引用

背景:视神经脊髓炎谱系障碍(NMOSD)是一种以急性视神经炎和横切性脊髓炎反复发作为特征的中枢神经系统(CNS)自身免疫性炎症性脱髓鞘疾病。水通道蛋白-4免疫球蛋白G (AQP4- igg)自身抗体靶向星形细胞膜上的水通道蛋白-4 (AQP4)，是NMOSD的致病因素。在AQP4-IgG与星形胶质细胞结合后，由aqp4 -谷氨酸转运体复合物内化引发的谷氨酸兴奋性毒性参与了早期NMOSD病理生理学。我们研究了n -甲基- d -天冬氨酸(NMDA)受体拮抗剂memantine对接受人AQP4-IgG的小鼠的运动损伤和脊髓病理的影响。方法:从aqp4 -IgG血清阳性NMOSD患者中纯化的IgG被动转移到血脑屏障破坏的成年C57BL-6小鼠。美金刚经口服灌胃。采用梁式行走试验对小鼠运动障碍进行评估。免疫荧光法和ELISA法检测小鼠脊髓。结果:口服memantine可改善AQP4-IgG引起的运动损伤，无论是在疾病发作前(预防性)还是在疾病发作后(治疗性)开始治疗。美金刚可显著减少AQP4和星形胶质细胞的损失，并可减轻AQP4- igg小鼠脊髓的脱髓鞘和轴突损失。 The protective effects of memantine were associated with inhibition of apoptosis and suppression of neuroinflammation, with decrease in microglia activation and neutrophil infiltration and reduction of increase in levels of proinflammatory cytokines including interleukin-1? (IL-1?), interleukin-6 (IL-6) and tumor necrosis factor-? (TNF- ?). In addition, memantine elevated growth factors including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) in the spinal cord. Conclusions: Our findings support that glutamate excitotoxicity and neuroinflammation plays important roles in complement-independent pathophysiology during early development of NMOSD lesions, and highlight the potential of oral memantine as a therapeutic agent in NMOSD acute attacks.