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.
Consensus Summary Statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care : A statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.
Neurocrit Care
PUBLISHED: 09-12-2014
Show Abstract
Hide Abstract
Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.
Related JoVE Video
Monitoring Biomarkers of Cellular Injury and Death in Acute Brain Injury.
Neurocrit Care
PUBLISHED: 09-12-2014
Show Abstract
Hide Abstract
Molecular biomarkers have revolutionalized diagnosis and treatment of many diseases, such as troponin use in myocardial infarction. Urgent need for high-fidelity biomarkers in neurocritical care has resulted in numerous studies reporting potential candidate biomarkers.
Related JoVE Video
GFAP Out-Performs S100? in Detecting Traumatic Intracranial Lesions on Computed Tomography in Trauma Patients with Mild Traumatic Brain Injury and Those with Extracranial Lesions.
J. Neurotrauma
PUBLISHED: 09-12-2014
Show Abstract
Hide Abstract
Abstract Both glial fibrillary acidic protein (GFAP) and S100? are found in glial cells and are released into serum following a traumatic brain injury (TBI), however, the clinical utility of S100? as a biomarker has been questioned because of its release from bone. This study examined the ability of GFAP and S100? to detect intracranial lesions on computed tomography (CT) in trauma patients and also assessed biomarker performance in patients with fractures and extracranial injuries on head CT. This prospective cohort study enrolled a convenience sample of adult trauma patients at a Level I trauma center with and without mild or moderate traumatic brain injury (MMTBI). Serum samples were obtained within 4?h of injury. The primary outcome was the presence of traumatic intracranial lesions on CT scan. There were 397 general trauma patients enrolled: 209 (53%) had a MMTBI and 188 (47%) had trauma without MMTBI. Of the 262 patients with a head CT, 20 (8%) had intracranial lesions. There were 137 (35%) trauma patients who sustained extracranial fractures below the head to the torso and extremities. Levels of S100? were significantly higher in patients with fractures, compared with those without fractures (p<0.001) whether MMTBI was present or not. However, GFAP levels were not significantly affected by the presence of fractures (p>0.05). The area under the receiver operating characteristics curve (AUC) for predicting intracranial lesions on CT for GFAP was 0.84 (0.73-0.95) and for S100? was 0.78 (0.67-0.89). However, in the presence of extracranial fractures, the AUC for GFAP increased to 0.93 (0.86-1.00) and for S100? decreased to 0.75 (0.61-0.88). In a general trauma population, GFAP out-performed S100? in detecting intracranial CT lesions, particularly in the setting of extracranial fractures.
Related JoVE Video
A Novel, Ultrasensitive Assay for Tau: Potential for Assessing Traumatic Brain Injury in Tissues and Biofluids.
J. Neurotrauma
PUBLISHED: 09-01-2014
Show Abstract
Hide Abstract
Traumatic brain injury (TBI) is a cause of death and disabilities and can lead to tauopathy-related dementia at an early age. Pathologically, TBI results in axonal injury which is coupled to tau hyperphosphorylation leading to microtubule instability and tau-mediated neurodegeneration. This suggests that the forms of this protein might serve as neuroinjury-related biomarkers for diagnosis of injury severity and prognosis of the neurological damage prior to clinical expression. We initially determined whether we could detect tau in body fluids using a highly sensitive assay. We used a novel immunoassay, EIMAF either alone or in combination with rolling circle amplification (a-EIMAF) for the detection of total (T) and phosphorylated (P) tau proteins from brains and biofluids (blood, CSF) of rodents following controlled cortical impact (CCI) and human patients post sTBI. This assay technology for tau is the most sensitive to date with a detection limit of approximately 100 ag/ml for either T-tau and P-tau. In the rodent models, T-tau and P-tau levels in brain and blood increased following CCI during the acute phase and remained high during the chronic phase (30 days). In human CSF samples, T-tau and P-tau increased during the sampling period (5-6 days). T-tau and P-tau in human serum rose during the acute phase and decreased during the chronic stage but was still detectable beyond 6 months post sTBI. Thus, EIMAF has the potential for both assessing the severity of the proximal injury as well as for prognoses using easily accessible samples.
Related JoVE Video
Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care : a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.
Intensive Care Med
PUBLISHED: 08-20-2014
Show Abstract
Hide Abstract
Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.
Related JoVE Video
Biomarkers Improve Clinical Outcome Predictors of Mortality Following Non-Penetrating Severe Traumatic Brain Injury.
Neurocrit Care
PUBLISHED: 07-24-2014
Show Abstract
Hide Abstract
This study assessed whether early levels of biomarkers measured in CSF within 24-h of severe TBI would improve the clinical prediction of 6-months mortality.
Related JoVE Video
Quantitative lobar cerebral blood flow for outcome prediction after traumatic brain injury.
J. Neurotrauma
PUBLISHED: 07-15-2014
Show Abstract
Hide Abstract
The goal of this study was to examine cortical cerebral blood flow (CBF) in patients with traumatic brain injury (TBI), and determine whether lobar cortical CBF is a better predictor of long-term neurological outcome assessed by Glasgow outcome scale (GOS) than global cortical CBF. Ninety-eight patients with TBI had a stable xenon computed tomography scan (Xe/CT-CBF study) performed at various time points after their initial injury. Spearman correlation coefficients and the Kruskal-Wallis test were used to examine the relationship between patient age, ER GCS, ISS, pre-hospital hypotension, pre-hospital hypoxia, mechanism of injury, type of injury, side of injury, global average CBF, lobar CBF, number of lobes with CBF below normal, and GOS (discharge, 3 months, 6 months). Univariate ordinal regression was performed using these same variable, and used in combination with principle component analysis, to determine independent variables for multivariate ordinal regression. Significant correlation between age, GCS, pre-hospital hypotension, type of injury, global average CBF, lobar CBF, number of lobes below normal CBF, and GOS was found. Individual lobar CBF was highly correlated with global CBF and the number of lobes below normal CBF. Principle component analysis found one principle component among these 3 CBF variables, therefore, average global CBF and number of lobes with CBF below normal were each chosen as independent variables for multiple ordinal regression, which found age, GCS, and pre-hospital hypotension, global average CBF, and number of lobes below normal CBF significantly associated with GOS. This study found global average CBF and lobar CBF significantly correlated with GOS at follow up. There was, however, no individual cerebral lobe that was more predictive than any other, which puts into question the value of calculating lobar CBF versus global CBF in predicting GOS.
