Microvascular decompression by interposition method for treatment of trigeminal neuralgia due to vertebrobasilar dolichoectasia: a retrospective single-center study.

Trigeminal neuralgia (TN) due to vertebrobasilar dolichoectasia (VBD) is a rare disease that can be challenging to treat. The objectives of this study are to investigate the characteristics of patients with TN due to VBD and to analyze the efficacy of microvascular decompression (MVD) by the interposition method for treatment of the condition. From 2010 until 2020, the data of 30 patients with TN due to VBD who were treated with MVD by the interposition method were analyzed retrospectively. The characteristics of the patients were compared with those of patients with non-VBD TN (n = 815). Kaplan-Meier survival analysis was performed to determine pain-free survival. The 30 patients (21 males, 9 females; mean age, 63.03 years) accounted for 3.55% of all patients with TN during the study period. In 30 patients, the offending vessel was the basilar artery (BA) in 1 patient, the vertebral artery (VA) in 6 patients, the VA plus the superior cerebellar artery (SCA) in 6 patients, the VA plus the anterior inferior cerebellar artery (AICA) in 12 patients, and the VA + SCA + AICA in 5 patients. Compared to non-VBD TN patients, those with TN due to VBD were significantly more likely to be male, to have TN of the left side, and to have hypertension (all P < 0.001). Mean age at surgery (P = 0.057) and symptom duration (P = 0.308) were comparable between the two groups. All 30 patients had immediate relief of facial pain after MVD and could stop medication. There were no postoperative complications. Over mean follow-up of 76.67 months, 3 patients had recurrence. The mean duration of pain-free survival was 70.77 months. In conclusions, TN due to VBD appears to be more likely in males, in those with hypertension, and to involve the left side. The interposition method performed by experienced and skilled neurosurgeons is a safe and effective treatment for TN due to VBD. Further studies are needed to analyze the associated long-term results and the pain recurrence rate among this special population.

Filament inadequate wall apposition of the different ends of flow diverters in the abdominal aorta of rabbits.

BACKGROUND: Flow diverters (FDs) with flared ends (FEs) or straight ends (SEs) are used either alone or when overlapped to treat complex intracranial aneurysms. We evaluated filament inadequate wall apposition (IWA) of the FEs and SEs of FDs in vivo. METHODS: A total of 24 FDs with FEs and SEs were placed in an overlapping manner in the abdominal aortae of six rabbits (two sets per rabbit). Digital subtraction angiography was performed immediately after stent insertion and three months later. The anatomical and histopathological aortic features at FEs and SEs were evaluated. RESULTS: Angiography revealed no significant difference in terms of changes in arterial diameter between the FE and SE groups (p = 0.877). Gross anatomical evaluation revealed IWA of the different ends of FDs but no thrombi or bleeding, showing that the metallic filaments were not in touch with the vessel wall and nor had they penetrated the vessel wall. The filaments' IWA rates of FEs and SEs were 8.33% and 8.85%, respectively. The IWA rate at overlapping ends was lower than that at non-overlapping ends. The maximum neo-intimal thickness at FEs was greater than that at SEs (149.4 ± 48.9 and 98.6 ± 26.6 µm, respectively; p < 0.001). CONCLUSIONS: Both the FEs and SEs of FDs can exhibit IMA. IWA events are reduced at the overlapped regions. On pathological evaluation, FEs increased neo-intimal thicknesses more than SEs did, but hyperplasia was minimal on angiography.

The bad seed gardener: Deubiquitinases in the cancer stem-cell signaling network and therapeutic resistance.

Tumors are comprised of highly heterogeneous populations of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumors in vivo. These rare cancer stem cells (CSCs) have been regarded as the "bad seeds" accounted for tumor initiation, progression, metastasis, relapse and therapeutic resistance. CSC-targeted therapy seems to be a better avenue for radical cure of cancer. Deubiquitinases (DUBs), specifically disassembling ubiquitin chains, have been demonstrated to play an important role in rigidly maintaining the balance between ubiquitination and deubiquitination for protein quality control and homeostasis in normal circumstances. Dysfunction or deregulation of DUBs always leads to a series of disorders, even malignant transformation. Despite the accumulative evidence that DUB inhibitors in cancer remedy mainly target the tumor bulk, side effects like toxicity and resistance are still hard nuts to crack. In this article, we review the concept of ubiquitin proteasome system (UPS) and hallmarks of CSCs related to tumor obstinacy. We primarily summarize the CSC-related factors and signaling pathways and focus on the function of DUBs on biological traits of CSCs. We also illustrate the opportunities and challenges for the application of DUB inhibitors in the CSC-targeted therapy. Finally, we discuss the complexity of cancer stem cell hierarchy complexity and argue that a combination therapy for both CSCs and non-CSCs should be a desirable option.

