AQP4 and multiple sclerosis: In NMOSD, extensive demyelination and inflammation affect multiple spinal cord segments, accompanied by astrocyte death, axonal loss, perivascular lymphocytic infiltration, and vascular proliferation [9]. AQP4 immunoglobulin G antibodies, the primary pathogenic factor in NMOSD, can cross the blood-brain barrier and bind to AQP4 in astrocyte end-feet, triggering complement recruitment and activation, which leads to complement-dependent cytotoxicity [10]. NMOSD causes more severe clinical symptoms than multiple sclerosis due to the massive inflammation of the spinal cord [11].