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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Guo
Zongduo
Z
Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Sun
Xiaochuan
X
He
Zhaohui
Z
Jiang
Yong
Y
Zhang
Xiaodong
X
Zhang
John H
JH
D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002452:Cell Count; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007797:Laminin / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D007797:Laminin; D020780:Matrix Metalloproteinase 9