Sevoflurane Preconditioning Downregulates GRIA1 Expression to Attenuate Cerebral Ischemia-Reperfusion-Induced Neuronal Injury

Neurotox Res. 2023 Feb;41(1):29-40. doi: 10.1007/s12640-022-00620-5. Epub 2023 Jan 3.

Abstract

Cerebral ischemia/reperfusion (I/R) injury is the main cause of death following trauma. The neuroprotective effect of sevoflurane (Sev) has been implicated in cerebral I/R injury. However, the mechanisms remain elusive. In this study, we aimed to explore its function in PC12 exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) and in rats challenged with I/R. Sev pretreatment reduced the damage of PC12 cells after OGD/R treatment. Moreover, Sev pretreatment ameliorated neurobehavioral deficits induced by I/R treatment, reduced brain infarct volume, and decreased apoptosis of neurons in hippocampal tissues. Sev pretreatment reduced the surface expression of glutamate receptor 1 (GRIA1) in neurons, while GRIA1 reduced the neuroprotective effects of Sev pretreatment in vitro and in vivo. There was no difference in the surface expression of GRIA2 in rats with I/R and PC12 cells exposed to OGD/R. The ratio of GRIA1/GRIA2 surface expression was reduced, and calcium permeable-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR) was blocked by Sev. Together, Sev might exert beneficial effects on cerebral I/R-induced neuronal injury through inhibiting the surface expression of GRIA1 and blocking CP-AMPAR.

Keywords: Calcium permeable-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; Cerebral ischemia/reperfusion injury; GRIA1; Neuronal injury; Sevoflurane.

MeSH terms

  • Animals
  • Apoptosis
  • Brain Ischemia* / complications
  • Cerebral Infarction / complications
  • Glucose / metabolism
  • Neurons* / metabolism
  • Neurons* / pathology
  • Neuroprotective Agents* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Oxygen
  • Rats
  • Receptors, AMPA* / drug effects
  • Receptors, AMPA* / metabolism
  • Reperfusion / adverse effects
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism
  • Sevoflurane / pharmacology

Substances

  • Glucose
  • Neuroprotective Agents
  • Oxygen
  • Sevoflurane
  • glutamate receptor ionotropic, AMPA 1
  • Receptors, AMPA