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01 January 2015, Volume 10 Issue on line Previous Issue    Next Issue

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Tricyclic antidepressant Imipramine protects retina ganglion against oxidative stress induced apoptosis through TrkB signaling pathway Minglei Han*, Guohua Liu, Jin Guo, Shujuan Yu, Jing Huang 2015, 10 (on line):  1-5.  Abstract ( 199 )   PDF (873KB) ( 766 )   Save BACKGROUND: Retina ganglion cell (RGC) degeneration in glaucoma is irreversible and tropomyosin-related kinase receptor B (TrkB) associated signaling pathways were implicated in this process. Our study thus examined whether imipramine (Imip), a tricyclic antidepressant, may protect RGC degeneration through the activation of TrkB pathway. METHODS: Retinal ganglion cell 5 (RGC-5) cell line was cultured in vitro. Various concentrations of Imip were added in the culture and the activation of TrkB pathway was examined by western blot on phosphorylation of ERK and TrkB proteins. H2O2 was applied in the culture to introduce oxidative stress in RGC-5 cells. Imip was then added to examine its protection on oxidative stress induced RGC-5 apoptosis by a TUNEL staining assay. Finally, the functional association of TrkB pathway and Imip protection against apoptosis was examined by adding functional TrkB blocking antibody, TrkB-IgG, into the RGC-5 culture. RESULTS: In the in vitro RGC-5 culture, western blot showed Imip activated TrkB pathways through ERK/TrkB phosphorylation. TUNEL staining assay demonstrated that H2O2 induced severe oxidative stress-related apoptosis in RGC-5 culture, and the addition of Imip ameliorated H2O2-induced apoptosis. Finally, TrkB-IgG was able to reverse the protective effect of Imip on H2O2-induced RGC-5 apoptosis.  CONCLUSION: We discovered a novel mechanism of tricyclic antidepressant Imip protecting oxidative stress induced apoptosis in retinal ganglion cells. Related Articles | Metrics

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Bumetanide promotes nerve regeneration and recovery of cognitive function in the dentate gyrus of the rat hippocampus after cerebral ischemia Wangshu Xu, Xuan Sun, Chengguang Song, Xiaopeng Mu and Chuansheng Zhao 2015, 10 (on line):  1-7.  Abstract ( 226 )   Save Bumetanide is a widely used diuretic in the clinic. In the acute stage of cerebral ischemia, bumetanide can reduce brain edema through the blood-brain barrier, decrease infarct size, and has a protective effect on the brain. However, no relevant studies concerned neuroprotection and nerve regeneration in the chronic stage of cerebral ischemia. This study sought to explore the effects of bumetanide on neurogenesis in the dentate gyrus of the rat hippocampus after the acute stage of cerebral ischemia. Adult Wistar rats weighing 200–250 g were randomly divided into four groups: (1) sham operation group (SHAM group), (2) sham operation + bumetanide group (SHAM + BUM group), (3) ischemia group (ISC group), and (4) ischemia + bumetanide group (ISC + BUM group). Models of cerebral ischemia were established by intracranial injection of endothelin-1. 1 week later, bumetanide was given in the skull using an osmotic pump for 3 weeks, 20 mg/kg per day. Morris water maze was used to assess learning and memory abilities in rats. Immumofluorescence method was utilized to observe DCX-positive cells in the dentate gyrus of the rat hippocampus. By confocal microscopy, series layer in the direction of Z-axis of DCX-positive cells in the dentate gyrus was obtained, and three-dimensional reconstruction was carried out in newborn dendrites and axons. NIH ImageJ software was then applied to track and measure dendrites, axons and their branches. Bumetanide promoted regeneration of neural stem cells and dendrite development in the hippocampal dentate gyrus after cerebral ischemia. Wangshu Xu and Xuan Sun contributed equally to this work. Related Articles | Metrics

