Aldskogius H, Kozlova E N
Department of Neuroscience, Biomedical Center, Uppsala, Sweden.
Prog Neurobiol. 1998 May;55(1):1-26. doi: 10.1016/s0301-0082(97)00093-2.
Axon injury rapidly activates microglial and astroglial cells close to the axotomized neurons. Following motor axon injury, astrocytes upregulate within hour(s) the gap junction protein connexin-43, and within one day glial fibrillary acidic protein (GFAP). Concomitantly, microglial cells proliferate and migrate towards the axotomized neuron perikarya. Analogous responses occur in central termination territories of peripherally injured sensory ganglion cells. The activated microglia express a number of inflammatory and immune mediators. When neuron degeneration occurs, microglia act as phagocytes. This is uncommon after peripheral nerve injury in the adult mammal, however, and the functional implications of the glial cell responses in this situation are unclear. When central axons are injured, the glial cell responses around the affected neuron perikarya appears to be minimal or absent, unless neuron degeneration occurs. Microglia proliferate, and astrocytes upregulate GFAP along central axons undergoing anterograde, Wallerian, degeneration. Although microglia develop into phagocytes, they eliminate the disintegrating myelin very slowly, presumably because they fail to release molecules which facilitate phagocytosis. During later stages of Wallerian degeneration, oligodendrocytes express clusterin, a glycoprotein implicated in several conditions of cell degeneration. A hypothetical scheme for glial cell activation following axon injury is discussed, implying the injured neurons initially interact with adjacent astrocytes. Subsequently, neighbouring resting microglia are activated. These glial reactions are amplified by paracrine and autocrine mechanisms, in which cytokines appear to be important mediators. The specific functional properties of the activated glial cells will determine their influence on neuronal survival, axon regeneration, and synaptic plasticity. The control of the induction and progression of these responses are therefore likely to be critical for the outcome of, for example, neurotrauma, brain ischemia and chronic neurodegenerative diseases.
轴突损伤会迅速激活靠近轴突切断神经元的小胶质细胞和星形胶质细胞。运动轴突损伤后，星形胶质细胞在数小时内上调缝隙连接蛋白连接蛋白43，并在一天内上调胶质纤维酸性蛋白（GFAP）。与此同时，小胶质细胞增殖并向轴突切断的神经元胞体迁移。在外周损伤的感觉神经节细胞的中枢终末区域也会出现类似反应。活化的小胶质细胞表达多种炎症和免疫介质。当神经元发生变性时，小胶质细胞会充当吞噬细胞。然而，在成年哺乳动物外周神经损伤后这种情况并不常见，而且在这种情况下胶质细胞反应的功能意义尚不清楚。当中枢轴突受损时，除非神经元发生变性，否则受影响神经元胞体周围的胶质细胞反应似乎很轻微或不存在。小胶质细胞增殖，星形胶质细胞沿正在进行顺行性沃勒变性的中枢轴突上调GFAP。尽管小胶质细胞会发育成吞噬细胞，但它们清除解体的髓磷脂的速度非常缓慢，推测是因为它们无法释放促进吞噬作用的分子。在沃勒变性的后期，少突胶质细胞表达聚集素，这是一种与多种细胞变性情况有关的糖蛋白。本文讨论了轴突损伤后胶质细胞活化的假设方案，这意味着受损神经元最初与相邻的星形胶质细胞相互作用。随后，邻近的静息小胶质细胞被激活。这些胶质反应通过旁分泌和自分泌机制放大，其中细胞因子似乎是重要的介质。活化的胶质细胞的特定功能特性将决定它们对神经元存活、轴突再生和突触可塑性的影响。因此，控制这些反应的诱导和进展可能对例如神经创伤、脑缺血和慢性神经退行性疾病的结果至关重要。
