Department of Neuroimmunology, Institute of Neurology, London, UK.
Autoimmunity. 2012 Jun;45(4):298-303. doi: 10.3109/08916934.2012.654865. Epub 2012 Feb 15.
Monitoring neuroaxonal loss in multiple sclerosis is an important objective to study the pathogenesis and response to treatment of the disease. The release of neurofilaments is a potential surrogate biomarker of neurodegeneration. One route to explore this aspect further is through the use of animal models that have well-defined, and predictable, disease courses. The release of neurofilaments into plasma across the course of relapsing-remitting and secondary progressive experimental autoimmune encephalomyelitis in Biozzi ABH was assessed, as well as measuring anti-neurofilament antibodies using ELISA. It was found that there was an immediate release in neurofilaments into the blood following the initial paralytic attack. Neurofilament release was continuous in relapse and remission but returned towards baseline in chronic disease, as animals entered the post-relapsing progressive phase of the disease. This was mirrored by a loss of neurofilament-specific antibodies. In contrast neurofilament levels increased dramatically as neurodegeneration and clinical disease occurred in the G93A SOD1 transgenic C57BL/6 x SJL mice, model of amyotrophic lateral sclerosis. These data further support neurofilament levels as a good surrogate measure of neurodegeneration and their potential use as a surrogate endpoint in neuroprotective studies.
监测多发性硬化症中的神经轴突丢失是研究疾病发病机制和治疗反应的重要目标。神经丝的释放是神经退行性变的潜在替代生物标志物。进一步探索这一方面的一种途径是使用具有明确且可预测疾病过程的动物模型。本研究评估了 Biozzi ABH 实验性自身免疫性脑脊髓炎中复发缓解型和继发进展型神经丝在血浆中的释放情况，并通过 ELISA 测量了抗神经丝抗体。结果发现，在最初的瘫痪发作后，神经丝立即释放到血液中。在复发和缓解期间，神经丝释放持续存在，但在慢性疾病中，随着动物进入疾病的复发后进行性阶段，神经丝释放恢复到基线水平。这与神经丝特异性抗体的丧失相吻合。相比之下，在肌萎缩侧索硬化症的 G93A SOD1 转基因 C57BL/6 x SJL 小鼠模型中，随着神经退行性变和临床疾病的发生，神经丝水平显著增加。这些数据进一步支持神经丝水平作为神经退行性变的良好替代测量指标，以及它们在神经保护研究中作为替代终点的潜在用途。
