Release of TNFα in the rat hippocampus following epileptic seizures and excitotoxic neuronal damage

WE studied the production of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) 2 and 7 days following status epilepticus (SE), induced in rats by intra-amygdala injection of kainate. At day 2 the release of both cytokines by hippocampal slices prepared from epileptic animals was increased compared to controls, whereas at day 7 only TNFα secretion was enhanced. Since SE-induced neuronal damage is probably due to excitotoxicity, we investigated the effects of agonists of glutamate receptors on TNFα release in organotypic hippocampal cultures. A correlation was found between the damage intensity and the release of TNFα, suggesting production of this cytokine by macrophagic microglia. We propose a role for TNFα and IL-6 in the adaptive phenomena which follow severe limbic seizures.