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Gender difference on neuroprotective effect of rat BMSCs aganist the hypoxia-induced apoptosis of RGCs Jing Yuan, Jian-xiong Yu 2015, 10 (on line):  1-7.  Abstract ( 338 )   PDF (1050KB) ( 557 )   Save Purpose: Bone marrow mesenchymal stem cells (BMSCs) have been shown neuro-protective effects in several disease models. However, no studies have examined whether gender influences the neuro-protective effects of BMSCs. Here, we explore the different neuro-protective effects of BMSCs due to gender source against hypoxia-induced apoptosis of retinal ganglion cells (RGCs). Methods: BMSCs was cultured from female and male juvenile rats by gradient density centrifugation and identified. The retinal tissues of newborn rats were prepared with enzymatic digestion to acquire primary RGCs. The RGCs were then co-cultured across a membrane insert with BMSCs in the transwell system under hypoxia injury. Cell apoptosis was detected using AnnexinV-FITC/PI assays and caspase-3 activity assay. Results: Our experiments demonstrated that there were marked increases in the percentage of apoptotic RGCs and the caspase-3 activity after 24 h under hypoxia condition compared with that under the normoxia condition (P < 0.05). When co-cultured with both female BMSCs and male BMSCs under hypoxic condition, the percentage of apoptotic RGCs and the caspase-3 activity had significant decreases compared with that when culture alone (both P < 0.05), and had a significant difference between the female BMSCs and male BMSCs (P < 0.05). Conclusion: Our results indicated that BMSCs have neuro-protective effects against hypoxia-induced apoptosis of RGCs, and female BMSCs have a greater neuro-protective ability compared with male BMSCs. A further understanding of the cellular biology underlying these differences may contribute to the development of new therapeutic strategies for neurological repair and regeneration. Related Articles | Metrics

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Neuroplasticity in post-stroke gait recovery and noninvasive brain stimulation Yi Xu, Qing-hua Hou, Shawn D. Russell, Bradford C. Bennett, Andrew J. Sellers, Qiang Lin, Dong-Feng Huang 2015, 10 (on line):  1-9.  Abstract ( 222 )   PDF (272KB) ( 1149 )   Save Related Articles | Metrics

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Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury Mu Jin, Yan-wei Yang, Wei-ping Cheng, Jia-kai Lu, Si-yu Hou, Xiu-hua Dong, Shi-yao Liu 2015, 10 (on line):  1-6.  Abstract ( 216 )   PDF (1839KB) ( 737 )   Save The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt) and phosphorylated ERK (p-ERK) increased immediately after reperfusion, peaked at 4 hours (p-Akt) or 2 hours (p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury. Related Articles | Metrics

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Acupuncture and vitamin B12 injection for Bell’s palsy:no high-quality evidence exists Li-li Wang, Ling Guan*, Peng-liang Hao, Jin-long Du, Meng-xue Zhang 2015, 10 (on line):  6-7.  Abstract ( 221 )   PDF (489KB) ( 743 )   Save OBJECTIVE: To assess the efficacy of acupuncture combined vitamin B12 acupoint injection versus acupuncture alone to reduce incomplete recovery in patients with Bell’s palsy.DATA SOURCE: A computer-based online retrieval of Medline, WEB of Science, CNKI, CBM databases until April 2014 was performed for relevant trials, using the key words “Bell’s palsy or idiopathic facial palsy or facial palsy” and “acupuncture or vitamin B12 or methylcobalamin”.STUDY SELECTION: All randomized controlled trials that compared acupuncture with acupuncture combined vitamin B12 in patients with Bell’s palsy were included in the meta-analysis.The initial treatment lasted for at least 4 weeks. The outcomes of incomplete facial recovery were monitored. The scoring index varied and the definition of healing was consistent. The combined effect size was calculated by using relative risk (RR) with 95% confidence interval (CI) using the fixed effect model of Review Manager. MAIN OUTCOME MEASURES: Incomplete recovery rates were chosen as the primary outcome.RESULTS: Five studies involving 344 patients were included in the final analysis. Results showed that the incomplete recovery rate of Bell’s palsy patients was 44.50% in the acupuncture combined vitamin B12 group but 62.57% in the acupuncture alone group. The major acupoints were Taiyang (EX-HN5), Jiache (ST6), Dicang (ST4) and Sibai (ST2). The combined effect size showed that acupuncture combined vitamin B12 was better than acupuncture alone for the treatment of Bell’s palsy (RR = 0.71, 95%CI: 0.58–0.87; P = 0.001), this result held true when 8 patients lost to follow up in one study were included into the analyses (RR = 0.70, 95%CI: 0.58–0.86; P = 0.0005).In the subgroup analyses, the therapeutic effect in patients of the electro-acupuncture subgroup was better than in the non-electroacupuncture subgroup (P = 0.024). There was no significant difference in the incomplete recovery rate by subgroup analysis on drug types and treatment period. Most of the included studies were moderate or low quality, and bias existed. CONCLUSION: In patients with Bell’s palsy, acupuncture combined vitamin B12 can reduce the risk of incomplete recovery compared with acupuncture alone in our meta-analysis. Because of study bias and methodological limitations, this conclusion is uncertain and the clinical application of acupuncture combined vitamin B12 requires further exploration. Related Articles | Metrics

