Reactive Gliosis as an Indicator of Neurotoxicity

Abstract

Diverse types of injury to the central nervous system result in hypertrophy of astrocytes, called reactive gliosis. The hallmark of this gliosis is the enhanced expression of the major intermediate filament protein of astrocytes, glial fibrillary acidic protein (GFAP). These morphological observations suggest that GFAP may be a useful biochemical indicator of neurotoxicity. This chapter focuses on studies that investigate this possibility by administering prototype neurotoxicants to experimental animals and then assessing the effects of these agents on the tissue content of GFAP by immunoassay. The assays of GFAP reveal dose-, time-, and region-dependent patterns of neural injury, often at toxicant dosages below those that result in light microscopic evidence of cell loss or damage. In rodent studies, measurement of GFAP has proven useful for distinguishing neurotoxic amphetamines, such as methamphetamine and methylenedioxymethamphetamine (MDMA), from non-neurotoxic non-amphetaminic anorectic agents, such as dexfenfluramine. The major conclusions that emerged from studies show that assays of GFAP provide a sensitive means for assessing neurotoxicity; increase in GFAP are specific and can differentiate long-term neurochemical changesfrom neurotoxic effects. In summary, assays of GFAP represent one approach for neurotoxicity assessment that can be used to differentiate pharmacological from neurotoxicological responses.