Excitotoxic brain damage in the rat induces interleukin-1? protein in microglia and astrocytes: Correlation with the progression of cell death

Interleukin-1 beta (IL-1β) has been proposed as a mediator of several forms of brain damage, including that induced by excitotoxins. In vitro studies suggest that glial cells are the effector cells of IL-1β-mediated neurodegeneration. We have investigated the expression of IL-1β protein by glial cells in vivo in response to NMDA receptor-mediated excitotoxicity in the rat parietal cortex and striatum. Expression of IL-1β by glial cells was investigated using immunocytochemistry 30 min to 7 days after infusion of the NMDA agonist cis-2,4-methanoglutamate (MGlu; 10 nmol) into the cortex. Early expression (1–4 h) of IL-1β by microglia was directly related to lesion development. Later expression by microglia (up to 24 h), and by astrocytes (2–7 days), was widespread compared to the area involved in excitotoxic cell death and co-localised with areas of reactive gliosis. Infusion of MGlu into the striatum induced a similar temporal pattern of IL-1β expression by microglia and astrocytes. However, IL-1β-expressing glial cells were localised strictly to the area of striatal cell death. Infusion of PBS or a subtoxic dose of MGlu into the cortex or striatum induced only limited neuronal death and negligible glial IL-1β expression. These studies reveal that IL-1β is expressed specifically by microglia during the early response to excitotoxicity in the adult rat cortex and striatum. However, the widespread and delayed IL-1β expression by astrocytes suggests diverse roles for IL-1β in response to excitotoxicity. GLIA 25:311–323, 1999. © 1999 Wiley-Liss, Inc.