RT Journal Article
SR Electronic
T1 Homocysteine impedes neurite outgrowth recovery after intracerebral haemorrhage by downregulating pCAMK2A
JF Stroke and Vascular Neurology
JO Stroke Vasc Neurol
FD BMJ Publishing Group Ltd
SP 335
OP 348
DO 10.1136/svn-2022-002165
VO 8
IS 4
A1 Guangyu Guo
A1 Jingfei Yang
A1 Wenliang Guo
A1 Hong Deng
A1 Haihan Yu
A1 Shuang Bai
A1 Gaigai Li
A1 Yingxin Tang
A1 Ping Zhang
A1 Yuming Xu
A1 Chao Pan
A1 Zhouping Tang
YR 2023
UL http://svn.bmj.com/content/8/4/335.abstract
AB 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.Data are available in a public, open access repository. The proteomic data can be accessed from iProX database (https://www.iprox.cn) under accession number IPX0004967000. The datasets generated during this study will be available from the corresponding authors upon reasonable request.