AJP - Regulatory, Integrative and Comparative Physiology, Vol 232, Issue 3 73-R79, Copyright © 1977 by American Physiological Society
Model for transport in the central nervous system
R. Spector, A. Z. Spector and S. R. Snodgrass
A pharmacokinetic model relating the flux of substances between blood, the
compartment consisting of the cerebrospinal fluid (CSF)-extracellular space
(ECS) of brain, and brain was developed. Transport equations for diffusion,
active transport, and bulk flow of CSF between these three compartments
were postulated, and kinetic constants were experimentally obtained. The
appropriate differential equations were solved on a digital computer to
predict concentrations in CSF and brain as a function of the plasma
concentration. The ability of the model to predict correctly CSF and brain
concentrations of ascorbic acid and mannitol with only knowledge of the
plasma concentrations in both steady-state and nonsteady-state conditions
was experimentally tested in rabbits. Ascorbic acid was chosen as a model
substance that is actively transported into the CSF-ECS of brain and also
into brain cells whereas mannitol enters CSF and brain by diffusion. The
model made accurate predictions when the assumptions were not violated.
Second, the model showed that the experimentally determined
Michaelis-Menten transport constant (KT = 0.8 mg=dl-1) for ascorbate
transport from blood into the CSF-ECS of brain optimizes ascorbate
homeostasis in brain.
