Abstract: Objective To investigate the effect of midazolam (MDZ) on brain injury in rats with cerebral ischemia-reperfusion injury(CI/RI). Methods Rats with CI/RI were divided into five groups: CI/RI group, MDZ-L group (intravenous injection of 0.05 mg/kg MDZ), MDZ-M group (0.15 mg/kg MDZ) and MDZ-H group (0.30 mg/kg MDZ). Additionally, there was an MDZ-H + verteporfin(inhibitor of Hippo/YAP signaling pathway) group (intraperitoneal injection of 10 mg/kg verteporfin). The control group received an equivalent volume of saline.Outcomes were evaluated by neurological deficits,infarct volume, histopathological changes in brain tissue, neuronal apoptosis, inflammatory cytokines and related protein expression. Results The CI/RI group showed loosening of neuronal arrangement, enlarged cell bodies, and nuclear shift as compared to the control group. The brain tissue damage was less severe in the MDZ-L, MDZ-M, and MDZ-H groups as compared to the CI/RI group. The MDZ-H + verteporfin group exhibited more severe brain tissue damage than the MDZ-H group. The CI/RI group showed increased neurological deficit scores, infarct volume, level of TNF-α and IL-1β in brain tissue, and neuronal apoptosis rate as compared to the control group, while the expression of YAP and TAZ proteins in brain tissue was decreased (P＜0.05). The MDZ-L, MDZ-M, and MDZ-H groups showed a decrease in neurological deficits, infarct size, inflammatory cytokines and apoptosis rate, along with increased YAP and TAZ protein expression compared to the CI/RI group (P＜0.05). The MDZ-H + verteporfin group showed a reversal picture of these indicators (P＜0.05). Conclusions MDZ can partially activate the Hippo/YAP signaling pathway and reduce brain tissue damage.

Key words: midazolam, Hippo/Yes-associated protein(YAP), cerebral ischemia-reperfusion, cerebral protection