Demonstration of elevation and localization of Rho-kinase activity in the brain of a rat model of cerebral infarction

• Published in: European journal of pharmacology Vol. 594; no. 1; pp. 77 - 83
• Main Authors: Yano, Kazuo, Kawasaki, Koh, Hattori, Tsuyoshi, Tawara, Shunsuke, Toshima, Yoshinori, Ikegaki, Ichiro, Sasaki, Yasuo, Satoh, Shin-ichi, Asano, Toshio, Seto, Minoru
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.10.2008; Elsevier
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Activating Transcription Factor 3 - metabolism; Amides - pharmacology; Animals; Biological and medical sciences; Blotting, Western; Brain - enzymology; Brain - pathology; Cerebral Cortex - enzymology; Cerebral Cortex - pathology; Cerebral infarction; Cerebral Infarction - enzymology; Cerebral Infarction - pathology; Cerebral thrombosis; Enzyme Inhibitors - pharmacology; Hippocampus - enzymology; Hippocampus - pathology; Immunohistochemistry; Male; MBS (myosin-binding subunit); Medical sciences; MLC (myosin light chain); Myosin Light Chains - metabolism; Neurology; Pharmacology. Drug treatments; Phosphorylation; Protein kinase; Proto-Oncogene Proteins c-fos - metabolism; Proto-Oncogene Proteins c-jun - metabolism; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; ROCK (Rho-kinase); Tissue Extracts - chemistry; Tissue Extracts - metabolism; Vascular diseases and vascular malformations of the nervous system; Cerebral infarction; MLC (myosin light chain); ROCK (Rho-kinase); MBS (myosin-binding subunit); Protein kinase; Rats; Cerebral thrombosis; Animal model; Rat; Non-specific serine/threonine protein kinase; Central nervous system; Cardiovascular disease; Light peptide chain; Subunit; Encephalon; Vascular disease; Myosin; Localization; Cerebrovascular disease; Nervous system diseases; Enzyme; Transferases; Rodentia; Thrombosis; Cerebral disorder; Vertebrata; Mammalia; Animal; Central nervous system disease
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.07.045

Evidence that Rho-kinase is involved in cerebral infarction has accumulated. However, it is uncertain whether Rho-kinase is activated in the brain parenchyma in cerebral infarction. To answer this question, we measured Rho-kinase activity in the brain in a rat cerebral infarction model. Sodium laurate was injected into the left internal carotid artery, inducing cerebral infarction in the ipsilateral hemisphere. At 6 h after injection, increase of activating transcription factor 3 (ATF3) and c-Fos was found in the ipsilateral hemisphere, suggesting that neuronal damage occurs. At 0.5, 3, and 6 h after injection of laurate, Rho-kinase activity in extracts of the cerebral hemispheres was measured by an ELISA method. Rho-kinase activity in extracts of the ipsilateral hemisphere was significantly increased compared with that in extracts of the contralateral hemisphere at 3 and 6 h but not 0.5 h after injection of laurate. Next, localization of Rho-kinase activity was evaluated by immunohistochemical analysis in sections of cortex and hippocampus including infarct area 6 h after injection of laurate. Staining for phosphorylation of myosin-binding subunit (phospho-MBS) and myosin light chain (phospho-MLC), substrates of Rho-kinase, was elevated in neuron and blood vessel, respectively, in ipsilateral cerebral sections, compared with those in contralateral cerebral sections. These findings indicate that Rho-kinase is activated in neuronal and vascular cells in a rat cerebral infarction model, and suggest that Rho-kinase could be an important target in the treatment of cerebral infarction.