Neutrophil-microglia interaction drives reversible motor dysfunction in neuromyelitis optica model induced by subarachnoid AQP4-IgG.

ABSTRACT: Neutrophils and neutrophil extracellular traps (NETs) contribute to early neuromyelitis optica (NMO) histopathology initiated by IgG targeting astrocytic aquaporin-4 water (AQP4) channels. Yet, the mechanisms recruiting neutrophils and their pathogenic roles in disease progression remain unclear. To investigate molecular-cellular events preceding classical complement cascade activation in a mouse NMO model, we continuously infused, via spinal subarachnoid route, a non-complement-activating monoclonal AQP4-IgG. Parenchymal infiltration of netting neutrophils containing C5a ensued with microglial activation and motor impairment, but no blood-brain barrier leakage. Motor impairment and neuronal dysfunction both reversed when AQP4-IgG infusion stopped. Two-photon microscopy and electron-micros

SUBMITTER: Qi F 

PROVIDER: S-EPMC12407706 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature