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Early activation of matrix metalloproteinase-9 is associated with blood–brain barrier disruption after photothrombotic cerebral ischemia in rats

  • Experimental Research
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Abstract

Background

The activation of matrix metalloproteinases (MMPs) is a critical event for disruption of the blood–brain barrier (BBB) during cerebral ischemia. Among the MMPs, MMP-2, and MMP-9 expression were reported to be significantly elevated after the onset of ischemia. The aim of this study was to investigate which one is more significant for BBB disruption in the photothrombotic cerebral ischemia.

Materials and methods

Male Sprague–Dawley rats weighing 250–300 g received focal cerebral ischemia by photothrombosis. MMP-2 and MMP-9 activities were assessed by gelatin zymography at various times from 2 h to 7 days. The BBB integrity was assessed using Evans blue dye with a spectrophotometric assay.

Findings

The Evans blue extravasation was increased within 2 h after cerebral ischemia, and was maximal at 12 and 24 h after the injury, and then gradually decreased. MMP-9 protein activity was detected as early as 2 h after the focal ischemic event; it rapidly increased at 6 h after ischemia, and reached a maximum level 48 h after the ischemic event. Thereafter, the MMP-9 level abruptly decreased and returned to the baseline at 72 h after the insult. By contrast, the MMP-2 protein activity was up-regulated at 6 h after the focal ischemic insult, and reached a maximum level at 72 h after the event. The elevated MMP-2 levels persisted for 7 days after the injury.

Conclusions

The early activation of MMP-9 was correlated with the increase in the permeability of the BBB. Our findings suggest that MMP-9 is the key factor involved in BBB disruption and subsequent brain injury after photothrombotic cerebral ischemia in rats.

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Acknowledgment

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (CNUH RICM-U-2006-031).

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Authors and Affiliations

  1. Department of Neurosurgery, Chonnam National University Medical School, Gwangju, Republic of Korea

    Min-Sheng Piao, Jung-Kil Lee & Soo-Han Kim

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

    Min-Sheng Piao, Jung-Kil Lee, Chun-Soon Park & Han-Seung Ryu

  3. Department of Forensic medicine, Chonnam National University Medical School, Gwangju, Republic of Korea

    Hyung-Seok Kim

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

    Jung-Kil Lee

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  1. Min-Sheng Piao
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Correspondence to Jung-Kil Lee.

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Piao, MS., Lee, JK., Park, CS. et al. Early activation of matrix metalloproteinase-9 is associated with blood–brain barrier disruption after photothrombotic cerebral ischemia in rats. Acta Neurochir 151, 1649–1653 (2009). https://doi.org/10.1007/s00701-009-0431-1

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  • DOI: https://doi.org/10.1007/s00701-009-0431-1

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