title: IL-1β increases necrotic neuronal cell death in the developing rat hippocampus after status epilepticus by activating type I IL-1 receptor (IL-1RI).
abstract: Interleukin-1β (IL-1β) is associated with seizure-induced neuronal cell death in the adult brain. The contribution of IL-1β to neuronal injury induced by status epilepticus (SE) in the immature brain remains unclear. In the present study, we investigated the effects of IL-1β administration on hippocampal neuronal cell death associated with SE in the immature brain, and the role of the type I receptor of IL-1β (IL-1RI). SE was induced with lithium-pilocarpine in 14-days-old (P14) rat pups. Six hours after SE onset, pups were i.c.v. injected in the right ventricle with IL-1β (0, 0.3, 3, 30, or 300 ng), 30 ng of IL-1RI antagonist (IL-1Ra) alone, or 30 ng of IL-1Ra plus 3ng of IL-1β. As control groups, pups without seizures were injected with 3 ng of IL-1β or vehicle. Twenty-four hours after SE onset, neuronal cell death in the CA1 field of dorsal hippocampus was assessed by hematoxylin-eosin, Fluoro-Jade B and in vivo propidium iodide (PI) staining; expression of active caspase-3 (aCas-3) was also determined, using immunohistochemistry. The concentration-response curve of IL-1β showed a bell-shape. Only pups injected with 3 ng of IL-1β after SE showed a significant increase in the number of cells with eosinophilic cytoplasm and pyknotic nuclei, as well as F-JB positive cells with respect to the vehicle group. This effect was prevented when IL-1β was injected with IL-1Ra. Injection of 3 ng of IL-1β increased the number of PI-positive cells in CA1 area after SE. Injection of 3 ng of IL-1β did not produce hippocampal cell death in rats without seizures. Active caspase-3 expression was not observed after treatments in hippocampus. The activation of the IL-1β/IL-1RI system increases necrotic neuronal cell death caused by SE in rat pups.
authors.affiliation: Doctorado en Neuroetología, Instituto de Neuroetología, Universidad Veracruzana, Av. Luis Castelazo s/n Carr. Xalapa-Veracruz, Km. 3.5 Col. Industrial-Ánimas, C.P. 91190 Xalapa, Veracruz, Mexico; Centro de Investigaciones Cerebrales, Universidad Veracruzana, Médicos y Odontólogos s/n, Col. Unidad del Bosque, C.P. 91010 Xalapa, Veracruz, Mexico.
authors.forename: Jesús-Servando
authors.initials: JS
authors.lastname: Medel-Matus
authors.affiliation: Centro de Investigaciones Cerebrales, Universidad Veracruzana, Médicos y Odontólogos s/n, Col. Unidad del Bosque, C.P. 91010 Xalapa, Veracruz, Mexico.
authors.forename: Dulce-Mariely
authors.initials: DM
authors.lastname: Álvarez-Croda
authors.affiliation: Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas-IPN, Wilfrido Massieu s/n Unidad Profesional Adolfo López Mateos, Gustavo A. Madero, C.P. 07738 México D.F., Mexico.
authors.forename: Joel
authors.initials: J
authors.lastname: Martínez-Quiroz
authors.affiliation: Centro de Investigaciones Cerebrales, Universidad Veracruzana, Médicos y Odontólogos s/n, Col. Unidad del Bosque, C.P. 91010 Xalapa, Veracruz, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Beltrán-Parrazal
authors.affiliation: Centro de Investigaciones Cerebrales, Universidad Veracruzana, Médicos y Odontólogos s/n, Col. Unidad del Bosque, C.P. 91010 Xalapa, Veracruz, Mexico.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Morgado-Valle
authors.affiliation: Centro de Investigaciones Cerebrales, Universidad Veracruzana, Médicos y Odontólogos s/n, Col. Unidad del Bosque, C.P. 91010 Xalapa, Veracruz, Mexico. Electronic address: leonorlopez@uv.mx.
authors.forename: María-Leonor
authors.initials: ML
authors.lastname: López-Meraz
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000254:growth & development / Q000473:pathology*; D007276:Injections, Intraventricular; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; D053148:Caspase 3
keywords: Developing rat; Hippocampus; IL-1RI; IL-1β; Status epilepticus