Scholarlink

<p>Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by recurrent optic neuritis and myelitis. Blood-brain barrier (BBB) disruption is a key pathological feature of NMOSD, but the role of neutrophil extracellular traps (NETs) in this process remains poorly defined. Serum proteomic profiling in patients with acute NMOSD revealed enrichment of the NET formation pathway. Neutrophils from these patients showed an increased propensity for NETosis, accompanied by elevated myeloperoxidase-DNA complexes, neutrophil elastase-DNA complexes, and cell-free DNA in serum, as well as increased neutrophil elastase-DNA complex levels in cerebrospinal fluid. In a murine NMOSD model, neutrophil depletion, peptidylarginine deiminase 4 inhibition (Cl-amidine), and NET degradation (DNase I) each attenuated astrocyte loss, demyelination, neuroinflammation, and BBB disruption. In vitro, patient-derived NETs downregulated tight junction proteins in bEnd.3 endothelial cells through mechanisms associated with myeloperoxidase and neutrophil elastase, while c-Jun N-terminal kinase inhibition mitigated NET-induced endothelial barrier disruption. Together, these findings suggest that aberrant NETosis may contribute to BBB disruption in acute NMOSD and support further investigation of NET-associated pathways as potential therapeutic targets.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Neutrophil extracellular traps exacerbate blood-brain barrier disruption in neuromyelitis optica spectrum disorder

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月9日

查看全文
  • Xue Ma,
  • Yao Wang,
  • Xin Chen,
  • Zonghao Pan,
  • Yi Li,
  • Kaixi Ren,
  • Daidi Zhao,
  • Hongzeng Li,
  • Jun Guo

摘要

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by recurrent optic neuritis and myelitis. Blood-brain barrier (BBB) disruption is a key pathological feature of NMOSD, but the role of neutrophil extracellular traps (NETs) in this process remains poorly defined. Serum proteomic profiling in patients with acute NMOSD revealed enrichment of the NET formation pathway. Neutrophils from these patients showed an increased propensity for NETosis, accompanied by elevated myeloperoxidase-DNA complexes, neutrophil elastase-DNA complexes, and cell-free DNA in serum, as well as increased neutrophil elastase-DNA complex levels in cerebrospinal fluid. In a murine NMOSD model, neutrophil depletion, peptidylarginine deiminase 4 inhibition (Cl-amidine), and NET degradation (DNase I) each attenuated astrocyte loss, demyelination, neuroinflammation, and BBB disruption. In vitro, patient-derived NETs downregulated tight junction proteins in bEnd.3 endothelial cells through mechanisms associated with myeloperoxidase and neutrophil elastase, while c-Jun N-terminal kinase inhibition mitigated NET-induced endothelial barrier disruption. Together, these findings suggest that aberrant NETosis may contribute to BBB disruption in acute NMOSD and support further investigation of NET-associated pathways as potential therapeutic targets.