Related JoVE Video
Predictors of outcome in civilians with gunshot wounds to the head upon presentation.
J. Neurosurg.
PUBLISHED: 07-04-2014
Show Abstract
Hide Abstract
Prediction of outcome from initial presentation after a gunshot wound to the head (GSWH) is essential to further clinical decision making. The authors' goals are to report the survival and functional outcomes of these patients, to identify prognostic factors, and to propose a scoring system that can predict their outcome.
Related JoVE Video
Dual vulnerability of TDP-43 to calpain and caspase-3 proteolysis after neurotoxic conditions and traumatic brain injury.
J. Cereb. Blood Flow Metab.
PUBLISHED: 05-21-2014
Show Abstract
Hide Abstract
Transactivation response DNA-binding protein 43 (TDP-43) proteinopathy has recently been reported in chronic traumatic encephalopathy, a neurodegenerative condition linked to prior history of traumatic brain injury (TBI). While TDP-43 appears to be vulnerable to proteolytic modifications under neurodegenerative conditions, the mechanism underlying the contribution of TDP-43 to the pathogenesis of TBI remains unknown. In this study, we first mapped out the calpain or caspase-3 TDP-43 fragmentation patterns by in vitro protease digestion. Concurrently, in cultured cerebrocortical neurons subjected to cell death challenges, we identified distinct TDP-43 breakdown products (BDPs) of 35, 33, and 12?kDa that were indicative of dual calpain/caspase attack. Cerebrocortical culture incubated with calpain and caspase-fragmented TDP-43 resulted in neuronal injury. Furthermore, increased TDP-43 BDPs as well as redistributed TDP-43 from the nucleus to the cytoplasm were observed in the mouse cortex in two TBI models: controlled cortical impact injury and overpressure blast-wave-induced brain injury. Finally, TDP-43 and its 35?kDa fragment levels were also elevated in the cerebrospinal fluid (CSF) of severe TBI patients. This is the first evidence that TDP-43 might be involved in acute neuroinjury and TBI pathology, and that TDP-43 and its fragments may have biomarker utilities in TBI patients.
Related JoVE Video
Enrollment of racially/ethnically diverse participants in traumatic brain injury trials: effect of availability of exception from informed consent.
Clin Trials
PUBLISHED: 04-02-2014
Show Abstract
Hide Abstract
The Final Rule regulations were developed to allow exception from informed consent (EFIC) to enable clinical trial research in emergency settings where major barriers exist for informed consent. There is little known evidence of the effect of the Final Rule in minority enrollment in clinical trials, particularly in traumatic brain injury (TBI) trials. A clinical trial funded by the National Institute of Neurological Disorders and Stroke was conducted to study the effects of erythropoietin on cerebral vascular dysfunction and anemia in subjects with TBI. There were periods of time when EFIC was and was not available for enrollment into the study.
Related JoVE Video
Endothelial nitric oxide synthase mediates the cerebrovascular effects of erythropoietin in traumatic brain injury.
Front Immunol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Erythropoietin (Epo) improves post-traumatic cerebral blood flow (CBF), pressure autoregulation, and vascular reactivity to l-arginine. This study examines the dependence of these cerebral hemodynamic effects of Epo on nitric oxide generated by endothelial nitric oxide synthase (eNOS).
Related JoVE Video
Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38-50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0-1 days) to late (7-10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients.
Related JoVE Video
Preinjury resilience and mood as predictors of early outcome following mild traumatic brain injury.
J. Neurotrauma
PUBLISHED: 11-07-2013
Show Abstract
Hide Abstract
There is significant heterogeneity in outcomes following mild traumatic brain injury (mTBI). While several host factors (age, gender, and preinjury psychiatric history) have been investigated, the influence of preinjury psychological resilience and mood status in conjunction with mild TBI remains relatively unexplored. Euthymic mood and high resilience are potentially protective against anxiety and postconcussion symptoms, but their relative contributions are currently unknown. This prospective study obtained preinjury estimates of resilience and mood measures in addition to measures of anxiety (Acute Stress Disorder Scale and PTSD-Checklist-Civilian form) and postconcussion symptom severity (Rivermead Post Concussion Symptoms Questionnaire) <24 hours (Baseline), 1 week, and 1 month postinjury in patients with either mTBI (n=46) or a comparison group with orthopedic injuries not involving the head (OI, n=29). The groups did not differ on preinjury resilience or mood status at baseline, but differed significantly on measures of anxiety and postconcussion symptom severity at each subsequent study occasion. Multivariate linear regression analyses were conducted to determine if preinjury resilience and mood were significant contributors to anxiety and postconcussion symptoms during the first month postinjury after accounting for other known host factors (e.g., age at injury, gender, and education). Injury group and preinjury mood status were significant predictors for all three dependent variables at each study occasion (all p<0.007). Preinjury resilience showed a positive trend only for acute stress severity at baseline, but demonstrated significant prediction of all three dependent measures at one week and one month postinjury. These results suggest that preinjury depressed mood and resilience are significant contributors to the severity of postinjury anxiety and postconcussion symptoms, even after accounting for effects of other specific host factors.
Related JoVE Video
Mild traumatic brain injury in translation.
J. Neurotrauma
PUBLISHED: 03-14-2013
Show Abstract
Hide Abstract
This Introduction to a Special Issue on Mild Traumatic Brain Injury (mTBI) highlights the methodological challenges in outcome studies and clinical trials involving patients who sustain mTBI. Recent advances in brain imaging and portable, computerized cognitive tasks have contributed to protocols that are sensitive to the effects of mTBI and efficient in time for completion. Investigation of civilian mTBI has been extended to single and repeated injuries in athletes and blast-related mTBI in service members and veterans. Despite differences in mechanism of injury, there is evidence for similar effects of acceleration-deceleration and blast mechanisms of mTBI on cognition. Investigation of repetitive mTBI suggests that the effects may be cumulative and that repeated mTBI and repeated subconcussive head trauma may lead to neurodegenerative conditions. Although animal models of mTBI using cortical impact and fluid percussion injury in rodents have been able to reproduce some of the cognitive deficits frequently exhibited by patients after mTBI, modeling post-concussion symptoms is difficult. Recent use of closed head and blast injury animal models may more closely approximate clinical mTBI. Translation of interventions that are developed in animal models to patients with mTBI is a priority for the research agenda. This Special Issue on mTBI integrates basic neuroscience studies using animal models with studies of human mTBI, including the cognitive sequelae, persisting symptoms, brain imaging, and host factors that facilitate recovery.
