| Project/Area Number |
12671385
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Toho University School of Medicine |
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Principal Investigator |
IWABUCHI Satoshi Toho University School of Medicine, 2nd. Department of Neurosurgery, Assistant Professor, 医学部, 講師 (30213309)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Kazuya Toho University School of Medicine, 2nd. Department of Neurosurgery, Instructor, 医学部, 助手 (50202461)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | subarachnoid hemorrhage (SAH) / vasospasm / vascular smooth muscle cell / intracellular free Ca^<2+> concentration / nucleotide / protein tyrosine kinase (PTK) / mitogen activated protein kinase (MAPK) / ATP / 脳血管平滑筋細胞 / 細胞内Ca^<2+>濃度 / クモ膜下出血 / 髄液 |
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| Research Abstract |
We investigated the effect of cerebrospinal fluid (CSF) following subarachnoid hemorrhage (SAH) on isolated smooth-muscle cells. The application of CSF obtained on day 3 following SAH induced the most contraction. An increase in the intracellular Ca^<2+> concentration of smooth-muscle cells was observed during contraction. There is a discrepancy between this observation and the peak of clinical vasospasm occurring about 7 days after SAH. Following SAH, CSF may take a few days to affect smooth-muscle cells in the media of cerebral arteries. Preincubation of cells with suramin, an antagonist of P2x and P2y purinoceptors, attenuated the contraction after application of CSF, suggesting that nucleotides may be involved in the contraction of vascular smooth-muscle cells after SAH.
We also investigated the role of mitogen-activated protein kinase (MAPK) and protein tyrosine kinase (PTK) in mediating ATP-induced Ca^<2+> mobilization in rat basilar artery smooth muscle cells. Extracellular ATP produced intracellular free Ca^<2+> elevation and MAPK phosphorylation in smooth muscle cells, and regulated by PTK. In the study using canine double hemorrhage model of SAH, MAPK immunoprecipitaion was significantly enhanced in the spastic arteries. The peak immunoprecipitaion occurred on day 3 after blood injection. MAPK kinase inhibitor PD98059 attenuated the MAPK immunoprecipitaion and vasoconstriction. PD98059 might be useful in the management of cebral vasospasm.
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