Rosmarinic Acid Exerts a Neuroprotective Effect in the Kainate Rat Model of Temporal Lobe Epilepsy: Underlying Mechanisms Publisher Pubmed



Khamse S¹ ; Sadr SS^{1, 2} ; Roghani M³ ; Hasanzadeh G⁴ ; Mohammadian M¹
Source: Pharmaceutical Biology Published:2015

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. © 2015 Informa Healthcare USA, Inc.