application-3d-printing-construction-burr-hole-ring-for-deep-brain

Application of 3D Printing in the Construction of Burr Hole Ring for Deep Brain Stimulation Implants

3D printing has been widely applied in the medical field since the 1980s, especially in surgery, such as preoperative simulation, anatomical learning and ...

Southern Medical University

To delineate the pterygoid canal (PC) configuration and its position in relation to surrounding important anatomical landmarks using three-dimensional reconstructive technology based on CT for the Chinese.

The anatomical and clinical details of the pterygoid canal: a three-dimensional reconstructive virtual anatomic evaluation based on CT.

Gait deficits are important clinical symptoms of Parkinson's disease (PD) but are rarely studied. In this study we made three different rat PD models by administration of 6-hydroxydopamine into caudate putamen (CPU), medial forebrain bundle (MFB) and substantia nigra compact (SNC). We evaluated the gait changes in these models by using a computer-assisted CatWalk system. Correlations of gait parameters with tyrosine hydroxylase protein levels in the CPU and SNC were also investigated. The gait readouts were significantly impaired in both the MFB and SNC groups. However, the MFB group showed a more pronounced impairment than the SNC group. In contrast, only mild and incomplete gait impairment occurred in the CPU group. In addition, some gait parameters demonstrated close correlation with the protein levels of TH. This paper suggests that the 6-hydroxydopamine-induced MFB model is more propitious to study gait dysfunction than the other two models and the CatWalk system can provide reliable and objective criteria to stratify gait changes arising from 6-hydroxydopamine lesioned rats. These findings may hold promise in the study of PD disease progression and new therapeutic methods. 

Gait analysis in three different 6-hydroxydopamine rat models of Parkinson's disease.

The aim of this study was to investigate voluntary wheel running behavior in the unilateral 6-hydroxydopamine (6-OHDA) rat model.

Impaired voluntary wheel running behavior in the unilateral 6-hydroxydopamine rat model of Parkinson's disease.

The pedunculopontine nucleus (PPN) is connected to spinal, cerebellar and cerebral motor control structures and can be activated with external electrodes. Intrinsic cholinergic neuronal degeneration in the PPN is associated with postural instabilities and gait disturbances (PIGD) in advanced Parkinson's disease (PD). Clinical studies have demonstrated that PPN stimulation may improve PIGD. We investigated this claim and the underlying mechanisms using the 6-hydroxydopamine (6-OHDA) hemilesion model of PD. In this study, gait-related parameters, including the base of support (BOS), stride length, and maximum contact area, were analyzed via CatWalk gait analysis following PPN-low frequency stimulation (LFS) of rats with unilateral 6-OHDA lesions. Additionally, neurotransmitter concentrations in the ventrolateral thalamic nucleus (VL) were measured by microdialysis and liquid chromatography-mass spectrometry (LC-MS). Our data revealed that unilateral 6-OHDA lesions of the medial forebrain bundle (MFB) induced significant gait deficits. PPN-LFS significantly improved the BOS (hindlimb) and maximum contact area (impaired forelimb) scores, whereas no other gait parameters were significantly affected. Unilateral 6-OHDA MFB lesions significantly decreased acetylcholine (ACh) and moderately decreased noradrenaline (NA) concentrations in the VL. PPN-LFS mildly reversed the ACh loss in the VL in the lesioned rats but did not alter the NA levels. Taken together, our data indicate that PPN-LFS is useful for treating gait deficits of PD and that these effects are probably mediated by a rebalancing of ACh levels in the PPN-VL pathway. Thus, our findings provide possible insight into the mechanisms underlying PIGD in PD. 

Low-frequency stimulation of the pedunculopontine nucleus affects gait and the neurotransmitter level in the ventrolateral thalamic nucleus in 6-OHDA Parkinsonian rats.

