KINETIC-ANALYSIS OF 5-HYDROXYINDOLEACETIC ACID EXCRETION FROM RAT-BRAIN AND CSF

  • 1 January 1976
    • journal article
    • research article
    • Vol. 11  (2) , 125-157
Abstract
A systematic investigation of the distribution of 14C-5-hydroxyindoleacetic acid (5HIAA) and 3H-inulin after intraventricular injection in rats was initiated. The amount of injected 14C-5HIAA recovered from brain homogenates decreased approximately linearly with the injection volume. The missing radioactivity could not be accounted for by needle-hole leakage or by rapid transport of injectate to the bloodstream. 14C-5HIAA and 3H-inulin rapidly appeared in cristernal fluid after injection due to bulk flow. As cisternal fluid is partially lost during brain dissection, this accounts for the low recovery of isotopes reported by previous investigators. Visual confirmation of this was obtained with .gamma. scintigraphic studies of the distribution of Tc99m-albumin after intraventricular injection using a micropinhole collimator which allows for detailed anatomic analysis of ventriculo-cisternal flow patterns. Mathematical methods based on a double-label isotope injection technique were developed which accounted for all of the intraventricular injected 14C-5HIAA and permitted calculation of the amount of the isotope in brain and total CSF of the rat after injection. A kinetic model was developed using a computer-stimulation technique which allows for the simultaneous analysis of the rate of change of labeled 5HIAA in several compartments based on equilibrium exchange, saturable active transport bulk flow and transient perturbations in the ventricular system resulting from the volume of the injectate. Using this program a physiologic model for 5HIAA compartmentation and transport was developed. Lumbar 5HIAA levels apparently do not accurately reflect brain 5HIAA content. On blocking active transport in a simulated probenecid test, the predicted 5HIAA buildups in brain, ventricles and extraventricular spaces were similar to actual values obtained by numerous investigators. The 5HIAA buildup in brain was secondary to the effects of probenecid on ventricular active transport and did not support the claim that there was direct transport of 5HIAA from brain to blood. The implications of these findings for the study of base line lumbar 5HIAA levels or probenecid-induced 5HIAA accumulations in neuropsychiatric patients were discussed.