PMID- 36854487
OWN - NLM
STAT- MEDLINE
DCOM- 20230828
LR  - 20230923
IS  - 2059-8696 (Electronic)
IS  - 2059-8688 (Print)
IS  - 2059-8688 (Linking)
VI  - 8
IP  - 4
DP  - 2023 Aug
TI  - Homocysteine impedes neurite outgrowth recovery after intracerebral haemorrhage 
      by downregulating pCAMK2A.
PG  - 335-348
LID - 10.1136/svn-2022-002165 [doi]
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.
CI  - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Guo, Guangyu
AU  - Guo G
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Yang, Jingfei
AU  - Yang J
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Guo, Wenliang
AU  - Guo W
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Deng, Hong
AU  - Deng H
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Yu, Haihan
AU  - Yu H
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Bai, Shuang
AU  - Bai S
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Li, Gaigai
AU  - Li G
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Tang, Yingxin
AU  - Tang Y
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Zhang, Ping
AU  - Zhang P
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Xu, Yuming
AU  - Xu Y
AUID- ORCID: 0000-0003-2689-9897
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
AD  - NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, 
      Zhengzhou, China.
FAU - Pan, Chao
AU  - Pan C
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China ddjtzp@163.com 
      punctualpc@163.com.
FAU - Tang, Zhouping
AU  - Tang Z
AUID- ORCID: 0000-0002-4153-8590
AD  - Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong 
      University of Science and Technology, Wuhan, Hubei, China ddjtzp@163.com 
      punctualpc@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230228
PL  - England
TA  - Stroke Vasc Neurol
JT  - Stroke and vascular neurology
JID - 101689996
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Humans
MH  - *Homocysteine
MH  - *Cerebral Hemorrhage/complications
MH  - Up-Regulation
MH  - Neuronal Outgrowth
PMC - PMC10512087
OTO - NOTNLM
OT  - Cerebrovascular Disorders
OT  - Hemorrhage
OT  - Stroke
COIS- Competing interests: None declared.
EDAT- 2023/03/01 06:00
MHDA- 2023/08/28 06:42
PMCR- 2023/02/28
CRDT- 2023/02/28 20:43
PHST- 2022/11/14 00:00 [received]
PHST- 2023/02/13 00:00 [accepted]
PHST- 2023/08/28 06:42 [medline]
PHST- 2023/03/01 06:00 [pubmed]
PHST- 2023/02/28 20:43 [entrez]
PHST- 2023/02/28 00:00 [pmc-release]
AID - svn-2022-002165 [pii]
AID - 10.1136/svn-2022-002165 [doi]
PST - ppublish
SO  - Stroke Vasc Neurol. 2023 Aug;8(4):335-348. doi: 10.1136/svn-2022-002165. Epub 
      2023 Feb 28.