Effect of bumetanide pretreatment on focal cerebral ischemia-reperfusion injury in rats

Objective To investigate the effect of bumetanide pretreatment on focal cerebral ischemiareperfusion(I/R) injury in rats.Methods One hundred and five male SD rats weighing 250-300 g were randomly divided into 3 groups (n =35 each ):sham operation group(group S),focal cerebral I/R group (group I/R) and bumetanide pretreatment group (group B).Focal cerebral I/R was induced by occluding the fight middle cerebral artery with a nylon thread with a rounded tip which was inserted into internal carotid artery and advanced cranically until resistance was met in groups I/R and B.In group B bumetanide 30 mg/kg was injected iv at 10 min before ischemia.Neurologic function was assessed and scored-neurologic deficit scores (0 =no deficit,4 =unable to move).The animals were sacrificed at 3,24 and 48 h of reperfusion and their brains were immediately removed for determination of cerebral water content and expression of Na+ -K+ -2Cl- cotransporter 1 (NKCC1).The infarct size was measured at 24 h of reperfusion.Results Focal cerebral I/R significantly increased neurelogic deficit scores,NKCC1 expression,cerebral water content and infarct size in group I/R as compared with group S.Bumetanide pretreatment significantly attenuated cerebral focal I/R-induced increase in neurologic deficit scores,NKCC1 expression and cerebral water content in group B as compared with group I/R.There was no significant difference in infarct size between groups I/R and B.Conclusion Bumetanide pretreatment can reduce focal cerebral I/R injury in rats,and down-regulation of NKCC1 expression is involved in the mechanism. Key words: Bumetanide;  Reperfusion injury;  Brain