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 

机构地区：[1]Department of Neurology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan Province,China [2]Department of Molecular Neuropathology,Beijing Neurosurgical Institute,Capital Medical University,Beijing,China [3]Department of Nutrition,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan Province,China [4]Department of Neurology,Henan Provincial People’s Hospital,Zhengzhou,Henan Province,China [5]Department of Human Anatomy,School of Basic Medical Sciences,Zhengzhou University,Zhengzhou,Henan Province,China [6]Neuroscience Research Institute,Zhengzhou University Academy of Medical Sciences,Zhengzhou,Henan Province,China

出　　处：《Neural Regeneration Research》2024年第12期2708-2722,共15页中国神经再生研究（英文版）

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)。

摘　　要：Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting 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 pain.However,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 symptoms.Moreover,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 rats.These 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.

关 键 词：central post-stroke pain hemorrhagic stroke histone deacetylase iron overload voltage-gated potassium ion channel 1.2 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]