The influx of pathogenic aquaporin-4 antibodies (AQP4-Abs) across the blood–spinal cord barrier (BSCB) is crucial for the development and exacerbation of neuromyelitis optica (NMO). We examined whether prophylactic intravenous administration of anti-repulsive guidance molecule-a antibodies (RGMa-Abs) has disease-modifying effects on BSCB dysfunction using an NMO model elicited by peripheral administration of AQP4-Abs to rats. RGMa-Ab treatment attenuated the acute exacerbation of perivascular astrocytopathy in the spinal cord and clinical symptoms, which were highly correlated with neurofilament light chain levels in both the cerebrospinal fluid (CSF) and serum. Additionally, RGMa-Ab treatment suppressed the expression of proinflammatory cytokines/chemokines and the infiltration of inflammatory cells into the spinal cord. CSF analysis of NMO rats revealed that RGMa-Ab treatment improved the CSF/serum albumin ratio and suppressed AQP4-Abs influx. RGMa inhibition using RGMa-Abs is suggested as a potential therapeutic option for BSCB dysfunction associated with NMO.

致病性水通道蛋白 4 抗体 (AQP4-Abs) 穿过血脊髓屏障 (BSCB) 的流入对于视神经脊髓炎 (NMO) 的发生和恶化至关重要。我们使用通过向大鼠外周施用 AQP4-Abs 引发的 NMO 模型，检查了预防性静脉内施用抗排斥引导分子 -a 抗体 (RGMa-Abs) 是否对 BSCB 功能障碍具有疾病缓解作用。 RGMa-Ab 治疗减轻了脊髓血管周围星形细胞病的急性加重和临床症状，这与脑脊液 (CSF) 和血清中的神经丝轻链水平高度相关。此外，RGMa-Ab 治疗抑制促炎细胞因子/趋化因子的表达以及炎症细胞向脊髓的浸润。 NMO 大鼠的 CSF 分析显示，RGMa-Ab 治疗改善了 CSF/血清白蛋白比率并抑制了 AQP4-Ab 流入。建议使用 RGMa-Ab 抑制 RGMa 作为与 NMO 相关的 BSCB 功能障碍的潜在治疗选择。