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J Neuroinflammation ; 15(1): 203, 2018 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-29996878

RESUMEN

BACKGROUND: Epilepsy is a prevalent neurological disorder worldwide. It is characterized by an enduring predisposition to generate seizures and its development is accompanied by alterations in many cellular processes. Organotypic slice cultures represent a multicellular environment with the potential to assess biological mechanisms, and they are used as a starting point for refining molecules for in vivo studies. Here, we investigated organotypic slice cultures as a model of epilepsy. METHODS: We assessed, by electrophysiological recordings, the spontaneous activity of organotypic slices maintained under different culture protocols. Moreover, we evaluated, through molecular-based approaches, neurogenesis, neuronal death, gliosis, expression of proinflammatory cytokines, and activation of NLRP3 inflammasome (nucleotide-binding, leucine-rich repeat, pyrin domain) as biomarkers of neuroinflammation. RESULTS: We demonstrated that organotypic slices, maintained under a serum deprivation culture protocol, develop epileptic-like activity. Furthermore, throughout a comparative study with slices that do not depict any epileptiform activity, slices with epileptiform activity were found to display significant differences in terms of inflammation-related features, such as (1) increased neuronal death, with higher incidence in CA1 pyramidal neurons of the hippocampus; (2) activation of astrocytes and microglia, assessed through western blot and immunohistochemistry; (3) upregulation of proinflammatory cytokines, specifically interleukin-1ß (IL-1ß), interleukin-6, and tumor necrosis factor α, revealed by qPCR; and (4) enhanced expression of NLRP3, assessed by western blot, together with increased NLRP3 activation, showed by IL-1ß quantification. CONCLUSIONS: Thus, organotypic slice cultures gradually deprived of serum mimic the epileptic-like activity, as well as the inflammatory events associated with in vivo epilepsy. This system can be considered a new tool to explore the interplay between neuroinflammation and epilepsy and to screen potential drug candidates, within the inflammatory cascades, to reduce/halt epileptogenesis.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Citocinas/metabolismo , Epilepsia/tratamiento farmacológico , Epilepsia/patología , Hipocampo/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Animales Recién Nacidos , Compuestos de Boro/metabolismo , Proteínas de Unión al Calcio/metabolismo , Caspasa 3/metabolismo , Medio de Cultivo Libre de Suero/toxicidad , Citocinas/genética , Modelos Animales de Enfermedad , Proteínas de Dominio Doblecortina , Epilepsia/inducido químicamente , Epilepsia/complicaciones , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/etiología , Gliosis/patología , Hipocampo/patología , Proteínas de Microfilamentos/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Neuropéptidos/metabolismo , Técnicas de Cultivo de Órganos , Embarazo , Ratas , Ratas Sprague-Dawley , Espectrina/metabolismo
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