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.
Neurobiology, Institute of Molecular Medicine, University of Southern Denmark Odense C, Denmark.
Nasrin
N
Asgari
Neurobiology, Institute of Molecular Medicine, University of Southern Denmark Odense C, Denmark.
Carsten Tue
CT
Berg
Neurobiology, Institute of Molecular Medicine, University of Southern Denmark Odense C, Denmark.
Marlene Thorsen
MT
Mørch
Neurobiology, Institute of Molecular Medicine, University of Southern Denmark Odense C, Denmark.
Reza
R
Khorooshi
Neurobiology, Institute of Molecular Medicine, University of Southern Denmark Odense C, Denmark.
Trevor
T
Owens