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


RESULTS
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.
Department of Neurosurgery, Chonnam National University Medical School and Hospital, 8 Hak-dong, Dong-ku, Gwangju, 501-757, Republic of Korea. jkl@chonnam.ac.kr
Jung-Kil
JK
Lee
Hyung-Jun
HJ
Kwak
Min-Sheng
MS
Piao
Jae-Won
JW
Jang
Soo-Han
SH
Kim
Hyung-Seok
HS
Kim
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology*; D007124:Immunoenzyme Techniques; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D015854:Up-Regulation / Q000187:drug effects
D061965:Matrix Metalloproteinase Inhibitors; D011794:Quercetin; D020778:Matrix Metalloproteinase 2