Rosmarinic acid exerts a neuroprotective effect in the kainate rat model of temporal lobe epilepsy: Underlying mechanisms

Abstract

Context: Temporal lobe epilepsy (TLE) is an intractable neurological disorder. Rosmarinic acid (RA) is a natural polyphenol with antioxidant, anti-apoptotic, and anti-inflammatory properties.

Objective: This study evaluates beneficial effect of RA in intrahippocampal kainate-induced model of TLE.

Materials and methods: Rats were divided into sham, RA-pretreated sham, kainate, and sodium valproate (VA) or RA-pretreated kainate groups. Rats received RA or VA p.o. at doses of 10 or 300?mg/kg/d, respectively, starting 1?week before the surgery. After 6?weeks, seizure intensity, apoptosis, and oxidative stress markers were evaluated in addition to determination of Timm index as an indicator of mossy fiber sprouting (MFS) and the number of Nissl-stained neurons.

Results: All rats in the kainate group had seizure and 24.3% of rats in the kainate?+?VA group and 36.7% of rats in the kainate?+?RA group showed seizure. The kainate group had a significant elevation of malondialdehyde (MDA) (p?<?0.05) and nitrite (p?<?0.01) and reduction of glutathione (GSH) and catalase activity (p?<?0.05) and pretreatment of kainate-lesioned rats with RA or VA significantly lowered MDA and nitrite content (p?<?0.05) and raised activity of catalase (p?<?0.05). The kainate group also had a significant reduction of neurons in CA1 and CA3 regions and an elevation of Timm index (p?<?0.05–0.001) and RA or VA significantly (p?<?0.05–0.01) prevented these changes.

Discussion and conclusion: RA could attenuate seizure, mitigates oxidative stress, augments the activity of defensive systems, and prevent hippocampal neuronal loss and MFS in the kainate model of TLE.