Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

作     者：He Fang Mengjie Li Jingchen Yang Shunping Ma Li Zhang Hongqi Yang Qiongyan Tang Jing Cao Weimin Yang He Fang;Mengjie Li;Jingchen Yang;Shunping Ma;Li Zhang;Hongqi Yang;Qiongyan Tang;Jing Cao;Weimin Yang

作者机构：Department of NeurologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Molecular NeuropathologyBeijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of NutritionThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of NeurologyHenan Provincial People’s HospitalZhengzhouHenan ProvinceChina Department of Human AnatomySchool of Basic Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Neuroscience Research InstituteZhengzhou University Academy of Medical SciencesZhengzhouHenan ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2024年第19卷第12期

页      面：2708-2722页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,Nos.U2004106 (to WY),81971061 (to JC) the Key Scientific Research Project of Colleges and Universities in Henan Province,No.21A320039 (to WY) 

主　　题：central post-stroke pain hemorrhagic stroke histone deacetylase iron overload voltage-gated potassium ion channel 1.2 

摘      要：Thalamic hemorrhage can lead to the development of central post-stroke *** in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic ***,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea ***,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus *** this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central ***,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain ***,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain *** results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.