| Project/Area Number |
14571330
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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 | Saitama Medical University |
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Principal Investigator |
ASANO Takao Saitama Medical School, Medicine, Professor, 医学部, 教授 (70090496)
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| Co-Investigator(Kenkyū-buntansha) |
MORIKAWA Eiharu Saitama Medical school, Medicine, Associate professor, 医学部, 助教授 (90251256)
MORI Takashi Saitama Medical school, Medicine, Associate professor, 医学部, 助教授 (60239605)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Cerebral Ischemia / Permanent focal cerebral ischemia / Rat / S-100 / Astrocyte / 永久脳虚血モデル / S-100蛋白 / アストロサイト / 永久局所脳虚血モデル |
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| Research Abstract |
The present study was undertaken to examine in terms of the following three aspects ; (i) the temporal as well as topographical correlation between the astrocytic S100B synthesis and the occurrence of delayed infarct expansion ; (ii) the analysis on the possible mechanisms underlying the S100B-induced brain damage ; (iii) the analysis on the possible therapeutic effects of an agent that suppresses astrocytic S100B synthesis on ischemic brain damage.
1) In 2002, we focused on whether activated astrocytes accumulating within the peri-infarct area is related to the occurrence of delayed infarct expansion after ischemia. The results showed a positive temporal and topographical correlation between the enhanced synthesis of S-100B by activated astrocytes in the peri-infarct area and the occurrence of delayed infarct expansion.
2) In 2003, using an astrocytic modulating agent, (P)-(-)-2-propyloctanoic acid (suppression of astrocytic activation through the negative regulation of S-100 protein sy
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nthesis), we examined the underlying mechanism(s) of delayed infarct expansion after ischemia. The results clearly showed that the enhanced astrocytic activation and subsequent production of S-100B protein in the peri-infarct area contribute to the occurrence of delayed infarct expansion.
3) In 2004, to extend the possible clinical application of the agent against stroke, we examined the optimal dose and the therapeutic time window of the agent. The results showed the optimal dose of 10 mg/kg/day and a wide therapeutic time window ranging from 0 to 48 hours after ischemia.
In summary, the present study contributed to substantiate the idea that activated astrocytes in the peri-infarct area do act to aggravate the ischemic brain damage during the subacute phase of permanent focal cerebral ischemia. We also demonstrated that suppression of astrocytic activation by the agent (R)-(-)-2-propyloctanoic acid (arundic acid) leads to mitigation of delayed infarct expansion and early improvement of neurological deficits. Based on the above data obtained from the consecutive studies during the past three years (2002 to 2004), we conclude that pharmacological modulation of astrocytic activation may confer a novel therapeutic strategy against stroke. Less
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