Microglial cell population dynamics in the injured adult central nervous system
Microglial cell population dynamics in the injured adult central nervous system
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DOI：
10.1016/j.brainresrev.2004.12.009
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发表时间：
2005-04-01
影响因子：
--
通讯作者：
Finsen, B
中科院分区：
文献类型：
--
作者：
Ladeby, R;Wirenfeldt, M;Finsen, B
反应性小胶质细胞增多症是创伤和中风以及炎症性和慢性神经退行性疾病的特征。小胶质细胞对急性神经损伤的反应的一个显著特征是小胶质细胞数量的大量扩张，并在损伤后几天达到高峰。基于使用辐射骨髓嵌合小鼠的新数据表明，这种扩张还包括招募骨髓来源的细胞，这些细胞迁移到神经实质并分化为小胶质细胞。在这里，我们讨论了骨髓来源的细胞在损伤诱导的小胶质细胞群扩张中的作用，在齿状回中可见，在内侧齿状回穿通径投射横断后，伴随着顺行轴突和终末突触的退化。在这种轻微脑损伤的范例中，骨髓来源的细胞远远多于激活的常驻小胶质细胞，这些小胶质细胞表达干细胞抗原CD34，同时具有显著的自我更新能力。对病变反应性小胶质细胞的观察表明，病变反应性小胶质细胞由功能不同的细胞群组成，其中包括较小的外源性骨髓来源的小胶质细胞亚群和较大的激活的常驻小胶质细胞群，其中大多数表达CD34并进行增殖。证明了损伤增强的骨髓来源的细胞被招募到穿支路径失神经的齿状回，增加了使用基因操纵的细胞作为病变部位特异性基因治疗的载体的可能性，即使在中枢神经系统的最小损伤区域也是如此。(C)2005 Elsevier B.V.保留所有权利。
Reactive microgliosis is characteristic of trauma and stroke as well as inflammatory and chronic neurodegenerative disease. A conspicuous feature of the microglial reaction to acute neural injury is a massive expansion of the microglial cell population which Peaks a few days following injury. New data based on the use of radiation bone marrow-chimeric mice suggest this expansion also involves recruitment of bone marrow-derived cells, which migrate into the neural parenchyma and differentiate into microglia. Here, we discuss the contribution of bone marrow-derived cells to the injury-induced expansion of the microglial cell population, seen in the dentate gyrus with ongoing anterograde axonal and terminal synaptic degeneration, subsequent to transection of the entorhino-dentate perforant path projection. In this paradigm of minor brain injury, the bone marrow-derived cells are grossly outnumbered by activated resident microglia, which express the stem cell antigen CD34 concurrent to a marked capacity for self-renewal. The observation of a mixed origin of lesion-reactive microglia, consisting of a smaller subpopulation of exogenous bone marrow-derived microglia, and a larger population of activated resident microglia, the majority of which express CD34 and undergo proliferation, suggests that lesion-reactive microglia consist of functionally distinct cell populations. The demonstration of an injury-enhanced recruitment of bone marrow-derived cells into the perforant path-denervated dentate gyrus, raises the possibility of using genetically manipulated cells as vectors for lesion-site-specific gene therapy even in minimally injured areas of the central nervous system. (c) 2005 Elsevier B.V. All rights reserved.