Induction of MMP-9 expression and endothelial injury by oxidative stress after spinal cord injury

Fengshan Yu, Hiroshi Kamada, Kuniyasu Niizuma, Hidenori Endo, Pak H. Chan

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Matrix metalloproteinase-9 (MMP-9) activation plays an important role in bloodbrain barrier (BBB) dysfunction after central nervous system injury. Oxidative stress is also implicated in the pathogenesis after cerebral ischemia and spinal cord injury (SCI), but the relationship between MMP-9 activation and oxidative stress after SCI has not yet been clarified. We examined MMP-9 expression after SCI using copper/zincsuperoxide dismutase (SOD1) transgenic (Tg) rats. Our results show that MMP-9 activity significantly increased after SCI in both SOD1 Tg rats and their wild-type (Wt) littermates, although the increase was less in the SOD1 Tg rats. This pattern of MMP-9 expression was further confirmed by immunostaining and Western blot analysis. In situ zymography showed that gelatinolytic activity increased after SCI in the Wt rats, while the increase was less in the Tg rats. Evans blue extravasation increased in both the Wt and Tg rats, but was less in the SOD1 Tg rats. Inhibitor studies showed that, with an intrathecal injection of SB-3CT (a selective MMP-2/MMP-9 inhibitor), the MMP activity, Evans blue extravasation, and apoptotic cell death decreased after SCI. We conclude that increased oxidative stress after SCI leads to MMP-9 upregulation, BBB disruption, and apoptosis, and that overexpression of SOD1 in Tg rats decreases oxidative stress and further attenuates MMP-9 mediated BBB disruption.

Original languageEnglish
Pages (from-to)184-195
Number of pages12
JournalJournal of Neurotrauma
Volume25
Issue number3
DOIs
Publication statusPublished - 2008 Mar 1
Externally publishedYes

Keywords

  • Bloodbrain barrier
  • Copper/zinc-superoxide dismutase
  • Endothelial
  • MMP-9
  • Spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology

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