IDENTIFICATION OF A SATURABLE UPTAKE SYSTEM FOR DEOXYRIBONUCLEOSIDES AT THE BLOOD-BRAIN AND BLOOD-CEREBROSPINAL FLUID BARRIERS

Substances can enter the brain either directly across the blood-brain barrier or indirectly across the choroid plexuses and arachnoid membra ne (blood-CSF barrier) into the CSF and then by diffusion into the bra in. Earlier studies have demonstrated a saturable thymidine uptake acr oss the blood-CSF barrier, but not across the blood-brain barrier. In this study transport of [H-3]thymidine across both barriers was measur ed in vivo by means of a bilateral vascular brain perfusion technique in the anaesthetised guinea-pig. This method allows simultaneous and q uantitative measurement of slowly penetrating solutes into both brain and CSF, under controlled conditions of arterial inflow. The results o f the present study carried out over perfusion periods of up to 30 min indicated a progressive uptake of [H-3]thymidine into brain and CSF, which was found to be significantly greater than the transport of D-[C -14]mannitol (a plasma space marker). Furthermore, the addition of 1 m M unlabelled thymidine in the perfusate caused saturation of [H-3]thym idine uptake into both brain and CSF. In conclusion, these findings su ggest that thymidine can cross both the blood-brain and blood-CSF barr iers in the guinea-pig by carrier-mediated transport systems.