title: Blood-brain barrier destruction determines Fisher/Bickerstaff clinical phenotypes: an in vitro study.
abstract: OBJECTIVE
  To ascertain the hypothesis that the phenotypic differences between Bickerstaff's brainstem encephalitis (BBE) and Miller Fisher syndrome (MFS) are derived from the differences in the effects of sera on blood-brain barrier (BBB) and blood-nerve barrier.
  
  
  BACKGROUND
  Antibodies against GQ1b are frequently detected in BBE and MFS, and these two disorders may share the same pathogenesis, but the clinical phenotypes of BBE and MFS are substantially different.
  
  
  METHODS
  The effects of sera obtained from BBE patients, MFS patients and control subjects were evaluated with regard to the expression of tight junction proteins and transendothelial electrical resistance in human brain microvascular endothelial cells (BMECs) and human peripheral nerve microvascular endothelial cells.
  
  
  RESULTS
  The sera obtained from BBE patients decreased the transendothelial electrical resistance values and claudin-5 protein expression in BMECs, although the sera obtained from MFS patients had no effect on BMECs or peripheral nerve microvascular endothelial cells. This effect was reversed after the application of matrix metalloproteinase (MMP) inhibitor, GM6001. The presence or absence of anti-GQ1b antibodies did not significantly influence the results. MMP-9 secreted by BMECs was significantly increased after exposure to the sera obtained from BBE patients, whereas it was not changed after exposure to the sera obtained from MFS patients.
  
  
  CONCLUSIONS
  Only the sera obtained from BBE patients destroyed BBB and it might explain the phenotypical differences between BBE and MFS. BBE sera disrupted BBB, possibly via the autocrine secretion of MMP-9 from BBB-composing endothelial cells.
authors.affiliation: Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1, Minamikogushi, Ube, Yamaguchi 7558505, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Saito
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Shimizu
authors.forename: Michiaki
authors.initials: M
authors.lastname: Koga
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Sano
authors.forename: Ayako
authors.initials: A
authors.lastname: Tasaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Abe
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Haruki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Maeda
authors.forename: Seiko
authors.initials: S
authors.lastname: Suzuki
authors.forename: Susumu
authors.initials: S
authors.lastname: Kusunoki
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanda
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000473:pathology*; D049428:Blood-Nerve Barrier / Q000473:pathology; D015153:Blotting, Western; D002196:Capillaries / Q000473:pathology; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology; D017097:Electric Impedance; D004660:Encephalitis / Q000097:blood / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification; D007202:Indicators and Reagents; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019846:Miller Fisher Syndrome / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011480:Protease Inhibitors / Q000494:pharmacology; D044967:Serum; D019108:Tight Junctions / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D004151:Dipeptides; D007074:Immunoglobulin G; D007202:Indicators and Reagents; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9
keywords: BLOOD-BRAIN BARRIER; GANGLIOSIDE; GUILLAIN-BARRE SYNDROME; NEUROIMMUNOLOGY