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

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Abstract

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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Acknowledgments

This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2007-331-H00007). The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Neurosurgery, Chonnam National University Medical School and Hospital, 8 Hak-dong, Dong-ku, Gwangju, 501-757, Republic of Korea

    Jung-Kil Lee, Hyung-Jun Kwak, Min-Sheng Piao, Jae-Won Jang & Soo-Han Kim

  2. Clinical Trial Center, Chonnam National University Hospital, Gwangju, South Korea

    Jung-Kil Lee & Min-Sheng Piao

  3. Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, South Korea

    Hyung-Seok Kim

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  1. Jung-Kil Lee
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Comment

The authors have examined the effects of antioxidant therapy on the generation of blood–brain barrier (BBB) disruptions in focal ischemia. This topic has been a promising one, with many animal models vaunting the protective effects of antioxidants in reducing neural damage following ischemia, even hours after the initial insult [1].

The manuscript provides convincing evidence of Quercetin’s ability to reduce permeability across the BBB post-ischemia and so reduce ischemia-induced cerebral edema. Their data demonstrating reductions in MMP9 post-quercetin administration also provide a potential mechanism for the compound’s ability to reduce ischemia damage to the BBB.

The topic of antioxidants in stroke has been a tantalizing and frustrating one, but these data build evidence for a novel drug that may be both protective and therapeutic for the secondary damage caused by stroke.

[1] Ginsberg MD (2008) Neuroprotection for ischemic stroke: past, present, and future. Neuropharmacology 55:363–89

Markus Bookland, M.D.

Christopher M. Loftus, M.D., F.A.C.S.

Philadelphia, USA

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Lee, JK., Kwak, HJ., Piao, MS. et al. Quercetin reduces the elevated matrix metalloproteinases-9 level and improves functional outcome after cerebral focal ischemia in rats. Acta Neurochir 153, 1321–1329 (2011). https://doi.org/10.1007/s00701-010-0889-x

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  • DOI: https://doi.org/10.1007/s00701-010-0889-x

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