Trapp Bruce D, Wujek Jerome R, Criste Gerson A, Jalabi Walid, Yin Xinghua, Kidd Grahame J, Stohlman Stephen, Ransohoff Richard
Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA.
Glia. 2007 Mar;55(4):360-8. doi: 10.1002/glia.20462.
Recent studies have described significant demyelination and microglial activation in the cerebral cortex of brains from multiple sclerosis patients. To date, however, experimental models of cortical demyelination or cortical inflammation have not been extensively studied. In this report we describe focal cortical inflammation induced by stereotaxic injection of killed bacteria (BCG), followed 1 month later by subcutaneous injection of the same antigen, a protocol that overcomes the immune privilege of the cortex. Intracerebral BCG injection produced focal microglial activation at the injection site (termed acute lesion). Ten days after peripheral challenge (termed immune-mediated lesion), larger areas and higher densities of activated microglia were found near the injection site. In both paradigms, activated microglia and/or their processes closely apposed neuronal perikarya and apical dendrites. In the immune-mediated lesions, approximately 45% of the axosomatic synapses was displaced by activated microglia. Upon activation, therefore, cortical microglial migrate to and strip synapses from neuronal perikarya. Since neuronal pathology was not a feature of either the acute or immune-mediated lesion, synaptic stripping by activated microglia may have neuroprotective consequences.
近期研究描述了多发性硬化症患者大脑皮质中显著的脱髓鞘和小胶质细胞激活现象。然而，迄今为止，皮质脱髓鞘或皮质炎症的实验模型尚未得到广泛研究。在本报告中，我们描述了通过立体定向注射灭活细菌（卡介苗）诱导的局灶性皮质炎症，1个月后皮下注射相同抗原，该方案克服了皮质的免疫特权。脑内注射卡介苗在注射部位产生局灶性小胶质细胞激活（称为急性病变）。外周激发后10天（称为免疫介导病变），在注射部位附近发现更大面积和更高密度的激活小胶质细胞。在这两种范例中，激活的小胶质细胞和/或其突起紧密贴附于神经元胞体和顶端树突。在免疫介导病变中，约45%的轴体突触被激活的小胶质细胞取代。因此，激活后，皮质小胶质细胞迁移至神经元胞体并剥去突触。由于神经元病理并非急性或免疫介导病变的特征，激活的小胶质细胞进行的突触剥脱可能具有神经保护作用。
