MICROGLIAL TURNOVER IN THE INJURED CNS - ACTIVATED MICROGLIA UNDERGO DELAYED DNA FRAGMENTATION FOLLOWING PERIPHERAL-NERVE INJURY
MICROGLIAL TURNOVER IN THE INJURED CNS - ACTIVATED MICROGLIA UNDERGO DELAYED DNA FRAGMENTATION FOLLOWING PERIPHERAL-NERVE INJURY
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DOI：
10.1097/00005072-199509000-00010
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发表时间：
1995-09-01
影响因子：
3.2
通讯作者：
BANATI, RB
中科院分区：
文献类型：
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作者：
GEHRMANN, J;BANATI, RB
小胶质细胞的增殖和活化是受损CNS中常见的事件。然而，激活的小胶质细胞在病理刺激后被消除的机制仍然知之甚少。因此，本研究探讨了小胶质细胞增殖的H-3-胸苷放射自显影和程序性细胞死亡的末端转移酶介导的缺口末端标记（TUNEL）和原位末端标记（ISEL）的核DNA片段在两个模型的周围神经损伤，即坐骨神经和舌下神经横断在大鼠。在这些模型中，小胶质细胞活化和增殖发生在CNS投射区域，即在腰脊髓的腹侧和背侧灰质中，以及在坐骨神经切断后的薄束核中，以及在轴突切断的舌下神经核中。在这些部位，小胶质细胞增殖在损伤后第2天和第3天之间有一个相对尖锐的峰值，然后迅速下降。从轴突切断后第6天开始，在凝集素（GSI-B-4）阳性小胶质细胞中检测到DNA片段化，在第21天达到明显峰值，并在第60天（即研究的最后时间点）下调。然而，bcl-2和c-myc的表达，即潜在控制程序性细胞死亡的基因，被发现在此期间没有变化。因此，程序性细胞死亡似乎是一种机制，通过该机制，活化的小胶质细胞在CNS损伤后逐渐消除，并且在体内实现小胶质细胞数量的稳态。小胶质细胞生长因子的表达可能有助于控制这些过程。
Microglial proliferation and activation are common events in the injured CNS. The mechanisms, however, by which activated microglia are eliminated following a pathological stimulus are still poorly understood. The present study has therefore examined microglial proliferation by H-3-thymidine autoradiography and programmed cell death by terminal transferase-mediated nick end labeling (TUNEL) and in situ end labeling (ISEL) of nuclear DNA fragments in two models of peripheral nerve injury, i.e. sciatic and hypoglossal nerve transection in the rat. In these models, microglial activation and proliferation occur in CNS projection areas, i.e. in the ventral and dorsal gray matter of lumbar spinal cord and in the nucleus gracilis after sciatic nerve transection as well as in the axotomized hypoglossal nucleus. At these sites, microglial proliferation had a relatively sharp peak between days 2 and 3 post-lesion and then rapidly declined. DNA fragmentation was detected in lectin (GSI-B-4)-positive microglia from day 6 after axotomy onward, reached an apparent peak at day 21 and was downregulated by day 60, i.e. the latest time point investigated. However, the expression of bcl-2 and c-myc, i.e. genes potentially controlling programmed cell death, was found to be unchanged during this period. Programmed cell death thus appears to be one mechanism by which activated microglia are gradually eliminated following CNS injury and steady state of microglial cell numbers is achieved in vivo. Expression of microglial growth factors may be instrumental in controlling these processes.