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Published on: January 3, 2025
Quercetin reduces the elevated matrix metalloproteinases-9 level and improves functional outcome after cerebral focal
Jung-Kil Lee1, Hyung-Jun Kwak, Min-Sheng Piao
1Department of Neurosurgery, Chonnam National University Medical School and Hospital, 8 Hak-dong, Dong-ku, Gwangju, 501-757, Republic of Korea. jkl@chonnam.ac.kr
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.
Insights
Quercetin reduces blood-brain barrier disruption and brain swelling after stroke by inhibiting MMP-9 activity. This natural compound shows promise for protecting brain cells from secondary injury in stroke patients.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Blood-brain barrier (BBB) disruption, driven by matrix metalloproteinase (MMP) activation, is a key factor in cerebral ischemia.
- Inhibiting MMPs presents a potential therapeutic strategy to mitigate secondary brain injury following stroke.
Purpose of the Study:
- To investigate the therapeutic effects of quercetin on BBB disruption and MMP activity.
- To evaluate quercetin's neuroprotective potential in a rat model of focal cerebral ischemia.
Main Methods:
- Focal cerebral ischemia was induced in rats using photothrombosis.
- Quercetin (25 μmol/kg) or vehicle was administered intraperitoneally starting 1 hour post-injury for 3 days.
- Assessed BBB permeability, brain edema, MMP-2 and MMP-9 activity, and neurological deficits.
Main Results:
- Quercetin significantly reduced MMP-9 upregulation at 24 and 48 hours post-ischemia.
- Treatment with quercetin markedly decreased BBB permeability and brain edema.
- Quercetin administration led to significant improvements in functional outcomes, as measured by the accelerating rotarod test.
Conclusions:
- Quercetin effectively attenuates BBB disruption in focal ischemia by inhibiting MMP-9 activity.
- These findings suggest quercetin holds therapeutic potential for protecting against neuronal damage in ischemic stroke.
