The Effect of Alpha-Lipoic Acid on Learning and Memory Deficit in a Rat Model of Temporal Lobe Epilepsy

Introduction: Epilepsy is a chronic neurological disorder in which patients experience spontaneous recurrent seizures and deficiency in learning and memory. Although the most commonly recommended therapy is drug treatment, some patients do not achieve adequate control of their seizures on existing drugs. New medications with novel mechanisms of action are needed to help those patients whose seizures are resistant to currently-available drugs. While alpha-lipoic acid as a antioxidant has some neuroprotective properties, but this action has not been investigated in models of epilepsy. Therefore, the protective effect of pretreatment with alpha-lipoic acid was evaluated in experimental model of temporal lobe epilepsy in male rats. Methods: In the present study, Wistar male rats were injected intrahippocampally with 0.9% saline(Sham-operated group), kainic acid(4 μg) alone, or α-lipoic acid (25mg and 50mg/kg) in association with kainic acid(4μg). We performed behavior monitoring(spontaneous seizure, learning and memory by Y-maze and passive avoidance test), intracranial electroencepholography (iEEG) recording, histological analysis, to evaluate the anti- epilepsy effect of α-lipoic acid in kainate-induced epileptic rats. Results: Behavior data showed that the kainate rats exhibit spontaneous seizures, lower spontaneous alternation score inY-maze tasks (p<0.01), impaired retention and recall capability in the passive avoidance test (p<0.05). Administration of alpha-lipoic acid, in both doses, significantly decrease the number of spontaneous seizures, improved alternation score in Y-maze task (p<0.005) and impaired retention and recall capability in the passive avoidance test (p<0.01) in kainite rats. Moreover, lipoic acid could improve the lipid peroxidation and nitrite level and superoxid dismutase activity. Discussion: This study indicates that lipoic acid pretreatment attenuates kainic acid-induced impairment of short-term spatial memory in rats probably due to its antioxidant activity.