Related JoVE Video
Erythropoietin and cytoprotective cytokines in experimental traumatic brain injury.
Methods Mol. Biol.
PUBLISHED: 03-05-2013
Show Abstract
Hide Abstract
The various biochemical cascades that follow primary brain injury result in secondary brain injury which can adversely affect the clinical outcome. Over the last few years it has been well established that molecules like erythropoietin (Epo) have a neuroprotective role in experimental traumatic brain injury (TBI). Epo is shown to produce this effect by modulating multiple cellular processes, including apoptosis, inflammation, and regulation of cerebral blood flow. Derivatives of Epo, including asialo Epo and carbamylated Epo, have been developed to separate the neuroprotective properties from the erythropoiesis-stimulating activities of Epo which may have adverse effects in clinical situations. Peptides that mimic a portion of the Epo molecule, including Helix B surface peptide and Epotris, have also been developed to isolate the neuroprotective activities. The TBI model in rodents most commonly used to study the effect of Epo and these derivatives in TBI is controlled cortical impact injury, which is a model of focal contusion following a high velocity impact to the parietal cortex. Following TBI, rodents are given Epo or an Epo derivative vs. placebo and the outcome is evaluated in terms of physiological parameters (cerebral blood flow, intracranial pressure, cerebral perfusion pressure), behavioral parameters (motor and memory), and histological parameters (contusion volumes, hippocampus cell counts).
Related JoVE Video
Erythropoietin in the neurology ICU.
Curr Treat Options Neurol
PUBLISHED: 02-26-2013
Show Abstract
Hide Abstract
Erythropoietin (EPO) is an approved drug that is used in the treatment of chronic anemia associated with chronic renal failure. In the Neuro ICU, there are 2 potential uses for treatment with EPO. Anemia is common in patients with acute neurological disorders and may be a cause of secondary insults. Studies of EPO to treat anemia associated with critical illness have not conclusively shown a beneficial risk/benefit ratio. The relatively small reduction in transfusion requirement with EPO in critically ill patients is likely due to the 7-10 days required to see an effect of EPO on hematocrit. For these reasons, EPO is not recommended to treat anemia of critical illness. Neuroprotection is the other potential use for EPO in the Neuro ICU. Many experimental studies demonstrate neuroprotective effects with EPO in a variety of acute neurological disorders. To date, no clinical studies have confirmed beneficial effects of EPO on neurological outcome although some studies have suggested a reduction in mortality rate in trauma patients treated with EPO. Additional clinical studies are needed before EPO administration can be recommended for cytoprotection in neurological disorders.
Related JoVE Video
Challenges in the development of rodent models of mild traumatic brain injury.
J. Neurotrauma
PUBLISHED: 01-05-2013
Show Abstract
Hide Abstract
Approximately 75% of traumatic brain injuries (TBI) are classified mild (mTBI). Despite the high frequency of mTBI, it is the least well studied. The prevalence of mTBI among service personnel returning from Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF) and the recent reports of an association between repeated mTBI and the early onset of Alzheimers and other types of dementias in retired athletes has focused much attention on mTBI. The study of mTBI requires the development and validation of experimental models and one of the most basic requirements for an experimental model is that it replicates important features of the injury or disease in humans. mTBI in humans is associated with acute symptoms such as loss of consciousness and pre- and/or posttraumatic amnesia. In addition, many mTBI patients experience long-term effects of mTBI, including deficits in speed of information processing, attention and concentration, memory acquisition, retention and retrieval, and reasoning and decision-making. Although methods for the diagnosis and evaluation of the acute and chronic effects of mTBI in humans are well established, the same is not the case for rodents, the most widely used animal for TBI studies. Despite the magnitude of the difficulties associated with adapting these methods for experimental mTBI research, they must be surmounted. The identification and testing of treatments for mTBI depends of the development, characterization and validation of reproducible, clinically relevant models of mTBI.
Related JoVE Video
Amyloid precursor protein revisited: neuron-specific expression and highly stable nature of soluble derivatives.
J. Biol. Chem.
PUBLISHED: 12-05-2011
Show Abstract
Hide Abstract
APP processing and amyloid-? production play a central role in Alzheimer disease pathogenesis. APP has been considered a ubiquitously expressed protein. In addition to amyloid-?, ?- or ?-secretase-dependent cleavage of APP also generates soluble secreted APP (APPs? or APPs?, respectively). Interestingly, APPs? has been shown to be subject to further cleavage to create an N-APP fragment that binds to the DR6 death receptor and mediates axon pruning and degeneration under trophic factor withdrawal conditions. By performing APP immunocytochemical staining, we found that, unexpectedly, many antibodies yielded nonspecific staining in APP-null samples. Screening of a series of antibodies allowed us to identify a rabbit monoclonal antibody Y188 that is highly specific for APP and prompted us to re-examine the expression, localization, and stability of endogenous APP and APPs? in wild-type and in APPs? knock-in mice, respectively. In contrast to earlier studies, we found that APP is specifically expressed in neurons and that its expression cannot be detected in major types of glial cells under basal or neuroinflammatory conditions. Both APPs? and APPs? are highly stable in the central nervous system (CNS) and do not undergo further cleavage with or without trophic factor support. Our results clarify several key questions with regard to the fundamental properties of APP and offer critical cellular insights into the pathophysiology of APP.
Related JoVE Video
Neuroprotection with an erythropoietin mimetic peptide (pHBSP) in a model of mild traumatic brain injury complicated by hemorrhagic shock.
