| Project/Area Number |
11307023
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Gunma University |
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Principal Investigator |
SASAKI Tomio Gunma University, School of Medicine, Professor, 医学部, 教授 (10134561)
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| Co-Investigator(Kenkyū-buntansha) |
KURIHARA Hideyuki Gunma University, School of Medicine, Assist. Prof., 医学部, 教授 (30261853)
TAKUWA Yo Kanazawa University, School of Medicine, Professor, 医学部, 教授 (60171592)
KOHAMA Kazuhiro Gunma University, School of Medicine, Professor, 医学部, 教授 (30101116)
TAKAHASHI Akio Gunma University, School of Medicine, Assist. Prof., 医学部, 助手 (60261856)
NEGISHI Masatoshi Gunma University, School of Medicine, Assist. Prof., 医学部, 助手 (80272235)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥29,560,000 (Direct Cost: ¥28,300,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2001: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2000: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1999: ¥17,500,000 (Direct Cost: ¥17,500,000)
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| Keywords | subarachnoid hemorrhage / cerebral vasospasm / vasocontraction / Ca^<2+> sensitization / experimental vasospasm / cerebral vasospasm / vascular smooth muscle / rho kinase / myosin light chain kinase / myosin binding subunit / phosphorylation / calcium sensitization / sphingosine 1-phosphate / protein kinase C / endothelin / Cerebral vasospasm / Myosin light chain kinase / Vascular smooth muscle / Calcium sensitization / Dephosphorylation |
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| Research Abstract |
The pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH) has been intensively investigated but is not still fully understood. Cerebral vasospasm is associated with changes in the activity of several intracellular signal transduction pathways including the activation of small GTPase Rho A and Rho-kinase. Activation of Rho-kinase by Rho A causes phosphorylation of the myosin-binding subunit of myosin phosphatase complex, which leads to the inactivation of myosin phosphatase. Thus, the stimulation of small G-protein signaling results in the continuous contraction of cerebral arteries without changes in [Ca^<2+>]i, which may be responsible for the pathophysiology of cerebral vasospasm. However, the systemic assessment of relationship Ca^<2+> sensitization and cerebral vasospasm has been lacked previously. First we recorded simultaneously isometric tension and intracellular Ca^<2+> concentration in basilar artery from dogs, and several agonists contract cerebral vessels through Ca^<2+> sensitization mechanism and Rho/Rho kinase pathway. Second, we recorded simultaneously isometric tension and intracellular Ca^<2+> concentration in basilar artery from experimental SAH model dogs. The tendency of increasing Ca^<2+> sensitization in spastic basilar arteries was observed. On the other hand, we attended a bioactive molecule, sphingosine-1-phosphate (S1P) that can be released from platelets and stimulates Rho/Rho-kinase system. We investigated whether or not S1P is considered as a novel spasmogenic substance involved in the cerebral vasospasm after SAH.
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