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Accumulation of immunoglobulin across the 'blood-nerve barrier' in spinal roots in adoptive transfer experimental autoimmune neuritis.

Abstract
At the onset of Guillain-Barré syndrome, disruption of diffusion barriers, such as the blood-nerve barrier, probably increases the exposure of spinal roots and peripheral nerves to macromolecules, some of which might be pathogenic. As a measure of such disruption, we measured the accumulation in the endoneurium of spinal roots and sciatic nerve of systemically administered 125I-labelled immunoglobulin in adoptive transfer experimental autoimmune neuritis (AT-EAN) in the rat. AT-EAN is a model of Guillain-Barré syndrome, induced by injection of activated T lymphocytes sensitized to myelin P2 protein. Immunoglobulin accumulation was expressed as counts/min/mg in fixative-perfused roots as a percentage of that in serum, measured 24 h after intraperitoneal injection of 0.1 micro Ci 125I-labelled immunoglobulin. Immunoglobulin accumulation in the roots of normal rats was 3 +/- 1% (mean +/- SE), but this first increased 3(1/2) days after cell injection, peaked at 22 +/- 2% on day 4(1/2), and declined to normal by day 8. T lymphocytes and polymorphonuclear leucocytes first appeared within the endoneurium at day 3(1/2), and macrophages and a few erythrocytes at day 4. Neurological deficit appeared on day 4 and was maximal on day 6. Demyelination and axonal degeneration began at day 5. The first abnormality detected in AT-EAN was a rapid increase in the passage of immunoglobulin into spinal roots, together with endoneurial infiltration of T lymphocytes and polymorphonuclear leucocytes. Accumulation of immunoglobulin was maximal during the worsening of neurological deficit, and declined rapidly before the onset of neurological recovery.
AuthorsR D M Hadden, N A Gregson, R Gold, K J Smith, R A C Hughes
JournalNeuropathology and applied neurobiology (Neuropathol Appl Neurobiol) Vol. 28 Issue 6 Pg. 489-97 (Dec 2002) ISSN: 0305-1846 [Print] England
PMID12445165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Immunoglobulins
Topics
  • Adoptive Transfer
  • Animals
  • Blood-Brain Barrier (immunology)
  • Demyelinating Diseases (pathology)
  • Erythrocytes (immunology, ultrastructure)
  • Female
  • Immunoglobulins (metabolism)
  • Macrophages (immunology, ultrastructure)
  • Nerve Degeneration (pathology)
  • Neuritis, Autoimmune, Experimental (immunology, pathology, physiopathology)
  • Neutrophils (immunology, ultrastructure)
  • Rats
  • Rats, Inbred Lew
  • Sciatic Nerve (immunology, pathology)
  • Spinal Nerve Roots (blood supply, immunology, pathology, ultrastructure)
  • T-Lymphocytes (immunology, ultrastructure)

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