J. Neurotrauma
PUBLISHED: 07-27-2011
Show Abstract
Hide Abstract
Pyroglutamate helix B surface peptide (pHBSP) is an 11 amino acid peptide, designed to interact with a novel cell surface receptor, composed of the classical erythropoietin (EPO) receptor disulfide linked to the beta common receptor. pHBSP has the cytoprotective effects of EPO without stimulating erythropoiesis. Effects on early cerebral hemodynamics and neurological outcome at 2 weeks post-injury were compared in a rat model of mild cortical impact injury (3m/sec, 2.5?mm deformation) followed by 50?min of hemorrhagic hypotension (MAP 40?mm Hg for 50?min). Rats were randomly assigned to receive 5000?U/kg of EPO, 30??g/kg of pHBSP, or an inactive substance every 12?h for 3 days, starting at the end of resuscitation from the hemorrhagic hypotension, which was 110?min post-injury. Both treatments reduced contusion volume at 2 weeks post-injury, from 20.8±2.8?mm(3) in the control groups to 7.7±2.0?mm(3) in the EPO-treated group and 5.9±1.5?mm(3) in the pHBSP-treated group (p=0.001). Both agents improved recovery of cerebral blood flow in the injured brain following resuscitation, and resulted in more rapid recovery of performance on beam balancing and beam walking tests. These studies suggest that pHBSP has neuroprotective effects similar to EPO in this model of combined brain injury and hypotension. pHBSP may be more useful in the clinical situation because there is less risk of thrombotic adverse effects.
Related JoVE Video
Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention.
Ann Emerg Med
PUBLISHED: 05-29-2011
Show Abstract
Hide Abstract
This study examines whether serum levels of glial fibrillary acidic protein breakdown products (GFAP-BDP) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography (CT) scan (positive CT result) and with having a neurosurgical intervention.
Related JoVE Video
Variants of the endothelial nitric oxide gene and cerebral blood flow after severe traumatic brain injury.
J. Neurotrauma
PUBLISHED: 05-04-2011
Show Abstract
Hide Abstract
Experimental studies suggest that nitric oxide produced by endothelial nitric oxide synthase (NOS3) plays a role in maintaining cerebral blood flow (CBF) after traumatic brain injury (TBI). The purpose of this study was to determine if common variants of the NOS3 gene contribute to hypoperfusion after severe TBI. Fifty-one patients with severe TBI were studied. Cerebral hemodynamics, including global CBF by the stable xenon computed tomography (CT) technique, internal carotid artery flow volume (ICA-FVol), and flow velocity in intracranial vessels, were measured within 12?h of injury, and at 48?h after injury. A blood sample was collected for DNA analysis, and genotyping of the following variants of the NOS3 gene was performed: -786T>C, 894G>T, and 27bp VNTR. Cerebral hemodynamics were most closely related to the-786T>C genotype. CBF averaged 57.7±3.0?mL/100?g/min with the normal T/T genotype, 47.0±2.5?mL/100?g/min with the T/C, and 37.3±8.8?mL/100?g/min with the C/C genotype (p=0.0146). Cerebrovascular resistance followed an inverse pattern with the highest values occurring with the C/C genotype (p=0.0027). The lowest ICA-FVol of 124±43?mL/min was found at 12?h post-injury in the more injured hemisphere of the patients with the C/C genotype (p=0.0085). The mortality rate was 20% in patients with the T/T genotype and 17% with the T/C genotype. In contrast, both of the patients with the C/C genotype were dead at 6 months post-injury (p=0.022). The findings in this study support the importance of NO produced by NOS3 activity in maintaining CBF after TBI, since lower CBF values were found in patients having the -786C allele. The study suggests that a patients individual genetic makeup may contribute to the brains response to injury and determine the patients chances of surviving the injury. The results here will need to be studied in a larger number of patients, but could explain some of the variability in outcome that occurs following severe TBI.
Related JoVE Video
Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids.
J. Neurotrauma
PUBLISHED: 04-08-2011
Show Abstract
Hide Abstract
Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a neuron-specific enzyme that has been identified as a potential biomarker of traumatic brain injury (TBI). The study objectives were to determine UCH-L1 exposure and kinetic metrics, determine correlations between biofluids, and assess outcome correlations in severe TBI patients. Data were analyzed from a prospective, multicenter study of severe TBI (Glasgow Coma Scale [GCS] score ? 8). Cerebrospinal fluid (CSF) and serum data from samples taken every 6 h after injury were analyzed by enzyme-linked immunosorbent assay (ELISA). UCH-L1 CSF and serum data from 59 patients were used to determine biofluid correlations. Serum samples from 86 patients and CSF from 59 patients were used to determine outcome correlations. Exposure and kinetic metrics were evaluated acutely and up to 7 days post-injury and compared to mortality at 3 months. There were significant correlations between UCH-L1 CSF and serum median concentrations (r(s)=0.59, p<0.001), AUC (r(s)=0.3, p=0.027), Tmax (r(s)=0.68, p<0.001), and MRT (r(s)=0.65, p<0.001). Outcome analysis showed significant increases in median serum AUC (2016 versus 265 ng/mL*min, p=0.006), and Cmax (2 versus 0.4 ng/mL, p=0.003), and a shorter Tmax (8 versus 19 h, p=0.04) in those who died versus those who survived, respectively. In the first 24 h after injury, there was a statistically significant acute increase in CSF and serum median Cmax((0-24h)) in those who died. This study shows a significant correlation between UCH-L1 CSF and serum median concentrations and biokinetics in severe TBI patients, and relationships with clinical outcome were detected.
Related JoVE Video
Pulmonary embolus from acute superior sagittal sinus thrombosis secondary to skull fracture: case report.
Neurosurgery
PUBLISHED: 03-11-2011
Show Abstract
Hide Abstract
Pulmonary embolus (PE) occurring concurrent with-and as a result of-traumatic superior sagittal sinus thrombosis (SSST) has never before been reported. We report the first case of a patient who presented with acute traumatic SSST and concomitant PE.
Related JoVE Video
Standardizing data collection in traumatic brain injury.
