Centre for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Wien, Austria.
Exp Neurol. 2010 Sep;225(1):2-8. doi: 10.1016/j.expneurol.2009.10.009. Epub 2009 Oct 17.
Axonal and neuronal injury and loss are of critical importance for permanent clinical disability in multiple sclerosis patients. Axonal injury occurs already early during the disease and accumulates with disease progression. It is not restricted to focal demyelinated lesions in the white matter, but also affects the normal appearing white matter and the grey matter. Experimental studies show that many different immunological mechanisms may lead to axonal and neuronal injury, including antigen-specific destruction by specific T-cells and auto-antibodies as well as injury induced by products of activated macrophages and microglia. They all appear to be relevant for multiple sclerosis pathogensis in different patients and at different stages of the disease. However, in MS lesions a major mechanism of axonal and neuronal damage appears to be related to the action of reactive oxygen and nitrogen species, which may induce neuronal injury through impairment of mitochondrial function and subsequent energy failure.
轴突和神经元损伤和丢失对多发性硬化症患者的永久性临床残疾至关重要。轴突损伤在疾病早期就已经发生，并随着疾病的进展而累积。它不仅限于在白质中出现局灶性脱髓鞘病变，还会影响正常的白质和灰质。实验研究表明，许多不同的免疫机制可能导致轴突和神经元损伤，包括特定 T 细胞和自身抗体的抗原特异性破坏，以及由活化的巨噬细胞和小胶质细胞产物引起的损伤。在不同的患者和疾病的不同阶段，它们似乎都与多发性硬化症的发病机制有关。然而，在 MS 病变中，轴突和神经元损伤的一个主要机制似乎与活性氧和氮物种的作用有关，这些物质可能通过损害线粒体功能和随后的能量衰竭来诱导神经元损伤。
