Intra-Arterial Chemotherapy as Primary Treatment for Advanced Unilateral Retinoblastoma in China.

Purpose: This study aimed to evaluate the efficacy and complications of intra-arterial chemotherapy (IAC) as a primary treatment for advanced unilateral retinoblastoma in Chinese patients. Methods: This study was a retrospective review of patients with advanced unilateral retinoblastoma treated with IAC as the primary treatment. The IAC procedures were performed using a balloon-assisted technique. The clinical status and treatment complications were recorded at each visit. Kaplan-Meier analysis was performed to estimate recurrence-free survival and ocular survival. Results: In total, 116 eyes of 116 patients with advanced unilateral retinoblastoma were enrolled, including 66 eyes (57%) in group D and 50 eyes (43%) in group E. All treated eyes received a mean of 3 cycles of IAC (range, 3-5), and 66% of the eyes were combined with local consolidation therapy. The median follow-up time was 39 months (range, 22-57 months). The 3-year recurrence-free survival and ocular survival rates were 68.8% (95% CI, 59.2-76.6%) and 88.5% (95% CI, 80.9-93.2%), respectively. Moreover, the 3-year ocular survival rate in group D was significantly higher than that in group E (96.9%, 76.3%; P < 0.01). The common ocular complication was vitreous hemorrhage (19.8%). No deaths or severe systemic complications occurred. Conclusion: Primary intra-arterial chemotherapy is effective for the treatment of advanced unilateral retinoblastoma, especially in group D, with acceptable toxicity.

CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage.

Aims: Subarachnoid hemorrhage (SAH) is a devastating stroke subtype. Following SAH, erythrocyte lysis contributes to cell death and brain injuries. Blockage of the anti-phagocytic receptor Cluster of Differentiation 47 (CD47) enhances phagocyte clearance of erythrocytes, though it has not been well-studied post-SAH. The current study aims to determine whether anti-CD47 treatment can enhance blood clearance after experimental SAH. Methods: The prechiasmatic blood injection model of SAH was used in mice. Mice were either treated with the CD47-blocking antibody or IgG as control. The effect of the anti-CD47 antibody on blood clearance and neurological function following SAH was determined. Neuroinflammation and neuronal injury were compared between the treatment and control samples on day 1 and day 7 after SAH using flow cytometry, immunofluorescence, Fluoro-Jade C, and Nissl staining, RT-PCR, and Western blot analysis. Results: CD47-blocking antibody sped-up blood clearance after SAH, and resulted in less neuronal injury and neurological deficits than control samples. Microglia played a role in the anti-CD47 blockade. Following SAH Following SAH, CD47 antibody-treated mice had less neuroinflammation and lower levels of apoptosis compared to controls and both one and 7 days. Conclusions: CD47 antibody treatment has a neuroprotective effect following SAH, by increasing blood clearance rate and reducing brain injury. These findings suggest CD47 antibody treatment may improve SAH patient outcomes.

Outcome of salvage intra-arterial chemotherapy for recurrent retinoblastoma.

PURPOSE: To examine the outcome of salvage intra-arterial chemotherapy (IAC) for patients with recurrent retinoblastoma after the initial course of IAC and determine the factors influencing clinical outcome. METHODS: A total of 73 eyes of 71 patients with recurrent retinoblastoma undergoing salvage IAC after initial successfully IAC between May 2014 and May 2019 were retrospectively reviewed for clinical outcomes. Ocular survival and progression-free survival were used to examine the efficacy of salvage IAC. The factors influencing clinical outcomes were determined using univariate and multivariate analyses. RESULTS: The salvage IAC was delivered at mean 9.4 months (median 7, range 2.1-38.3 months) following the last cycle of initial IAC. 86.5% (64/73) eyes relapsed 16 months after the initial IAC. After the salvage IAC, 57 eyes (78.1%) were salvaged, and no further-line therapies were required for 36 eyes (49.3%). The 2-year Kaplan-Meier ocular survival and progression-free survival estimates after salvage IAC were 66.4% (95% CI, 31.5-42.1%) and 38.2% (95% CI, 17.8-28.8%), respectively. Univariate and multivariate analyses showed that the ocular survival and progression-free survival after salvage IAC were significantly associated with the history of vitreous seeds (p = 0.02 and p = 0.03, respectively). CONCLUSION: Salvage IAC is effective for the management of recurrent retinoblastoma after the initial successful IAC. Eyes with a history of vitreous seeds in the course of the disease are more likely to relapse and with worse ocular survival. A close follow-up strategy is imperative to treat the recurrent tumour after salvage IAC.