J. Neurotrauma
PUBLISHED: 02-05-2011
Show Abstract
Hide Abstract
Collaboration among investigators, centers, countries, and disciplines is essential to advancing the care for traumatic brain injury (TBI). It is thus important that we "speak the same language." Great variability, however, exists in data collection and coding of variables in TBI studies, confounding comparisons between and analysis across different studies. Randomized controlled trials can never address the many uncertainties concerning treatment approaches in TBI. Pooling data from different clinical studies and high-quality observational studies combined with comparative effectiveness research may provide excellent alternatives in a cost-efficient way. Standardization of data collection and coding is essential to this end. Common data elements (CDEs) are presented for demographics and clinical variables applicable across the broad spectrum of TBI. Most recommendations represent a consensus derived from clinical practice. Some recommendations concern novel approaches, for example assessment of the intensity of therapy in severely injured patients. Up to three levels of detail for coding data elements were developed: basic, intermediate, and advanced, with the greatest level of detail attained in the advanced version. More detailed codings can be collapsed into the basic version. Templates were produced to summarize coding formats, explanation of choices, and recommendations for procedures. Endorsement of the recommendations has been obtained from many authoritative organizations. The development of CDEs for TBI should be viewed as a continuing process; as more experience is gained, refinement and amendments will be required. This proposed process of standardization will facilitate comparative effectiveness research and encourage high-quality meta-analysis of individual patient data.
Related JoVE Video
Improved cerebrovascular function and reduced histological damage with darbepoietin alfa administration after cortical impact injury in rats.
J. Pharmacol. Exp. Ther.
PUBLISHED: 01-26-2011
Show Abstract
Hide Abstract
Darbepoetin alfa (darbEpo) is an erythropoietic glycoprotein that activates the erythropoietin receptor. The aim of our study was to determine whether darbEpo is neuroprotective in a cortical impact injury (CII) model and to determine the characteristics of dose response and time window. To better understand the vascular mechanism of darbEpo neuroprotection, the reactivity of cerebral blood flow (CBF) to l-arginine administration was also studied. Rats were given saline or darbEpo from 2.5 to 50 ?g/kg at 5 min after CII or a dose of 25 ?g/kg darbEpo at times ranging from 5 min to 24 h after CII. Histological assessment was determined 2 weeks after a severe CII. Other rats were given either darbEpo (25 ?g/kg) or saline daily for 3 days before injury. Five minutes after severe CII, they were given either l-arginine or d-arginine. Hemodynamic variables were monitored for 2 h after injury. In the dose-response study, darbEpo in doses of 25 and 50 ?g/kg significantly reduced contusion volume from 39.1 ± 6.7 to 8.1 ± 3.1 and 11.2 ± 6.0 mm(3), respectively. In the time window study, darbEpo reduced contusion volume when given in a dose of 25 ?g/kg at 5 min to 6 h after the impact injury. In animals pretreated with darbEpo, the CBF response to l-arginine was significantly greater than in the animals pretreated with saline. These data demonstrate that darbEpo has neuroprotective effects in traumatic brain injury in a dose- and time-dependent manner and that vascular effects of darbEpo may have a role in neuroprotection.
Related JoVE Video
Traumatic brain injury in mice lacking the K channel, TREK-1.
J. Cereb. Blood Flow Metab.
PUBLISHED: 12-15-2010
Show Abstract
Hide Abstract
The purpose of this study was to determine whether the potassium channel, TREK-1, was neuroprotective after traumatic brain injury (TBI). Since there are no selective blockers, we used TREK-1 knockout (KO) mice for our study. Wild-type (WT) and TREK-1 KO mice were anesthetized and subjected to controlled-cortical impact injury (deformation of the brain by 1.5?mm by a 3-mm diameter rod traveling at a 3?m/s). Laser Doppler perfusion (LDP) decreased by ?80% in the injured cortex and remained at that level in both WT and TREK-1 KO mice (n=10 and 11, respectively). Laser Doppler perfusion decreased by 50% to 60% in cortical areas directly adjacent to the site of injury. There were no statistical differences in LDP between genotype. The contusion volume, determined 15 days after the TBI using hematoxylin and eosin-stained coronal brain sections, was 4.1±0.8 (n=10) and 5.1±0.5 (n=11) mm(3) for WT and TREK-1 KO, respectively (not significant, P=0.34). Cell counts of viable neurons in the CA1 and CA3 regions of the hippocampus were similar between WT and TREK-1 KO mice (P=0.51 and 0.84 for CA1 and CA3, respectively). We conclude that TREK-1 expression does not provide brain protection after TBI.
Related JoVE Video
Influence of alcohol on early Glasgow Coma Scale in head-injured patients.
J Trauma
PUBLISHED: 11-12-2010
Show Abstract
Hide Abstract
To assess the depressant effects of alcohol on the level of consciousness of patients admitted with head injuries, this study examined the changes that occur in the Glasgow Coma Scale (GCS) of traumatic brain injury patients over time.
Related JoVE Video
Cerebral hemodynamic effects of acute hyperoxia and hyperventilation after severe traumatic brain injury.
J. Neurotrauma
PUBLISHED: 09-17-2010
Show Abstract
Hide Abstract
The purpose of this study was to examine the effects of hyperventilation or hyperoxia on cerebral hemodynamic parameters over time in patients with severe traumatic brain injury (TBI). We prospectively studied 186 patients with severe TBI. CO? and O? reactivity tests were conducted twice a day on days 1-5 and once daily on days 6-10 after injury. During hyperventilation there was a significant decrease in intracranial pressure (ICP), mean arterial pressure (MAP), jugular venous oxygen saturation (Sjvo?), brain tissue Po? (Pbto?), and flow velocity (FV). During hyperoxia there was an increase in Sjvo? and Pbto?, and a small but consistent decrease in ICP, end-tidal carbon dioxide (etco?), partial arterial carbon dioxide pressure (Paco?), and FV. Brain tissue oxygen reactivity during the first 12?h after injury averaged 19.7?±?3.0%, and slowly decreased over the next 7 days. The autoregulatory index (ARI; normal?=?5.3?±?1.3) averaged 2.2?±?1.5 on day 1 post-injury, and gradually improved over the 10 days of monitoring. The ARI significantly improved during hyperoxia, by an average of 0.4?±?1.8 on the left, and by 0.5?±?1.8 on the right. However, the change in ARI with hyperoxia was much smaller than that observed with hyperventilation. Hyperventilation increased ARI by an average of 1.3?±?1.9 on the left, and 1.5?±?2.0 on the right. Pressure autoregulation, as assessed by dynamic testing, was impaired in these head-injured patients. Acute hyperoxia significantly improved pressure autoregulation, although the effect was smaller than that induced by hyperventilation. The very small change in Paco? induced by hyperoxia does not appear to explain this finding. Rather, the vasoconstriction induced by acute hyperoxia may allow the cerebral vessels to respond better to transient hypotension. Further studies are needed to define the clinical significance of these observations.
