Neuroprotection of Dexmedetomidine against Cerebral Ischemia-Reperfusion Injury in Rats: Involved in Inhibition of NF-κB and Inflammation Response

Dexmedetomidine is an alpha 2-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induded cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of 1 mu g/kg load dose, followed by 0.05 mu g/kg/min infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-1 beta, interleukin-6 and tumor nevrosis factor-alpha as well as the protein expression of inducible nitric Oxide synthase, cyclooxygenase-2, nuclear factor-kappa Bp65, inhibitor of kappa B alpha and phosphorylated of kappa B alpha in hippocampus were asessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-kappa B pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.