Down-regulation of miR-204-5p ameliorates sevoflurane-induced brain injury in neonatal rats through targeting VCAM1

Toxicol Mech Methods. 2023 May;33(4):307-315. doi: 10.1080/15376516.2022.2128705. Epub 2022 Oct 18.

Abstract

To confirm the regulation of miR-204-5p on VCAM1 and its effect on sevoflurane-induced brain injury in neonatal rats. We adopted the sevoflurane-induced brain injury model, and the double luciferase reporter gene assay was applied to explore the targeting relationship between vascular adhesion factor 1 (VCAM1) and miR-204-5p. RT-qPCR was applied to assess the levels of miR-204-5. VCAM1, LC3, P62 and cleaved-caspase 3 levels in the hippocampus were estimated by western blot. The number of autophagosomes in the cerebral cortex was assessed via Transmission electron microscopy (TEM), and histopathological changes within the hippocampus by HE staining. miR-204-5p levels were remarkably increased, but VCAM1 expression was decreased after neonatal rat brain injury. Furthermore, miR-204-5p directly targeted VCAM1. The escape latency, swimming distance, autophagosome number, neuronal apoptosis ratio, LC3 II and Cleaved-caspase 3 expression were reduced after miR-204-5p inhibition interference, whereas crossing times, and P62 expression increased in the sevoflurane-induced brain injury model. Furthermore, down-regulation of VCAM1 reversed the trend of these indices. These results suggest that down-regulation of miR-204-5p ameliorates sevoflurane-induced cognitive impairment and hippocampal pathology and inhibits neuronal autophagy and apoptosis by targeting VCAM1.

Keywords: VCAM1; autophagy; brain injury; miR-204-5p; sevoflurane.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis
  • Brain Injuries* / chemically induced
  • Caspase 3 / metabolism
  • Down-Regulation*
  • MicroRNAs* / genetics
  • Rats
  • Sevoflurane*

Substances

  • Caspase 3
  • MicroRNAs
  • MIRN204 microRNA, rat
  • Sevoflurane