Adenosines scavenged hydroxyl radicals and prevented posttraumatic epilepsy

Abstract

Intracortical injection of iron ions has been used as a model of posttraumatic epilepsy. Oxidation of lipids in neural membranes by reactive oxygen species, especially hydroxyl radicals (OH), is involved in the mechanisms responsible for iron-induced seizures. We examined the scavenging effects of adenosine (Ado) and 2-chloroadenosine (Cl-Ado) on OH radicals and superoxide (O 2 ·-) using an electron spin resonance (ESR) spectrometer, and the occurrence of epileptic discharges in electrocorticogram (ECoG) induced by FeCl 3 injection into the sensorimotor cortex of rats. Though DMPO-O 2 ·- spin adducts generated by the hypoxanthine-xanthine oxidase system were not quenched by Ado or Cl-Ado, 5 mM of each showed a quenching effect on DMPO-OH spin adducts (5.3 × 10 16 spins/ml) generated by the Fenton reagent. In ECoG of rats, spike discharges appeared 15–45 min after FeCl 3 injection (500 nmol) into the sensorimotor cortex, and polyspikes and/or ictal patterns were observed 70–90 min after the injection. Cl-Ado (1 mg/kg) or Ado (5 mg/kg) injected intraperitoneally 30 min prior to the FeC1 3 injection suppressed or delayed the occurrence of epileptic discharges induced by FeC1 3. Cl-Ado and Ado may suppress the occurrence of epileptic discharges by scavenging OH and by their anticonvulsant effect.