Dexmedetomidine attenuates neuronal injury induced by cerebral ischemia‑reperfusion by regulating miR‑199a

Mol Med Rep. 2021 Aug;24(2):574. doi: 10.3892/mmr.2021.12213. Epub 2021 Jun 10.

Abstract

As is well known, dexmedetomidine (DEX) serves a neuroprotective role in cerebral ischemia‑reperfusion (CIR) injury, and microRNA (miR)‑199a has been re‑ported to be associated with IR injury. However, the association between DEX and miR‑199a in CIR injury remains unknown. Thus, the aim of the present study was to verify whether the neuroprotective effect of DEX on cerebral ischemia‑reperfusion rats is associated with miR‑199a. A rat model of CIR was established, and the modified neurological severity score (mNSS) was evaluated. The effect of DEX on the patholog‑ical structure of the cerebral cortex in CIR rats was observed by hematoxylin and eosin and Nissl staining. Reverse transcription‑quantitative PCR was used to analyze the expression levels of miR‑199a in brain tissue following intracerebroventricular injection of miR‑199a antagomir. The co‑expression of NeuN and microtubule‑associated proteins 1A/1B light chain 3B in the cerebral cortex was analyzed by immunofluorescence staining. Western blotting and immunohistochemistry were performed to analyze the expression of autophagy‑associated proteins in the brain tissue. DEX inhibited the expression of miR‑199a, decreased the mNSS and improved pathological damage to the cerebral cortex. DEX also inhibited autophagy and expression levels of associated proteins and decreased nerve cell injury. In conclusion, DEX inhibited expression of miR‑199a and improved neurocyte injury induced by CIR.

Keywords: autophagy; cerebral ischemia‑reperfusion; dexmedetomidine; microRNA‑199a.

MeSH terms

  • Animals
  • Antigens, Nuclear / metabolism
  • Beclin-1 / metabolism
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / etiology
  • Brain Ischemia / genetics*
  • Brain Ischemia / pathology
  • Caspase 3 / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Dexmedetomidine / administration & dosage
  • Dexmedetomidine / pharmacology*
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / complications
  • Injections
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • RNA-Binding Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / etiology
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / pathology

Substances

  • Antigens, Nuclear
  • Beclin-1
  • Becn1 protein, rat
  • LC3 protein, rat
  • MIRN199 microRNA, rat
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • RNA-Binding Proteins
  • Rbfox3 protein, rat
  • Dexmedetomidine
  • Casp3 protein, rat
  • Caspase 3