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{% rtitle A "two-hit" pharmacological seizure model in zebrafish for studying microglia dynamics in the developing epileptic brain %}
Teresa G. Martins, Remon Soliman, Cristina Donato, Corrado Ameli, Laurent Mombaerts, Maria Lorena Cordero-Maldonado, Alexander Skupin, Francesca Peri, Alexander D. Crawford
Teresa G. Martins, Remon Soliman, Cristina Donato, Maria Lorena Cordero-Maldonado, Corrado Ameli, Laurent Mombaerts, Alexander Skupin, Francesca Peri, Alexander D. Crawford
Epilepsy is a chronic brain disorder characterized by unprovoked and recurrent seizures, of which 60% are of unknown etiology. Recent studies implicate microglia in the pathophysiology of epilepsy. However, their role in this process, e.g. following early-life seizures, remains poorly understood in part due to the lack of suitable experimental models allowing the in vivo imaging of microglial activity using minimally-invasive techniques. Given the advantage of zebrafish larvae for such imaging approaches, we sought to develop a "two-hit" pharmacological seizure model in zebrafish suitable for studying microglia response after acute seizures. Towards this end, different concentrations of kainate were microinjected intravenously into 3 days post-fertilization transgenic zebrafish larvae with mCherry-labeled microglia followed by acute incubation with pentylenetetrazole at 5 days post-fertilization. Kainate-treated larvae exhibited increased numbers of microglia in the brain, and were more susceptible to subsequent pentylenetetrazole-induced seizures, as shown by higher locomotor and encephalographic activity as compared to vehicle-injected larvae. These results are comparable to experimental kainate-induced rodent seizure models and suggest the suitability of our model for future studies. Such studies could contribute to elucidate microglial dynamic changes after seizure induction in the developing brain, and to understand how these modulate seizure susceptibility later in life.
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