional based maximal surgical resection. The median follow-up since initial radiological diagnosis was 5.9 years (range, 1.4-11). The median time to malignant transformation was 5.9 years. Six patients (35 %) had 1p19q codeletion, 12 patients (70 %) with IDH mutation and MGMT promoter methylation, and eight patients (47 %) had p53 overexpression. Chemotherapy reduced tumor volume (median -35.6 %, range -61.6 to -5.1 %) in contralateral hemisphere through the corpus callosum in seven cases (41 %) and in ipsi-lesional functional areas in ten cases (59 %). Chemotherapy significantly decreased the imaging tumor growth (measured by the velocity of diametric expansion VDE) with a median of -3.2 mm/year (range, -29.8 to -0.9 mm/year) (p < 0.001). A tumor volume decrease of more than 20 % was correlated with a lower postoperative residual tumor (median 2 cc, p = 0.04), a greater extent of resection (93.1 vs. 89.5 %), a higher probability of total/subtotal removal. Neoadjuvant chemotherapy with Temozolomide could optimize the surgical resection of DLGGs and could impact their natural history. Further large prospective studies with long-term follow-up are needed.
Related JoVE Video
Lower motor neuron findings after upper motor neuron injury: insights from postoperative supplementary motor area syndrome.
Front Hum Neurosci
PUBLISHED: 03-01-2013
Show Abstract
Hide Abstract
Hypertonia and hyperreflexia are classically described responses to upper motor neuron injury. However, acute hypotonia and areflexia with motor deficit are hallmark findings after many central nervous system insults such as acute stroke and spinal shock. Historic theories to explain these contradictory findings have implicated a number of potential mechanisms mostly relying on the loss of descending corticospinal input as the underlying etiology. Unfortunately, these simple descriptions consistently fail to adequately explain the pathophysiology and connectivity leading to acute hyporeflexia and delayed hyperreflexia that result from such insult. This article highlights the common observation of acute hyporeflexia after central nervous system insults and explores the underlying anatomy and physiology. Further, evidence for the underlying connectivity is presented and implicates the dominant role of supraspinal inhibitory influence originating in the supplementary motor area descending through the corticospinal tracts. Unlike traditional explanations, this theory more adequately explains the findings of postoperative supplementary motor area syndrome in which hyporeflexia motor deficit is observed acutely in the face of intact primary motor cortex connections to the spinal cord. Further, the proposed connectivity can be generalized to help explain other insults including stroke, atonic seizures, and spinal shock.
Related JoVE Video
HSulf sulfatases catalyze processive and oriented 6-O-desulfation of heparan sulfate that differentially regulates fibroblast growth factor activity.
FASEB J.
PUBLISHED: 03-01-2013
Show Abstract
Hide Abstract
Sulfs are extracellular sulfatases that have emerged recently as critical regulators of heparan sulfate (HS) activities through their ability to catalyze specific 6-O-desulfation of the polysaccharide. Consequently, Sulfs have been involved in many physiological and pathological processes, and notably for Sulf-2, in the development of cancers with poor prognosis. Despite growing interest, little is known about the structure and activity of these enzymes and the way they induce dynamic remodeling of HS 6-O-sulfation status. Here, we have combined an array of analytical approaches, including mass spectrometry, NMR, HS oligosaccharide sequencing, and FACS, to dissect HSulf-2 sulfatase activity, either on a purified octasaccharide used as a mimic of HS functional domains, or on intact cell-surface HS chains. In parallel, we have studied the functional consequences of HSulf-2 activity on fibroblast growth factor (FGF)-induced mitogenesis and found that the enzyme could differentially regulate FGF1 and FGF2 activities. Notably, these data supported the existence of precise 6-O-sulfation patterns for FGF activation and provided new insights into the saccharide structures involved. Altogether, our data bring to light an original processive enzymatic mechanism, by which HSulfs catalyze oriented alteration of HS 6-O-desulfation patterns and direct fine and differential regulation of HS functions.
Related JoVE Video
Qualitative and quantitative analysis of vetiver essential oils by comprehensive two-dimensional gas chromatography and comprehensive two-dimensional gas chromatography/mass spectrometry.
