2006 Fiscal Year Final Research Report Summary
Involvement of MAPK cascade in ischemic neuronal damage
| Project/Area Number |
17390398
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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, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (90252452)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Nobuo Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (40135570)
TAKAGI Yasushi Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (40312227)
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| Project Period (FY) |
2005 – 2006
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| Keywords | cerebral ischemia / ischemic tolerance / MAPK / 脳神経疾患 |
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| Research Abstract |
It remains to be shown whether or not the activations of MAPK cascades may affect ischemic neuronal damage and ischemic tolerance induced by sublethal ischemia. We obtained evidence suggesting that p38 was activated in the gerbil hippocampus after 5-minute transient forebrain ischemia in vivo and that the inhibition of the activity of p38 protected against delayed neuronal death in CA1 pyramidal cells. We also confirmed the activation of p38 mitogen-activated protein kinase in the gerbil hippocampus by Western blotting and immunohistochemistry after 2 minutes of global sublethal ischemia, and pretreatment with SB203580,an inhibitor of active p38,30 minutes before the 2-minute ischemia reduced the ischemic tolerance effect in a dose-dependent manner.
JNKI also attenuated CA1 ischemic damage.Genetic disruption of STAT1, a targeted molecule of p38,reduced ischemic damage in a mice ischemic model. These findings suggest that p38 may contribute to both ischemic damage and tolerance in CA1 neurons of the hippocampus and that components of the p38 cascade can be target molecules to modify neuronal survival after ischemia.
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Research Products
(17 results)
