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Am J Physiol Regul Integr Comp Physiol 279: R148-R151, 2000;
0363-6119/00 $5.00
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Vol. 279, Issue 1, R148-R151, July 2000

Brain-blood permeability: TNF-alpha promotes escape of protein tracer from CSF to blood

Jodi B. Dickstein1, Harvey Moldofsky1, and John B. Hay2

1 Centre for Sleep and Chronobiology, 2 Departments of Immunology and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5T 2S8

The objective of this study was to determine the effect of tumor necrosis factor (TNF)-alpha on the efflux of protein from the central nervous system to blood based on assessing the clearance of radiolabeled albumin from the cerebrospinal fluid (CSF) to blood in rats. 125I-labeled human serum albumin (125I-HSA) was injected into a lateral ventricle, and venous blood was sampled hourly to determine the basal CSF protein clearance into the blood. After this, rats were intraventricularly infused with 10 µl TNF-alpha and 10 µl 131I-HSA (n = 6) or 10 µl saline and 10 µl 131I-HSA (n = 6). Venous blood was sampled hourly for 3 h. 131I-HSA tracer recovery increased threefold in the venous blood and was significantly higher in the spleen, muscles, and skin in animals treated with TNF-alpha . No significant changes were observed in control animals treated with saline. The data suggest that TNF-alpha promotes the clearance of protein macromolecules from the CSF to the venous blood.

tumor necrosis factor-alpha ; cerebrospinal fluid; arachnoid villi





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