The recent development of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) for the treatment of parkinsonian patients, particularly those in advanced stages with axial symptoms, has ignited interest into the study of this brain nucleus. In contrast to the extensively studied alterations of neural activity that occur in the basal ganglia in Parkinson's disease (PD), our understanding of the activity of the PPN remains insufficient. In recent years, however, a series of studies recording oscillatory activity in the PPN of parkinsonian patients have made important findings. Here, we briefly review recent studies that explore the different kinds of oscillations observed in the PPN of parkinsonian patients, and how they underlie the pathophysiology of PD and the efficacy of PPN-DBS in these disorders. 

Oscillations in pedunculopontine nucleus in Parkinson's disease and its relationship with deep brain stimulation.

Oscillatory activity has been well-studied in many structures within cortico-basal ganglia circuits, but it is not well understood within the pedunculopontine nucleus (PPN), which was recently introduced as a potential target for the treatment of gait and postural impairments in advanced stages of Parkinson's disease (PD). To investigate oscillatory activity in the PPN and its relationship with oscillatory activity in cortico-basal ganglia circuits, we simultaneously recorded local field potentials in the PPN, primary motor cortex (M1), and subthalamic nucleus (STN) of 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats during resting and walking. After analysis of power spectral density, coherence, and partial Granger causality, three major findings emerged: 1) after 6-OHDA lesions, beta band oscillations were enhanced in all three regions during walking; 2) the direction of information flow for beta oscillations among the three structures was STN→M1, STN→PPN, and PPN→M1; 3) after the treatment of levodopa, beta activity in the three regions was reduced significantly and the flow of beta band was also abrogated. Our results suggest that beta activity in the PPN is transmitted from the basal ganglia and probably comes from the STN, and the STN plays a dominant role in the network of causal interactions for beta activity. Thus, the STN may be a potential source of aberrant beta band oscillations in PD. Levodopa can inhibit beta activity in the PPN of parkinsonian rats but cannot relieve parkinsonian patients' axial symptoms clinically. Therefore, beta oscillations may not be the major cause of axial symptoms.

The network of causal interactions for beta oscillations in the pedunculopontine nucleus, primary motor cortex, and subthalamic nucleus of walking parkinsonian rats.

The emergence of L-DOPA-induced dyskinesia (LID) in patients with Parkinson disease (PD) could be due to maladaptive plasticity of corticostriatal synapses in response to L-DOPA treatment. A series of recent studies has revealed that LID is associated with marked morphological plasticity of striatal dendritic spines, particularly cell type-specific structural plasticity of medium spiny neurons (MSNs) in the striatum. In addition, evidence demonstrating the occurrence of plastic adaptations, including aberrant morphological and functional features, in multiple components of cortico-basal ganglionic circuitry, such as primary motor cortex (M1) and basal ganglia (BG) output nuclei. These adaptations have been implicated in the pathophysiology of LID. Here, we briefly review recent studies that have addressed maladaptive plastic changes within the cortico-BG loop in dyskinetic animal models of PD and patients with PD.

Maladaptive Synaptic Plasticity in L-DOPA-Induced Dyskinesia.

Many patients of advanced Parkinson's disease (PD) suffer from intractable axial symptoms (severe gait and postural impairments), which were recently speculated to be more relevant to cholinergic degeneration in the brainstem than dopaminergic degeneration in the substantia nigra compacta (SNc). To investigate the role of the cholinergic cells of the pedunculopontine tegmental nucleus (PPTg) on motor deficits, especially the axial motor impairments, we measured and analyzed the gait performance of sham lesion rats, SNc dopaminergic lesion rats, PPTg cholinergic lesion rats, and combined lesion rats by using the CatWalk system. Motor performance of PPTg cholinergic lesion rats was also tested on the rotarod. Independent loss of cholinergic neurons in the PPTg did not induce gait disturbance in CatWalk, but PPTg lesion rats showed motor impairments on the rotarod when the demands of the motor task increased. Both SNc lesion rats and combined lesion rats displayed significant changes in many gait parameters, but the terminal dual stance increased much higher in combined lesion group than SNc lesion group. Furthermore, combined lesion rats showed more severe freezing of gait (FOG) than SNc lesion rats during behavioral re-evaluations after lesion. These results suggest that the PPTg cholinergic neurons play a vital role in the occurrence of FOG in PD.