J Chromatogr A
PUBLISHED: 02-25-2013
Show Abstract
Hide Abstract
Vetiver essential oils (VEO) are important raw ingredients used in perfume industry, entering the formula of numerous modern fragrances. Vetiver oils are considered to be among the most complex essential oils, resulting most of the time in highly coeluted chromatograms whatever the analytical technique. In this context, conventional gas chromatography has failed to provide a routine tool for the accurate qualitative and quantitative analysis of their constituents. Applying comprehensive two-dimensional gas chromatography techniques (GC×GC-FID/MS) afforded the mean to separate efficiently vetiver oil constituents in order to identify them in a more reliable way. Moreover, this is the first time that a complete true quantitation of each constituent is carried out on such complex oils by means of internal calibration. Finally, we have studied the influence of the injection mode on the determined chemical composition, and showed that several alcohols underwent dehydration under defined chromatographic conditions (splitless mode) usually recommended for quantitation purposes.
Related JoVE Video
The "onco-functional balance" in surgery for diffuse low-grade glioma: integrating the extent of resection with quality of life.
Acta Neurochir (Wien)
PUBLISHED: 02-07-2013
Show Abstract
Hide Abstract
Diffuse low-grade glioma (DLGG) is a growing pre-cancerous tumor, often diagnosed in patients with no or only mild deficit. Maximal and early surgical resection is currently the first therapeutic option, in order to delay the malignant transformation and thus increase the overall survival. Preserving the quality of life (QoL) is nonetheless another priority. Here, our purpose is to weight the value of the extent of resection versus the neurological worsening that could be voluntarily generated by a radical resection; that is, to study the "onco-functional balance" at the individual level. To this end, we will examine DLGG involving the supplementary motor area and DLGG involving visual pathways. We will consider the benefit-risk ratio of different strategies of resection, according to the brain structures actually invaded and their plastic potential. The aim is to increase both the quantity of life and the time with a normal QoL, on the basis of strong interactions between the tumor course, brain reorganization and multistage surgical approach adapted to each patient over time. To this end, beyond the conceptual and technical issues, the most important point remains the honest and unique relationship between the surgical oncologist and the patient, based on clear and complete information about the behavior of DLGG versus the expected medical and social consequences of a resection over years. In other words, in the era of "evidence-based medicine", it is crucial to not forget "individual-based medicine" by offering tailored resections adapted to each patient.
Related JoVE Video
Velocity of tumor spontaneous expansion predicts long-term outcomes for diffuse low-grade gliomas.
Neuro-oncology
PUBLISHED: 02-07-2013
Show Abstract
Hide Abstract
Supratentorial diffuse low-grade gliomas present a slow macroscopic tumor growth that can be quantified through the measurement of their velocity of diametric expansion. We assessed whether spontaneous velocity of diametric expansion can predict long-term outcomes as a categorical variable and as a continuous predictor.
Related JoVE Video
Distinct IDH1/IDH2 mutation profiles in purely insular versus paralimbic WHO Grade II gliomas.
J. Neurosurg.
PUBLISHED: 01-18-2013
Show Abstract
Hide Abstract
The molecular profile of diffuse WHO Grade II gliomas involving the insular lobe, with a possible impact on outcome, is controversial. The authors undertook this study to investigate a possible difference of molecular patterns between purely insular Grade II gliomas and paralimbic Grade II gliomas that involve both the insular lobe and the frontal and/or temporal structures.
Related JoVE Video
Limited plastic potential of the left ventral premotor cortex in speech articulation: Evidence From intraoperative awake mapping in glioma patients.
Hum Brain Mapp
PUBLISHED: 01-13-2013
Show Abstract
Hide Abstract
Objectives: Despite previous lesional and functional neuroimaging studies, the actual role of the left ventral premotor cortex (vPMC), i.e., the lateral part of the precentral gyrus, is still poorly known. Experimental design:We report a series of eight patients with a glioma involving the left vPMC, who underwent awake surgery with intraoperative cortical and subcortical language mapping. The function of the vPMC, its subcortical connections, and its reorganization potential are investigated in the light of surgical findings and language outcome after resection. Principal observations: Electrostimulation of both the vPMC and subcortical white matter tract underneath the vPMC, that is, the anterior segment of the lateral part of the superior longitudinal fascicle (SLF), induced speech production disturbances with anarthria in all cases. Moreover, although some degrees of redistribution of the vPMC have been found in four patients, allowing its partial resection with no permanent speech disorders, this area was nonetheless still detected more medially in the precentral gyrus in the eight patients, despite its invasion by the glioma. Moreover, a direct connection of the vPMC with the SLF was preserved in all cases. Conclusions: Our original data suggest that the vPMC plays a crucial role in the speech production network and that its plastic potential is limited. We propose that this limitation is due to an anatomical constraint, namely the necessity for the left vPMC to remain connected to the lateral SLF. Beyond fundamental implications, such knowledge may have clinical applications, especially in surgery for tumors involving this cortico-subcortical circuit. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
Related JoVE Video
Human Immunodeficiency Virus and Heparan Sulfate: From Attachment to Entry Inhibition.
