Complement inhibition rapidly blocks lesion extension and facilitates remyelination in neuromyelitis optica.

IF 6.2 2区医学 Q1 NEUROSCIENCES

Acta Neuropathologica Communications Pub Date : 2025-06-12 DOI:10.1186/s40478-025-02019-7

Katherine S Given, Elizabeth G Acker, Wendy B Macklin, Dan Carlin, Gregory P Owens, Jeffrey L Bennett

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Abstract

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.

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补体抑制迅速阻断病变扩展，促进视神经脊髓炎的髓鞘再生。

神经脊髓炎视谱障碍（NMOSD）的累积性残疾是由于炎症、脱髓鞘攻击后的不完全恢复。回顾性病例研究和目前的临床实践表明，快速治疗急性发作与采血限制伤害和提高恢复。我们在小鼠离体小脑NMOSD损伤模型中评估了分离和补体抑制对病变进展和恢复的影响。虽然这两种策略相对于载体治疗都减少了病变的形成，但我们观察到eculizumab的抗c5补体抑制迅速阻止了星形胶质细胞的破坏，并立即减少了病变的扩展；而实验模拟免疫吸附（IA），允许持续低水平的星形胶质细胞破坏。在病变恢复过程中，与IA相比，C5补体抑制导致少突胶质细胞再生速度更快，髓鞘修复改善。补体抑制可能为治疗急性NMOSD发作提供多种益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Neuropathologica Communications Medicine-Pathology and Forensic Medicine

CiteScore

11.20

自引率

2.80%

发文量

162

审稿时长

8 weeks

期刊介绍： "Acta Neuropathologica Communications (ANC)" is a peer-reviewed journal that specializes in the rapid publication of research articles focused on the mechanisms underlying neurological diseases. The journal emphasizes the use of molecular, cellular, and morphological techniques applied to experimental or human tissues to investigate the pathogenesis of neurological disorders. ANC is committed to a fast-track publication process, aiming to publish accepted manuscripts within two months of submission. This expedited timeline is designed to ensure that the latest findings in neuroscience and pathology are disseminated quickly to the scientific community, fostering rapid advancements in the field of neurology and neuroscience. The journal's focus on cutting-edge research and its swift publication schedule make it a valuable resource for researchers, clinicians, and other professionals interested in the study and treatment of neurological conditions.