RIPC alleviates post-stroke synaptic damage by inhibiting NMDA receptor overactivation

  • WANG Zhiguang ,
  • YAN Lei ,
  • SHAO Guo ,
  • LIU You ,
  • JIANG Shuyuan
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  • 1. School of Pharmacy, Baotou Medical College, Baotou 014040, China;
    2. School of Basic Medicine and Forensic Medicine, Baotou Medical College;
    3. Center for Translational Medicine, the Third People's Hospital of Longgang District, Shenzhen, Guangdong

Received date: 2025-05-27

  Online published: 2026-03-03

Abstract

Objective: To investigate the mechanism of remote ischemic preconditioning in achieving neuroprotection by regulating synaptic plasticity proteins via the NR2B subunit of the NMDA receptor. Methods: In animal experiments, 30 male mice were randomly divided into four groups: sham operation group (SHAM group), middle cerebral artery occlusion group (MCAO/R group), middle cerebral artery occlusion plus remote ischemic preconditioning group (MCAO/R+RIPC group), middle cerebral artery occlusion plus remote ischemic preconditioning plus exosome inhibitor group (MCAO/R+RIPC+GW4869 group). In cell experiments, mouse hippocampal neurons were divided into three groups: control group C (Control) after oxygen-glucose deprivation and reperfusion (OGD/R ), NC group treated with exosomes from normal mice and treated with oxygen-glucose deprivation and reperfusion (OGD/R), RIPC group treated with exosomes from RIPC mice and treated with oxygen-glucose deprivation and reperfusion (OGD/R). The expression of synapse-related genes (GAP-43, SYN, PSD95) and NR2B was detected by real-time fluorescence quantitative PCR and Western blot, respectively. Results: Animal experiment: Compared with SHAM group, the expression of GAP43, SYN and PSD95 in MCAO/R group was decreased (P<0.05), and the expression of NR2B was increased (P<0.05). Compared with the MCAO/R group, the expression of synaptic-related proteins was increased after RIPC treatment (P<0.05), and the expression of NR2B was decreased (P<0.05). Compared with the MCAO/R+RIPC group, the expression of synaptic-related proteins was decreased after the addition of exosome inhibitors (P<0.05), and the expression of NR2B was increased (P<0.05). Cell experiments: Compared with group C, the levels of synapse-related genes (GAP43, SYN and PSD95) in RIPC group were increased (P<0.05), and the expression of NR2B was decreased (P<0.05). Conclusion: Remote ischemic preconditioning may enhance synaptic function through NMDARs, thereby alleviating cognitive dysfunction and ischemic brain injury.

Cite this article

WANG Zhiguang , YAN Lei , SHAO Guo , LIU You , JIANG Shuyuan . RIPC alleviates post-stroke synaptic damage by inhibiting NMDA receptor overactivation[J]. Journal of Baotou Medical College, 2025 , 41(12) : 26 -32 . DOI: 10.16833/j.cnki.jbmc.2025.12.006

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