Clearance of [125I]-tumor necrosis factor-alpha from the brain into the blood after intracerebroventricular injection in rats.
To test the hypothesis that brain to blood clearance is a mechanism by which brain inflammation and damage can increase circulating acute phase cytokines, rate of transfer of [125I]-tumor necrosis factor-alpha ([125I]-TNF) from brain to blood was determined. Acid precipitable [125I]-TNF appeared in peripheral blood within 5 min of intracerebroventricular (i.c.v.) injection and was cleared from brain to blood following first order kinetics at a fractional rate of 0.01123 +/- 0.0030/min, a value virtually identical with a previously determined clearance rate of [125I]-IL-6. Area under blood concentration curve compared with that after intravenous injection shows that 31.6 +/- 5.8% of the intracerebral dose reached peripheral blood in 4 h. Elevated ratios of superior sagittal sinus to aortic blood radioactivity concentration at 1 and 3 h (1.48 +/- 0. 26, p = 0.042; 1.95 +/- 0.39, p = 0.026, respectively) indicate that TNF-alpha drains from brain at least in part via the sagittal sinus. Escherichia coli lipopolysaccharide i.c.v. injection increased the rate of brain efflux of TNF-alpha.
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Department of Medicine, College of Medicine, University of Arizona, The University of Arizona Health Sciences Center, Tucson, Ariz., USA reichlin@u.arizona.edu
Reichlin
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D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics*
D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha