Transport Mechanisms in the Cerebrospinal Fluid System for Removal of Acid Metabolites from Developing Brain

Abstract

Postnatal development of a “blood-brain-barrier” for protecting the central nervous system from fluctuating concentrations of charged lipophobic molecules in blood, parallels the maturation of unique and highly efficient transport mechanisms for the intracranial removal of organic acids^3,4. Prior studies have clearly delineated anatomic barriers called “tight junctions” in brain capillaries which prohibit penetration of proteins having molecular diameters larger than 20 Ź³. The permeability of this same barrier to smaller and more polar molecules has not been determined. Recent observations strongly suggest that homeostatic mechanisms designed to protect the internal milieu of brain may be viewed not only as a membranous barrier for blood-borne molecules based on their size, lipid solubility, and ionization constant, but as a series of selective filtration sites for carrier-mediated transport of watersoluble, polar molecules from the intracranial cavity into the systemic circulation^{13, 17}.