Abstracts

Rationale: Resveratrol has recently gained attention due to its anti-oxidant, anti-inflammatory, and neuroprotective properties. In adult rats, several studies independently reported protection from kainic acid (KA)-induced convulsions and the associated hippocampal neurotoxicity. Increased neuronal survival was correlated with reduced lipid peroxidation. Since free radical generation after KA is age-dependent, the present study investigated whether chronic resveratrol treatment could act as a pre-conditioning stimulus and protect the juvenile hippocmapus from KA-induced injury at the onset of hippocampal vulnerability, at postnatal (P) day 21. Methods: Rat pups were treated with daily injections of resveratrol beginning on P9 for 12 days by increasing (e.g. doubling) the dosage every other day (from 2-50 mg/kg). Post-treatment was continued daily at the highest dosage until sacrifice at 72 hrs following KA-induced seizures. Oxidative stress was estimated with hippocampal level of malondialdehye (MDA) at three ages (P15, P21, and P100). Weight, behavior, electrographic (EEG) seizures, histology, and NMDA receptor expression were simultaneously assessed. Results: Chronic resveratrol treatment did not interfere with normal growth and had little or no ability to attenuate KA-induced paroxysmal activity in the EEG, prevent the hippocampal injury, or loss of NMDA receptors. MDA level was inversely related to age; baseline lipid peroxidation was approximately 14 fold higher in adults compared to P14 and P21 rats. After 100 M glutamate application, peroxidation products in CA1 were stimulated to a much greater degree in adult homogenates compared to the younger ages (P14: 144% vs. P21: 198% vs. P100: 477%) indicating that oxidative stress after status epilepticus indeed increases with age. Conclusions: Results indicate that antioxidant therapy may not be appropriate treatment to hinder epileptic activity and neurodegeneration at young ages when production of free radicals and lipid peroxidation are limited in the immature hippocampus.