QUANTITATIVE ASPECTS OF DRUG AND TOXICANT-INDUCED ASTROGLIOSIS

A universal cellular reaction to damage of the CNS is hypertrophy of a strocytes. The hallmark of this response, often termed 'reactive glios is', is the enhanced expression of the major intermediate filament pro tein of astrocytes, glial fibrillary acidic protein (GFAP). This latte r observation suggests that increased synthesis of GFAP would occur in response to diverse neurotoxic insults. To investigate this possibili ty, prototype neurotoxicants were administered to experimental animals and the effects of these agents on the tissue content of GFAP was det ermined by immunoassay. Assays of GFAP were found to reveal dose-, tim e- and region-dependent patterns of neurotoxicity at toxicant dosages below those that cause light microscopic evidence of cell loss or dama ge. Moreover, the temporal and regional increments in GFAP correspond to the temporal and regional patterns of argyrophilia, as revealed by the cupric silver degeneration stain of de Olmos. Our findings indicat e that assays of GFAP represent a sensitive, simple and quantitative a pproach for evaluation of nervous system damage. Combining this indire ct yet quantitative indicator of neurotoxicity with more traditional n euroanatomical endpoints, should augment the armamentarium of techniqu es useful for detection and characterization of neurotoxicity.