Related JoVE Video
Increased intracranial pressure is associated with elevated cerebrospinal fluid ADH levels in closed-head injury.
Neurol. Res.
PUBLISHED: 08-31-2010
Show Abstract
Hide Abstract
Head injury frequently results in increased intracranial pressure and brain edema. Investigators have demonstrated that ischemic injury causes an increase in cerebrospinal fluid (CSF) levels of antidiuretic hormone (ADH); increased CSF ADH levels exacerbate cerebral edema, and inhibition of the ADH system with specific ADH antagonists reduces cerebral edema. The current study was designed to test the hypothesis that elevated levels of ADH are present in the CSF of subjects with head injury.
Related JoVE Video
L-arginine reactivity in cerebral vessels after severe traumatic brain injury.
Neurol. Res.
PUBLISHED: 08-16-2010
Show Abstract
Hide Abstract
Traumatic brain injury (TBI) causes an early reduction of cerebral blood flow (CBF). The purpose was to study cerebrovascular endothelial function by examining the reactivity of cerebral vessels to L-arginine.
Related JoVE Video
Clinical evaluation of a portable near-infrared device for detection of traumatic intracranial hematomas.
J. Neurotrauma
PUBLISHED: 06-24-2010
Show Abstract
Hide Abstract
The purpose of this multicenter observational clinical study was to evaluate the performance of a near-infrared (NIR)-based, non-invasive, portable device to screen for traumatic intracranial hematomas. Five trauma centers collected data using the portable NIR device at the time a computed tomography (CT) scan was performed to evaluate a suspected traumatic brain injury (TBI). The CT scans were read by an independent neuroradiologist who was blinded to the NIR measurements. Of 431 patients enrolled, 365 patients were included in the per-protocol population analyzed. Of the 365 patients, 96 were determined by CT scan to have intracranial hemorrhages of various sizes, depths, and anatomical locations. The NIR device demonstrated sensitivity of 88% (95% confidence interval [CI] 74.9,95.0%), and specificity of 90.7% (95% CI 86.4,93.7%), in detecting the 50 intracranial hematomas that were large enough to be clinically important (larger than 3.5?mL in volume), and that were less than 2.5?cm from the surface of the brain. For all 96 cases with intracranial hemorrhage, regardless of size and type of hemorrhage, the sensitivity was 68.7% (CI 58.3,77.6%), and specificity was 90.7% (CI 86.4,93.7%). These results confirm the results of previous studies that indicate that a NIR-based portable device can reliably screen for intracranial hematomas that are superficial and of a size likely to be of clinical importance. The NIR device cannot replace CT scanning in the diagnosis of TBI, but the device might be useful to supplement clinical information used to triage TBI patients, and in situations in which CT scanning is not readily available.
Related JoVE Video
?II-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients.
J. Neurotrauma
PUBLISHED: 04-23-2010
Show Abstract
Hide Abstract
In this study we assessed the clinical utility of quantitative assessments of alphaII-spectrin breakdown products (SBDP145 produced by calpain, and SBDP120 produced by caspase-3) in cerebrospinal fluid (CSF) as markers of brain damage and outcome after severe traumatic brain injury (TBI). We analyzed 40 adult patients with severe TBI (Glasgow Coma Scale [GCS] score 6 ng/mL) and SBDP120 levels (>17.55 ng/mL) strongly predicted death (odds ratio 5.9 for SBDP145, and 18.34 for SBDP120). The time course of SBDPs in nonsurvivors also differed from that of survivors. These results suggest that CSF SBDP levels can predict injury severity and mortality after severe TBI, and can be useful complements to clinical assessment.
Related JoVE Video
Impact of arginase II on CBF in experimental cortical impact injury in mice using MRI.
J. Cereb. Blood Flow Metab.
PUBLISHED: 04-07-2010
Show Abstract
Hide Abstract
Traumatic brain injury (TBI) results in reduced cerebral blood flow (CBF) and low levels of the vasodilator nitric oxide (NO) may be involved. Arginase II negatively regulates NO production through competition for the substrate L-arginine. We determined whether arginase II-deficient (ArgII(-/-)) mice would show improved CBF after TBI through arterial spin-labeling magnetic resonance imaging (MRI). The ArgII(-/-) mice exhibit a significantly improved CBF recovery after trauma in the perilesional brain (P=0.0015) and in various other brain regions. In conclusion, arginase II deficiency leads to a better CBF recovery after TBI and implicates arginase II in hemodynamic processes.
Related JoVE Video
Common data elements for traumatic brain injury: recommendations from the interagency working group on demographics and clinical assessment.
Arch Phys Med Rehabil
PUBLISHED: 04-01-2010
Show Abstract
Hide Abstract
Comparing results across studies in traumatic brain injury (TBI) has been difficult because of the variability in data coding, definitions, and collection procedures. The global aim of the Working Group on Demographics and Clinical Assessment was to develop recommendations on the coding of clinical and demographic variables for TBI studies applicable across the broad spectrum of TBI, and to classify these as core, supplemental, or emerging. The process was consensus driven, with input from experts over a broad range of disciplines. Special consideration was given to military and pediatric TBI. Categorizing clinical elements as core versus supplemental proved difficult, given the great variation in types of studies and their interests. The data elements are contained in modules, which are grouped together in categories. Three levels of detail for coding data elements were developed: basic, intermediate, and advanced, with the greatest level of detail in the advanced version. In every case, the more detailed coding can be collapsed into the basic version. Templates were produced to summarize coding formats, motivation of choices, and recommendations for procedures. Work is ongoing to include more international participation and to provide an electronic data entry format with pull-down menus and automated data checks. This proposed standardization will facilitate comparison of research findings across studies and encourage high-quality meta-analysis of individual patient data.
Related JoVE Video
Feasibility of the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) in adults.
