Sobhan Haghani - Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Mehrdad Roghani - Neurophysiology Research Center, Shahed University, Tehran, Iran
Nida Jamali-Raeufy - Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Tourandokht Baluchnejadmojarad - Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

Objectives: Although drug therapy is the most common treatment for epilepsy, proper seizure control is not achieved with current medications. The present study was conducted to evaluate the protective effects of hepatocyte growth factor(HGF) in a rat model of temporal lobe epilepsy (TLE) and explore possible molecular mechanisms. Materials and Methods: A rat model of temporal lobe epilepsy was established using intra-hippocampal injection of kainic acid(4μg).Intra-cerebrovascular injectionof HGF(6 μg)was performed 30 min before injection of kainic acid. Learning and memory impairment were investigated by behavioral tests.ELISA assay was used to determine astrogliosis and DNA fragmentation.Changes in neuronal density and mossy fiber sprouting were evaluated by Nissl and Timm staining,respectively. Results: Behavioral assessments indicated that kainate treated rats showed spontaneous seizure and their alternation percentage scores in Y-Maze test were lower (P<0.001). Likewise,the passive avoidance test confirmed learning disability in Kainate treated rats(P<0.001). HGF administration reduced the number of spontaneous seizures, alternation percentage score (P<0.001), and cognitive disturbances (P<0.001).The histopathological results also showed that HGF administration protected contributed to reduction of neuronal loss in the CA3 subregion of hippocampus and inhibited formation of aberrant mossy fiber sprouting (MFS) (P<0.01). Also, 2ELISA assay showed a significant decrease in GFAP (P <0.01), and DNA fragmentation (P<0.05) following HGF administration. Conclusion: Our findings demonstrate the validity of HGF in protection against progression of the kainate-induced TLE in rats by improvement of learning, cognitive disturbances and inhibiting of apoptosis and astrogliosis.

Hepatocyte growth factor; Temporal lobe epilepsy; Astrogliosis; Apoptosis; memory impairment.