| 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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