Interference with Protease-activated Receptor 1 Alleviates Neuronal Cell Death Induced by Lipopolysaccharide-Stimulated Microglial Cells through the PI3K/Akt Pathway.

Excessive microglial cells activation in response to inflammatory stimuli leads to synaptic loss, dysfunction, and neuronal cell death. Activated microglia are involved in the pathogenesis of neurological conditions and frequently contribute to several complications. Accumulating evidence suggests that signaling through PAR-1 is involved in inflammation, however, its function has yet to be fully elucidated. Here, we have demonstrated that the suppression of PAR-1 leads to down-regulation of inflammatory factors including IL-1ß, IL-6, TNF-α, NO, as well as the prevention of activation of NF-κB in BV2 cells. In addition, we found that a PAR-1 antagonist, SCH, prevented LPS-induced excessive microglial activation in a dose-dependent manner. As a result of SCH treatment, neuronal cell death via up-regulation of Akt-mediated pathways was reduced. Our results demonstrate that the beneficial effects of SCH are linked to its ability to block an inflammatory response. Further, we found that SCH inhibited the death of PC12 neurons from the cytotoxicity of activated BV2 cells via activation of the PI3K/Akt pathway. These neuro-protective effects appear to be related to inhibition of PAR-1, and represents a novel neuroprotective strategy that could has potential for use in therapeutic interventions of neuroinflammatory disease.

Impaired white-matter integrity in photosensitive epilepsy: a DTI study using tract-based spatial statistics.

BACKGROUND AND PURPOSE: The present study was designed to map alterations in brain white-matter in photosensitive epilepsy (PSE) by applying tract-based spatial statistics (TBSS) analysis. METHODS: Diffusion tensor-imaging (DTI) data from MRI brain scans were collected from eight PSE patients and 16 gender- and age-matched non-epileptic controls using a SIEMENS Trio 3.0-Tesla scanner. For the white-matter analysis, DTI scans were processed using FSL software (http://www.fmrib.ox.ac.uk/fsl/index.html). Fractional anisotropy (FA) values in the PSE and control groups were compared using TBSS analysis corrected for multiple comparisons using threshold-free cluster enhancement. RESULTS: Compared with the control subjects, the corpus callosum of PSE patients had significantly lower FA values. CONCLUSION: Our DTI study indicates that white-matter in the corpus callosum was abnormal in PSE patients, and that DTI methods can serve as useful non-invasive tools to evaluate white-matter changes in PSE patients.

miR-193b promotes cell proliferation by targeting Smad3 in human glioma.

Studies have shown that several miRNAs play important roles in regulating a variety of cellular processes in gliomas. In these reports, upregulation of miR-193b has been found to be associated with a poor prognosis for glioma, but its functional mechanism in glioma remains unclear. This study investigates the roles of miR-193b in glioma tumor growth. We first showed that the expression of miR-193b was elevated in both glioma samples and glioma cells. Furthermore, downregulation of miR-193b by inhibitors was statistically correlated with a decrease in cell growth and a restored G1 accumulation. Luciferase assay and Western blot analysis revealed that Smad3 is a direct target of miR-193b. To prove that miR-193b regulated cell growth through the transforming growth factor-ß (TGF-ß) pathway in glioma cells by regulating Smad3, we tested endogenous targets of the TGF-ß pathway by measuring the accumulation of p21 mRNAs after downregulation of miR-193b. The results confirmed that induction of p21 was promoted by miR-193b inhibitors in glioma cells, although this induction disappeared when Smad3 was knocked down with siRNA. Moreover, downregulation of Smad3 mitigates the miR-193b suppression of glioma proliferation. In conclusion, these results suggest that miR-193b regulated cell growth in glioma through the TGF-ß pathway by regulating Smad3. Thus, our study indicates that miR-193b promotes cell proliferation by targeting Smad3 in human glioma, which may serve as a potentially useful target for development of miRNA-based therapies in the future.

