title: Metabolically dependent blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis.
abstract: We have studied chronic relapsing experimental allergic encephalomyelitis (CREAE), a model of immune-mediated demyelination, using gadolinium (Gd)-enhanced magnetic resonance imaging in vivo and the blood-brain barrier (BBB) markers, lanthanum nitrate and Gd nitrate, histologically. In regions of the spinal cord showing Gd enhancement, there was evidence for vesicular transport as a mechanism of BBB breakdown in CREAE, shown by an increased number of endothelial vesicles containing lanthanide (lanthanum or Gd, whichever had been perfused) and deposition of tracer in the perivascular space; tight interendothelial junctions remained intact. Prior perfusion with 2,4-dinitrophenol, a metabolic inhibitor, suppressed the appearance of endothelial vesicles containing lanthanide and tracer in the perivascular space. We conclude that an important contribution to BBB breakdown in CREAE is mediated by a metabolic change in the endothelial cells associated with increased vesicular transport.
authors.affiliation: Institute of Neurology, National Hospital, Queen Square, London, UK.
authors.forename: C P
authors.initials: CP
authors.lastname: Hawkins
authors.forename: P M
authors.initials: PM
authors.lastname: Munro
authors.forename: D N
authors.initials: DN
authors.lastname: Landon
authors.forename: W I
authors.initials: WI
authors.lastname: McDonald
mesh_terms: D019297:2,4-Dinitrophenol; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002908:Chronic Disease; D004140:Dinitrophenols / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005682:Gadolinium; D006168:Guinea Pigs; D007811:Lanthanum; D008279:Magnetic Resonance Imaging; D004369:Pentetic Acid; D010477:Perfusion; D010539:Permeability; D012008:Recurrence
chemical_list: D004140:Dinitrophenols; D007811:Lanthanum; D004369:Pentetic Acid; D005682:Gadolinium; D019297:2,4-Dinitrophenol