The vitamin-E analog trolox and the NMDA antagonist MK-801 protect pyramidal neurons in hippocampal slice cultures from IL-1β-induced neurodegeneration

The neurotoxic effect of the pro-inflammatory cytokine interleukin (IL)-1β was studied in monolayer cultures, obtained using roller-drum incubation of hippocampal slices from neonatal Sprague Dawley rats. Following exposure to recombinant rat IL-1β for four days, a concentration dependent loss was observed in the number of NMDAR1 receptor subunit immunoreactive pyramidal neurons in the cultures, reaching significance at 10 ng/ml rIL-1β. Also incubation with recombinant mouse IL-1β caused a loss of pyramidal neurons, with a significant effect at a concentration of 30 pg/ml. The vitamin E analog trolox (30 μM) was found to exert a protective effect against the rIL-1β-induced neuronal degeneration. A neuroprotective action against rIL-1β was also found after co-incubation with the NMDA antagonist dizocilpine (MK-801; 30 μM), while no protection was found with the GABAA mimetic clomethiazole. Hence, the proinflammatory cytokine IL-1β is neurotoxic to hippocampal pyramidal neurons when studied in anin vitro system with advanced phenotypic characteristics. The neuroprotective effects exerted by trolox and MK-801 suggest that free radicals and NMDA receptor-mediated processes are involved in IL-1β-induced neurodegeneration.