Selective cholinergic depletion of pedunculopontine tegmental nucleus aggravates freezing of gait in parkinsonian rats.

Synchronized oscillatory neuronal activity in the beta frequency range has been reported in the basal ganglia (BG) of patients with Parkinson disease (PD) and PD animal models. The coherent abnormal oscillatory activities in the dorsolateral striatum (dStr) and substantia nigra pars reticulata (SNr) that accompany parkinsonian states have not been resolved. In this study, we recorded local field potentials (LFPs) in the dStr and SNr of 6-hydroxydopamine (6-OHDA)-induced dopamine (DA)-lesioned rats in an awake, resting state. Analyses of power spectral density and coherence data demonstrated augmented LFP power in the 24-36-Hz (high beta) range in both the dStr and SNr together with increased dStr-SNr coherence in the 24-36-Hz range, relative to sham controls; both effects were reversed by levodopa (L-dopa) treatment. Partial Granger causality analysis revealed a dStr→SNr propagation directionality of these beta oscillations. These findings support the involvement of increased synchronization of high beta activity in the dStr and the SNr, and suggest that dorsolateral striatal activity plays a determinant role in leading the coherent activity with the SNr in the development of parkinsonian pathophysiology.

Granger causality supports abnormal functional connectivity of beta oscillations in the dorsolateral striatum and substantia nigra pars reticulata in hemiparkinsonian rats.

BACKGROUND UCA1 is a long non-coding RNA that has been found to be aberrantly upregulated in various cancers. The aim of this study was to determine the expression level and function of UCA1 in medulloblastoma, the most common malignant brain tumor during childhood. MATERIAL AND METHODS Real-time PCR was used to detect the expression of UCA1 in medulloblastoma specimens and cell lines. Lentiviral-mediated expression of a short hairpin RNA (shRNA) targeting UCA1 or a negative control shRNA was also achieved with the medulloblastoma cell line, Daoy. Cell proliferation and cell cycle progression were subsequently characterized with cell counting kit (CCK)-8 and flow cytometry. Cell migration was examined in wound healing and Transwell migration assays. RESULTS Levels of UCA1 mRNA were higher in the medulloblastoma specimens (p<0.05) and cell lines (p<0.05) compared to the corresponding nontumor adjacent tissue specimens and a glioblastoma cell line, respectively. For the Daoy cells with silenced UCA1, their proliferation was reduced by 30% compared to the Daoy cells expressing a negative control shRNA (p=0.017). Cell cycle arrest in the G0/G1 phase, resulting in a decreased number of cells in the S phase, as well as reduced cell migration in both wound scratch healing (p=0.001) and Transwell migration assays (p=0.021) were also observed for the Daoy cells with silenced UCA1. CONCLUSIONS UCA1 was highly expressed in part of medulloblastoma specimens and cell lines examined. In addition, knockdown of UCA1 significantly inhibited the proliferation and migration of medulloblastoma cells in vitro.

Silencing of Urothelial Carcinoma Associated 1 Inhibits the Proliferation and Migration of Medulloblastoma Cells.

As the bearing structure of fixation device in deep brain stimulation (DBS), burr hole ring is fixed on the skull and used in conjunction with Stimloc and plastic cap. But in patients with traumatic event, excessive movements are likely to bring strain on the anchoring system, which will finally cause the fixation device to fall off from the skull.

3-D printing for constructing the burr hole ring of lead fixation device in deep brain stimulation.

