Folate transport in the central nervous system

Methyltetrahydrofolic acid or folic acid was infused intravenously at a constant rate into conscious untreated or methotrexate-pretreated rabbits. After 150 min, at equivalent plasma concentrations, folic acid or methyltetrahydrofolic acid readily entered the cerebrospinal fluid and probably brain by a saturable transport system. In contrast, after intraventricular injections, folic acid but not methyltetrahydrofolic acid was cleared from cerebrospinal fluid to blood by a saturable system. Intraventribular injection of folic acid at concentrations that saturated folic acid clearance from cerebrospinal fluid did not affect the transport of methyltetrahydrofolic acid from blood into cerebrospinal fluid. These results suggest that the transport system for mehtyltetrahydrofolic acid, which is about half-saturated at normal plasma concentrations, helps maintain the cerebrospinal fluid and probably brain methyltetrahydrofolic acid concentrations within relatively narrow limits. Moreover, folic acid, which the brain cannot utilize, is transported from cerebrospinal fluid. A possible locus for the systems that transport folic acid from and methyltetrahydrofolic acid into the cerebrospinal fluid is the choroid plexus.