Quercetin reduces the elevated matrix metalloproteinases-9 level and improves functional outcome after cerebral focal ischemia in rats

Abstract

Blood-brain barrier (BBB) disruption mediated by matrix metalloproteinase (MMPs) activation is a critical event during cerebral ischemia. The inhibition of MMP might be a potential approach to protect against secondary injury. The present study was designed to determine the effects of quercetin on BBB disruption and MMP activity, in a focal ischemia model induced by photothrombosis, in rats. Adult male Sprague-Dawley rats received focal ischemia by photothrombosis. The injured animals were divided into two groups: one group received 25μmol/kg of quercetin intraperitoneally, starting 1h after injury with continued treatment at 12-h intervals for 3days, while animals in the control group received weight-adjusted doses of a saline vehicle. The effects of quercetin on BBB disruption, brain edema, MMP activities, and neurological deficits were determined. Quercetin treatment markedly reduced ischemia-induced up-regulation of MMP-9 at 24 and 48h after ischemic injury. No significant change in MMP-2 activity was observed throughout the experimental period. Post-ischemic increase in BBB permeability and brain edema were significantly reduced in the quercetin-treated group compared to the vehicle-treated ischemia control. Quercetin treatment significantly improved the functional outcomes assessed by the accelerating rotarod test. The results of this study demonstrated that quercetin attenuated BBB disruption during focal ischemia through inhibitory effects on MMP-9 activity. These results suggest that quercetin might have a potential role in the protection against neuronal injury in patients with focal ischemic stroke.