Clearance of [125I]-tumor necrosis factor-alpha from the brain into the blood after intracerebroventricular injection in rats

Neuroimmunomodulation. Sep-Oct 1998;5(5):261-9. doi: 10.1159/000026346.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood-Brain Barrier
  • Brain / drug effects
  • Brain / metabolism*
  • Injections, Intravenous
  • Injections, Intraventricular
  • Iodine Radioisotopes
  • Lipopolysaccharides / pharmacology
  • Male
  • Metabolic Clearance Rate / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / pharmacokinetics*

Substances

  • Iodine Radioisotopes
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha