Dexmedetomidine treatment prevents cerebral ischemic reperfusion injury through HIF-1α/Beclin1-mediated autophagy

ABSTRACT

Objective

Cerebral ischemic reperfusion injury (CIRI) is a common cerebrovascular disorder with high disability and morbidity that threatens human health. Former investigations found that dexmedetomidine (DEX) has a protective effect against CIRI, but regulatory mechanism is unclear.

Methods

The current study utilized C57BL/6 mice to establish a focal cerebral ischemic reperfusion model. Cerebral infarct volume was defined by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. BV2 cells and primary neurons were utilized for molecular mechanism studies after treatment with DEX or autophagy inhibitor 3-Methyladenine (3-Ma).

Results

Data revealed that DEX pretreatment protected nerves against CIRI. In vitro studies also found that DEX pretreatment enhanced microglial M2 polarization and protected against neuronal apoptosis by autophagy activation. Downregulation of hypoxia inducible factor (HIF)-1α or Beclin-1 inhibited the promotional effects of DEX on microglial M2 polarization and inhibited the protective effects of DEX against neuronal apoptosis.

Conclusion

The present study found that DEX treatment protects against CIRI by modulating microglial polarization via HIF-1α/Beclin1-mediated autophagy.

KEYWORDS:

• Dexmedetomidine
• cerebral ischemia reperfusion injury
• microglial polarization
• HIF-1α
• Beclin1
• autophagy

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

The animal experiment was approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Radiation Medicine.

Data availability

Raw data are available from the corresponding author upon reasonable request.

Author’s contributions

ZB H and SY Y contributed to the study conception and design. All authors collected the data and performed the data analysis. All authors contributed to the interpretation of the data and the completion of figures and tables. All authors contributed to the drafting of the article and approved the final submitted version.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.