Relationship between chronic hyperglycemia and contrast extravasation in revascularization of symptomatic intracranial atherosclerotic stenosis: A retrospective single-center study.

BACKGROUND AND PURPOSE: Contrast extravasation is one of the most common perioperative complications in symptomatic intracranial atherosclerotic stenosis (ICAS) patients after percutaneous transluminal angioplasty and/or stenting (PTAS). This study aimed to investigate the correlations between the relevant serum biochemical indicators of carbohydrate metabolism and the occurrence of contrast extravasation. METHODS: Patients' demographic characteristics, vascular risk factors and laboratory examination data were collected. Blood routine test, blood biochemical examination and hormone level test within 1 week before surgery were measured in all enrolled subjects. Patients underwent non-contrast CT scans immediately after the endovascular procedure. Follow-up non-contrast CT scans were performed in the next 24 h and repeated as per clinical condition. RESULTS: 104 patients who have undergone effective PTAS were involved in this study. 18 patients have identified as contrast extravasation and there was no obvious abnormality in another 86 cases. There were significant differences in the pre-operative HbA1c, fasting blood sugar and cortisol levels in the subjects regardless of gender between two groups (p < 0.001, p < 0.001 and p = 0.001, respectively). Furthermore, there were statistical differences in E2 and testosterone levels between two groups in both male population (p = 0.035 and p = 0.028, respectively) and female population (p = 0.036 and p = 0.003, respectively). Besides, the AUC value of HbA1c, fasting blood sugar and cortisol levels were all over 0.7 (0.858, 0.780 and 0.752, respectively). The highest AUC value of various combinations was obtained from the combination of HbA1c and cortisol level, which was 0.898. CONCLUSIONS: Patient with chronic hyperglycemia is closely related to contrast extravasation after PTAS. Specific mechanisms might be explored and regarded as promising candidates to prevent contrast extravasation.

Comparision of Mechanical Thrombectomy With Contact Aspiration or Stent Retriever in Patients With Large-vessel Occlusion in Acute Ischemic Stroke.

OBJECTIVES: Whether the direct aspiration approach of thrombectomy for recanalization in patients with acute ischemic stroke has a similar efficacy and safety compared to the stent-retriever still remains uncertain. METHODS: A retrospective data analysis was performed to identify patients with large cerebral artery acute ischemic stroke treated with endovascular thrombectomy. The study was conducted between January 2018 and December 2019 in a single stroke center. RESULTS: Twenty patients met inclusion criteria for this study with a mean age 66.64 ±â€Š17.92 years' old. The symptom occurred on the left side were in 13, and the right side in 7. The location of occlusion was 8 in M1 of the middle cerebral artery of M2, and 6 in internal carotid artery. Nine patients were randomized to first-line treatment with contact aspiration and eleven to first-line treatment with a stent retriever. The mean time from admission time to groin puncture was 55.51 ±â€Š31.03 minutes. The average time from groin puncture to maximal revascularizion after mechanical thrombectomy was 50.9 ±â€Š22.5 minutes in contact aspiration group, but this time was 71.37 ±â€Š25.45 minutes in the group of stent retriever. The overall successful revascularization rate (TICI 2b-3) was 88.9% in contact aspiration (TICI2a = 1, TICI 2b = 4 patients, TICI 3 = 4 patients), and 90.1% in stent retriever (TICI2a = 1, TICI 2b = 6 patients, TICI 3 = 4 patients). DISCUSSION: First-line thrombectomy with contact aspiration did not result in a higher successful revascularization rate at the end of the procedure but had a short time from groin puncture to maximal revascularizion.

