Mechanisms of microglial stress response in injured central nervous tissue

作为一个整体，激活的小胶质细胞是作为神经元的保护者还是攻击者，以应对某些病理状况，如创伤？本研究使用小胶质细胞特异性免疫毒素Mac-1-SAPORIN在损伤时暂时清除小胶质细胞，观察小鼠穿透性创伤性脑损伤后的效果。损伤后24小时，小胶质细胞消融组损伤部位周围很少有小胶质细胞凋亡，而小胶质细胞凋亡在损伤部位周围或同侧海马中广泛分布，未消融组小胶质细胞沿针径稀疏分布。在损伤后7天，即使在免疫毒素治疗（小胶质细胞消融）组，损伤部位周围或整个同侧海马也可见许多树突状小胶质细胞。在损伤后72小时和7天，未消融小胶质细胞组损伤部位周围的胶质瘤更为明显。损伤后72小时，与消融组相比，非消融组神经元细胞丢失明显。然而，在损伤后7天，没有观察到统计学上的显著差异。免疫毒素消融小胶质细胞可改善小鼠海马穿透性创伤性脑损伤后齿状回神经元细胞的损失。小胶质细胞消融还能抑制外伤性脑损伤后星形胶质细胞的肥厚变化和增殖。我们认为，在穿透性脑损伤急性期，活化的小胶质细胞主要通过吞噬功能和/或改变星形细胞-神经元相互作用，作为攻击者作用于损伤神经元。

As a whole, whether activated microglia are acting as protectors or attackers to the neurons in response to the certain pathological condition such as trauma? In this study we used microglia-specific immunotoxin, Mac-1-SAPORIN, at the time of injury to temporally eliminate microglia to see the effects following penetrating traumatic brain injury in mice.At 24 hours after injury, very few arborized microglia were observed around the injury site in microglia ablation group, while arborized microglia were widely distributed around the injury site or throughout the ipsilateral hippocampus and round-shaped microglia/macrophage were sparsely distributed along the needle track in microglia non-ablation group. At 7 days after injury, many arborized microglia were observed around the injury site or throughout the ipsilateral hippocampus even in immunotoxin treated (microglia ablation) group. Gliosis around the injury site was more evident in microglia non-ablation group at 72 hours and 7 days following injury. At 72 hours after injury, the neuronal cell loss became evident in the non-ablation group compared to that in ablation group. However, at 7 days after injury, no statistically significant difference was observed.The microglia ablation with immunotoxin ameliorated the neuronal cell loss in the dentate gyrus following penetrating traumatic brain injury in the mouse hippocampus. The microglia ablation also inhibited the hypertrophic change and proliferation of astrocytes following traumatic brain injury. We concluded that activated microglia in the acute stage of penetrating brain injury are considered to mainly act on the neurons suffering from injury as attackers through their phagocytic function and/or modification of astrocyte-neuron interaction.