Attenuation of Canine Cerebral Vasospasm after Subarachnoid Hemorrhage by Protein Kinase C Inhibitors despite Augmented Phosphorylation of Myosin Light ChainNishizawa S.a · Obara K.b · Koide M.a · Nakayama K.b · Ohta S.a · Yokoyama T.a
aDepartment of Neurosurgery, Hamamatsu University School of Medicine, Hamamatsu, and bDepartment of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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The purpose of the present study is to assess the roles of protein kinase C (PKC) isoforms, especially PKCδ and α, and 20-kD myosin light chain (MLC20) phosphorylation in the mechanism of cerebral vasospasm following subarachnoid hemorrhage (SAH). We had shown that those PKC isoforms are involved in the development of cerebral vasospasm. Using PKC isoform-specific inhibitors in a ‘two- hemorrhage’ canine model, we examined changes in the development of cerebral vasospasm, translocation of PKC isoforms and MLC20 phosphorylation level in canine basilar arteries. A PKC inhibitor (5 µM rottlerin for PKCδ or chelerythrine for PKCα) was injected into the cisterna magna on day 4 before the second hemorrhage. The treatment was continued daily until day 7. Rottlerin inhibited the initial phase of vasospasm and PKCδ translocation, but did not significantly inhibit PKCα translocation. Chelerythrine inhibited cerebral vasospasm, and the translocation of both PKCδ and α throughout the entire course of the study. Although cerebral vasospasm after SAH was inhibited by each PKC inhibitor, the MLC20 phosphorylation level remained elevated as in the untreated hemorrhage-control study. We conclude that cerebral vasospasm following SAH depends on PKCδ and α, while the enhancement of MLC20 phosphorylation contributes little to this form of vasospasm.
© 2003 S. Karger AG, Basel
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