Dexmedetomidine attenuates cerebral ischemia/reperfusion injury in neonatal rats by inhibiting TLR4 signaling

Abstract

Objective: The sedative dexmedetomidine plays a role in multi-organ protection by inhibiting toll-like receptor (TLR) 4 expression in ischemia/reperfusion injury. The present study investigated whether the neuroprotective effects of dexmedetomidine could be blocked by the TLR4 agonist lipopolysaccharide. Methods: We established a cerebral ischemia/reperfusion model in neonatal Sprague-Dawley rats through bilateral carotid artery occlusion for 20 minutes followed by a 2-hour reperfusion. Rats were assigned to four groups: Sham operation, ischemia/reperfusion, ischemia/reperfusion preceded by dexmedetomidine treatment (10 µg/kg), and ischemia/reperfusion preceded by dexmedetomidine (10 µg/kg) and lipopolysaccharide (500 µg/kg) treatments. Cerebral tissue injury was assessed by hematoxylin and eosin staining, and cerebral TLR4 expression was evaluated by real-time PCR and western blot. Results: Pretreatment with dexmedetomidine reduced ischemia-induced morphological changes in the hippocampal CA3 region and downregulated TLR4 expression, but these neuroprotective effects were partially blocked by co-treatment with the TLR4 agonist lipopolysaccharide. Conclusion: Our results indicate that inhibition of cerebral TLR4 expression is related to the neuroprotective effects of dexmedetomidine in this neonatal rat cerebral ischemia/reperfusion model.