ABSTRACT
The contribution of Interleukin-1ß (IL-1ß) to neuronal injury induced by status epilepticus (SE) in the immature brain remains unclear. The goal of this study was to determine the hippocampal expression of IL-1ß and its type 1 receptor (IL-1RI) following SE induced by the lithium-pilocarpine model in fourteen-days-old rat pups; control animals were given an equal volume of saline instead of the convulsant. IL-1ß and IL-1RI mRNA hippocampal levels were assessed by qRT-PCR 6 and 24 h after SE or control conditions. IL-1ß and IL-1RI expression was detected in the dorsal hippocampus by immunohistochemical procedures; Fluoro-Jade B staining was carried out in parallel sections in order to detect neuronal cell death. IL-1ß mRNA expression was increased 6 h following SE, but not at 24 h; however IL-1RI mRNA expression was unaffected when comparing with the control group. IL-1ß and IL-1RI immunoreactivity was not detected in control animals. IL-1ß and IL-1RI were expressed in the CA1 pyramidal layer, the dentate gyrus granular layer and the hilus 6 h after SE, whereas injured cells were detected 24 h following seizures. Early expression of IL-1ß and IL-1RI in the hippocampus could be associated with SE-induced neuronal cell death mechanisms in the developing rat.
Subject(s)
Hippocampus/metabolism , Interleukin-1beta/metabolism , Receptors, Interleukin-1/metabolism , Status Epilepticus/metabolism , Animals , Convulsants , Disease Models, Animal , Interleukin-1beta/genetics , Lithium , Pilocarpine , RNA, Messenger/metabolism , Rats , Receptors, Interleukin-1/genetics , Status Epilepticus/chemically inducedABSTRACT
Interleukin-1ß (IL-1ß) is associated with seizure-induced neuronal cell death in the adult brain. The contribution of IL-1ß to neuronal injury induced by status epilepticus (SE) in the immature brain remains unclear. In the present study, we investigated the effects of IL-1ß administration on hippocampal neuronal cell death associated with SE in the immature brain, and the role of the type I receptor of IL-1ß (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-1ß (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-1ß. As control groups, pups without seizures were injected with 3 ng of IL-1ß 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-1ß showed a bell-shape. Only pups injected with 3 ng of IL-1ß 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-1ß was injected with IL-1Ra. Injection of 3 ng of IL-1ß increased the number of PI-positive cells in CA1 area after SE. Injection of 3 ng of IL-1ß 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-1ß/IL-1RI system increases necrotic neuronal cell death caused by SE in rat pups.
Subject(s)
Hippocampus/pathology , Neurons/drug effects , Receptors, Interleukin-1 Type I/metabolism , Status Epilepticus/complications , Status Epilepticus/pathology , Age Factors , Animals , Animals, Newborn , Caspase 3/metabolism , Cell Count , Cell Death/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Hippocampus/growth & development , Injections, Intraventricular , Interleukin 1 Receptor Antagonist Protein/pharmacology , Interleukin-1beta/pharmacology , Male , Rats , Status Epilepticus/chemically inducedABSTRACT
Epilepsy is a neurological disorder affecting almost 1% of the world population. Experimental human and animal studies suggest that inflammation mediators, like cytokines, participate in the physiopathology of epilepsy. Interleukin-1beta (IL-1ß) could influence susceptibility for seizures, as well as neuronal death caused by seizures, although some findings are contradictory. This document reviews the current knowledge establishing a connection between IL-1ß, seizures and neuronal death.
Subject(s)
Interleukin-1beta/physiology , Neurons/physiology , Seizures/etiology , Animals , Cell Death/physiology , HumansABSTRACT
La epilepsia es un trastorno neurológico que afecta aproximadamente al 1% de la población mundial. Estudios realizados en humanos y animales de experimentación sugieren que mediadores de inflamación, como las citocinas, participan en la fisiopatología de la epilepsia; entre ellos, la interleucina-1beta (IL-1ß) podría participar en la susceptibilidad para generar crisis convulsivas así como en la muerte neuronal causada por las convulsiones, aunque algunos hallazgos son contradictorios. En este documento se revisa el conocimiento actual que establece una relación entre la IL-1ß, las crisis convulsivas y la muerte neuronal.
Epilepsy is a neurological disorder affecting almost 1% of the world population. Experimental human and animal studies suggest that inflammation mediators, like cytokines, participate in the physiopathology of epilepsy. Interleukin-1beta (IL-1ß) could influence susceptibility for seizures, as well as neuronal death caused by seizures, although some findings are contradictory. This document reviews the current knowledge establishing a connection between IL-1ß, seizures and neuronal death.
