THROMBOXANE SYNTHETASE INHIBITOR AMELIORATES DELAYED NEURONAL DEATH IN THE CA1 SUBFIELD OF THE HIPPOCAMPUS AFTER TRANSIENT GLOBAL-ISCHEMIA IN GERBILS

Thromboxane A(2) accumulates in the hippocampus after global ischemia and may play a key role in postischemic hypoperfusion. Thromboxane syn thetase inhibitor (OKY-046) inhibits the accumulation of thromboxane A (2) and promotes prostacycline production. Therefore, we set out to de termine whether the inhibition of thromboxane synthesis would ameriola te postischemic neuronal death. Three groups of six Mongolian gerbils were subjected to different treatments: untreated control, untreated i schemia, and treated ischemia, Immediately after forebrain ischemia, O KY-046 (10 mg/kg) was injected intraperitoneally into the treated grou p. After 7 days of survival, the histopathology of the brain was exami ned, Pyramidal cell density in the CA1 sector in the treated group was 147 +/- 70 nuclei/mm (mean +/- SD), which was significantly (p < 0.05 ) higher than that in the untreated group (33 +/- 10 nuclei/mm). The f indings were, 231 +/- 7 nuclei/mm for the control group. No significan t difference was seen in the profile of temporal muscle temperature be fore and after ischemia between the groups. Ultrastructurally, the ves sels in the CA1 sector showed lumen patency in the treated group, wher eas occluded vessels with an extended perivascular space were observed in the untreated group. Thromboxane synthetase inhibitor thus partly ameliorates the selective vulnerability of the hippocampus after foreb rain ischemia, suggesting that thromboxane A(2) is involved in the dev elopment of delayed neuronal death, independently of any thermal effec t.