论文部分内容阅读
脑的炎症反应是神经退行性疾病的危险因素之一。有趣的是,黑质密部(SNpc)严重的炎性反应会加速帕金森病的发作和进展。本研究通过比较SNpc与皮质的炎性过程来检测SNpc严重炎性反应的潜在机制。在完整的脑组织中,SNpc和皮质的CD11b+小胶质细胞密度是相似的。但是,脂多糖注射可增加SNpc的CD11b+细胞数目,而不能增加皮质中的。以前作者曾报道内毒素注射之后,黑质密部有CD11b和MPO双阳性的中性粒细胞浸润(GLIA55:1577-1588)。值得注意的是,MPO+中性粒细胞数量在SNpc中显著增加,而在皮质中只有轻微提高。中性粒细胞浸润的范围与神经元损伤相关。作者证实,内毒素注射后,中性粒细胞减少大鼠的SNpc中的神经元丢失较正常大鼠显著减少。此外,完整的SNpc中的星形胶质细胞密度明显低于皮质。而且,内毒素注射后,SNpc的内皮细胞和星形胶质细胞的损害以及血脑屏障的通透性均有显著变化。这些结果都提示,过度的中性粒细胞浸润和环境因子,例如低星形胶质细胞浓度和高血脑屏障通透性,会导致SNpc的重度炎症和神经元死亡。
Brain inflammatory response is one of the risk factors of neurodegenerative diseases. Interestingly, the severe inflammatory response of the substantia nigra pars compacta (SNpc) accelerates the onset and progression of Parkinson’s disease. This study examined the underlying mechanism of SNpc-induced severe inflammatory response by comparing SNpc with cortical inflammatory processes. In intact brain tissue, SNpc and cortical CD11b + microglial densities were similar. However, lipopolysaccharide injection increased the number of CD11b + cells in SNpc but not in the cortex. Previous authors have reported that CD11b and MPO double-positive neutrophil infiltration (GLIA55: 1577-1588) has been reported in the substantia nigra pars compacta following endotoxin injection. Notably, the number of MPO + neutrophils increased significantly in SNpc, with only a slight increase in cortex. The extent of neutrophil infiltration is associated with neuronal damage. The authors confirmed that neuronal loss in SNpc was significantly reduced in neutropenic rats compared with normal rats after endotoxin injection. In addition, astrocyte density was significantly lower in intact SNpc than in cortex. Moreover, there was a significant change in the damage of endothelial cells and astrocytes of SNpc and the permeability of the blood-brain barrier after endotoxin injection. These results suggest that excessive neutrophil infiltration and environmental factors such as low astrocyte concentration and high BBB permeability lead to severe SNpc inflammation and neuronal death.