Cerebrospinal fluid aquaporin‐4‐immunoglobulin G disrupts blood brain barrier

To clarify the significance of immunoglobulin G autoantibody specific for the astrocyte water channel aquaporin‐4 in cerebrospinal fluid, aquaporin‐4‐immunoglobulin G from a neuromyelitis optica patient was administered intrathecally to naïve mice, and the distribution and pathogenic impact was evaluated. A distinct distribution pattern of aquaporin‐4‐immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition. Perivascular astrocyte‐destructive lesions were associated with blood‐borne horseradish peroxidase leakage indicating blood‐brain barrier breakdown. The cerebrospinal fluid aquaporin‐4‐immunoglobulin G therefore distributes widely in brain to initiate astrocytopathy and blood‐brain barrier breakdown.