2001 Fiscal Year Final Research Report Summary
Molecular mechanism of ever induced by brain injury
| Project/Area Number |
11670067
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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 |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Kyoto University |
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Principal Investigator |
MATSUMURA Kiyoshi Kyoto Univ., Grad. Sch. Informatics, Associate Prof., 情報学研究科, 助教授 (10157349)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Shingo Kyoto Univ., Grad. Sch. Informatics, Prof., 情報学研究科, 教授 (40124797)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Prostaglandin / Gyclooxygenase / PGE syuthase / microglia / Brain eudethelial cells |
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| Research Abstract |
1. Fever evoked by brain injury in rats was suppressed by indomethacin, a cyclooxygenase (COX) inhibitor. Prostaglandin E2 (PGE2) level in brain extracellular fluid increased after brain injury. These results indicate that PGE2 is involved in brain injury-evoked fever as in the case of infection-induced fever.
2. In infection-induced fever, brain endothelial cells seemed to produce PGE2 because these cells expressed two enzymes for PGE2 synthesis, I.e., COX-2 and mPGES in response to infectious challenge.
3. On the other hand, in a brain-injury model, inductions of these two enzymes were insignificant, suggesting the involvement of enzymes other than COX-2 and mPGES.
4. Western blot analysis revealed that brain constitutively express another group of PGE2 synthesizingenzymes, i.e. COX-1 and cPGES.
5. Immunohistochemical and in situ hybridization studies revealed that COX-1 was constitutively expressed in microglia, a subset of neurons, and arterial endothelial cells. On the other hand, cPGES was constitutively expressed in oligodendroglia and a subset of neurons.
6. Coexpression of COX-1 and cPGES was rarely found in these cells.
7. The above results strongly suggest the involvement of COX-1 in brain injury-induced fever. However, the exact responsible cells and the mechanism of COX-1 to PGE2 conversion remain to be elucidated.
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