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- W2022356885 abstract "Neuromyelitis optica (NMO) is a chronic demyelinating autoimmune disease that particularly affects the optic nerves and spinal cord. In most patients an autoantibody directed against the water channel aquaporin 4 (AQP4) is found, leading to complement-mediated astrocyte destruction. AQP4 is highly expressed on the astrocytic end feet that form, together with the endothelial cells, pericytes and the basal lamina, the blood brain barrier (BBB). The close interaction of these components, which is necessary for maintaining the integrity of the BBB, is still poorly understood. In this study we investigated the time course and structural correlates of BBB-damage in a model of NMO and the impact of astrocyte loss on the breakdown and restoration of the BBB. Using an in vivo model of focal NMO in rats based on injection of a recombinant human anti-AQP4 antibody and complement, we found a prominent opening of the BBB to endogenous albumin, immunoglobulin G and fibrinogen and the exogenous marker molecules FITC-albumin and Texas Red Cadaverine at early stages (6 h) of lesion development. The extravasation of these molecules was on protein level accompanied by the loss of the tight junction (TJ) molecule occludin from the blood vessels in the lesions, while the TJ molecules claudin5 and claudin3 were largely preserved. On mRNA level a compensatory upregulation of these TJ molecules was observed at the same time. Interestingly, the BBB integrity was rapidly restored (within 24 h), although astrocyte loss was highest at this time point and occludin was still lacking from the lesion, thus indicating compensatory mechanisms at the BBB independent of astrocyte signaling. In conclusion, there is a prominent breakdown of the BBB in early stages of experimental NMO associated with loss of astrocytes and tight junction molecules. Several hours later, the BBB is restored again, even though astrocytes are still absent from the lesion." @default.
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- W2022356885 date "2014-10-01" @default.
- W2022356885 modified "2023-09-22" @default.
- W2022356885 title "Early breakdown of the blood–brain barrier in a model of neuromyelitis optica" @default.
- W2022356885 doi "https://doi.org/10.1016/j.jneuroim.2014.08.094" @default.
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