AN EXPERIMENTAL-MODEL OF ACUTE ENCEPHALOPATHY AFTER TOTAL-BODY IRRADIATION IN THE RAT - EFFECT OF LIPOSOME-ENTRAPPED CU ZN SUPEROXIDE-DISMUTASE/

Purpose: To develop an experimental model of acute encephalopathy foll owing total body irradiation in rats and to define the therapeutic eff ect of liposome-entrapped Cu/Zn superoxide dismutase. Methods and Mate rials: A total of 120 4-month-old rats received 4.5 Gy total body irra diation (TBI) while 120 rats received sham irradiation. A behavioral s tudy based on a conditioning test of negative reinforcement, the one-w ay avoidance test, was performed 5 hours before irradiation and repeat ed the following days. Subcutaneous treatment was started 1 hour after irradiation and repeated daily for 2 weeks. In both the irradiated an d sham group, three subgroups were defined according to the treatment received: liposome-entrapped Cu/Zn superoxide dismutase (0.5 mg/kg), l iposomes only, normal saline. Results: This work comprised two consecu tive studies. In study A (90 rats) the one-way avoidance test was admi nistered daily from day 0 to day 4 with a recall session at day 14. In study B (validation phase in 150 rats) the behavioral test was perfor med only from day 0 to day 6. Before irradiation, all rats showed a si milar behavioral response. Study A (6 groups of 15 rats): Following TB I, irradiated rats treated with liposomes only or saline demonstrated a significant delay in learning the one-way avoidance test in comparis on with sham-irradiated rats (0.05 < p <0.001 depending upon the day o f evaluation and the subgroup type). In contrast, irradiated rats trea ted with liposome-entrapped Cu/Zn superoxide dismutase did not differ from sham-irradiated rats. Study B (6 groups of 25 rats): The results were the same as those in study A, demonstrating a significant delay i n the learning of the test in the liposome and saline-treated irradiat ed rats in comparison with sham-irradiated rats (0.02 < p < 0.001). Th e irradiated rats, treated with liposome-entrapped Cu/Zn superoxide di smutase did not differ from the sham-irradiated controls. Conclusion: This study indicates that a relatively low dose of total body irradiat ion induces a substantial acute learning dysfunction in the rat. This effect is prevented by the administration of liposome-entrapped Cu/Zn superoxide dismutase. (C) 1998 Elsevier Science Inc.