Our data suggest that the pathogenic antibodies can induce the typical astrocytopathy with loss of AQP4 and GFAP, and mobilize neutrophils especially at AQP4 abundant lesion edge in dose dependent manner, resulting in early lesion expansion of NMO lesion with tissue vacuolation, secondary demyelination and axonal injury. Here, AQP4 is linked to neuromyelitis optica.