Protective effects of cyclosporine and allopurinol on transient global cerebral ischemia in gerbils

Abstract

The effects of cyclosporine and allopurinol on neuronal death following global cerebral ischemia were evaluated in Mongolian gerbils. The animals were randomly divided into four groups of 12 each: (1) sham operation as control, (2) occlusion of the bilateral common carotid arteries for 12 min and treatment with physiological saline, (3) occlusion plus treatment with 5 mg/kg of cyclosporine, and (4) occlusion plus treatment with 100 mg/kg of allopurinol 30 min before cerebral ischemia and daily thereafter for 6 days. On the 7th day after ischemia or sham operation, the gerbils' brains were removed. The number of necrotic pyramidal cells in the cortex and hippocampal CA1 was evaluated and tissue chemiluminescence (reflecting the presence of superoxide radicals) and lipid peroxides were examined. The number of necrotic pyramidal cells in each field of view (×100) of the cortex was 115±79 after ischemia, which was significantly larger than 14±8 in the control group, and was 45±33 and 60±49 after treatment with cyclosporine and allopurinol, respectively. The number of surviving pyramidal cells per mm length after ischemia in CA1 was 37±14, which was significantly smaller than 174±30 in the control group, but 78±31 following treatment with was cyclosporine, and 108±53 with allopurinol. A reduced number of necrotic pyramidal cells was associated with lower tissue chemiluminescence and lipid peroxides. The results suggest that both cyclosporine and allopurinol can inhibit neuronal death after global cerebral ischemia, and that autoimmunization and superoxide radicals are partially responsible for neuronal death.