QUANTIFICATION OF EFFLUX INTO THE BLOOD AND BRAIN OF INTRAVENTRICULARLY PERFUSED [H-3] THYMIDINE IN THE ANESTHETIZED RABBIT

Studies using choroid plexuses incubated in vitro have led to the conc lusion that pyrimidine deoxyribonucleosides, such as thymidine, enter the brain predominantly through the blood-cerebrospinal fluid (CSF) ba rrier across the choroid plexuses. In order to examine this hypothesis , ventriculocisternal perfusions were carried out to determine the mag nitude of the passage of [H-3]thymidine from the CSF into the brain an d blood. These experiments demonstrated that approximately 50 % of the [H-3]thymidine was eliminated from the CSF perfusate, some 41.6 +/- 5 .6 % passing into the blood and only 7.6 +/- 0.6 % to the brain. Efflu x into both the blood and brain was saturable, with a K-m of 17.8 mu M and a V-max of 0.47 nM min(-1), and partially nitrobenzylthioinosine (NBMPR) sensitive. However, a non-saturable component did exist (K-d, 13.8 mu l min(-1)). Overall, the rapid removal of [H-3]thymidine from the CSF and its low uptake from the CSF into the brain suggests that t he choroid plexuses would be an inefficient pathway for the entry of t his pyrimidine deoxyribonucleoside into the brain.