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Mechanisms of microglial stress response in injured central nervous tissue

损伤中枢神经组织小胶质细胞应激反应机制

基本信息

批准号：
12671341
负责人：
YAMAURA Akira
金额：
$ 2.18万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671341/
关键词：
traumatic brain injury microglia astroglia immunotoxin neuron 頭部外傷脳挫傷

项目摘要

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.

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来响应特定的病理条件，如创伤？在本研究中，我们在损伤时使用小胶质细胞特异性免疫毒素Mac-1-SAPORIN暂时消除小胶质细胞，以观察小鼠穿透性创伤性脑损伤后的效果。在损伤后24小时，小胶质细胞消融组在损伤部位周围观察到很少的树枝状小胶质细胞，而树枝状小胶质细胞广泛分布于损伤部位周围或整个同侧海马，圆形小胶质细胞/小胶质细胞非消融组巨噬细胞沿着针道稀疏分布。在损伤后7天，即使在免疫毒素治疗（小胶质细胞消融）组中，也可以在损伤部位周围或整个同侧海马中观察到许多树枝状的小胶质细胞。伤后72小时和7天，小胶质细胞未消融组损伤部位周围胶质细胞增生更明显。伤后72 h，非消融组神经细胞丢失较消融组明显。然而，在伤后7天，没有观察到统计学上的显著差异。免疫毒素的小胶质细胞消融改善了小鼠海马穿透性创伤性脑损伤后齿状回神经元细胞的丢失。小胶质细胞去除还能抑制脑外伤后星形胶质细胞的增生和肥大。我们的结论是，激活的小胶质细胞在穿透性脑损伤的急性期被认为是主要作用于遭受损伤的神经元作为攻击者，通过其吞噬功能和/或修改星形胶质细胞-神经元的相互作用。