title: Rosmarinic acid exerts a neuroprotective effect in the kainate rat model of temporal lobe epilepsy: Underlying mechanisms.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Physiology, School of Medicine, Tehran University of Medical Sciences , Tehran , Iran .
authors: Safoura
authors: S
authors: Khamse
authors: Seyed Shahabeddin
authors: SS
authors: Sadr
authors: Mehrdad
authors: M
authors: Roghani
authors: Gholamreza
authors: G
authors: Hasanzadeh
authors: Maryam
authors: M
authors: Mohammadian
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002934:Cinnamates / Q000302:isolation & purification / Q000627:therapeutic use*; D053630:Depsides / Q000302:isolation & purification / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000097123:Rosmarinic Acid
chemical_list: D000975:Antioxidants; D002934:Cinnamates; D053630:Depsides; D007608:Kainic Acid; D018696:Neuroprotective Agents; D000097123:Rosmarinic Acid
keywords: Hippocampus; Kainic acid; Timm index; mossy fiber sprouting; oxidative stress; valproate