[Disruption of the blood-brain barrier in inflammatory neurological diseases]

The blood-brain barrier (BBB) restricts the exchange of humoral factors and cells between the blood and brain and thus plays a crucial role in maintaining cerebral homeostasis. Disruption of the BBB has been considered the initial key step of the disease process in some inflammatory neurological diseases, including multiple sclerosis (MS), neuromyelitis optica (NMO), and neuropsychiatric systemic lupus erythematosus (NPSLE). In MS, the BBB may be impaired before the formation of demyelinating foci or T-cell infiltration around small vessels; however, once the BBB is disrupted, massive infiltration of T cells, augmented expression of adhesion molecules on the endothelial cell surface, and leakage of inflammatory cytokines and antibodies aggravate the MS lesions. Recently, the disease-specific and pathogenic autoantibody "anti-AQP4" was detected in the sera of NMO patients. Thus, the destruction of the BBB is an important step in the development of NMO because the circulating anti-AQP4 antibodies have to pass through the BBB to reach the astrocytic endfeet, where AQP4 is localized. Several studies have shown an association between anti-NR2 antibodies in the serum or cerebrospinal fluid of NPSLE patients and neuropsychological manifestations. These antibodies may be involved in the pathogenesis of NPSLE, and the leaky BBB that allows the intrusion of circulating anti-NR2 antibodies is considered to play a crucial role in the disease process. Although some medications, including glucocorticoids and type 1 interferons, are known to repair the integrity of the BBB in an additive manner, the development of a novel disease-specific therapy, which focuses on repairing the integrity of the BBB, is awaited.