Ngu Emmanuel Mbaku, Sahley Christie L, Muller Kenneth J
Department of Physiology & Biophysics, University of Miami School of Medicine, Miami, FL 33136, USA.
J Comp Neurol. 2007 Jul 1;503(1):101-9. doi: 10.1002/cne.21386.
The role of mammalian microglia in central nervous system (CNS) repair is controversial. Microglia accumulate at lesions where they act as immune cells and phagocytize debris, and they may secrete neurotrophins, but they also produce molecules that can be cytotoxic, like nitric oxide (NO). To determine the importance of microglial accumulation at lesions on growth of severed CNS axons in the leech (Hirudo medicinalis), in which axon and synapse regeneration are notably successful even when isolated in tissue culture medium, microglial migration to lesions was reduced. Pressure (P) sensory neurons were injected with biocytin to reveal the extent of their sprouting 24 hours after lesioning. To reduce microglia accumulation at lesions, cords were treated for 3.5 hours with 3 mM ATP or 2 mM N(omega)-nitro-L-arginine methyl ester (L-NAME) or 50 microM Reactive blue-2 (RB2) beginning 30 minutes before injury. Lesioned controls were either not treated with drug or treated 3 hours later with one of the drugs, after the migration and subsequent accumulation of most microglia had occurred, but before the onset of axon sprouting, for a total of seven separate conditions. There was a significant reduction in total sprout lengths compared with controls when microglial accumulation was reduced. The results suggest that microglial cells are necessary for the usual sprouting of injured axons.
哺乳动物小胶质细胞在中枢神经系统（CNS）修复中的作用存在争议。小胶质细胞在损伤部位聚集，在那里它们作为免疫细胞吞噬碎片，并且可能分泌神经营养因子，但它们也产生具有细胞毒性的分子，如一氧化氮（NO）。为了确定水蛭（医用水蛭）中损伤部位小胶质细胞聚集对切断的中枢神经系统轴突生长的重要性，在水蛭中，即使在组织培养基中分离培养，轴突和突触再生也非常成功，实验中减少了小胶质细胞向损伤部位的迁移。向压力（P）感觉神经元注射生物素，以显示损伤后24小时其发芽的程度。为了减少损伤部位小胶质细胞的聚集，在损伤前30分钟开始，用3 mM ATP或2 mM N（ω）-硝基-L-精氨酸甲酯（L-NAME）或50 μM活性蓝-2（RB2）处理神经索3.5小时。损伤对照组要么不进行药物处理，要么在大多数小胶质细胞迁移并随后聚集后、轴突发芽开始前3小时用其中一种药物处理，总共七种不同条件。当小胶质细胞聚集减少时，与对照组相比，总发芽长度显著降低。结果表明，小胶质细胞对于受损轴突的正常发芽是必需的。
