Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke  

作　　者：Lin-Yan Huang Yi-De Zhang Jie Chen Hai-Di Fan Wan Wang Bin Wang Ju-Yun Ma Peng-Peng Li Hai-Wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua Qi 

机构地区：[1]School of Medical Technology,Xuzhou Key Laboratory of Laboratory Diagnostics,Xuzhou Medical University,Xuzhou,Jiangsu Province,China [2]School of Pharmacy,Xuzhou Medical University,Xuzhou,Jiangsu Province,China [3]Department of Laboratory Medicine,Branch Hospital of Huai’an First People’s Hospital,Huai’an,Jiangsu Province,China [4]Department of Laboratory Medicine,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu Province,China [5]School of Chinese Medicine,The University of Hong Kong,Hong Kong Special Administrative Region,China

出　　处：《Neural Regeneration Research》2025年第3期845-857,共13页中国神经再生研究（英文版）

基　　金：supported by the Natural Science Foundation of Jiangsu Province of China,No.BK20211348(to SHQ);Xuzhou Basic Research Program,No.KC21030(to LYH);Leadership Program of Xuzhou Medical University,No.JBGS202203(to SHQ);Research Grant Council GRF of Hong Kong Special Administrative Region of China,No.17105220(to JGS)。

摘　　要：It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关 键 词：cell differentiation cerebral ischemia/reperfusion injury CHLORINATION hypochlorous acid MICROGLIA neural stem cell NEUROGENESIS nuclear translocation stroke β-catenin 

分 类 号：R743.3[医药卫生—神经病学与精神病学]