Loss of blood-brain barrier integrity in the spinal cord is common to experimental allergic encephalomyelitis in knockout mouse models.
Experimental allergic encephalomyelitis (EAE) is an inflammatory demyelinating disease of the CNS that is used to model certain parameters 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 NF-kappaB, TNF-alpha, IFN-alphabeta receptors, IFN-gamma receptors, and inducible nitric oxide synthase. Although increased myelin oligodendrocyte glycoprotein-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. On the other hand, disease severity during the acute phase of EAE directly correlated with the extent of BBB permeability. Thus, the loss of BBB integrity seems to be a requisite event in the development of EAE and can occur in the absence of important inflammatory mediators.
Fabis
Marzena J
MJ
Center for Neurovirology, Department of Cancer Biology, Biotechnology Foundation Laboratories, Thomas Jefferson University, Philadelphia, PA 19107-6799, USA.
Scott
Gwen S
GS
Kean
Rhonda B
RB
Koprowski
Hilary
H
Hooper
D Craig
DC
D000818:Animals; D001812:Blood-Brain Barrier; D049109:Cell Proliferation; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability; D012737:Sex Factors; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology
D007371:Interferon-gamma