AJP - Endocrinology and Metabolism, Vol 271, Issue 4 E636-E642, Copyright © 1996 by American Physiological Society

ARTICLES

Differential permeability of the BBB in acute EAE: enhanced transport of TNT-alpha

W. Pan, W. A. Banks, M. K. Kennedy, E. G. Gutierrez and A. J. Kastin
Department of Neuroscience, Tulane University School of Medicine, New Orleans, Louisiana, USA.

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 to 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.

This article has been cited by other articles:

				C. Forster, M. Burek, I. A. Romero, B. Weksler, P.-O. Couraud, and D. Drenckhahn Differential effects of hydrocortisone and TNF{alpha} on tight junction proteins in an in vitro model of the human blood-brain barrier J. Physiol., April 1, 2008; 586(7): 1937 - 1949. [Abstract] [Full Text] [PDF]

				J. D. Huber, R. L. VanGilder, and K. A. Houser Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2660 - H2668. [Abstract] [Full Text] [PDF]

				B. Osburg, C. Peiser, D. Domling, L. Schomburg, Y. T. Ko, K. Voigt, and U. Bickel Effect of endotoxin on expression of TNF receptors and transport of TNF-alpha at the blood-brain barrier of the rat Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E899 - E908. [Abstract] [Full Text] [PDF]

				W. Pan, G. Cornelissen, F. Halberg, and A. J. Kastin Functional Genomics of Sleep and Circadian Rhythm: Selected Contribution: Circadian rhythm of tumor necrosis factor-alpha uptake into mouse spinal cord J Appl Physiol, March 1, 2002; 92(3): 1357 - 1362. [Abstract] [Full Text] [PDF]

				W. Pan, A. J. Kastin, R. L. Bell, and R. D. Olson Upregulation of Tumor Necrosis Factor alpha  Transport across the Blood-Brain Barrier after Acute Compressive Spinal Cord Injury J. Neurosci., May 1, 1999; 19(9): 3649 - 3655. [Abstract] [Full Text] [PDF]

				L. Calza, L. Giardino, M. Pozza, C. Bettelli, A. Micera, and L. Aloe Proliferation and phenotype regulation in the subventricular zone during experimental allergic encephalomyelitis: In vivo evidence of a role for nerve growth factor PNAS, March 17, 1998; 95(6): 3209 - 3214. [Abstract] [Full Text] [PDF]