Kinetic analysis of [36Cl]-, [22Na]- and [3H]mannitol uptake into the in vivo choroid plexus-cerebrospinal fluid brain system: ontogeny of the blood brain and blood-CSF barriers

Abstract

The kinetics of penetration of radioactive [36Cl]-, [22Na]- and [3H]mannitol into the choroid plexus-CSF brain system was investigated in 1-week, 2-week and adult Sprague-Dawley rats. For adult rats (5 weeks), 36Cl and 22Na uptake by the choroid plexus of lateral ventricle (LVCP) and fourth ventricle (4VCP) resolved into a fast component (t1/2 0.02 - 0.05 h) representing isotope distribution within the extracellular and residual erythrocyte compartments, and a slow component (t1/2 0.8 - 1.9 h) representing isotope movement into the epithelial cell compartment. From steady-state distribution data, choroid cell [Cl] in both LVCP and 4VCP was calculated to be 67 mmol/kg cell H2O, a level nearly 4 times greater than that predicted by the membrane potential for passive distribution. In 1-week immature rats cell [Cl] and [Na] in the choroid plexuses were even greater than the corresponding levels in adults, probably because ion transport across the basolateral membrane is not yet coupled with ion movement from cell to CSF. In mature rats the 36Cl and 22Na uptake into the CSF resolved into 2 components (t1/2 0.18 h, fractional volume 0.24 and t1/2 1.2 h, fractional volume 0.76); however, the fast component of CSF uptake, which likely represents isotope movement across the choroid plexuses, was negligible in the 1-week animals. Permeability-surface area products (PA) were determined for the blood-CSF barrier (i.e. the choroid plexuses) as well as the blood-brain barrier (cerebral cortex and cerebellum). The PA values for 36Cl and 22Na as determined by the fast component of CSF uptake (choroid plexus secretion?) were an order of magnitude less in the 1-week rats than in adults. In contrast, the effective permeability of the blood-CSF barrier as well as the blood-brain barrier, as evaluated by changes in PA of [3H]mannitol, decreased steadily with advancing age.