From the Neuropathology Unit, Institute of Experimental Neurology (NR, LC, TD, GD, FC, GC, AQ) and Division of Neuroscience (NR, LC, DU, FB, FC, PP, UDC, GC, AQ), IRCCS San Raffaele Scientific Institute; Laboratory of Molecular Neurobiology, Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche Mario Negri (MP, GS, CB); Department of Neurorehabilitation Sciences, Casa Cura Policlinico (MC); and Vita e Salute San Raffaele University (GC), Milan, Italy.
J Neuropathol Exp Neurol. 2014 Jul;73(7):658-70. doi: 10.1097/NEN.0000000000000081.
Growing evidence indicates that alterations within the peripheral nervous system (PNS) are involved at an early stage in the amyotrophic lateral sclerosis (ALS) pathogenetic cascade. In this study, magnetic resonance imaging (MRI), neurophysiologic analyses, and histologic analyses were used to monitor the extent of PNS damage in the hSOD-1 ALS rat model. The imaging signature of the disease was defined using in vivo MRI of the sciatic nerve. Initial abnormalities were detected in the nerves by an increase in T2 relaxation time before the onset of clinical disease; diffusion MRI showed a progressive increase in mean and radial diffusivity and reduction of fractional anisotropy at advanced stages of disease. Histologic analysis demonstrated early impairment of the blood-nerve barrier followed by acute axonal degeneration associated with endoneurial edema and macrophage response in motor nerve compartments. Progressive axonal degeneration and motor nerve fiber loss correlated with MRI and neurophysiologic changes. These functional and morphologic investigations of the PNS might be applied in following disease progression in preclinical therapeutic studies. This study establishes the PNS signature in this rat ALS model (shedding new light into pathogenesis) and provides a rationale for translating into future systematic MRI studies of PNS involvement in patients with ALS.
越来越多的证据表明，在肌萎缩侧索硬化症 (ALS) 的发病级联反应的早期，周围神经系统 (PNS) 内的改变就已经涉及其中。在这项研究中，使用磁共振成像 (MRI)、神经生理分析和组织学分析来监测 hSOD-1 ALS 大鼠模型中 PNS 损伤的程度。通过对坐骨神经的体内 MRI 来定义疾病的成像特征。在临床疾病发作之前，通过 T2 弛豫时间的增加检测到神经中的最初异常；在疾病的晚期，扩散 MRI 显示平均扩散率和径向扩散率逐渐增加，各向异性分数降低。组织学分析表明，血神经屏障早期受损，随后发生急性轴突变性，伴有运动神经间隙的神经内膜水肿和巨噬细胞反应。进行性轴突变性和运动神经纤维丢失与 MRI 和神经生理变化相关。这些对 PNS 的功能和形态学研究可以应用于临床前治疗研究中疾病的进展。本研究在该大鼠 ALS 模型中建立了 PNS 特征（为发病机制提供了新的见解），并为将来对 ALS 患者 PNS 参与的系统 MRI 研究提供了依据。
