Differential permeability of the bbb in acute eae: enhanced
transport of tnf[alpha].
Pan, Weihong, William A. Banks, Mary K. Kennedy, Enrique G. Gutierrez,
and Abba J. Kastin.
Departments of Neuroscience and Medicine, Tulane University School
of Medicine, and VA Medical Center, New Orleans, LA 70146, and
Department of Immunology, Immunex Research and Development
Corporation, Seattle, Washington, USA
APStracts 3:0109E, 1996.
The impairment of the blood-brain barrier (BBB) in experimental
autoimmune encephalomyelitis (EAE) has been frequently attributed to
disruption without much consideration of saturable transport
processes. In mice with EAE we studied the permeability of the BBB
for radioactively labeled albumin and sucrose, markers of BBB
disruption, and tumor necrosis factor-[alpha] (TNF[alpha]), a
cytokine transported across the BBB by a saturable system and thought
to play a role in the pathogenesis of EAE. Permeation of the BBB was
increased to all three substances during the acutely ill stage, was
greatest in the lumbar spine, and returned to normal with recovery.
The change in BBB permeability to sucrose was greater than to the
larger albumin, and is consistent with a partial disruption of the
BBB. The enhanced permeability to TNF[alpha] was comparable to that
for sucrose even though TNF[alpha] is similar in size to albumin.
This paradoxically high uptake of TNF[alpha] could be explained by an
enhancement of its endogenous saturable transport system. Thus, the
changes in BBB function during EAE extend beyond disruption to
include changes in the saturable transport systems for substances
involved in the disease process.
Received 24 December 1995; accepted in final form 17 May 1996.
APS Manuscript Number E601-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96