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

Jung-Kil Lee, Hyung-Jun Kwak, Min-Sheng Piao, Jae-Won Jang, Soo-Han Kim, Hyung-Seok Kim
Acta Neurochirurgica 2011, 153 (6): 1321-9; discussion 1329

BACKGROUND: 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.

METHODS: Adult male Sprague-Dawley rats received focal ischemia by photothrombosis. The injured animals were divided into two groups: one group received 25 μmol/kg of quercetin intraperitoneally, starting 1 h after injury with continued treatment at 12-h intervals for 3 days, 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.

FINDINGS: Quercetin treatment markedly reduced ischemia-induced up-regulation of MMP-9 at 24 and 48 h 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.

CONCLUSIONS: 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.

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