Combined intra-arterial chemotherapy and intravitreal melphalan for the treatment of advanced unilateral retinoblastoma.

AIM: To evaluate the efficacy and safety of combined intra-arterial chemotherapy (IAC) and intravitreal melphalan (IVM) for the treatment of advanced unilateral retinoblastoma. METHODS: This retrospective study involved 30 consecutive eyes from 30 Chinese patients with advanced unilateral retinoblastoma. All patients were initially treated with IAC combined with IVM. The clinical status and complications were recorded at each visit. RESULTS: The International Intraocular Retinoblastoma Classification groups were D in 23 eyes and E in 7 eyes. All eyes showed severe cloud vitreous seeds at the first visit. The mean number of IAC cycles and intravitreal injections was 3.2 (range, 3-4) and 6 (range, 1-14), respectively. The median follow-up time was 29mo (range, 7-36mo). Treatment success with regression of the retinal tumor and vitreous seeds was achieved in 29 of 30 eyes (96.7%). Globe salvage was attained in 93.3% (28/30) eyes, and enucleation (n=2) was performed due to neovascular glaucoma and persistent vitreous hemorrhage. Complications included retinal pigment epithelium (RPE) atrophy (n=13; 43%), mild lens opacity (n=7; 23%), vitreous hemorrhage (n=5; 17%) and rhegmatogenous retinal detachment (n=1; 3%). No extraocular tumor extension or metastasis occurred. CONCLUSION: Combined IAC and IVM is effective and safe for the treatment of advanced unilateral retinoblastoma.

Analysis of Peripheral Blood Cells' Transcriptome in Patients With Subarachnoid Hemorrhage From Ruptured Aneurysm Reveals Potential Biomarkers.

BACKGROUND: Subarachnoid hemorrhage (SAH) is an uncommon disease. Considering ruptured intracranial aneurysms as the main cause of this disease and only a minority of the intracranial aneurysms will rupture sooner or later, to understand the underlying pathology or a specific gene expression profile of an impending ruptured intracranial aneurysm is of great importance. METHODS: The transcriptome in peripheral blood cells of patients with SAH from ruptured aneurysm was compared with that of control patients suffering from headaches. The microarray dataset GSE36791 comprised 43 patients with SAH from ruptured aneurysms and 18 control patients. Differential expression analysis was performed with the R language packages to identify differentially expressed genes (DEGs). Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway database analysis were performed to identify significantly altered biological functions and pathways, respectively. The protein-protein interaction networks were constructed with information from the STRING database. RESULTS: A total of 528 DEGs were identified, of which 311 were upregulated and 217 downregulated. Clustering analysis confirmed that these genes can distinguish ruptured aneurysm SAH patients from the control patients. The DEGs were mainly enriched for immune/inflammation response and related pathways. Among the DEGs, 8 genes (ARG1, MAPK14, RPS2, SPI1, FYN, CEBPB, FLOT1, and CD4) were identified as the key regulators in the Protein-Protein Interaction network. MAPK14, CEBPB, FLOT1, and CD4 might be potential biomarkers of SAH. CONCLUSION: This study identified a range of DEGs SAH patients with ruptured aneurysms, which may enhance our current knowledge on this disease and may provide potential biomarkers of this disease.

Exogenous Netrin-1 Inhibits Autophagy of Ischemic Brain Tissues and Hypoxic Neurons via PI3K/mTOR Pathway in Ischemic Stroke.

