Characterization Of Preclinical Biomarkers For Epileptogenesis

Nowadays the treatment for temporal lobe epilepsy (TLE) consists of a chronic administration of antiepileptic drugs. This treatment strategy only suppresses convulsions at a symptomatic basis and has no impact on the pathogenesis of the disease. Approximately 40% of the patients however are resistant to any drug treatment. TLE arises mostly as result of an initial insult. A latent time period exists between the occurrence of this initial insult and the development of chronic epilepsy, the epileptogenic phase. Neurodegenerative and neuroinflammatory processes are generally assumed to play an import role in the pathogenesis of TLE. Neuroprotective and anti-inflammatory treatments are considered a promising therapy in the prevention and treatment of TLE. Ideally, these treatments are anti-epileptogenic and prevent or at least diminish the development of an initial insult into chronic epilepsy. According to many studies, antidepressants have anti-inflammatory and neuroprotective qualities. Moreover antidepressants symptomatically suppress acute convulsions. In the present research project, we will investigate whether preclinical biomarkers for neurodegeneration and neuroinflammation are candidate biomarkers for epileptogenesis. Simultaneously the neuroprotective, anti-inflammatory and antiepileptogenic properties of several antidepressants will be evaluated. To conduct the present study, the kainic acid induced post-status epilepticus rat model for TLE will be used. This chemoconvulsant epilepsy model is one of the most widely used and thus best characterised animal model for the simulation of TLE. The first phase of this study exists in a screening experiment at mRNA level, using PCR arrays focused on inflammatory and neurotrophic genes. In the second phase, we will study the selected biomarkers at protein level using western blotting and histology. The third phase of this study consists of a long term study of the antiepileptogenic effect of antidepressants by measuring the spontaneous seizure activity. Status induction and chronic follow-up of the animals will be performed using 24h video-radiotelemetric electrocorticography.