Biodegradable flow-diverting device for the treatment of intracranial aneurysm: short-term results of a rabbit experiment.

INTRODUCTION: One main complication of a flow-diverting device (FD) in treating intracranial aneurysm is stenosis of parent artery (PA) or occlusion of side branches. The use of a biodegradable device may satisfy the need for aneurysm occlusion and eliminate potential complications. METHODS: Twenty elastase-induced aneurysm rabbit models were divided into three groups: in group 1 (n = 7), polyglycolic acid FDs (PGA-FDs) were implanted across the necks of aneurysms and the abdominal aortas (AA), covering the ostium of a lumbar artery; in group 2 (n = 7), the PGA-FDs were replaced by metal FDs; and in group 3 (n = 6), the PGA-FDs were only implanted across the necks of aneurysms. Animals in group 3 underwent angiography at 6 weeks; those in groups 1 and 2 underwent angiography at 3 months. The status of aneurysm embolization and patency of side branches were assessed. RESULTS: Complete aneurysm occlusion rates in groups 1 and 3 were 83.3 and 66.7 %, respectively, compared with 0 % in group 2. No side branch occlusions were noted. PA neointimal hyperplasia was minimal, and there were no significant differences between groups 1 and 2 (P = 0.233). The neointimal coverage ratio of the branch ostium in AA in group 1 was not significantly different from that in group 2 (P = 0.605). The neointima comprised predominantly smooth muscle cells and collagen fibers. CONCLUSIONS: The PGA-FD was an effective device for the treatment of aneurysms and was safe for side branches at the 3-month follow-up.

Reduced white matter integrity in primary open-angle glaucoma: a DTI study using tract-based spatial statistics.

BACKGROUND AND PURPOSE: The present study was designed to map the alteration of white matter in primary open-angle glaucoma (POAG) by applying tract-based spatial statistics (TBSS) analysis. METHODS: Diffusion tensor imaging (DTI) data from MRI brain scans were collected from 15 POAG patients and 15 gender- and age-matched non-glaucoma controls using a SIEMENS Trio 3.0-Tesla scanner. For the white-matter analysis, DTI images were processed using FSL software (http://www.fmrib.ox.ac.uk/fsl/index.html). Fractional anisotropy (FA) between the POAG and control groups was compared by TBSS analysis corrected for multiple comparisons using threshold-free cluster enhancement (TFCE). RESULTS: Compared with non-glaucoma subjects, the occipital white matter in POAG patients had significantly lower FA values (p<0.05, corrected). CONCLUSION: The change in white-matter FA may indicate atrophy of the visual cortex that may be important in the diagnosis and treatment of POAG patients.

Functional recovery in rat spinal cord injury induced by hyperbaric oxygen preconditioning.

BACKGROUND: It is a common belief that neurosurgical interventions can cause inevitable damage resulting from the procedure itself in surgery especially for intramedullary spinal cord tumors. The present study was designed to examine if hyperbaric oxygen preconditioning (HBO-PC) was neuroprotective against surgical injuries using a rat model of spinal cord injury (SCI). METHODS: Sprague-Dawley rats were randomly divided into three groups: HBO-PC group, hypobaric hypoxic preconditioning (HH-PC) control group, and normobaric control group. All groups were subjected to SCI by weight drop device. Rats from each group were examined for neurological behavior and electrophysiological function. Tissue sections were analyzed by using immunohistochemistry, TdT-mediated dUTP-biotin nick end labeling, and axonal tract tracing. RESULTS: Significant neurological deficits were observed after SCI and HBO-PC and HH-PC improved neurological deficits 1 week post-injury. The latencies of motor-evoked potential and somatosensory-evoked potential were significantly delayed after SCI, which was attenuated by HBO-PC and HH-PC. Compared with normobaric control group, pretreatment with HBO and hypobaric hypoxia significantly reduced the number of TdT-mediated dUTP-biotin nick end labeling-positive cells, and increased nestin-positive cells. HBO-PC and HH-PC enhanced axonal growth after SCI. CONCLUSIONS: In conclusion, preconditioning with HBO and hypobaric hypoxia can facilitate functional recovery and suppress cell apoptosis after SCI and may prove to be a useful preventive strategy to neurosurgical SCI.

