Matrix metalloproteinase-9 potentiates early brain injury after subarachnoid hemorrhage

Neurol Res. 2010 Sep;32(7):715-20. doi: 10.1179/016164109X12478302362491. Epub 2009 Aug 21.

Abstract

Objective: This study investigated the role of matrix metalloproteinase-9 (MMP-9) in early brain injury after subarachnoid hemorrhage (SAH).

Method: Sprague-Dawley male rats (n=36) weighing between 250 and 300 g were used. SAH was produced by injecting autologous arterial blood into the pre-chiasmatic cistern. MMP-9 protein expression and activity were measured by Western blot and zymogram; laminin expression and neuronal cell in hippocampus were studied by immunohistochemistry and TUNEL staining at 24 hours after SAH in the presence or absence of a selective MMP-9 inhibitor SB-3CT.

Result: MMP-9 was activated by SAH and inhibited by SB-3CT at 24 hours after SAH (p<0.01). Laminin, the substrate of MMP-9, was decreased at 24 hours after SAH, and SB-3CT prevented laminin degradation. The number of TUNEL-positive neurons in hippocampus was increased after SAH and decreased by SB-3CT (p<0.01). In addition, brain water content and neurological functional abnormalities were attenuated by SB-3CT.

Conclusion: MMP-9 may be involved in early brain injury through degradation of laminin and neuronal death, and inhibition of MMP-9 may be a potential direction for brain protection after SAH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Blotting, Western
  • Cell Count
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Laminin / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Neurons / metabolism
  • Neurons / pathology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage / etiology
  • Subarachnoid Hemorrhage / metabolism*
  • Subarachnoid Hemorrhage / pathology

Substances

  • Laminin
  • Matrix Metalloproteinase 9