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

The objective of this study was to determine the effect of tumor necrosis factor (TNF)-α 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-α and 10 μl131I-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-α. No significant changes were observed in control animals treated with saline. The data suggest that TNF-α promotes the clearance of protein macromolecules from the CSF to the venous blood.