大脑皮层GABA能神经元缺血性损伤:易损性,机制和病理影响（英文）  

Ischemic Injury of Cortical GABAergic Neurons:Vulnerability,Mechanism and Pathological Impacts

作　　者：王晋辉 黄丽[2] 陈娜 WANG Jin-hui;HUANG Li;CHEN Na(University of Chinese Academy of Sciences,Beijing,100049,China;Department of Pathophysiology,Bengbu Medical College,Bengbu,200031,China)

机构地区：[1]中国科学院大学 [2]蚌埠医学院病理生理学教研室

出　　处：《神经药理学报》2018年第2期8-25,共18页Acta Neuropharmacologica

基　　金：国家基础研究计划项目(No.2013CB531304,2016YFC1307100);国家自然科学基金项目(No.81671071,81471123)

摘　　要：大脑缺血性中风是老年人常见的神经疾病,其治疗策略包括抗凝、溶栓、神经保护和抗炎等,但疗效并非达到完全治愈。因而研究缺血性脑中风的新的病理机制和新的防治策略尤为重要。大脑γ氨基丁酸(gamma aminobutyric acid,GABA)能神经元因细胞活跃、代谢旺盛及其缓冲能力低下,对缺氧、氧化应激和毒素敏感,因而易受环境因素的影响而损伤。脑血流降低首先导致大脑星形胶质细胞和GABA能神经元缺血性病理变化,GABA能神经元的损伤诱导大脑兴奋和抑制的失平衡,导致兴奋毒性神经损伤和缺血性神经细胞死亡。因而,澄清GABA能神经元易损性的机制将有助于发现新的保护神经元功能而防治脑损伤的策略。Cerebral ischemic stroke is a common neurological disease in senior individuals.Therapeutic strategies include anticoagulation,thrombolysis,neuroprotection and anti-inflammation.These efforts have not shown to fully improve stroke patients.Although studies have provided valuable insights for early interventions in neuroprotection,searching mechanisms underlying ischemic stroke is critically needed.Cerebral GABAergic neurons have been found to be vulnerable to pathological situations,such as ischemia,oxidative stress,acidosis and toxic molecules.The high consumption of cellular energy and the low volume of cellular buffer system make GABAergic neurons being vulnerable to the hazard internal environment.Insufficient blood flow initiates ischemic processes in brain cells,especially in GABAergic neurons and astrocytes.These changes activate intracellular signaling pathways and influence membrane components in GABAergic neurons.Moreover,an ischemic failure for astrocytes to reuptake glutamates exacerbates the dysfunction of GABAergic cells.Their dysfunctions in encoding spikes and transmitting synaptic signals may shift neural balance toward the excitotoxicity,which leads to the ischemic stroke of nerve cells.The studies of mechanisms underlying GABAergic cell vulnerability to toxic environments should provide the clues for developing therapeutic strategies in the protection of neuronal functions from ischemic injury.

关 键 词：缺血 Γ氨基丁酸 神经元 突触 神经胶质细胞 大脑 

分 类 号：R964[医药卫生—药理学]