Early microglial activation following neonatal excitotoxic brain damage in mice: A potential target for neuroprotection
Early microglial activation following neonatal excitotoxic brain damage in mice: A potential target for neuroprotection
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DOI：
10.1016/s0306-4522(03)00558-x
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Gressens, P
中科院分区：
文献类型：
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作者：
Dommergues, MA;Plaisant, F;Gressens, P
先前在模拟人类脑瘫脑损伤的新生儿兴奋性毒性脑损伤小鼠模型中进行的研究显示，在脑内注射谷氨酸能类似物ibotenate后24小时内小胶质细胞激活。利用该模型，我们研究了血源性细胞标记物CD-45抗原在被激活的小胶质细胞中的表达，这些细胞被Griffonia simplicifolia I isolectin B4标记。在兴奋性毒性病变早期进行的免疫组织化学检查显示，大多数用隔离素B4标记的细胞cd -45阴性，这表明这些早期激活的小胶质细胞主要来自常驻小胶质细胞，而不是来自循环单核细胞。我们还直接验证了激活的常驻小胶质细胞和/或血源性单核细胞在兴奋性毒性脑损伤的病理生理中发挥作用的假设。在注射伊博酸酯之前和/或之后，反复滴注氯喹、氯喹+秋水仙碱、米诺环素或与毒素皂苷偶联的抗mac1抗体，可显著降低隔离素b4阳性细胞的密度。这种抑制小胶质细胞和/或血源性单核细胞的激活，伴随着伊博腾酸盐诱导的脑损伤的严重程度的显著降低（在米诺环素最高剂量下，病变大小可减少79%），以及伊博腾酸盐诱导的皮质caspase-3激活（减少49%）。(c) 2003年。Elsevier Ltd.出版。版权所有。
Previous studies in a mouse model of neonatal excitotoxic brain damage mimicking the brain lesions in human cerebral palsy showed microglial activation within 24 h after intracerebral injection of the glutamatergic analog ibo-tenate. Using this model, we studied the expression of CD-45 antigen, a marker of blood-derived cells, by these activated microglial cells labeled by Griffonia simplicifolia I isolectin B4. Immunohistochemistry performed during early development of excitotoxic lesions showed that most cells labeled with the isolectin B4 were CD-45-negative, suggesting that these early activated microglial cells were deriving chiefly from resident microglia and not from circulating monocytes. We also directly tested the hypothesis that activated resident microglia and/or blood-derived monocytes play a role in the pathophysiology of excitotoxic brain damage. Repeated i.p. administrations of chloroquine, chloroquine+colchicine, minocycline, or an anti-MAC1 antibody coupled to the toxin saporin before and/or after ibotenate injection induced a significant reduction in the density of isolectin B4-positive cells. This inhibition of resident microglial and/or blood-derived monocytes activation was accompanied by a significant reduction in the severity of ibotenate-induced brain lesions (up to 79% lesion size reduction with the highest minocycline dose) as well as of ibotenate-induced cortical caspase-3 activation (49% reduction). (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.