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

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.

Automated summary

The neuroprotective effects of sevoflurane on cerebral ischemia/reperfusion (I/R) injury were investigated. Sevoflurane pretreatment reduced PC12 cell damage after oxygen-glucose deprivation/reoxygenation (OGD/R) and improved behavioral deficits and neuronal apoptosis in rats challenged with I/R. This effect was mediated by inhibiting the surface expression of glutamate receptor 1 (GRIA1) and blocking calcium permeable-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR).