Given Katherine S, Acker Elizabeth G, Macklin Wendy B, Carlin Dan, Owens Gregory P, Bennett Jeffrey L
Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Acta Neuropathol Commun. 2025 Jun 12;13(1):129. doi: 10.1186/s40478-025-02019-7.
Cumulative disability in neuromyelitis optica spectrum disorder (NMOSD) results from incomplete recovery following inflammatory, demyelinating attacks. Retrospective case studies and current clinical practice indicate that rapid treatment of acute attacks with apheresis limits injury and improves recovery. We evaluated the effects of apheresis and complement inhibition on lesion progression and recovery in a murine ex vivo cerebellar explant model of NMOSD injury. While both strategies reduced lesion formation relative to vehicle treatment, we observed that anti-C5 complement inhibition with eculizumab rapidly halted astrocyte destruction and immediately curtailed lesion extension; whereas an experimental mimic of immunoadsorption (IA), allowed for continued low level astrocyte destruction. During lesion recovery, C5 complement inhibition resulted in a faster rate of oligodendrocyte repopulation and improved myelin repair compared to IA. Complement inhibition may offer multiple benefits for the treatment of acute NMOSD attacks.
视神经脊髓炎谱系障碍（NMOSD）中的累积残疾是由炎症性脱髓鞘发作后恢复不完全所致。回顾性病例研究和当前临床实践表明，采用血液分离术对急性发作进行快速治疗可限制损伤并改善恢复情况。我们在NMOSD损伤的小鼠离体小脑外植体模型中评估了血液分离术和补体抑制对病变进展和恢复的影响。虽然相对于载体治疗，这两种策略均减少了病变形成，但我们观察到，使用依库珠单抗进行抗C5补体抑制可迅速阻止星形胶质细胞破坏并立即减少病变扩展；而免疫吸附（IA）的实验模拟则允许持续的低水平星形胶质细胞破坏。在病变恢复期间，与IA相比，C5补体抑制导致少突胶质细胞再填充速度更快且髓鞘修复得到改善。补体抑制可能为急性NMOSD发作的治疗带来多种益处。
