PT  - JOURNAL ARTICLE
AU  - Guangyu Guo
AU  - Jingfei Yang
AU  - Wenliang Guo
AU  - Hong Deng
AU  - Haihan Yu
AU  - Shuang Bai
AU  - Gaigai Li
AU  - Yingxin Tang
AU  - Ping Zhang
AU  - Yuming Xu
AU  - Chao Pan
AU  - Zhouping Tang
TI  - Homocysteine impedes neurite outgrowth recovery after intracerebral haemorrhage by downregulating pCAMK2A
AID  - 10.1136/svn-2022-002165
DP  - 2023 Aug 01
TA  - Stroke and Vascular Neurology
PG  - 335--348
VI  - 8
IP  - 4
4099  - http://svn.bmj.com/content/8/4/335.short
4100  - http://svn.bmj.com/content/8/4/335.full
SO  - Stroke Vasc Neurol2023 Aug 01; 8
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.