Neuroprotection by inhibition of matrix metalloproteinases in a mouse model of intracerebral haemorrhage

Jian Wang, Stella E. Tsirka

Research output: Contribution to journalArticle

Abstract

Intracerebral haemorrhage (ICH) is an acute neurological disorder without effective treatment. Mechanisms of acute brain injury after ICH remain to be clarified. Although a few studies suggested a detrimental role for the gelatinase matrix metalloproteinase (MMP)-9 in ICH, the relationship between MMP-9 activity and acute brain injury after ICH is not determined. In this study, we first examined the expression of gelatinases in vivo using a collagenase-induced mouse model of ICH. Gel zymography revealed that MMP-9 was activated and upregulated after ICH. In situ zymography showed that gelatinase activity was mostly co-localized with neurons and endothelial cells of the blood vessel matrix. Inhibition with a broad-spectrum metalloproteinase inhibitor GM6001 (100 mg/kg) ameliorated dysregulated gelatinase activity, neutrophil infiltration, production of oxidative stress, brain oedema and degenerating neurons. Functional improvement and a decrease in injury volume were also observed. We provide evidence that MMP-9 may play a deleterious role in acute brain injury within the first 3 days after ICH. Blockade of MMP activity during this critical period may have efficacy as a therapeutic strategy for the treatment of acute brain injury after ICH.

Original languageEnglish (US)
Pages (from-to)1622-1633
Number of pages12
JournalBrain
Volume128
Issue number7
DOIs
StatePublished - Jul 2005
Externally publishedYes

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Keywords

  • Intracerebral haemorrhage
  • Matrix metalloproteinase
  • Mouse
  • Neutrophil
  • Reactive oxygen species
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)

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