BACKGROUND AND OBJECTIVE: Ischemic stroke is a serious disease that endangers human health. How to reduce the damage of neurons in ischemic regions is an urgent problem to be explored. Autophagy is an important pathophysiological process in cerebral ischemia and Netrin-1 is an effective neuroprotective protein. This study aims to investigate the effect of Netrin-1 on autophagy of ischemic brain tissues and hypoxic neurons. METHODS: We constructed rat persistent middle cerebral artery occlusion model in vivo and constructed the Oxygen Glucose-Deprivation model in vitro. Rats and cells were treated with or without Netrin-1. Western blot analysis was performed to detect autophagy related proteins LC3B, P62 and pathway related proteins PI3K, p-PI3K, mTOR, p-mTOR. CCK-8 assay was performed to detect the viability of hypoxic neurons. We also performed western-blot analysis and qRT-PCR test to detect levels of Netrin-1 protein and mRNA. RESULTS: Autophagy enhanced both in ischemic brain tissues and hypoxic neurons. Netrin-1 inhibited autophagy through PI3K/mTOR pathway both in vivo and in vitro. At the same time, we found that exogenous Netrin-1 can promote the secretion of Netrin-1 protein by neurons themselves, which indicated that Netrin-1 can further amplify the neuroprotective effect through the positive feedback mechanism. CONCLUSIONS: Exogenous Netrin-1 alleviates damage of ischemic brain tissues and enhances viability of hypoxic neurons by inhibiting autophagy via PI3K/mTOR pathway. This effect can be amplified by positive feedback mechanism.

Intraluminal spindle-shaped-head suture induced occlusion of middle cerebral artery in the rats.

OBJECTIVE: This study aimed to introduce a modified animal model of middle cerebral arterial occlusion (MCAO) through placement of intraluminal spindle-shaped head suture by comparing the traditional MCAO model. METHODS: A total of 60 male Spraque-Dawley (SD) rats were divided into two groups and MCAO was induced using spindle-shaped head suture or round head suture. The mortality, infarct volume, neurological function, success rate of the surgery, and stability of modeling were examined to evaluate the effectiveness of this model. RESULTS: Our results showed the success rate was 90.0% in spindle-shaped head group and 83.3% in round head group showing no significant difference; spindle-shaped head achieved a better establishment of MCAO model as shown in neurological examination. The infarct volume was 31.99 ± 5.44% in spindle-shaped head group and was significantly higher than in round head group (24.59 ± 7.17%; p < 0.05), and the coefficient of variation of infarct volume in spindle-shaped head group was lower than in round head group. CONCLUSION: Our findings indicate that the modified suture induces a more reproducible and stable ischemic stroke following MCAO in SD rats.

Glycyrrhizic acid exerts anti-inflammatory effect to improve cerebral vasospasm secondary to subarachnoid hemorrhage in a rat model.

This study aimed to investigate the therapeutic effect of glycyrrhizic acid (GA) on the cerebral vasospasm (CVS) in a rat subarachnoid hemorrhage (SAH) model and to explore the potential mechanism. A total of 44 healthy male rats were randomly assigned into 3 groups: control group (n = 12), SAH group (n = 16) and GA group (n = 16). No treatment was conducted in control group; in SAH group and GA group, experimental CVS was induced using a double-hemorrhage model and then rats were intraperitoneally injected with normal saline and GA at 10 mg/kg, respectively, once daily. Three days later, neurological function was evaluated. Then, animals were sacrificed, and the basilar artery was collected. The inner diameter and vascular wall thickness were determined. Western blotting was employed to detect high mobility group protein B1 (HMGB1) protein expression and RT-PCR to detect the mRNA expression of IL-1ß, IL-6, TNF-α, and IL-10 in the basilar artery. GA treatment significantly improved the neurological function following SAH. In GA group, the basilar artery diameter increased markedly and vascular wall thickness reduced significantly when compared with SAH group (p < 0.05). HMGB1 protein expression and mRNA expression of IL-1ß, IL-6, TNF-α, and IL-10 in SAH group were significantly higher than in control group (p < 0.05). However, GA dramatically reduced IL-1ß, IL-6, and TNF-α, and further elevated IL-10 expression as compared to SAH group (p < 0.05). GA may inhibit HMGB1 expression and subsequent production of inflammatory cytokines to prevent CVS following SAH.

CD151 mediates netrin-1-induced angiogenesis through the Src-FAK-Paxillin pathway.

