McGavern D B, Murray P D, Rivera-Quiñones C, Schmelzer J D, Low P A, Rodriguez M
Molecular Neuroscience Program, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Brain. 2000 Mar;123 Pt 3(Pt 3):519-31. doi: 10.1093/brain/123.3.519.
Recent pathological studies have re-emphasized that axonal injury is present in patients with multiple sclerosis, the most common demyelinating disease of the CNS in humans. However, the temporal profile of demyelination and axonal loss in multiple sclerosis patients and their independent contributions to clinical and electrophysiological abnormalities are not completely understood. In this study, we used the Theiler's murine encephalomyelitis virus model of progressive CNS inflammatory demyelination to demonstrate that demyelination in the spinal cord is followed by a loss of medium to large myelinated fibres. By measuring spinal cord areas, motor-evoked potentials, and motor coordination and balance, we determined that axonal loss following demyelination was associated with electrophysiological abnormalities and correlated strongly with reduced motor coordination and spinal cord atrophy. These findings demonstrate that axonal loss can follow primary, immune-mediated demyelination in the CNS and that the severity of axonal loss correlates almost perfectly with the degree of spinal cord atrophy and neurological deficits.
最近的病理学研究再次强调，轴突损伤存在于多发性硬化症患者中，多发性硬化症是人类中枢神经系统最常见的脱髓鞘疾病。然而，多发性硬化症患者脱髓鞘和轴突损失的时间特征及其对临床和电生理异常的独立作用尚未完全明确。在本研究中，我们使用进行性中枢神经系统炎性脱髓鞘的泰勒氏鼠脑脊髓炎病毒模型，证明脊髓脱髓鞘后会出现中到大有髓纤维的损失。通过测量脊髓面积、运动诱发电位以及运动协调和平衡能力，我们确定脱髓鞘后的轴突损失与电生理异常有关，并且与运动协调性降低和脊髓萎缩密切相关。这些发现表明，中枢神经系统原发性免疫介导的脱髓鞘后会出现轴突损失，并且轴突损失的严重程度与脊髓萎缩程度和神经功能缺损几乎完全相关。
