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Updated: Jul 7, 2026
Experimental Models to Study the Neuroprotection of Acidic Postconditioning Against Cerebral Ischemia
Published on: July 31, 2017
N6-methyladenosine demethylase ALKBH5 mediates remote ischemic postconditioning in cerebral ischemia-reperfusion
Aimei Wang1, Weiqi Wu1, Yin Mei1
1Department of Neurology, the Second Affiliated Hospital of Kunming Medical University, No.374 Dianmian Avenue, Kunming, Yunnan 650101, China.
Abstract:
This study aimed to investigate the role of the m6A demethylase ALKBH5 in RIPostC against CI/R injury and its underlying regulatory mechanism. A rat model of CI/R was established using the MCAO method. Subsequently, RIPostC was performed to evaluate its therapeutic potential against CI/R injury. The effects of overexpressing ALKBH5 and KLF4 on CI/R injury were also examined in the rat model. A cellular model of CI/R was established by inducing OGD/R in PC12 cells. The effects of ALKBH5 and KLF4 on cellular function in the CI/R model were investigated, and the specific regulatory role of ALKBH5 in the m6A modification of KLF4 was elucidated. The mRNA expression of ALKBH5 and KLF4 in acute ischemic stroke patients and healthy individuals was measured by RT-qPCR. The results demonstrated that ALKBH5 and KLF4 expression was decreased in acute ischemic stroke patients, as well as in CI/R rats and OGD/R-induced cells. RIPostC treatment alleviated MCAO-induced neurological deficits, reduced cerebral infarct volume, apoptosis, and inflammatory cytokine levels. Furthermore, RIPostC upregulated the expression of ALKBH5 and KLF4 in CI/R rats. Overexpression of ALKBH5 and KLF4 further enhanced the therapeutic efficacy of RIPostC in CI/R rats. Overexpression of ALKBH5 and KLF4 alleviated OGD/R-induced cellular injury. Mechanistically, overexpression of ALKBH5 upregulated KLF4 expression by promoting m6A demethylation of KLF4 mRNA. In conclusion, overexpression of ALKBH5 upregulates KLF4 by promoting m6A demethylation, thereby attenuating CI/R injury.
Insights
Reperfusion post-conditioning (RIPostC) protects against cerebral ischemia-reperfusion (CI/R) injury by increasing ALKBH5 and KLF4. ALKBH5 promotes KLF4 expression via m6A demethylation, reducing CI/R injury.
Area of Science:
- Biomedical Science
- Molecular Biology
- Cardiovascular Research
Background:
- Cerebral ischemia-reperfusion (CI/R) injury remains a significant health concern.
- The role of m6A demethylase ALKBH5 and its interaction with KLF4 in CI/R injury requires further elucidation.
Purpose of the Study:
- To investigate the protective role of reperfusion post-conditioning (RIPostC) against CI/R injury.
- To explore the underlying mechanism involving ALKBH5 and KLF4 in CI/R injury.
Main Methods:
- Established rat and cellular models of CI/R (MCAO and OGD/R).
- Investigated the effects of RIPostC, ALKBH5, and KLF4 overexpression.
- Utilized RT-qPCR to measure gene expression in patients and animal models.
- Elucidated the regulatory mechanism of ALKBH5 on KLF4 mRNA m6A modification.
Main Results:
- ALKBH5 and KLF4 expression was decreased in CI/R injury models and acute ischemic stroke patients.
- RIPostC treatment alleviated CI/R injury, upregulated ALKBH5 and KLF4, and enhanced therapeutic effects.
- Overexpression of ALKBH5 and KLF4 reduced cellular injury in OGD/R models.
- ALKBH5 promoted KLF4 expression through m6A demethylation of KLF4 mRNA.
Conclusions:
- ALKBH5 plays a crucial protective role in attenuating CI/R injury.
- ALKBH5 upregulates KLF4 via m6A demethylation, offering a potential therapeutic strategy for ischemic stroke.
