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The loss of blood‐brain barrier integrity as an essential event in the development of experimental allergic encephalomyelitis
Author(s) -
Fabis Marzena J,
Scott Gwen S,
Kean Rhonda B,
Koprowski Hilary,
Hooper Douglas C
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.467
Subject(s) - multiple sclerosis , encephalomyelitis , experimental autoimmune encephalomyelitis , immunology , blood–brain barrier , central nervous system , inflammation , medicine , pathogenesis , spinal cord , immune system , tumor necrosis factor alpha , pathology , psychiatry
Experimental allergic encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS) that is widely employed as an animal model of multiple sclerosis. To establish the relative contributions of T cell reactivity, the loss of blood‐brain barrier (BBB) integrity, CNS inflammation, and lesion formation toward the pathogenesis of EAE we assessed the incidence of EAE and these parameters in mice lacking nuclear factor‐kappa B, tumor necrosis factor alpha, interferon alpha beta receptors, interferon gamma receptors, and inducible nitric oxide synthase. Increased MOG‐specific T cell reactivity was generally associated with a more rapid onset or increased disease severity. The loss of BBB integrity and cell accumulation in spinal cord tissues was invariably associated with the development of neurological disease signs. Histological and real time RT‐PCR analyses revealed differences in the nature of immune/inflammatory cell accumulation in the spinal cord tissues of the different mouse strains. Disease severity during the acute phase of EAE directly correlated with the extent of BBB permeability. Thus, the loss of BBB integrity appears to be a requisite event in the development of EAE and can occur in the absence of important inflammatory mediators. This research was supported by a grant from the National Multiple Sclerosis Society.