Jørgensen M B, Finsen B R, Jensen M B, Castellano B, Diemer N H, Zimmer J
PharmaBiotec, University of Copenhagen, Denmark.
Exp Neurol. 1993 Mar;120(1):70-88. doi: 10.1006/exnr.1993.1041.
The aim of this study was to characterize the microglial and astroglial reactions to degeneration of (a) hippocampal CA1 pyramidal cells and dentate hilar neurons induced by cerebral ischemia and (b) CA3 pyramidal cells and dentate hilar neurons induced by intraventricular injections of kainic acid (KA). The microglial reactions to ischemia, as monitored by histochemical staining for the enzyme nucleoside diphosphatase (NDPase) and immunohistochemical staining for the complement type 3 receptor (CR3), could be divided into (1) initial and generalized, but transient, reactions which also included areas devoid of subsequent neural degeneration and (2) protracted, degeneration-specific reactions in the areas with neural degeneration. Due to more widespread hippocampal involvement a similar distinction was not possible after KA lesions. After both ischemia and KA application the protracted degeneration-specific reactions were characterized by increased NDPase/CR3 reactivity and prominent morphological changes. In the dentate hilus, reactive microglial cells clustered around the degenerating hilar neurons. In stratum radiatum of CA1, reactive microglial cells transformed into either (1) "rod cells," aligned along the postischemic, degenerating pyramidal cell dendrites, followed by subsequent transformation into ameboid-like cells, or (2) "bushy" cells, in response to degeneration of Schaffer collaterals induced by KA lesioning of CA3 pyramidal cells. Within stratum radiatum of the KA-lesioned CA3, where both dendrites and axons were degenerating, the microglial cells developed into stellate cells with thickened, retracted processes and plump cell bodies. These cells were supplemented by rounded macrophage-like cells. Astroglial reactions, monitored by immunohistochemical staining for the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin (VIM), and the normal plasma constituent immunoglobulin G (IgG), showed an initial and generalized astroglial immunoreactivity for IgG, which paralleled the initial and transient microglial reactions, while the reactive changes in GFAP and VIM immunohistochemistry paralleled the protracted, degeneration-specific reactions with regard to timing, strength, and distribution. In the KA-lesioned CA3, the most prominent finding was a prompt loss of astroglial GFAP immunoreactivity corresponding to the degenerating pyramidal cell layer and the adjacent mossy fiber layer. The results strongly indicate that stimuli other than neural degeneration initiated the activation of both microglial and astroglial cells, which then upon further activation by actual neuronal damage and degeneration adjust according to which neuronal structures were undergoing degeneration.
(a) 脑缺血诱导的海马CA1锥体细胞和齿状回门区神经元变性，以及(b) 脑室内注射 kainic 酸 (KA) 诱导的CA3锥体细胞和齿状回门区神经元变性。通过对核苷二磷酸酶 (NDPase) 进行组织化学染色以及对补体3型受体 (CR3) 进行免疫组织化学染色监测，小胶质细胞对缺血的反应可分为：(1) 初始的、全身性但短暂的反应，该反应也包括后续无神经变性的区域；(2) 神经变性区域中持续存在的、与变性相关的特异性反应。由于KA损伤后海马受累范围更广，因此无法进行类似的区分。在缺血和应用KA后，持续存在的与变性相关的特异性反应的特征均为NDPase/CR3反应性增加以及显著的形态学变化。在齿状回门区，反应性小胶质细胞聚集在变性的门区神经元周围。在CA1的辐射层，反应性小胶质细胞转变为：(1) “杆状细胞”，沿缺血后变性的锥体细胞树突排列，随后转变为类阿米巴样细胞；或(2) “浓密”细胞，这是对CA3锥体细胞KA损伤诱导的Schaffer侧支变性的反应。在KA损伤的CA3的辐射层内，树突和轴突均发生变性，小胶质细胞发育为具有增厚、缩回的突起和饱满细胞体的星形细胞。这些细胞由圆形的巨噬细胞样细胞补充。通过对中间丝蛋白胶质纤维酸性蛋白 (GFAP)、波形蛋白 (VIM) 和正常血浆成分免疫球蛋白G (IgG) 进行免疫组织化学染色监测星形胶质细胞反应，结果显示，最初存在全身性的IgG星形胶质细胞免疫反应性，这与最初的、短暂的小胶质细胞反应平行，而GFAP和VIM免疫组织化学的反应性变化在时间、强度和分布方面与持续存在的、与变性相关的特异性反应平行。在KA损伤的CA3中，最显著的发现是对应于变性锥体细胞层和相邻苔藓纤维层的星形胶质细胞GFAP免疫反应性迅速丧失。结果强烈表明，除神经变性外的其他刺激引发了小胶质细胞和星形胶质细胞的激活，然后在实际神经元损伤和变性的进一步激活下，它们根据正在发生变性的神经元结构进行调整。
