Status epilepticusduring neurodevelopment increases seizure susceptibility: a model study in zebrafish (Danio rerio)

Abstract

AbstractEpilepsy is among the most common neurological diseases, affecting more than 50 million people worldwide. Unfortunately, one-third of people with epilepsy fail to respond to any current treatment and present a decreased quality of life. Nevertheless, different studies suggest that epilepsies acquired from an initial insult asstatus epilepticus(SE) followed byepileptogenesiscan be prevented. Therefore, it is necessary to establish animal models ofepileptogenesisinduced by SE. Thus, here we proposed an animal model ofepileptogenesistriggered by SE that occurred during the neurodevelopment of zebrafish (Danio rerio). Zebrafish larvae at the 7thday post-fertilization (dpf) were randomly assigned to two experimental groups. One group was exposed to embryo medium. The other group was exposed to pentylenetetrazol (15 mM PTZ) to induce SE. At the 8thdpf, each larva was subjected to the open tank test (OTT) to analyze locomotion and behavioral parameters. After the OTT, each initial group was divided into two groups: animals maintained in embryo medium and animals exposed to PTZ (3 mM), and the susceptibility to PTZ-induced seizure-like behavior was analyzed. Data showed that animals submitted to SE on the 7thdpf showed altered locomotion and behavior 24 hours later. Interestingly, zebrafish larvae submitted to SE on the 7thdpf showed decreased latency to reach seizure-like behavioral stages when exposed to a low concentration of PTZ on the 8thdpf. Concluding, our results show that SE during neurodevelopment increases the susceptibility of zebrafish larvae to present PTZ-induced seizure-like behavior. Our study contributes to the establishment of a model ofepileptogenesisin developing zebrafish. Finally, the next step is to improve this model by characterizing molecular, biochemical and physiological markers.