Matrix metalloproteinase-9 potentiates early brain injury after subarachnoid hemorrhage

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.