Neuroprotective effects of low dose minocycline against focal cerebral ischemia reperfusion injury in rats

Abstract

Objective To investigate the neuroprotective effects of low dose intravenous minocycline against ischemia reperfusion injury in rats after focal cerebral ischemia reperfusion and to explore the possible mechanism.Methods Seventy-two rats were randomly divided into sham-operated group(S group),cerebral ischemia/reperfusion group(I/R group),and minocycline intervention group(I/R+ MC group).Focal cerebral ischemia was induced by filament medial cerebral artery occlusion method.Minocycline(3mg/kg)in saline was administered intravenously via the caudal vein twice a day for 14 days in the I/R+ MC group.At 2days after ischemia reperfusion,the infarct volume was evaluated using TTC staining,the permeability of blood-brain barrier was assessed by Evan's blue(EB)dye extravasation,and the expressions of high mobility group box-1protein(HMGB1)and Iba1,a marker of activated microglia,were analyzed by using Western blotting analysis.The neurological function recovery was evaluated using the modified neurological severity score(mNSS)at 2d,7d,and 14 d after ischemia/reperfusion.Results Two days after cerebral ischemia reperfusion,the brain infarction volume and the extravasations of EB were significantly increased and the expressions of HMGB1 and Iba1were significantly up-regulated in I/R group compared with sham group(P0.05).Compared with I/R group,minocycline at 3 mg/kg via the caudal veinsignificantly reduced the infarct volume in ischemic brain(P0.05),extravasation of EB and expressions of HMGB1 and Iba1(P0.05).Additionally,the rats in I/R+MC group exhibited a significantly decreased neurological severity score compared with I/R group(P0.05).Conclusion Minocycline exerts a neuroprotective effect in rats with cerebral ischemia reperfusion injury,which may be related to decrease of infarct size,inhibition of EB extravasation and microglia activation.