Description |
Transport and permeability properties of the blood-cerebrospinal fluid and blood-brain barriers were determined by kinetic analysis of radioisotope uptake from the plasma into the central nervous system of adult and infant rats. For adult rats (5 wk of age), 36CI and 22Na uptake into the lateral ventricle (LVCP) and fourth ventricle (4VCP) choroid plexuses were resolved into two components, a fast component (t,½ 0.02-0.05 h) which represents isotope distribution within the extracellular and residual erythrocyte compartments and a slow component (t ½ 0.85-1.93 h) representing isotope movement into the epithelial cell compartment. Calculated LVCP and 4VCPcell [CI], 67 mmol/kg cell HO, were 3.9x greater than that predicted for passive distribution by the membrane potential. It is postulated that CI is actively transported into the choroid ependymal cell across the basolateral membrane; the energy for active CI transport may be the Na electrochemical potential gradient which is twice that of the CI electrochemical potential difference. 36CI and 22Na uptake into the cerebrospinal fluid (CSF) were resolved into two components, a fast component (t ½ 0.18 h, fractional volume 0.24) and a slow component (t ½ 1.2 h, fractional volume 0.76). Evidence suggests that the fast component represents isotope movement across the blood-CSF barrier, i.e., the choroid plexuses. The slow component may reflect isotope exchange primarily from brain extracellular fluid into the CSF. Cerebral cortex and cerebellum uptake of 36CI and 22 Na were resolved into two components. The fast component (t ½ 0.02-0.05 h, fractional volume 0.04-0.08) Is comprised of the vascular compartment and a small perivascular space. The slow component (t ½ 1.1-1.7 h, fractional volume 0.92-0.96) represents isotope movement across the blood-brain barrier into the brain extracellular and cellular compartments. The extracellular fluid volume of the cerebral cortex and cerebellum was estimated as ~13% from the initial slope of the brain space versus CSF space curve. Like the choroid plexuses, the glial cell compartment of the brain would appear to actively accumulate CI from 2-6x that predicted for passive distribution. The relative permeability of the blood-CSF and blood-brain barriers to 36CI, 22Na, and 3H-mannitol was determined by calculating permeability surface-area products (PA). Analysis of the PA values for all three isotopes indicates that the effective permeability of the choroidal epithelium (blood-CSF barrier) is significantly greater than that of the cerebral cortex or cerebellum capillary endothelium (blood-brain barrier). Analysis of radioisotope uptake by the 1- and 2-wk rat central nervous system revealed significant maturational differences from that of the 5-wk rat. The calculated LVCPand 4VCP cell [CI] and [Na] were markedly greater in the 1-wk than in the 5-wk rat. Likewise, a significant CSF fast component was not observed for radioisotope uptake at 1 wk of age. It is postulated that while the immature choroid plexus can actively accumulate CI across the basolateral membrane of the cell, the mechanisms which regulate CI exit from the choroidal cell into the CSF have not fully developed. Thus, at 1 wk, epithelial cell [CI] and [Na] were substantially greater than at 2 or 5 wk because ion transport into the choroidal cell across the basolateral membrane was not coupled with ion movement from the cell into the CSF. The onset of choroid plexus fluid secretion {~2 wk), as indicated by the volume of the CSF fast component, corresponds in time to the decrease in choroid plexus cell [CI] and [Na] (1-2 wk). Lastly, the cerebral cortex and cerebellum PA for all three radioisotopes decreased significantly between 1 and 5 wk of age (barrier tightening) while the CSF (fast component) PA to 36CI and 22Na increased with age (transepithelial choroid plexus NaCI transport). |