EICOSANOID PRODUCTION IN THE CAUDATE-NUCLEUS AND DORSAL HIPPOCAMPUS AFTER FOREBRAIN ISCHEMIA - A MICRODIALYSIS STUDY

Thromboxane (Tx)B2 and 6-keto-prostaglandin (6-keto-PG) F1-alpha formation in the hippocampus and caudate nucleus were evaluated by microdialysis during and following forebrain ischemia. Spontaneously hypertensive rats were subjected to bilateral carotid artery occlusion with simultaneous hypotension for 8, 14, or 20 min. Dialysate was collected during the ischemic interval and during the reperfusion period. TxB2 and 6-keto-PGF1-alpha levels were measured by radioimmunoassay. In both structures, TxB2 production increased significantly during the reperfusion period in all three ischemic groups. By contrast, increased 6-keto-PGF1-alpha elaboration was observed after only the longest ischemic duration. While TxB2 levels gradually decreased during the 3-h reperfusion period in all groups, the levels in the group subjected to 8 min of ischemia returned to control values most rapidly. A relationship between the duration of ischemia and TxB2 production was therefore evident. 6-Keto-PGF1-alpha levels increased in only the group subjected to 20 min of ischemia and, by contrast to the pattern of TxB2 change, 6-keto-PGF1-alpha levels remained elevated throughout the reperfusion period. During reperfusion, the ratio of TxB2 to 6-keto-PGF1-alpha increased substantially versus the preischemic period in both structures. The data demonstrate that eicosanoid elaboration following cerebral ischemia can be evaluated by the microdialysis technique. In addition, they indicate that the thresholds (duration of ischemia) for the postischemic production and the temporal profiles of TxB, and 6-keto-PGF1-alpha in the caudate and hippocampus differ. They also demonstrate that there is regional heterogeneity in the patterns of eicosanoid elaboration after forebrain ischemia.