Crosstalk between the nervous and vascular systems is important during development and in response to injury, and the laminin-like axonal guidance protein netrin-1 has been studied for its involvement in angiogenesis and vascular remodelling. In this study, we examined the role of netrin-1 in angiogenesis and explored the underlying mechanisms. The effect of netrin-1 on brain tissues and endothelial cells was examined by immunohistochemistry and western blotting in a middle cerebral artery occlusion model and in human umbilical vein endothelial cells. Cell proliferation and cell cycle progression were assessed by the MTT assay and flow cytometry, and the Transwell and tube formation assays were used to examine endothelial cell motility and function. Netrin-1 up-regulated CD151 and VEGF concomitant with the activation of focal adhesion kinase (FAK), Src and Paxillin in vitro and in vivo and the induction of cell proliferation, migration and tube formation in vitro. Silencing of CD151 abolished the effects of netrin-1 on promoting cell migration and tube formation mediated by the activation of FAK/Src signalling. Netrin-1 promoted angiogenesis in vitro and in vivo by activating the FAK/Src/Paxillin signalling pathway through a mechanism dependent on the expression of the CD151 tetraspanin, suggesting the existence of a netrin-1/FAK/Src/CD151 signalling axis involved in the modulation of angiogenesis.

Neuroprotection by intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats in a model of ischemic stroke.

Our previous studies showed that bone marrow mononuclear cells (BMMNCs) from 5-fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to further explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in the same model. Rats were intravenously pre-treated with 5-FU, and BMRMNCs were collected 7 days later and subjected to flow cytometry for detection of CD34, CD45 and CD90. Middle cerebral artery occlusion (MCAO) was induced in rats, and BMMNCs and BMRMNCs were independently transplanted via the tail vein at 24 h after MCAO. NISSL staining was performed 14 days after cell transplantation and the viable cells in the hippocampus were counted. Stromal cell-derived factor 1 (SDF-1) mRNA expression was detected in the penumbra at 7 and 14 days after treatment. The contents of pro-inflammatory cytokines and growth factors as well as microvessel density (MVD) were determined at 14 days. Results showed more BMRMNCs were positive for CD34, CD45 and CD90. After transplantation, more viable cells were observed in the hippocampus of BMRMNCs treated rats. In addition, BMRMNCs transplantation significantly increased MVD, reduced pro-inflammatory cytokines and raised growth factors in the penumbra. However, the SDF-1 mRNA expression was comparable between BMRMNCs group and BMMNCs group. Our results indicate that BMRMNCs are likely to more effectively improve the local microenvironment to increase viable cells and elevate angiogenesis, exerting neuroprotective effects on cerebral ischemia in rats.

Overexpression of TREM2 enhances glioma cell proliferation and invasion: a therapeutic target in human glioma.

Gliomas are the most common and aggressive type of primary adult brain tumors. Although TREM2 mutation is reported to be related to Nasu-Hakola disease and Alzheimer's disease, little is known about the association between TREM2 and gliomas. Here, we reported that TREM2 was significantly overexpressed in glioma tissues compared with non-tumorous brain tissues. Furthermore, TREM2 expression was closely related to pathological grade and overall survival of patients with gliomas. Down-regulation of TREM2 in two glioma cell lines, U87 and U373, resulted in a significant reduction in cell proliferation, migration and invasion and a dramatic increase in S phase arrest and apoptosis. In vivo tumorigenesis experiment also revealed that depletion of TREM2 expression inhibited U87 cell proliferation. Moreover, based on gene set enrichment analysis (GSEA) with The Cancer Genome Atlas (TCGA) dataset, we found that TREM2 was positive related to Kyoto Encyclopedia of Genes and Genomes (KEGG) apoptosis, Cromer metastasis and KEGG chemokine pathways, which was further validated by western blot in TREM2 knockdown glioma cells and indicated a possible mechanism underlying its effects on glioma. In summary, our study suggests that TREM2 may work as an oncogene and a new effective therapeutic target for glioma treatment.

The strategy of microvascular decompression for hemifacial spasm: how to decide the endpoint of an MVD surgery.