J. Neurotrauma
PUBLISHED: 03-10-2010
Show Abstract
Hide Abstract
This article describes the design and initial implementation of the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) as an adaptation of the National Institutes of Health Stroke Scale (NIHSS), specifically for clinical and research use in patients with TBI, including (1) the addition of items specific to TBI, (2) adjustment to the scoring algorithm to allow quantification of deficits in patients who are comatose/vegetative or agitated, and (3) the reassignment of items (i.e., limb ataxia) that are problematic in TBI as supplemental items. The feasibility of using the NOS-TBI is discussed and limitations of the scale are highlighted. This scale offers (1) a cost-effective, brief, practicable, standardized, and quantifiable method of communicating and analyzing neurological deficits in a way that traditional neurological assessment alone cannot currently provide, and (2) a measure that non-physicians can administer. The NOS-TBI may serve a role in clinical practice in patients with TBI similar to the way the NIHSS has functioned for patients following stroke, by serving as a tool for initial stratification of injury severity, and as an outcome measure in clinical trials.
Related JoVE Video
Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury.
J. Neurosurg.
PUBLISHED: 02-02-2010
Show Abstract
Hide Abstract
Authors of several studies have implied a key role of glutamate, an excitatory amino acid, in the pathophysiology of traumatic brain injury (TBI). However, the place of glutamate measurement in clinical practice and its impact on the management of TBI has yet to be elucidated. The authors objective in the present study was to evaluate glutamate levels in TBI, analyzing the factors affecting them and determining their prognostic value.
Related JoVE Video
Microdialysis: is it ready for prime time?
Curr Opin Crit Care
PUBLISHED: 07-07-2009
Show Abstract
Hide Abstract
This review highlights recent advances in cerebral microdialysis for investigational and clinical neurochemical monitoring in patients with critical neurological conditions.
Related JoVE Video
Outcome in patients with blunt head trauma and a Glasgow Coma Scale score of 3 at presentation.
J. Neurosurg.
PUBLISHED: 03-31-2009
Show Abstract
Hide Abstract
A Glasgow Coma Scale (GCS) score of 3 on presentation in patients with severe traumatic brain injury due to blunt trauma has been recognized as a bad prognostic factor. The reported mortality rate in these patients is very high, even approaching 100% in the presence of fixed and dilated pupils in some series. Consequently, there is often a tendency to treat these patients less aggressively because of the low expectations for a good recovery. In this paper, the authors purpose is to report their experience in the management of this patient population, analyzing the mortality rate, prognostic factors, and functional outcome of survivors.
Related JoVE Video
alphaII-Spectrin breakdown product cerebrospinal fluid exposure metrics suggest differences in cellular injury mechanisms after severe traumatic brain injury.
J. Neurotrauma
PUBLISHED: 02-12-2009
Show Abstract
Hide Abstract
Traumatic brain injury (TBI) produces alphaII-spectrin breakdown products (SBDPs) that are potential biomarkers for TBI. To further understand these biomarkers, the present study examined (1) the exposure and kinetic characteristics of SBDPs in cerebrospinal fluid (CSF) of adults with severe TBI, and (2) the relationship between these exposure and kinetic metrics and severity of injury. This clinical database study analyzed CSF concentrations of 150-, 145-, and 120-kDa SBDPs in 38 severe TBI patients. Area under the curve (AUC), mean residence time (MRT), maximum concentration (C(max)), time to maximum concentration (T(max)), and half-life (t(1/2)) were determined for each SBDP. Markers of calpain proteolysis (SBDP150 and SBDP145) had a greater median AUC and C(max) and a shorter MRT than SBDP120, produced by caspase-3 proteolysis in the CSF in TBI patients ( p < 0.001). AUC and MRT for SBDP150 and SBDP15 were significantly greater in patients with worse Glasgow Coma Scale (GCS) scores at 24 h after injury compared to those whose GCS scores improved (AUC p=0.013, MRT p=0.001; AUC p=0.009, MRT p=0.021, respectively). A positive correlation was found between patients with longer elevations in intracranial pressure (ICP) measurements of 25mmHg or higher and those with a greater AUC and MRT for all three biomarkers. This is the first study to show that the biomarkers of proteolysis differentially associated with calpain and caspase-3 activity have distinct CSF exposure profiles following TBI that suggest a prominent role for calpain activity. Further studies are being conducted to determine if exposure and kinetic metrics for biofluid-based biomarkers can predict clinical outcome.
Related JoVE Video
I?B? deficiency in brain leads to elevated basal neuroinflammation and attenuated response following traumatic brain injury: implications for functional recovery.
Mol Neurodegener
Show Abstract
Hide Abstract
The transcription factor NF?B is an important mediator of cell survival and inflammation in the immune system. In the central nervous system (CNS), NF?B signaling has been implicated in regulating neuronal survival following acute pathologic damage such as traumatic brain injury (TBI) and stroke. NF?B is normally bound by the principal inhibitory protein, I?B?, and sequestered in the cytoplasm. Activation of NF?B requires the degradation of I?B?, thereby freeing NF?B to translocate to the nucleus and activate the target genes. Mice deficient in I?B? display deregulated and sustained NF?B activation and early postnatal lethality, highlighting a critical role of I?B? in NF?B regulation.
Related JoVE Video
The effect of blood alcohol level and preinjury chronic alcohol use on outcome from severe traumatic brain injury in Hispanics, anglo-Caucasians, and African-americans.
J Head Trauma Rehabil
Show Abstract
Hide Abstract
To examine (a) ethnic differences in blood alcohol level (BAL) and preinjury chronic alcohol use (PI-ETOH) within a severe closed head injury (CHI) sample and (b) the main and interaction effects of BAL, PI-ETOH, and ethnicity on functional outcome following severe CHI.
Related JoVE Video
Antioxidant carbon particles improve cerebrovascular dysfunction following traumatic brain injury.
