naa a22 4500 510775977 CHVBK 20180411083230.0 cr unu---uuuuu 180411e20130601xx s 000 0 eng 10.1007/s12975-012-0247-9 doi (NATIONALLICENCE)springer-10.1007/s12975-012-0247-9 Suppression of the Rho/Rho-Kinase Pathway and Prevention of Cerebral Vasospasm by Combination Treatment with Statin and Fasudil After Subarachnoid Hemorrhage in Rabbit [Elektronische Daten] [Masato Naraoka, Akira Munakata, Naoya Matsuda, Norihito Shimamura, Hiroki Ohkuma] The Rho/Rho-kinase pathway is considered important in the pathogenesis of sustained smooth muscle cell contraction during cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The aims of this study were to investigate whether combination treatment, with pitavastatin as an inhibitor of RhoA and fasudil as an inhibitor of Rho-kinase, prevents the cerebral vasospasm. SAH was simulated using the double-hemorrhage rabbit model, and pitavastatin, or fasudil, or both (combination treatment) were administrated. The basilar artery (BA) cross-sectional area only in the combination treatment group was statistically larger than in the SAH group (p < 0.05). BA Rho-kinase, as measured by ELISA, was statistically reduced only in the combination treatment group compared with the SAH group (p < 0.05). In the other two treatment groups, pitavastatin or fasudil treatment group showed larger BA cross-sectional areas and lower value for BA Rho-kinase, but there were no statistically significant differences compared with the SAH group. The expression of endothelial nitric oxide synthase (eNOS), evaluated by immunohistochemistry in the pitavastatin group and the combination group, was higher than in the SAH group. Results indicate that combination treatment could extensively prevent cerebral vasospasm due to the synergic effect of combining pitavastatin and fasudil on the Rho/Rho-kinase pathway and on eNOS. The Author(s), 2013 Cerebral vasospasm nationallicence Pitavastatin nationallicence Fasudil nationallicence Rho/Rho-kinase pathway nationallicence eNOS nationallicence Naraoka Masato Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8216, Hirosaki, Japan aut Munakata Akira Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8216, Hirosaki, Japan aut Matsuda Naoya Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8216, Hirosaki, Japan aut Shimamura Norihito Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8216, Hirosaki, Japan aut Ohkuma Hiroki Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8216, Hirosaki, Japan aut Translational Stroke Research Springer-Verlag 4/3(2013-06-01), 368-374 1868-4483 4:3<368 2013 4 12975 https://doi.org/10.1007/s12975-012-0247-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-012-0247-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Naraoka Masato Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8216, Hirosaki, Japan aut NATIONALLICENCE 700 1- Munakata Akira Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8216, Hirosaki, Japan aut NATIONALLICENCE 700 1- Matsuda Naoya Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8216, Hirosaki, Japan aut NATIONALLICENCE 700 1- Shimamura Norihito Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8216, Hirosaki, Japan aut NATIONALLICENCE 700 1- Ohkuma Hiroki Department of Neurosurgery, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8216, Hirosaki, Japan aut NATIONALLICENCE 773 0- Translational Stroke Research Springer-Verlag 4/3(2013-06-01), 368-374 1868-4483 4:3<368 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer