NEURODEGENERATION PRODUCED BY INTRAHIPPOCAMPAL INJECTION OF PARAQUAT IS REDUCED BY SYSTEMIC ADMINISTRATION OF THE 21-AMINOSTEROID U74389F IN RATS

The behavioural, electrocortical (ECoG) and neurodegenerative effects of intrahippocampal injection of paraquat, a well-known free radical p roducing agent, were studied in rats. Injection of paraquat (100 nmol) into one dorsal hippocampus produced limbic motor and ECoG seizures. These effects were accompanied at 24 h by severe damage to CA1, CA3 an d CA4 hippocampal pyramidal neurones and dentate gyrus granule cells. In comparison to the cell number counted in control, untreated, side o f the hippocampus, significant (P < 0.05) neuronal loss was observed i n the CAI and CA3 pyramidal cell layers of the treated hippocampus. A lower dose of the herbicide (10 nmol) did not produce consistent motor and ECoG effects and in no instance was significant neuronal loss obs erved. A pretreatment with U74389F l)-1-piperazinyl-pregna-1,4,9(11)tr iene-3,20-dione monomethansulfonate] (30 mg/kg i.p., 15 min before par aquat) completely protected rats from motor and ECoG epileptogenic eff ects induced by intrahippocampal paraquat (100 nmol). This dose of U74 389F also reduced the hippocampal damage typically produced by paraqua t and no significant neuronal loss was reported in the CAI and CA3 pyr amidal cell layers. A lower dose of U74389F (10 mg/kg i.p.) did not af ford any protection against the epileptogenic effects produced by para quat (100 nmol); in these animals hippocampal damage was still evident though neuronal loss did not reach statistical significance. In concl usion, the present data show that systemic administration of U74389F p ossesses neuroprotective effects against seizures and neurodegeneratio n typically elicited by intrahippocampal injection of paraquat.