Long-Lasting Post-Mortem Activity of Spinal Microglia In Situ in Mice
Long-Lasting Post-Mortem Activity of Spinal Microglia In Situ in Mice
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DOI：
10.1002/jnr.22402
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发表时间：
2010-08-15
影响因子：
4.2
通讯作者：
Schomburg, Eike D.
中科院分区：
文献类型：
--
作者：
Dibaj, Payam;Steffens, Heinz;Schomburg, Eike D.
作为中枢神经系统巨噬细胞，小胶质细胞表现出高度自发运动的过程，不断地测量其微环境。在中枢神经系统损伤后，小胶质细胞通过立即的细胞极化和向病变部位的过程延伸以及随后的变形虫病变定向迁移和吞噬做出反应。为了确定在没有生命支持的情况下，小胶质细胞在特殊损伤组织中发挥作用的能力，我们研究了心脏和呼吸停止后，即死后，在逐渐退化的神经组织中，脊髓背柱原位小胶质细胞的活性和对激光诱导轴突损伤的反应。为此，我们使用延时双光子激光扫描显微镜观察了双转基因小鼠，这些小鼠在小胶质细胞中表达增强的绿色荧光蛋白，在投射神经元中表达增强的黄色荧光蛋白。根据动物生前的情况，小胶质细胞的活性和反应性在死后可维持5-10小时。因此，持续减少的胶质反应是独立于氧气和葡萄糖供应的，但需要残余的ATP，这表明一种寄生形式的能量，如从受损神经组织释放的ATP的跨膜摄取。尽管最初小胶质细胞能够在血液供应中断后检测到轴突损伤，但死后神经胶质反应的后期方面，如变形虫转化和迁移，是不存在的，这与小胶质细胞无法防止神经组织损伤后的继发性损伤相对应。(C) 2010 Wiley-Liss, Inc。
As CNS macrophages, microglia show a high spontaneous motility of their processes, continuously surveying their microenvironment. Upon CNS injury, microglia react by immediate cellular polarization and process extension toward the lesion site as well as by subsequent amoeboid lesion-directed migration and phagocytosis. To determine the ability of microglia to fulfill their role within distinctively lesioned tissue in the absence of life support, we investigated microglial activity and responsiveness to laser-induced axonal injuries in the spinal dorsal columns in situ after cardiac and respiratory arrest, i.e., post-mortem, in the progressively degrading nervous tissue. For this purpose, we used time-lapse two-photon laser scanning microscopy in double transgenic mice expressing enhanced green fluorescent protein in microglia and enhanced yellow fluorescent protein in projection neurons. Depending on the premortal condition of the animal, microglial activity and responsiveness remain for up to 5-10 hr post-mortem. Thereby, the continuously decreasing glial reaction is independent of oxygen and glucose supply but requires residual ATP, suggesting a parasitic form of energy, such as a transmembrane uptake of ATP released from injured nervous tissue. Even though initially microglia are able to detect axonal injury after disruption of the blood supply, the later aspects of glial reaction, for example amoeboid conversion and migration, are absent postmortem, corresponding to the failure of microglia to prevent secondary damage after injury of nervous tissue. (C) 2010 Wiley-Liss, Inc.