Front Immunol
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
By targeting cells that provide protection against infection, HIV-1 causes acquired immunodeficiency syndrome. Infection starts when gp120, the viral envelope glycoprotein, binds to CD4 and to a chemokine receptor usually CCR5 or CXCR4. As many microorganisms, HIV-1 also interacts with heparan sulfate (HS), a complex group of cell surface associated anionic polysaccharides. It has been thought that this binding, occurring at a step prior to CD4 recognition, increases infectivity by pre-concentrating the virion particles at the cell surface. Early work, dating from before the identification of CCR5 and CXCR4, showed that a variety of HS mimetics bind to the gp120 V3 loop through electrostatic interactions, compete with cell surface associated HS to bind the virus and consequently, neutralize the infectivity of a number of T-cell line-adapted HIV-1 strains. However, progress made to better understand HIV-1 attachment and entry, coupled with the recent identification of additional gp120 regions mediating HS recognition, have considerably modified this view. Firstly, the V3 loop from CXCR4-using viruses is much more positively charged compared to those using CCR5. HS inhibition of cell attachment is thus restricted to CXCR4-using viruses (such as T-cell line-adapted HIV-1). Secondly, studies aiming at characterizing the gp120/HS complex revealed that HS binding was far more complex than previously thought: in addition to the V3 loop of CXCR4 tropic gp120, HS interacts with several other cryptic areas of the protein, which can be induced upon CD4 binding, and are conserved amongst CCR5 and CXCR4 viruses. In view of these data, this review will detail the present knowledge on HS binding to HIV-1, with regards to attachment and entry processes. It will discuss the perspective of targeting the gp120 co-receptor binding site with HS mimetic compounds, a strategy that recently gave rise to entry inhibitors that work in the low nanomolar range, independently of co-receptor usage.
Related JoVE Video
Resection probability maps for quality assessment of glioma surgery without brain location bias.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Intraoperative brain stimulation mapping reduces permanent postoperative deficits and extends tumor removal in resective surgery for glioma patients. Successful functional mapping is assumed to depend on the surgical teams expertise. In this study, glioma resection results are quantified and compared using a novel approach, so-called resection probability maps (RPM), exemplified by a surgical team comparison, here with long and short experience in mapping.
Related JoVE Video
Pathological neural attractor dynamics in slowly growing gliomas supports an optimal time frame for white matter plasticity.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Neurological function in patients with slowly growing brain tumors can be preserved even after extensive tumor resection. However, the global process of cortical reshaping and cerebral redistribution cannot be understood without taking into account the white matter tracts. The aim of this study was to predict the functional consequences of tumor-induced white matter damage by computer simulation. A computational model was proposed, incorporating two cortical patches and the white matter connections of the uncinate fasciculus. Tumor-induced structural changes were modeled such that different aspects of the connectivity were altered, mimicking the biological heterogeneity of gliomas. The network performance was quantified by comparing memory pattern recall and the plastic compensatory capacity of the network was analyzed. The model predicts an optimal level of synaptic conductance boost that compensates for tumor-induced connectivity loss. Tumor density appears to change the optimal plasticity regime, but tumor size does not. Compensatory conductance values that are too high lead to performance loss in the network and eventually to epileptic activity. Tumors of different configurations show differences in memory recall performance with slightly lower plasticity values for dense tumors compared to more diffuse tumors. Simulation results also suggest an optimal noise level that is capable of increasing the recall performance in tumor-induced white matter damage. In conclusion, the model presented here is able to capture the influence of different tumor-related parameters on memory pattern recall decline and provides a new way to study the functional consequences of white matter invasion by slowly growing brain tumors.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.