OBJECTIVE: Microvascular decompression (MVD) has become the standard treatment for hemifacial spasm. As not all patients get complete relief, this strategy is still controversial. The study aimed to figure out how to tell the proper endpoint to the surgery. METHODS: A series of 356 consecutive patients with hemifacial spasm were enrolled in this study. All patients fell into two groups according to the period they presented. Two different criteria (simple criterion vs. complex criterion) to end an operation were applied respectively. The intra-operative finding, results and complications of these two groups were compared. The advantage of the complex criterion was analyzed. RESULTS: The group which used complex criterion got better results than the group which used simple criterion. The complex criterion which combines full-length evidence, vascular evidence and electrophysiological evidence proved to be reliable to tell the proper endpoint to the surgery. CONCLUSION: MVD operations can be ended only after the full-length evidence, vascular evidence and electrophysiological evidence are all present.

Clear cell meningioma: clinical features, CT, and MR imaging findings in 23 patients.

BACKGROUND: Clear cell meningioma (CCM) is a rare meningioma, with radiologic features not well characterized in literature. The purpose of this study was to describe and characterize the clinical features and imaging findings of CCM. MATERIALS AND METHODS: The computed tomography (n = 16) and magnetic resonance (n = 23) images of 23 patients (12 men and 11 women; mean age, 34.6 years) were retrospectively reviewed. All of the patients underwent surgical resection. Follow-up was performed through clinical observations. RESULTS: Cerebellopontine angle was the most frequently presenting location (n = 10). The tumors were isointense (n = 12) or hypointense but associated with isointense (n = 7) appearance to gray matter on T1-weighted images. However, the tumors seemed to be isointense (n = 6) or isointense and hyperintense (n = 13) on T2-weighted images. On gadolinium-enhanced T1-weighted images, heterogeneous enhancement was seen in 14 lesions. Four lesions had amorphous calcifications, 18 showed peritumoral edema, 14 had cystic areas, 2 had bone hyperostosis, and 8 manifested bone destruction. On initial surgery, 17 patients underwent complete resection, whereas 5 patients underwent subtotal resection of their tumors. The operative result for the remaining patient was unknown. Follow-up was possible in 22 patients. Eleven patients had recurrence and 2 had died. CONCLUSIONS: Clear cell meningioma is a rare subtype of meningioma that occurs in younger patients and often recurs. Cerebellopontine angle is the most affected area in this series. The extent of initial surgical resection is the most important prognostic factor. In radiological studies, CCM tends to have marked heterogeneous enhancement, prominent peritumoral edema, intratumoral cystic components, and involvement of the adjacent bone.

A successful treatment of coexistent hemifacial spasm and trigeminal neuralgia caused by a huge cerebral arteriovenous malformation: a case report.

Regardless hemifacial spasm (HFS) or trigeminal neuralgia (TN) is commonly caused by an offending artery, 36 cases caused by an arteriovenous malformation (AVM) have been reported in the literature. However, the concurrent HFS and TN caused by AVM have never been reported so far. We reported a case of coexistent HFS-TN associated with a huge AVM, and the symptoms of both spasm and pain relieved gradually after endovascular embolization of the nidus. The etiology and pathogenesis as well as the treatment of this disorder are discussed and reviewed in the article.

Beclin 1, an autophagy-related gene, augments apoptosis in U87 glioblastoma cells.

Beclin 1 acts as a tumor suppressor and is an essential mediator of autophagy. Beclin 1 also interacts with Bcl-2 and can induce apoptosis by activating the mitochondrion permeabilizing function of proapoptotic multidomain proteins from the Bcl-2 family. Moreover, these Bcl-2 family members can activate autophagy by liberating Beclin 1 from its inhibition by Bcl-2/Bcl-XL at the level of the endoplasmic reticulum. We found that overexpression of Beclin 1 in U87 glioblastoma cells enhanced the capacity for cellular autophagy and induced apoptosis. Silencing of Beclin 1 decreased autophagic capacity but had little effect on apoptosis and cell proliferation. Beclin 1-Bcl-2 and Beclin 1-Bcl-xL complexes were detected by immunoprecipitation in cells that overexpressed Beclin 1. Furthermore, the levels of cytochrome c in the cytosol and the activity of caspases-3/-9 in the cytosol increased after overexpression of Beclin 1. Our results suggest that Beclin 1 induces apoptosis via binding to Bcl-2 and Bcl-xL, followed by the release of cytochrome c into the cytosol and activation of caspases-3/-9.

