High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke  

作　　者：Jing Luo Yuan Feng Zhongqiu Hong Mingyu Yin Haiqing Zheng Liying Zhang Xiquan Hu 

机构地区：[1]Department of Rehabilitation Medicine,The Third Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong Province,China [2]Department of Hepatobiliary Surgery,The Third Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong Province,China

出　　处：《Neural Regeneration Research》2024年第8期1772-1780,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.81672261(to XH),81972151(to HZ),82372568(to JL);the Natural Science Foundation of Guangdong Province,Nos.2019A1515011106(to HZ),2023A1515030080(to JL)。

摘　　要：Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenes

关 键 词：AKT/β-catenin signaling brain stimulation Ca2+influx cell proliferation ischemic stroke middle cerebral artery occlusion neural stem cells neurological rehabilitation repetitive transcranial magnetic stimulation 

分 类 号：R743.3[医药卫生—神经病学与精神病学]