ACS Nano
Show Abstract
Hide Abstract
Injury to the neurovasculature is a feature of brain injury and must be addressed to maximize opportunity for improvement. Cerebrovascular dysfunction, manifested by reduction in cerebral blood flow (CBF), is a key factor that worsens outcome after traumatic brain injury (TBI), most notably under conditions of hypotension. We report here that a new class of antioxidants, poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), which are nontoxic carbon particles, rapidly restore CBF in a mild TBI/hypotension/resuscitation rat model when administered during resuscitation--a clinically relevant time point. Along with restoration of CBF, there is a concomitant normalization of superoxide and nitric oxide levels. Given the role of poor CBF in determining outcome, this finding is of major importance for improving patient health under clinically relevant conditions during resuscitative care, and it has direct implications for the current TBI/hypotension war-fighter victims in the Afghanistan and Middle East theaters. The results also have relevancy in other related acute circumstances such as stroke and organ transplantation.
Related JoVE Video
Treatment of mild traumatic brain injury with an erythropoietin-mimetic peptide.
J. Neurotrauma
Show Abstract
Hide Abstract
Mild traumatic brain injury (mTBI) results in an estimated 75-90% of the 1.7 million TBI-related emergency room visits each year. Post-concussion symptoms, which can include impaired memory problems, may persist for prolonged periods of time in a fraction of these cases. The purpose of this study was to determine if an erythropoietin-mimetic peptide, pyroglutamate helix B surface peptide (pHBSP), would improve neurological outcomes following mTBI. Sixty-four rats were randomly assigned to pHBSP or control (inactive peptide) 30??g/kg IP every 12?h for 3 days, starting at either 1 hour (early treatment) or 24?h (delayed treatment), after mTBI (cortical impact injury 3?m/sec, 2.5?mm deformation). Treatment with pHBSP resulted in significantly improved performance on the Morris water maze task. Rats that received pHBSP required 22.3±1.3?sec to find the platform, compared to 26.3±1.3?sec in control rats (p=0.022). The rats that received pHBSP also traveled a significantly shorter distance to get to the platform, 5.0±0.3 meters, compared to 6.1±0.3 meters in control rats (p=0.019). Motor tasks were only transiently impaired in this mTBI model, and no treatment effect on motor performance was observed with pHBSP. Despite the minimal tissue injury with this mTBI model, there was significant activation of inflammatory cells identified by labeling with CD68, which was reduced in the pHBSP-treated animals. The results suggest that pHBSP may improve cognitive function following mTBI.
Related JoVE Video
Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention.
J Trauma Acute Care Surg
Show Abstract
Hide Abstract
This study compared early serum levels of ubiquitin C-terminal hydrolase (UCH-L1) from patients with mild and moderate traumatic brain injury (TBI) with uninjured and injured controls and examined their association with traumatic intracranial lesions on computed tomography (CT) scan (CT positive) and the need for neurosurgical intervention (NSI).
Related JoVE Video
Erythropoietin neuroprotection with traumatic brain injury.
Pathophysiology
Show Abstract
Hide Abstract
Numerous experimental studies in recent years have suggested that erythropoietin (EPO) is an endogenous mediator of neuroprotection in various central nervous system disorders, including TBI. Many characteristics of EPO neuroprotection that have been defined in TBI experimental models suggest that it is an attractive candidate for a new treatment of TBI. EPO targets multiple mechanisms known to cause secondary injury after TBI, including anti-excitotoxic, antioxidant, anti-edematous, and anti-inflammatory mechanisms. EPO crosses the blood-brain barrier. EPO has a known dose response and time window for neuroprotection and neurorestoration that would be practical in the clinical setting. However, EPO also stimulates erythropoiesis, which can result in thromboembolic complications. Derivatives of EPO which do not bind to the classical EPO receptor (carbamylated EPO) or that have such a brief half-life in the circulation that they do not stimulate erythropoiesis (asialo EPO and neuro EPO) have the neuroprotective activities of EPO without these potential thromboembolic adverse effects associated with EPO administration. Likewise, a peptide based on the structure of the Helix B segment of the EPO molecule that does not bind to the EPO receptor (pyroglutamate Helix B surface peptide) has promise as another alternative to EPO that may provide neuroprotection without stimulating erythropoiesis.
Related JoVE Video
Position of probe determines prognostic information of brain tissue PO2 in severe traumatic brain injury.
Neurosurgery
Show Abstract
Hide Abstract
Monitoring brain tissue PO2 (PbtO2) is part of multimodality monitoring of patients with traumatic brain injury (TBI). However, PbtO2 measurement is a sampling of only a small area of tissue surrounding the sensor tip.
Related JoVE Video
Serial Atlas-based DTI Study of Uncomplicated Mild Traumatic Brain Injury in Adults.
J. Neurotrauma
Show Abstract
Hide Abstract
In this report, we applied diffusion tensor imaging (DTI) methods in 36 patients with uncomplicated mild traumatic brain injury (mTBI) and a comparison group of 37 participants with orthopedic injury. Our goal was to characterize regional and global macrostructural and microstructural attributes of white matter (WM), gray matter (GM) in addition to volume and diffusivity of cerebrospinal fluid (CSF) to identify and differentiate patterns of acute and short-term recovery. Given that previous DTI reports on mTBI in adults using a region-of-interest approach implicated the corona radiata, corpus callosum, and hippocampus, we analyzed and quantified DTI metrics of these regions using atlas-based methods. The normalized volume percentages of global CSF, GM and WM were not different between the mTBI and orthopedic comparison (OC) groups at either the baseline or follow-up time point or between the baseline and follow-up time points within the OC group (p>0.17; uncorrected for multiple comparisons). The DTI metrics did not differ between groups at either occasion. However, an increase was noted on follow-up in OC group in the global MD of GM (uncorrected p=0.003) and WM (uncorrected p=0.02), indicating a decrease in diffusivity at the 3 month post-injury as compared to the baseline scan. An analysis of the DTI data collected longitudinally in the corona radiata (CR) show insignificant changes in the OC group (p>0.08; N=37). The CR radial diffusivity was found to be elevated in the between group comparison at baseline (mTBI1 vs. OC1), but did not differ in the within group comparison (mTBI1 vs. mTBI2; N=19), suggesting the possible resolution of edema. Our analysis of the cross-sectional and follow-up data which is uncorrected for multiple comparisons demonstrates dissociation between volumetric (macrostructural) and tissue integrity (microstructural) attributes and shows the potential utility of DTI to capture transient edema in the corona radiata.
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.