Time course of glial proliferation and glial apoptosis following excitotoxic CNS injury

Activation of microglial cells and astrocytes after CNS injury results in c hanges in their morphology, immunophenotype and proliferative activity and has neurotrophic as well as neurotoxic consequences. However, little is kno wn about the exact time course of glial activation as regards their prolife rative activity and their fate. In this study, quantification of the densit ies of proliferating and non-proliferating microglial cells and astrocytes was carried out over 30 days by counting differentially labeled cells in th e striatum and substantia nigra pars reticulata (SNr) after injection of qu inolinic acid into the rat striatum. The TdT-mediated dUTP nick end labelin g (TUNEL)-reaction was used to detect possible apoptotic mechanisms which l imit the glial reaction. At 1 day post injection (p.i.) non-proliferating a meboid microglia/macrophages were seen in the striatum, but at 3 and 5 days p.i. many proliferating, ameboid microglia/macrophages and hypertrophic mi croglia were detected. At 10 days p.i., the time point with the highest den sity of hypertrophic microglia, TUNEL-positive microglial cells were observ ed indicating that apoptotic processes play a role in restricting this reac tion. In contrast to this, at early time points, a reduction in the density and glial fibrillary acidic protein (GFAP)-immunoreactivity of astrocytes in the striatum was detected. At later time points, a dense astrogliosis wi th proliferating astrocytes developed in the dorsal and medial striatum. At 30 days p.i., in the entire striatum a dense astrogliosis was detected. Th e SNr showed a short period of microglial activation and proliferation and a long lasting astrogliosis without proliferation. (C) 2001 Elsevier Scienc e B.V. All rights reserved.