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Role of Rho Kinase in Microvascular Damage Following Cerebral Ischemia Reperfusion in Rats
Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Department of Neurology, the 456th Hospital of PLA, Jinan 250031, China
These authors contributed equally to the work.
* Author to whom correspondence should be addressed.
Received: 12 December 2010; in revised form: 21 January 2011 / Accepted: 7 February 2011 / Published: 18 February 2011
Abstract: Rho kinase (ROCK) is a well-known downstream effector of Rho and plays an important role in various physiopathological processes. In this study, we aim to investigate the correlation between ROCK and microvascular damage in rat brain subjected to middle cerebral artery occlusion (MCAO) and reperfusion, and to elucidate the mechanisms underlying the microvascular damage. ROCK and matrix metalloproteinase 9 (MMP9) mRNA levels were determined by real time quantitative PCR, Laminin was detected by immunofluorescence and Blood Brain Barrier (BBB) permeability was examined by Evans Blue (EB) in rat MCAO models. We observed similar patterns of changes in ROCK expression, brain EB content, and Laminin expression at different time points after brain ischemia. Statistical analysis further confirmed a significant linear correlation of ROCK expression with the onset of microvascular damage in brain. Furthermore, the ROCK inhibitor fasudil decreased brain EB content but increased Laminin expression. These results provide strong evidence that ROCK mediates microvascular damage. In addition, we found that fasudil could significantly inhibit MMP9 expression induced by ischemia. Thus, our findings suggest that ROCK promotes microvascular damage by upregulating MMP9 and reveal ROCK as a promising therapeutic target for stroke.
Keywords: ischemia reperfusion; MMP9; blood brain barrier; Laminin; Rho kinase
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MDPI and ACS Style
Liu, K.; Li, Z.; Wu, T.; Ding, S. Role of Rho Kinase in Microvascular Damage Following Cerebral Ischemia Reperfusion in Rats. Int. J. Mol. Sci. 2011, 12, 1222-1231.
Liu K, Li Z, Wu T, Ding S. Role of Rho Kinase in Microvascular Damage Following Cerebral Ischemia Reperfusion in Rats. International Journal of Molecular Sciences. 2011; 12(2):1222-1231.
Liu, Kang; Li, Zhen; Wu, Tao; Ding, Suju. 2011. "Role of Rho Kinase in Microvascular Damage Following Cerebral Ischemia Reperfusion in Rats." Int. J. Mol. Sci. 12, no. 2: 1222-1231.