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Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats Bei Zhang, Qiang He, Ying-ying Li, Ce Li, Yu-long Bai, Yong-shan Hu,Feng 2015, 10 (on line):  8-9.  Abstract ( 170 )   PDF (834KB) ( 691 )   Save Motor function impairment is a common outcome of stroke. Constraint-induced movement therapy (CIMT) involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of ‘learned non-use’ and improve limb function after stroke. However, the underlying mechanism of CIMT remains unclear. In the present study, rats were randomly divided into a middle cerebral artery occlusion (model) group, a CIMT + model(CIMT) group, or a sham group. Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups. Compared with the model group, CIMT significantly improved the forelimb functional performance in rats. By western blot assay, the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group, and was similar to sham group levels. These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi. Related Articles | Metrics

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Bioinformatics analysis of microRNA expression profiles in rat cortex following focal cerebral ischemia and reperfusion Xiao-li Min, Ting-yong Wang, Yi Cao, Jia Liu, Jin-tao Li, Ting-hua Wang 2015, 10 (on line):  11-12.  Abstract ( 235 )   PDF (2966KB) ( 923 )   Save Ischemic stroke is a serious disease of brain caused by the blood obstruction. Reperfusion is a necessary treatment for ischemic stroke, but itself also causes the secondary injury termed cerebral ischemia/ reperfusion (CIR) injury. In order to elucidate the molecular mechanism of CIR injury, We detected the miRNAs expression profile in rats cortex after focal cerebral ischemia and reperfusion by using miRNA microarray technique, and systematically analyzed the gene ontology function classifications as well as signaling pathways of genes targeted by these differentially expressing miRNAs with bioinformatics tools. The results showed that miRNAs expression profiles were significantly changed in the reperfusion phrase of focal cerebral ischemia, and a total of 15 miRNAs were up-regulated and 44 miRNAs down-regulated. The target genes of these differentially expressed miRNAs were mainly involved in metabolic process and cellular process, which were identified as the hub node of miRNA-GO-network. The most correlated pathways included D-Glutamine and D-glutamate metabolism, renin-angiotensin system, peroxisome, PPAR signaling pathway, SNARE interactions in vesicular transport, and calcium signaling pathway. Our study suggested that miRNAs might play an important role in the pathological process of cerebral ischemia/ reperfusion injury. Understanding miRNAs expression and functions may shed a new light on illustrating the molecular mechanism of CIR injury. Related Articles | Metrics

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Neuroprotective effect of rapamycin on spinal cord injury via activation of theWnt/β-catenin signaling pathway Kai Gao, Yan-song Wang, Ya-jiang Yuan, Zhang-hui Wan, Tian-chen Yao, Hai-hong Li, Pei-fu Tang, Xi-fan Mei 2015, 10 (on line):  772-778.  Abstract ( 277 )   PDF (1318KB) ( 746 )   Save The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guidance,neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord injury, by intraperitoneally injecting spinal cordinjured rats with rapamycinover 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, ca spase-3 protein and brain-derived neurotrophic factor protein,components of theWnt/β-catenin signaling pathway.Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury.Our experimental findings suggest that the neuroprotectiveeffect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury. Related Articles | Metrics