Ontogeny of blood-brain barrier permeability to, and cerebrospinal fluid sink action on, [14C]urea

To ascertain the ontogeny of CSF sink action on a small hydrophilic solute, we investigated the rate and extent of uptake of [14C]urea by lateral ventricle choroid plexus (CP), cisternal cerebrospinal fluid (CSF), cerebral cortex, and cerebellum in 0.5- to 4-wk-old etherized nephrectomized rats. Five hours after ip injection, radiourea penetrated the entire H2O of tissue and CSF in 1-wk-old brain; moreover, for animals 1-4 wk old there was a marked inverse relationship between age and magnitude of steady-state [14C]urea space in all regions. However, there was lack of progression (with advancing age) in distribution times to steady state, undoubtedly a reflection of the complexity of maturational factors (CSF secretion, barrier permeability, biphasic changes in cerebral blood flow, etc.) that affect solute penetration into central nervous system. Analysis of [14C]urea uptake curves for various regions at different stages of development (1 vs. 2 wk) revealed half times (slow component) that were significantly greater at 1 wk (1.2-1.4 h) than at 2 wk (0.5-0.8 h). Steady-state concentration gradients for tracer urea, plasma to CP to CSF, indicated negligible molecular sieving of urea by CP 1 wk after birth; however, after the 2nd postnatal wk CSF sink action on urea became manifest due to development of CSF secretion and molecular sieving at the blood-CSF and blood-brain barriers.