| Project/Area Number |
08457359
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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 | NIIGATA UNIVERSITY |
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Principal Investigator |
ABE Hiroshi NIIGATA UNIVERSITY MEDECAL HOSPITAL,ASSISTANT, 医学部附属病院, 助手 (60240769)
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| Co-Investigator(Kenkyū-buntansha) |
MORII Ken NIIGATA UNIVERSITY MEDECAL HOSPITAL,ASSISTANT, 医学部附属病院, 助手 (20230089)
藤井 幸彦 新潟大学, 医学部・附属病院, 助手 (40283014)
竹内 茂和 新潟大学, 脳研究所, 助教授 (50143772)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | cerebral ischemia / ischemic tolerance / immediate early gene / heat shock protein / DC potential / depolarization / Immediate early gene / Immediate - early gene / geatshock protein / Immediate-early gene / heatshock protein |
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| Research Abstract |
Brief ischemia can induce tolerance to later more severe ischemia, but reported effects are highly variable. It has been suggested that changes in gene expression may contribute to ischemic tolerance, but relationships are difficult to test without a quantitatively reproducible model. Anoxic depolarization is a classical indicator of energy failure during ischemia. In this study we have used DC potential recording to precisely define the interval of postischemic depolarization necessary to achieve reproducible tolerance induction in hippocampi of anesthetized gerbils, and have compared this threshold with that required for induction of hsp72, as well as the immediate early gene products of c-fos, junB, junD and c-jun.
Depolarization of 6.5 min or longer produced maximum CAL neuron loss. Maximum tolerance effect was achieved by the ischemic insult of depolarization interval controlled between 2.5 to 3.5 min. No detectable hsp72 expression was seen in CA1 within 1h recirculation after ischemic insults that induce maximum tolerance, but hsp72 induction increased as the depolarization interval reached the threshold for neuronal injury. In contrast to hsp72, c-fos, junB, junD, and c-jun all showed increased expression in the depolarization range associated with ischemic tolerance.
We have established a highly reproducible ischemic tolerance model in the gerbil by carefully monitoring the interval of ischemic depolarization during each insult. We have demonstrated that the threshold depolarization required to induce tolerance was comparable to those for induction of transcription factor mRNAs of the Fos and Jun families, suggesting that complex cascades of target gene expression contribute to mechanisms of induced neuronal protection, while hsp72 mRNA was strongly induced only after more severe insults that approached for neuronal injury.
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