Homocysteine impedes neurite outgrowth recovery after intracerebral haemorrhage by downregulating pCAMK2A  

作　　者：Guangyu Guo Jingfei Yang Wenliang Guo Hong Deng Haihan Yu Shuang Bai Gaigai Li Yingxin Tang Ping Zhang Yuming Xu Chao Pan Zhouping Tang 

机构地区：[1]Department of Neurology,Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology,Wuhan,Hubei,China [2]Department of Neurology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan,China [3]NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases,Zhengzhou,China

出　　处：《Stroke & Vascular Neurology》2023年第4期335-348,I0038-I0049,共26页卒中与血管神经病学（英文）

摘　　要：Hyperhomocysteinemia(HHcy)is independently associated with poorer long-term prognosis in patients with intracerebral haemorrhage(ICH);however,the effect and mechanisms of HHcy on ICH are still unclear.Here,we evaluated neurite outgrowth and neurological functional recovery using simulated models of ICH with HHcy in vitro and in vivo.We found that the neurite outgrowth velocity and motor functional recovery in the ICH plus HHcy group were significantly slower than that in the control group,indicating that homocysteine(Hcy)significantly impedes the neurite outgrowth recovery after ICH.Furthermore,phosphoproteomic data and signalome analysis of perihematomal brain tissues suggested that calmodulin-dependent protein kinases 2(CAMK2A)kinase substrate pairs were significantly downregulated in ICH with HHcy compared with autologous blood injection only,both western blot and immunofluorescence staining confirmed this finding.Additionally,upregulation of pCAMK2A significantly increased neurite outgrowth recovery in ICH with HHcy.Collectively,we clarify the mechanism of HHcy-hindered neurite outgrowth recovery,and pCAMK2A may serve as a therapeutic strategy for promoting neurological recovery after ICH.

关 键 词：INTRACEREBRAL INJECTION SLOWER 

分 类 号：R743.34[医药卫生—神经病学与精神病学]