Endothelial nitric oxide synthase protects neurons against ischemic injury through regulation of brain-derived neurotrophic factor expression.

AIMS: Several lines of evidence demonstrated that endothelial nitric oxide synthase (eNOS) confers protective effects during cerebral ischemia. In this study, we explored the underlying cellular and molecular mechanisms of neuroprotection by eNOS. METHODS: A series of in vivo and in vitro ischemic models were employed to study the role of eNOS in maintaining neuronal survival and to identify the downstream factors. RESULTS: The current data showed that pretreatment with a specific eNOS inhibitor, L-N5-(1-iminoethyl) ornithine (L-NIO), aggravated the neuronal loss in the rat cerebral ischemic model, accompanied by reduction in brain-derived neurotrophic factor (BDNF) level, which was consistent with the findings in an oxygen-glucose deprivation model (OGD) with two neuronal cells: primary rat cortical neurons and human neuroblastoma SH-SY5Y cells. Furthermore, the extensive neuronal loss induced by L-NIO was totally abolished by exogenous BDNF in both in vitro and in vivo models. On the other hand, eNOS overexpression through an adenoviral vector exerted a prominent protective effect on the neuronal cells subject to OGD, and the protective effect was totally abrogated by a neutralizing anti-BDNF antibody. CONCLUSION: Collectively, our results indicate that the neuroprotection of neuron-derived eNOS against the cerebral ischemia was mediated through the regulation of BDNF secretion. In conclusion, our discovery provides a novel explanation for the neuroprotective effect of eNOS under pathological ischemic conditions such as stroke.

Surgical treatment of hemifacial spasm with zone-4 offending vessel.

BACKGROUND: Increasing evidence shows that vascular compression on any of the four zones of facial nerve may cause hemifacial spasms. Vascular compression on zone 4 (the cisternal portion) of the nerve is quite common, but only a very small percentage of such compression will elicit hemifacial spasm, because zone 4 is less susceptible than zone 3 (the root exit zone). Therefore, it seems difficult for the neurosurgeons to distinguish the real culprit vessels in zone 4. Here, our experience in treating vascular compression located in zone 4 of the facial nerve is reported. METHODS: Twelve patients of HFS due to compression of zone 4 were treated with microvascular decompression (MVD) surgery with the aid of combined monitoring of abnormal muscle response (AMR) and Z-L response (ZLR). RESULTS: All of the 12 patients had a zone 4 compression. In addition, there were vascular compressions on zone 3 (the root exit zone) and/or zone 2 (the attached segment) in six cases. AMR was absent in two cases, unstable in one case, and persisted after vascular decompression in another one case. ZLR was stable before decompression of zone 4 and disappeared after decompression in all cases. After MVD surgery, 11 patients were cured and one patient achieved good resolution of spasm. One patient had postoperative transient tinnitus. CONCLUSIONS: The neurosurgeon should not ignore vascular compression at zone 4, especially when compressions at zones 2 and 3 co-exist. With the aid of AMR and ZLR, we are able to judge whether offending vessels exist at zone 4.

Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?

Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohistological staining and reverse transcription-PCR detection showed that transplanted bone marrow cells and bone marrow regenerative cells could migrate and survive in the ischemic regions, such as the cortical and striatal infarction zone. These cells promote vascular endothelial cell growth factor mRNA expression in the ischemic marginal zone surrounding the ischemic penumbra of the cortical and striatal infarction zone, and have great advantages in promoting the recovery of neurological function, reducing infarct size and promoting angiogenesis. Bone marrow regenerative cells exhibited stronger neuroprotective effects than bone marrow cells. Our experimental findings indicate that bone marrow regenerative cells are preferable over bone marrow cells for cell therapy for neural regeneration after cerebral ischemia. Their neuroprotective effect is largely due to their ability to induce the secretion of factors that promote vascular regeneration, such as vascular endothelial growth factor.