Abstract: AIM:Although ginsenoside Rg1 possesses potent neuroprotective effects,it cannot easily be transported to brain parenchyma because of the blood-brain barrier(BBB).This study was aimed to verify the hypothesis that the ginsenoside Rg1 neuroprotective effect might be mainly derived from its direct protective effects on BBB.METHODS:Male Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion(MCAO) by using the suture insertion method followed by 22 h of reperfusion.In the Rg1-treated group,Rg1(45 mgkg-1) was administrated via tail venous(i.v.)1 h before focal ischemia and 3 h after reperfusion.The integrity of the BBB was measured in vivo,MDA and SOD were estimated in vitro.The expression and activity of matrix metalloproteinases(MMPs),and the expression of tissue inhibitor of matrix metalloproteinases(TIMPs) mRNA,were determined to evaluate the protective effect of Rg1 on BBB structure both in vivo and in vitro.RESULTS:In ischemia/reperfusion rats,using the EB dye extravasation,the expression and activity of MMPs were increased as compared to sham rats,while in Rg1-treated rats,these increases were inhibited.The expression of TIMP-2 mRNA in the ischemia/reperfusion rats was decreased as compared to sham rats,while in Rg1-treated rats,these decreases were ameliorated.The results of in vitro models were consistent with those of in vivo models.CONCLUSION:Ginsenoside Rg1 may exert its protective effect of CNS indirectly by protecting the structure of the BBB,through protecting BMECs and reducing the expression and activity of MMPs in pathological conditions.