Exchange of inulin and dextran between blood and cerebrospinal fluid

¹ Clinical Pharmacology and Experimental Therapeutics Service, National Cancer Institute; and Section on Theoretical Statistics and Mathematics, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland

C¹⁴-labeled inulin (mol. wt. 5,000) and C¹⁴-labeled dextran (mol. wt. 12,800 and 77,700) were studied for entry rate into CSF and steady state ratio of drug in cerebrospinal fluid (CSF) to drug in plasma, in nephrectomized dogs. For all three of these compounds the entry rates and steady state ratios were very similar. Exit rates of C¹⁴-inulin and C¹⁴-dextran (mol. wt. 77,700) were studied in nephrectomized and nonnephrectomized dogs. The exit rates were rapid and very similar for the two compounds. Acetazolamide increased the steady state ratio and decreased the exit rates significantly. These data suggest the presence of leaks in the blood CSF barrier of at least 60 A in diameter and indicate that bulk flow of CSF from the subarachnoid spaces to the venous system is an important means of exit of substances present in the CSF. Compounds which enter the CSF slowly fail to achieve diffusion equilibrium because of their relatively rapid exit by means of bulk flow.