Reperfusion and cytoprotective agents are a mutually beneficial pair in ischaemic stroke therapy:an overview of pathophysiology,pharmacological targets and candidate drugs focusing on excitotoxicity and free radical  

作　　者：Xiumei Xu Mingyu Chen Dongya Zhu 

机构地区：[1]School of Pharmacy,Nanjing Medical University,Nanjing,Jiangsu,China

出　　处：《Stroke & Vascular Neurology》2024年第4期351-359,共9页卒中与血管神经病学（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(82090042);the National Key Research and Development Program of China(2021YFA1101803).

摘　　要：Stroke is the second-leading cause of death and the leading cause of disability in much of the world.In particular,China faces the greatest challenge from stroke,since the population is aged quickly.In decades of clinical trials,no neuroprotectant has had reproducible efficacy on primary clinical end points,because reperfusion is probably a necessity for neuroprotection to be clinically beneficial.Fortunately,the success of thrombolysis and endovascular thrombectomy has taken us into a reperfusion era of acute ischaemic stroke(AIS)therapy.Brain cytoprotective agents can prevent detrimental effects of ischaemia,and therefore‘freeze’ischaemic penumbra before reperfusion,extend the time window for reperfusion therapy.Because reperfusion often leads to reperfusion injury,including haemorrhagic transformation,brain oedema,infarct progression and neurological worsening,cytoprotective agents will enhance the efficacy and safety of reperfusion therapy by preventing or reducing reperfusion injuries.Therefore,reperfusion and cytoprotective agents are a mutually beneficial pair in AIS therapy.In this review,we outline critical pathophysiological events causing cell death within the penumbra after ischaemia or ischaemia/reperfusion in the acute phase of AIS,focusing on excitotoxicity and free radicals.We discuss key pharmacological targets for cytoprotective therapy and evaluate the recent advances of cytoprotective agents going through clinical trials,highlighting multitarget cytoprotective agents that intervene at multiple levels of the ischaemic and reperfusion cascade.

关 键 词：protective injuries DRUGS 

分 类 号：R743.3[医药卫生—神经病学与精神病学]