IL-1β increases necrotic neuronal cell death in the developing rat hippocampus after status epilepticus by activating type I IL-1 receptor (IL-1RI)

Interleukin-1 beta (IL-1 beta) is associated with seizure-induced neuronal cell death in the adult brain. The contribution of IL-1 beta to neuronal injury induced by status epilepticus (SE) in the immature brain remains unclear. In the present study, we investigated the effects of IL-1 beta administration on hippocampal neuronal cell death associated with SE in the immature brain, and the role of the type I receptor of IL-1 beta (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-1 beta (0, 0.3, 3, 30, or 300 ng), 30 ng of IL-1RI antagonist (IL-1Ra) alone, or 30 ng of IL-1Ra plus 3 ng of IL-1 beta. As control groups, pups without seizures were injected with 3 ng of IL-1 beta 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-1 beta showed a bell-shape. Only pups injected with 3 ng of IL-1 beta 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-1 beta was injected with IL-1Ra. Injection of 3 ng of IL-1 beta increased the number of PI-positive cells in CA1 area after SE. Injection of 3 ng of IL-1 beta 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-1 beta/IL-1RI system increases necrotic neuronal cell death caused by SE in rat pups. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved.