Summary:Purpose: Intracortical injection of iron ion induces recurrent seizures and epileptic discharges in the electrocorticogram. This observation may be used as a model of posttraumatic epilepsy. The involvement of iron-mediated oxygen free radical species and neuronal lipid peroxidation in ironinduced seizure has been suggested. Melatonin exerts free radical scavenging properties. In this study, we examined the protective effect of melatonin against iron-induced seizures.Methods: We examined the protective effect of melatonin against in vitro iron-induced oxidative damage in homogenates from rat cerebral cortex, by measuring the concentration of thiobarbituric acid reactive substances (TBARS), as an index of oxidative damage. We also examined the effect of melatonin on the appearance of epileptic discharges in the EEG following injection of FeC1, into the sensorimotor cortex in anesthetized rats, and by measuring the concentration of TBARS in the brain tissue.Results: FeCI, increased the concentration of TBARS in brain homogenates in a concentration-dependent manner, and melatonin reduced FeC1,-induced rise in TBARS in a doseresponse fashion. Pretreatment with melatonin suppressed or delayed the development of FeC1,-induced epileptic discharges and decreased the concentration of TBARS in brain tissues.Conclusions: Our results suggest that iron ion generates oxygen free radical species that induce neuronal macromolecular peroxidation and seizure, and that melatonin inhibits ironinduced seizures by scavenging free radicals. Key Words: Melatonin-Iron-induced seizures-Perioxidation-Thiobarbituric acid-Reactive substances-TBARS-Free radical.Neurotrauma with extravasation of red blood cells followed by hemolysis and deposition of iron compounds such as hemosiderin within the brain tissue (1) is associated with the development of post-traumatic epilepsy (2). Similarly, intracortical injection of iron salts or heme compounds into the rodent brain induces recurrent seizures and epileptic discharges in the EEGs (3-5). These observations strongly suggest that trauma or hemorrhagic cortical infarction associated with extravasation of blood and decompartmentalization of iron within the brain may induce epileptic discharge (3, although the specific mechanisms of the epileptogenic effect of iron salts remain unknown. It has been proposed that active oxygen free radicals generated by iron-mediated reactions in the brain (6) peroxidize lipids in neural membranes, resulting in cell death and the formation of an epileptic focus (7). In support of this hypothesis, previ-