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.
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.
Authors: Major Gooyit; Mark A Suckow; Valerie A Schroeder; William R Wolter; Shahriar Mobashery; Mayland Chang Journal: ACS Chem Neurosci Date: 2012-07-30 Impact factor: 4.418
Authors: Mijoon Lee; Masahiro Ikejiri; Dennis Klimpel; Marta Toth; Mana Espahbodi; Dusan Hesek; Christopher Forbes; Malika Kumarasiri; Bruce C Noll; Mayland Chang; Shahriar Mobashery Journal: ACS Med Chem Lett Date: 2012-05-02 Impact factor: 4.345
Authors: Richard F Keep; Anuska V Andjelkovic; Jianming Xiang; Svetlana M Stamatovic; David A Antonetti; Ya Hua; Guohua Xi Journal: J Cereb Blood Flow Metab Date: 2018-05-08 Impact factor: 6.200