| Project/Area Number |
11470288
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
NOZAKI Kazuhiko Kyoto University, Neurosurgery, Assistant Professor, 医学研究科, 講師 (90252452)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Eisuke Kyoto University, Biophysics, Professor, 理学研究科, 教授 (60143369)
HASHIMOTO Nobuo Kyoto University, Neurosurgery, Professor, 医学研究科, 教授 (40135570)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1999: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | Cerebral ischemia / Ischemic tolerance / MAPK / gerbil / Delayed neuronal death / C-Jun NH_2-terminal kinase / p38 mitogen-activated protein kinase / Extracellular signal-regulated kinase / transient global ischemia / ischemic tolerance / hippo campus / gerbil |
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| Research Abstract |
Molecular mechanisms of ischemic neuronal death and ischemic tolerance in brain remain to be elucidated. We studied in this project how mitogen-activated protein kinases (MAPKs) cascades would be involved in cerebral ischemia using immunoblotting and immunohistochemistry in rodent models. In gerbil hippocampus, ERK, JNK and p38 were strongly activated (that is, phosphorylated) with specific temporal and spatial patterns after transient forebrain ischemia, and a specific inhibitor for p38 attenuated ischemic neuronal death in CA1 of the hippocampus. MAPK cascades were also activated in rat striatum after mitochondrial impairment by 3-nitropropionic acid and in mouse hippocampus after transient forebrain ischemia. Mild ischemia, which induced ischemic tolerance in gerbil hippocampus, also activated MAPK cascades and an inhibitor of p38 reduced ischemic tolerance. These data suggested that p38 might play a significant role in neuronal death and survival after cerebral ischemia and that control of MAPK cascades would modify clinical outocomes of stroke patients.
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