Time course of glial proliferation and glial apoptosis following excitotoxic CNS injury
Time course of glial proliferation and glial apoptosis following excitotoxic CNS injury
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DOI：
10.1016/s0006-8993(01)02378-2
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发表时间：
2001-06-01
期刊：
影响因子：
2.9
通讯作者：
Töpper, R
中科院分区：
文献类型：
--
作者：
Dihné, M;Block, F;Töpper, R
中枢神经系统损伤后小胶质细胞和星形胶质细胞的活化导致其形态、免疫表型和增殖活性的改变，并具有神经营养和神经毒性后果。然而，关于胶质细胞的增殖活性和它们的命运，我们对胶质细胞激活的确切时间过程知之甚少。本研究通过对大鼠纹状体注射喹啉酸后纹状体和网状黑质中差异标记细胞（SNr）的计数，在30天内定量测定增殖和非增殖小胶质细胞和星形胶质细胞的密度。利用tdt介导的dUTP缺口末端标记（TUNEL）反应来检测可能限制胶质细胞反应的凋亡机制。注射后第1天纹状体内可见未增殖的阿米巴样小胶质细胞/巨噬细胞，注射后第3、5天纹状体内可见大量增殖的阿米巴样小胶质细胞/巨噬细胞和增生性小胶质细胞。在第10天，即肥厚性小胶质细胞密度最高的时间点，观察到tunel阳性小胶质细胞，表明凋亡过程对该反应起限制作用。与此相反，在早期时间点，检测到纹状体星形胶质细胞的密度和胶质纤维酸性蛋白（GFAP）免疫反应性降低。在较晚的时间点，密集的星形胶质细胞增生出现在背侧和内侧纹状体。在p.i.第30天，在整个纹状体中检测到致密的星形胶质细胞。SNr显示小胶质细胞的激活和增殖周期短，星形胶质细胞增生持续时间长，但不增生。(C) 2001 Elsevier Science B.V.版权所有
Activation of microglial cells and astrocytes after CNS injury results in changes in their morphology, immunophenotype and proliferative activity and has neurotrophic as well as neurotoxic consequences. However, little is known about the exact time course of glial activation as regards their proliferative activity and their fate. In this study, quantification of the densities of proliferating and non-proliferating microglial cells and astrocytes was carried out over 30 days by counting differentially labeled cells in the striatum and substantia nigra pars reticulata (SNr) after injection of quinolinic acid into the rat striatum. The TdT-mediated dUTP nick end labeling (TUNEL)-reaction was used to detect possible apoptotic mechanisms which limit the glial reaction. At 1 day post injection (p.i.) non-proliferating ameboid microglia/macrophages were seen in the striatum, but at 3 and 5 days p.i. many proliferating, ameboid microglia/macrophages and hypertrophic microglia were detected. At 10 days p.i., the time point with the highest density of hypertrophic microglia, TUNEL-positive microglial cells were observed indicating that apoptotic processes play a role in restricting this reaction. 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 with proliferating astrocytes developed in the dorsal and medial striatum. At 30 days p.i., in the entire striatum a dense astrogliosis was detected. The SNr showed a short period of microglial activation and proliferation and a long lasting astrogliosis without proliferation. (C) 2001 Elsevier Science B.V. All rights reserved.