|Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
The role of arachdonic acid cascade in the develppent of delayed neuronal death following forebrain ischemia was investigated in the gerbils. First, immunohistochemical localization of prostaglandin(PG)F_<2alpha> synthesized during the recirculation phase following ischemia was studied. Frozen sebtions containing hippocampi were incubated with rabbit anti-PGF_<2alpha> serum and stained by the avidin-biotin-peroxidase complex method. In the control animals having sham operation, blood vessels were faintly stained with anti-PGF_<2alpha> serum. Less or no stain was found in neurons and glial cells. After recirculation, the experimental animals demonstrated marked positive staining for PGF_<2alpha> in blood vessels, neurons, especially hippocampal pyramidal neurons, and glial cells. Next, we examined the possibility that indomethain, a cyclooxygenase inhibiro, prevents ischemic delayed neuronal death in the gerbil hippocampus. Forebrain ischemia for 5 min was prduced by bilateral carotid occlusion. Animals received intraperitoneal injection of indomethacin(1, 2, 5 and 10mg/kg)30 min before ischemic insult. They were perfusion-fixed 7 days afere ischemic insult, and the neuronal density in the CA_1 sector was counted. Indomethacin at each dose significantly prevented delaye neuronal death in the hippocampal CA_1 sector. Effects of cyclooxygenase inhibior other than indomethacin and lipoxygenase inhibior delayed neuronal death were also examined in the same gerbil model. Piroxycam(10mg/kg)and Flurbiprofen(10mg/kg)ameliorated significantly delayed neuronal death. However, lipoxygenase inhibiotrs, AA801 and BW755C, did not ameliorated delayed neuronal death. Above results strongly suggest that cylooxygenase products may involved in the development of delayed neuronal death following forebrain ischemia in the ferels.