Intracellular Ca2+ overload and the following Ca2+-toxicity are an important mechanism underlying ischemic brain injury.However,recent clinical trials using antagonists of the N-methyl-daspartate(NMDA) to prevent isch...Intracellular Ca2+ overload and the following Ca2+-toxicity are an important mechanism underlying ischemic brain injury.However,recent clinical trials using antagonists of the N-methyl-daspartate(NMDA) to prevent ischemic brain injury in humans have been largely disappointing.Activation of glutamate receptors resulting in intracellular Ca2+ overload and excitotoxicity couldn’t explain the whole process of ischemic brain injury,and emerging new studies have suggested that activation of several glutamate receptor-independent Ca2+-toxicity pathways also contribute to ischemic brain injury.This review focus on the roles of acid sensing ion channels(ASICs),Na+-Ca2+ exchanger(NCX) and transient receptor potential(TRP) channels in the ischemic brain injury.展开更多
Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of tr...Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia. In this study, we investigated the effects of 5-minute (mild), 15-minute (severe), and 20-minute (lethal) transient ischemia by bilateral common carotid artery occlusion (BCCAO) on behavioral change and neuronal death and gliosis (astrocytosis and microgliosis) in gerbil hippocampal subregions (CA1-3 region and dentate gyrus). We performed spontaneous motor activity test to evaluate gerbil locomotor activity, cresyl violet staining to detect cellular distribution, neuronal nuclei immunohistochemistry to detect neuronal distribution, and Fluoro-Jade B histofluorescence to evaluate neuronal death. We also conducted immunohistochemical staining for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 (Ibal) to evaluate astrocytosis and microgliosis, respectively. Animals subjected to 20-minute BCCAO died in at least 2 days. BCCAO for 15 minutes led to pyramidal cell death in hippocampal CA1-3 region 2 days later and granule cell death in hippocampal de匚tate gyrus 5 days later. Similar results were not found in animals subjected to 5-minute BCCAO. Gliosis was much more rapidly and severely progressed in animals subjected to 15-minute BCCAO than in those subjected to 5- minute BCCAO. Our results indicate that neuronal loss in the hippocampal formation following transient ischemia is significantly different according to regions and severity of transient ischemia. The experimental protocol was approved by Institutional Animal Care and Use Committee (AICUC) of Kangwon National University (approval No. KW-180124-1) on May 22, 2018.展开更多
文摘目的：探讨短暂性脑缺血发作（transient ischaemic attack, TIA）患者发作次数和持续时间与早期缺血性卒中风险的相关性。方法回顾性纳入2013年1月至2017年7月在六安市人民医院神经内科住院的TIA患者，根据首次发生TIA后72 h内头颅CT或MRI复查结果分为无卒中组和卒中组，比较两组患者人口统计学和临床资料。结果共纳入171例TIA患者，其中卒中组54例，无卒中组117例。两组性别、心房颤动、发病前使用抗凝药、基线血压（收缩压和舒张压）、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、空腹血糖、TIA病因学（心源性栓塞）、TIA发作频率（≥2次）、TIA症状持续时间、ABCD2评分（6分和7分）以及发病后使用抗高血压药存在显著性差异。多变量logistic回归分析显示，高舒张压[优势比（odds ratio, OR）1.121，95%可信区间（confidence interval, CI）1.016～1.238；P＝0.023]、高空腹血糖（OR 10.866，95% CI 3.658～30.945；P＝0.001）、ABCD2评分为6分（OR 4.221，95% CI 1.906～9.352；P〈0.001）和7分（OR 4.207，95% CI 2.040～9.961；P〈0.001）、TIA症状持续时间≥60 min（OR 3.682，95% CI 1.961～9.989；P〈0.001）和TIA发作≥2次（OR 4.220，95% CI 1.953～9.118；P〈0.001）为早期发生缺血性卒中的独立危险因素，而发病前使用抗凝药为独立保护因素（OR 0.300，95% CI 0.097～0.923；P＝0.036）。
结论症状发作次数≥2次和症状持续时间≥60 min的TIA患者早期更易发生缺血性卒中。
文摘Intracellular Ca2+ overload and the following Ca2+-toxicity are an important mechanism underlying ischemic brain injury.However,recent clinical trials using antagonists of the N-methyl-daspartate(NMDA) to prevent ischemic brain injury in humans have been largely disappointing.Activation of glutamate receptors resulting in intracellular Ca2+ overload and excitotoxicity couldn’t explain the whole process of ischemic brain injury,and emerging new studies have suggested that activation of several glutamate receptor-independent Ca2+-toxicity pathways also contribute to ischemic brain injury.This review focus on the roles of acid sensing ion channels(ASICs),Na+-Ca2+ exchanger(NCX) and transient receptor potential(TRP) channels in the ischemic brain injury.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2016R1D1A1B01011790 to JHC)+3 种基金Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(NRF-2017R1A2B4009079 to MHW)Cooperative Research Program for Agriculture Science and Technology Development(Project No.PJ01329401to MHW) Rural Development Administration,Republic of Korea
文摘Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia. In this study, we investigated the effects of 5-minute (mild), 15-minute (severe), and 20-minute (lethal) transient ischemia by bilateral common carotid artery occlusion (BCCAO) on behavioral change and neuronal death and gliosis (astrocytosis and microgliosis) in gerbil hippocampal subregions (CA1-3 region and dentate gyrus). We performed spontaneous motor activity test to evaluate gerbil locomotor activity, cresyl violet staining to detect cellular distribution, neuronal nuclei immunohistochemistry to detect neuronal distribution, and Fluoro-Jade B histofluorescence to evaluate neuronal death. We also conducted immunohistochemical staining for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 (Ibal) to evaluate astrocytosis and microgliosis, respectively. Animals subjected to 20-minute BCCAO died in at least 2 days. BCCAO for 15 minutes led to pyramidal cell death in hippocampal CA1-3 region 2 days later and granule cell death in hippocampal de匚tate gyrus 5 days later. Similar results were not found in animals subjected to 5-minute BCCAO. Gliosis was much more rapidly and severely progressed in animals subjected to 15-minute BCCAO than in those subjected to 5- minute BCCAO. Our results indicate that neuronal loss in the hippocampal formation following transient ischemia is significantly different according to regions and severity of transient ischemia. The experimental protocol was approved by Institutional Animal Care and Use Committee (AICUC) of Kangwon National University (approval No. KW-180124-1) on May 22, 2018.