In vivo magnetic resonance imaging tracking of SPIO-labeled human umbilical cord mesenchymal stem cells.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) can be efficiently labeled by superparamagnetic iron oxide (SPIO) nanoparticles, which produces low signal intensity on magnetic resonance imaging (MRI) in vitro. This study was to evaluate the feasibility of in vivo tracking for hUC-MSCs labeled by SPIO with noninvasive MRI. SPIO was added to cultures at concentrations equivalent to 0, 7, 14, 28, and 56 µg Fe/ml (diluted with DMEM/F12) and incubated for 16 h. Prussian Blue staining was used to determinate the labeling efficiency. Rats were randomly divided into three groups, control group, hUC-MSCs group, and SPIO-labeled hUC-MSCs group. All groups were subjected to spinal cord injury (SCI) by weight drop device. Rats were examined for neurological function. In vivo MRI was used to track SPIO-labeled hUC-MSCs transplanted in rats spinal cord. Survival and migration of hUC-MSCs were also explored using immunofluorescence. Significant improvements in locomotion were observed in the hUC-MSCs groups. There was statistical significance compared with control group. In vivo MRI 1 and 3 weeks after injection showed a large reduction in signal intensity in the region transplanted with SPIO-labeled hUC-MSCs. The images from unlabeled hUC-MSCs showed a smaller reduction in signal intensity. Transplanted hUC-MSCs engrafted within the injured rats spinal cord and survived for at least 8 weeks. In conclusion, hUC-MSCs can survive and migrate in the host spinal cord after transplantation, which promote functional recovery after SCI. Noninvasive imaging of transplanted SPIO-labeled hUC-MSCs is feasible.

Role of acid-sensing ion channel 1a in the secondary damage of traumatic spinal cord injury.

OBJECTIVE: To determine the cellular and molecular mechanisms by which acid-sensing ion channel 1a (ASIC1a) plays its role in the secondary injury after traumatic spinal cord injury (SCI), and validate the neuroprotective effect of ASIC1a suppression in SCI model in vivo. BACKGROUND: Secondary damage after traumatic SCI contributes to the exacerbation of cellular insult and thereby contributes to spinal cord dysfunction. However, the underlying mechanisms remain largely unknown. Acidosis is commonly involved in the secondary injury process after the injury of central nervous system, but whether ASIC1a is involved in secondary injury after SCI is unclear. METHODS: Male Sprague-Dawley rats were subjected to spinal contusion using a weight-drop injury approach. Western blotting and immunofluorescence assays were used to observe the change of ASIC1a expression after SCI. The TUNEL staining in vivo as well as the cell viability and death assays in spinal neuronal culture were employed to assess the role of ASIC1a in the secondary spinal neuronal injury. The electrophysiological recording and Ca(2+) imaging were performed to reveal the possible underlying mechanism. The antagonists and antisense oligonucleotide for ASIC1a, lesion volume assessment assay and behavior test were used to estimate the therapeutic effect of ASIC1a on SCI. RESULTS: We show that ASIC1a expression is markedly increased in the peri-injury zone after traumatic SCI. Consistent with the change of ASIC1a expression in injured spinal neurons, both ASIC1a-mediated whole-cell currents and ASIC1a-mediated Ca(2+) entry are significantly enhanced after injury. We also show that increased activity of ASIC1a contributes to SCI-induced neuronal death. Importantly, our results indicate that down-regulation of ASIC1a by antagonists or antisense oligonucleotide reduces tissue damage and promotes the recovery of neurological function after SCI. CONCLUSION: This study reveals a cellular and molecular mechanism by which ASIC1a is involved in the secondary damage process after traumatic SCI. Our results suggest that blockade of Ca(2+) -permeable ASIC1a may be a potential neuroprotection strategy for the treatment of SCI patients.