Open AccessExosomes containing miR‐451a is involved in the protective effect of cerebral ischemic preconditioning against cerebral ischemia and reperfusion injury
Author(s) -
Li He,
Luo Yin,
Liu Peng,
Liu Pei,
Hua Weilong,
Zhang Yongxin,
Zhang Lei,
Li Zifu,
Xing Pengfei,
Zhang Yongwei,
Hong Bo,
Yang Pengfei,
Liu Jianmin
Publication year - 2021
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13612
Subject(s) - microvesicles , ischemia , rac1 , pharmacology , medicine , oxidative stress , reperfusion injury , downregulation and upregulation , microrna , chemistry , microbiology and biotechnology , biology , signal transduction , biochemistry , gene
Aim To study the role of exosomes in the protective effect of cerebral ischemic preconditioning (cerebral‐IPC) against cerebral I/R injury. Method Mouse models of cerebral‐IPC and MCAO/R were established as described previously, and their behavioral, pathological, and proteomic changes were analyzed. Neuro‐2a subjected to OGD/R were treated with exosomes isolated from the plasma of sham‐operated and cerebral‐IPC mice. The differentially expressed miRNAs between exosomes derived from sham‐operated (S‐exosomes) and preconditioned (IPC‐exosomes) mice were identified through miRNA array, and their targets were identified through database search. The control and OGD/R cells were treated with the IPC‐exosomes, miRNA mimic or target protein inhibitor, and their viability, oxidative, stress and apoptosis rates were measured. The activated pathways were identified by analyzing the levels of relevant proteins. Results Cerebral‐IPC mitigated the cerebral injury following ischemia and reperfusion, and increased the number of plasma exosomes. IPC‐exosomes increased the survival of Neuro‐2a cells after OGD/R. The miR‐451a targeting Rac1 was upregulated in the IPC‐exosomes relative to S‐exosomes. The miR‐451a mimic and the Rac1 inhibitor NSC23766 reversed OGD/R‐mediated activation of Rac1 and its downstream pathways. Conclusion Cerebral‐IPC ameliorated cerebral I/R injury by inducing the release of exosomes containing miR‐451a.