Oscillatory activities within basal ganglia (BG) circuitry in L-DOPA induced dyskinesia (LID), a condition that occurs in patients with Parkinson disease (PD), are not well understood. The aims of this study were firstly to investigate oscillations in main BG input and output structures-the dorsolateral striatum (dStr) and substantia nigra pars reticulata (SNr), respectively- including the direction of oscillation information flow, and secondly to investigate the effects of 5-HT1A/B receptor agonism with eltoprazine on oscillatory activities and abnormal involuntary movements (AIMs) characteristic. To this end, we conducted local field potential (LFP) electrophysiology in the dStr and SNr of LID rats simultaneous with AIM scoring. The LFP data were submitted to power spectral density, coherence, and partial Granger causality analyses. AIM data were analyzed relative to simultaneous oscillatory activities, with and without eltoprazine. We obtained four major findings. 1) Theta band (5-8 Hz) oscillations were enhanced in the dStr and SNr of LID rats. 2) Theta power correlated with AIM scores in the 180-min period after the last LID-inducing L-DOPA injection, but not with daily summed AIM scores during LID development. 3) Oscillatory information flowed from the dStr to the SNr. 4) Chronic eltoprazine reduced BG theta activity in LID rats and normalized information flow directionality, relative to that in LID rats not given eltoprazine. These results indicate that dStr activity plays a determinative role in the causal interactions of theta oscillations and that serotonergic inhibition may suppress dyskinesia by reducing dStr-SNr theta activity and restoring theta network information flow.

Eltoprazine prevents levodopa-induced dyskinesias by reducing causal interactions for theta oscillations in the dorsolateral striatum and substantia nigra pars reticulate.

Article	Year
The anatomical and clinical details of the pterygoid canal: a three-dimensional reconstructive virtual anatomic evaluation based on CT. Surgical and radiologic anatomy : SRA\| PubMed ID: 23824143	2014
Gait analysis in three different 6-hydroxydopamine rat models of Parkinson's disease. Neuroscience letters\| PubMed ID: 25449863	2015
Impaired voluntary wheel running behavior in the unilateral 6-hydroxydopamine rat model of Parkinson's disease. Journal of Korean Neurosurgical Society\| PubMed ID: 25733987	2015
Low-frequency stimulation of the pedunculopontine nucleus affects gait and the neurotransmitter level in the ventrolateral thalamic nucleus in 6-OHDA Parkinsonian rats. Neuroscience letters\| PubMed ID: 26054938	2015
Oscillations in pedunculopontine nucleus in Parkinson's disease and its relationship with deep brain stimulation. Frontiers in neural circuits\| PubMed ID: 26388741	2015
The network of causal interactions for beta oscillations in the pedunculopontine nucleus, primary motor cortex, and subthalamic nucleus of walking parkinsonian rats. Experimental neurology\| PubMed ID: 27163550	2016
Maladaptive Synaptic Plasticity in L-DOPA-Induced Dyskinesia. Frontiers in neural circuits\| PubMed ID: 28066191	2016
Selective cholinergic depletion of pedunculopontine tegmental nucleus aggravates freezing of gait in parkinsonian rats. Neuroscience letters\| PubMed ID: 28803956	2017
Granger causality supports abnormal functional connectivity of beta oscillations in the dorsolateral striatum and substantia nigra pars reticulata in hemiparkinsonian rats. Experimental brain research\| PubMed ID: 28819676	2017
Silencing of Urothelial Carcinoma Associated 1 Inhibits the Proliferation and Migration of Medulloblastoma Cells. Medical science monitor : international medical journal of experimental and clinical research\| PubMed ID: 28916736	2017
3-D printing for constructing the burr hole ring of lead fixation device in deep brain stimulation. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia\| PubMed ID: 30454691	2018
Eltoprazine prevents levodopa-induced dyskinesias by reducing causal interactions for theta oscillations in the dorsolateral striatum and substantia nigra pars reticulate. Neuropharmacology\| PubMed ID: 30612008	2019

Wangming Zhang

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