Intrahipokampal Kainik Asit Enjeksiyonu ile Oluşturulan Temporal Lob Epilepsi Modelinde Grup I Metabotropik Glutamat Reseptörlerinin Ekspresyonu ve Levetirasetamın Ekspresyona Etkisi

Abstract

Introduction: Mesial temporal lobe epilepsy is the most common type of epilepsy in adults and is usually caused by hippocampal sclerosis. Approximately 30% of cases of temporal lobe epilepsy (TLE) are drug resistant. The molecular mechanisms behind TLE are still unknown. The widespread synaptic exitement triggered by glutamate causing interaction between ionotropic and metabotropic glutamate receptors is considered as an important process in the pathophysiology of TLE. Several in vitro and in vivo studies have shown hippocampal group I mGluR receptor’s (mGluR 1 and 5) role in epileptogenesis. Group I mGluR receptors are widely expressed in the brain, have modulating effect and are considered important from etiological perspective as well as potential targets for epilepsy treatment. Aim: The aim of this study is to research the group I mGluR receptor expression as well as the effect of an antiepileptic agent levetiracetam (LEV) on this expression in epilepsy model triggered by intrahippocampal injection of kainic acid. Methods: There were four groups in this study: group 1 burr hole only (Sham), group 2 normal saline injection (NS), group 3 intrahippocampal kainic acid injection (KA), group 4 intrahippocampal kainic acid + intraperitoneal levatiracetam (KA+LEV). Injections were done with Hamilton needle on a stereotactic frame (groups 2, 3 and 4). After 2 weeks of latent period animals were sacrificed by decapitation and were send for either immunohistochemistry or WB analysis. Results: After intrahippocampal KA injection we observed histopathological evidence of hippocampal sclerosis in groups 3 and 4. Histopathologically the hippocampal sclerosis was mostly observed in CA3, although there was a partial neuronal loss in CA1 as well. Dentate gyrus and CA2 were unaffected. Although statistically not significant, in KA groups right hippocampi demonstrated more mGluR1 and mGluR5 expressions. Levatiracetam did not affect the expression of mGluR1 in KA injection group. V Conclusion: We observed the development of epilepsy model after the intrahippocampal kainic acid injection. There was no significant increase in group I mGluR expression according to immunohistochemistry and Western blot analysis. Levatiracetam did not affect the expression of group I mGluR.