Brain and Mind Research Institute, Nerve Research Foundation, The University of Sydney, Camperdown, NSW, Australia.
J Peripher Nerv Syst. 2011 Mar;16(1):15-23. doi: 10.1111/j.1529-8027.2011.00323.x.
Early pathological studies in patients with acute and chronic inflammatory demyelinating neuropathies, and the animal model experimental autoimmune neuritis (EAN) showed similarities in the process of demyelination. These studies focused on compact myelin proteins and peptides as targets of immune attack in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and EAN. However, serological studies in patients with subsets of GBS highlighted the importance of gangliosides - glycolipids enriched in non-compact Schwann cell regions and the node, paranodal, and internodal axolemma. In the acute motor axonal neuropathy (AMAN) rabbit model, antibodies to the ganglioside GM1 bind in the nodal region, impair Na channel clustering and disturb Schwann cell/axon organisation. Schwann cell neurobiological studies now highlight the importance of adhesion molecules, including neurofascins, gliomedin, contactins, and NrCAM to Schwann cell/axon integrity. Changes to nodal fine structure by immune responses against such molecules may provide a mechanism for reversible conduction failure or block. Recovery of patients with CIDP or multifocal motor neuropathy (MMN) following treatment may sometimes be better explained by reversal of conduction failure than remyelination or regeneration. This review considers the importance of the intricate molecular arrangements at the nodal and paranodal regions in inflammatory neuropathies such as CIDP. Early images of compact myelin stripping and phagocytosis, may have diverted the research focus away from these vital non-compact myelin Schwann cell areas.
早期对急性和慢性炎症性脱髓鞘性神经病患者的病理学研究，以及实验性自身免疫性神经炎（EAN）动物模型研究表明，脱髓鞘过程存在相似性。这些研究集中在髓鞘紧密蛋白和肽上，它们是吉兰-巴雷综合征（GBS）、慢性炎症性脱髓鞘性多发性神经病（CIDP）和 EAN 中免疫攻击的靶点。然而，GBS 亚组患者的血清学研究强调了神经节苷脂的重要性——富含非致密施万细胞区和结、结旁和结间轴膜的糖脂。在急性运动轴索性神经病（AMAN）兔模型中，针对神经节苷脂 GM1 的抗体结合在结区，损害 Na 通道聚集并扰乱施万细胞/轴突的组织。施万细胞神经生物学研究现在强调了黏附分子的重要性，包括神经束蛋白、神经胶质蛋白、接触蛋白和 NrCAM 对施万细胞/轴突完整性的重要性。针对这些分子的免疫反应引起的结区精细结构变化可能为可逆性传导失败或阻滞提供一种机制。CIDP 或多灶性运动神经病（MMN）患者在治疗后恢复，其原因可能更多地是由于传导失败的逆转，而不是髓鞘的再形成或再生。这篇综述考虑了在 CIDP 等炎症性神经病中，结和结旁区复杂分子排列的重要性。早期关于髓鞘紧密结构剥离和吞噬的图像可能使研究重点偏离了这些重要的非致密髓鞘施万细胞区域。
