EXPLORING DIFFERENT THERAPEUTIC APPROACHES FOR SEIZURE SUPPRESSION USING THE ZEBRAFISH MODEL

Abstract

Epilepsy is a neurological disease characterized by the presence of spontaneous and recurrent seizures that affect around 70 million people worldwide. Although the vast majority of patients respond well to drug therapy, approximately 30% are pharmacoresistant. Pharmacoresistance in epilepsy is associated with reduced quality of life and an increased risk of sudden death. Therefore there is a need for the discovery of new compounds with anticonvulsant properties. The understanding of the molecular mechanisms that trigger generation of seizures is essential for the development of new therapeutic approaches. In this context, the present study investigated the effect of anti-inflammatory, antioxidative and hypothermia therapies in suppressing the generation of pentylenetetrazole-induced seizures in the zebrafish model. In addition, the CRISPR/Cas9 genome editing tool was used to create a Lafora Disease model, a form of progressive myoclonic epilepsy, in order to test anti-inflammatory compounds for this specific condition. Taken together, our data provide evidence of the anticonvulsant effects of each therapy and highlight how each therapy can act to minimize the changes/damage associated with seizure activity.