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Blood-brain barrier permeability changes during acute allergic encephalomyelitis induced in the guinea pig
Authors:B. V. Zlokovic  D. S. Skundric  M. B. Segal  J. Colover  R. M. Jankov  N. Pejnovic  V. Lackovic  J. Mackic  M. N. Lipovac  H. Davson  E. Kasp  D. Dumonde  Lj. Rakic
Affiliation:(1) Institutes of Physiology, Pathophysiology, and Histology, Medical Faculty, University of Belgrade, Belgrade, Yugoslavia;(2) Sherrington School of Physiology and Department of Immunology, St. Thomas's Hospital, London, England;(3) Department of Chemistry, University of Science, Belgrade, Yugoslavia;(4) Military Medical Academy, Belgrade, Yugoslavia;(5) Clinical Center, University of Belgrade, Belgrade, Yugoslavia
Abstract:Blood-brain barrier permeability to homologous serum125I-IgG and to D-[3H]mannitol was studied by means of the brain vascular perfusion method in guinea pigs with experimental allergic encephalomyelitis (EAE). EAE was induced with homologous myelin basic protein (MBP) after pretreatment with foreign protein and muramyl dipeptide (MDP). The results suggest a significant comparable increase in IgG blood-to-brain clearance in the parietal cortex, hippocampus, and caudate nucleus, during vascular perfusion of the brains of animals, after 7 and 20 days of EAE. On the other hand, unidirectional transfer of mannitol in the same period of EAE was markedly augmented only in the hippocampus, but no significant changes in the parietal cortex or caudate nucleus were observed. Cerebrospinal fluid (CSF)/serum ratios for IgG and albumin were both significantly increased, suggesting an increase in blood-CSF barrier permeability, but more for albumin than for IgG. The results were confirmed by immunohistochemical determination of the IgG deposits in the brains of EAE animals, during vascular perfusion with unlabeled homologous IgG. An important role of the blood-brain barrier for the central nervous system immunoglobulin homeostasis during EAE is suggested.
Keywords:experimental allergic encephalomyelitis (EAE)  blood-brain barrier  guinea pig  immunoglobulin G
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