THERAPEUTIC TIME WINDOW FOR THE 21-AMINOSTEROID, U-74389G, IN GLOBAL CEREBRAL-ISCHEMIA

A NOVEL 21-AMINOSTEROID (U-74389G), a new potent antioxidant, was eval uated for its protective effect on transient global cerebral ischemia. Ischemia was induced by 20 minutes of four-vessel occlusion in adult male Wistar rats. Injection of 21-aminosteroid (U-74389G, 5 mg/kg intr aperitoneally injected) was repeated three times. The second injection was performed 30 minutes after the first injection, and the third inj ection was performed 210 minutes after that. Experimental animals were divided into five groups according to the time drug administration wa s initiated. Group I (n = 8) began vehicle administration 30 minutes b efore occlusion. Group II (n = 9) started 21-aminosteroid administrati on 30 minutes before occlusion. Drug administration in Group III (n = 9) began at the time of reperfusion, in Group IV (n = 8), 30 minutes a fter reperfusion, and in Group V (n = 6), 60 minutes after reperfusion . Animals in the control group (n = 5) underwent sham operations. One week after ischemia, the number of viable pyramidal neurons was counte d in the hippocampal CA1 subfield. The results were as follows: the nu mber of living neurons in Group I was 18.8 +/- 8.7; in Group II, was 4 4.7 +/- 9.5; in Group III, was 46.4 +/- 9.4; in Group IV, was 40.3 +/- 6.6; in Group V, was 10.2 +/- 2.5; and in the control group was 131 /- 3.3. Groups II, III, and IV demonstrated significantly higher numbe rs of living neurons compared with Group I (P < 0.05). The present stu dy revealed that U-74389G attenuated delayed neuronal death in global cerebral ischemia when it was administered before or soon after the is chemic episode.