The Role of Casr Inhibition-Mediated M2 Microglial Transformation in Ischemic Preconditioning Against Stroke  

作　　者：Zhi-hao Zhai Zuo-yu Huang Kai-xun Huang Yuan-qiang Zhong En-xiang Tao Yun-feng Yang 

机构地区：[1]Department of Neurosurgery,The Eighth Affiliated Hospital,Sun Yat-Sen University,Shenzhen,518000,China [2]Department of Physiology,School of Medicine,Shenzhen Campus of Sun Yat-Sen University,Shenzhen,518000,China [3]Neurobiology Research Center,School of Medicine,Shenzhen Campus of Sun Yat-Sen University,Shenzhen,518000,China [4]Department of Neurology,The Eighth Affiliated Hospital,Sun Yat-Sen University,Shenzhen,518000,China

出　　处：《Current Medical Science》2025年第1期82-92,共11页当代医学科学(英文)

基　　金：supported by the National Natural Science Foundation of China(grant numbers 81371440,82271454 and 81971195).

摘　　要：Objective Stroke is a main cause of disability and mortality worldwide.It has been reported that ischemic preconditioning(IP)has neuroprotective effects against stroke.This study aimed to verify the mechanism by which calcium-sensing recep-tor(Casr)inhibition-mediated M2 microglial transformation in the IP protects against stroke,which will provide a potential therapeutic target for stroke.Methods Middle cerebral artery occlusion(MCAO)rats and oxygen-glucose deprivation(OGD)neurons were used in this study.IP was induced via the transient MCAO and OGD methods.RNA sequencing(RNA-Seq)was used to explore the underlying key molecules.Western blotting and immunohistochemistry were performed to detect the expression of Casr and the M1 and M2 microglial markers.CCK8 was used to detect cell viability.The calcium concentration was detected via the use of Fluo-4 AM,a fluorescence probe.The Casr inhibitor NPS2143 and the Casr activator R568 were used to explore the role of Casr in M2 microglial transformation and neuroprotection.Results We first revealed that IP induced M2 microglial transformation in ischemic injury.In addition,MCAO injury increased Casr expression and the calcium concentration,which was inhibited by IP.Furthermore,Casr activation inhibited the M2 microglial transformation induced by IP.Finally,we found that Casr inhibition improved the survival rate,alleviated neurological deficits,and reduced the infarct volume induced by MCAO.Conclusions We confirmed that Casr-related neuroprotection induced by IP is associated with the transformation of M2 microglia.These findings can be used to understand the protective mechanisms of IP against ischemic stroke.

关 键 词：STROKE Transient ischemic attacks Calcium-sensing receptor Microglial transformation Ischemic preconditioning 

分 类 号：R743.3[医药卫生—神经病学与精神病学]