The role of iron-induced hippocampal peroxidation in acute epileptogenesis

Intracortical injection of iron salts causes lipid peroxidation, focal edema, necrosis, gliosis, and the development of behavioral and electrographic seizures. Tocopherol pretreatment prevents the histopathologic perturbations associated with iron injection, and appears to accelerate the resolution of focal accumulation of peroxidation products. In this experiment, rats were pretreated with 500 mg/kg DL-alpha-tocopherol acetate prior to the injection of 3 microliter of 100 mM FeCl2 into the dorsal hippocampus, or induction of convulsive seizures by s.c. injection of 0.8 mg/100 g bicucullin. Tocopherol pretreatment prevented the occurrence of convulsive seizures in a significant number of iron-salts injected animals. Lipid peroxidation measured in the dissected hippocampus was significantly increased in untreated rats developing iron-induced seizures and in rats treated with tocopherol, but developing convulsive seizures. Tocopherol failed to prevent bicucullin-induced seizures. Further, convulsive seizures induced by bicucullin failed to alter hippocampal fluorescence levels. Hence, we concluded that the epileptogenic effects of hippocampal injection of iron salts appear to be related to the induction of peroxidation of neural lipids within the injection site.