Blood-brain barrier permeability of 11C-labeled alcohols and 15O-labeled water

Abstract

The extraction of 11C-labeled methanol, ethanol, and isopropanol, as well as 15O-labeled water by the brain during a single capillary transit, was studied in vivo in six adult rhesus monkeys by external detection of the time course of these tracers subsequent to their internal carotid artery injection. The data demonstrate the feasibility of accurately measuring brain permeability of highly diffusible substances by this technique and show that neither water nor the alcohols studied freely equilibrate with brain when the cerebral blood flow exceeds 30 ml/100 g min-1. At a cerebral blood flow of 50 ml/100 g min-1 only about 93% of an injected bolus of labeled water freely exchanges with brain, compared with methanol (93%), ethanol (97%), and isopropanol (99%). The brain capillary permeability-surface area (PS) products computed from these data were 0.023 cm3/s g-1 (water), 0.024 cm3/s g-1 (methanol), 0.030 cm3/s g-1 (ethanol), and 0.062 cm3/s g-1 (isopropanol). This sequence of PS products is consistent with the individual lipid solubilities of the alcohols studied and underscores the unique brain permeability characteristics of lipid-insoluble water.

Single‐coil arterial spin‐tagging for estimating cerebral blood flow as viewed from the capillary: Relative contributions of intra‐ and extravascular signal

“…For PS ϭ 2000, which approximates instantaneous blood-tissue equilibration, the tissue population of inverted protons is virtually linear with flow. At PS-products at the low end of the physiological range (that is, below 200 ml/100 g-min), the total inverted population in the tissue approaches an asymptote at high flows, consistent with what is known about water as a diffusionlimited indicator (9,37,38). Even though an asymptote may not be reached, for PS-products of 200 and flows above 100 ml/100 g-min, inverted tissue populations begin to be strongly nonlinear with flow.…”

An Intravenous Technique for the Measurement of Cerebral Vascular Extraction Fraction in the Rat

“…Eichling et al (1974) showed that Ew, measured by external detection methods for I50-water in the rhesus monkey, varied with flow alterations induced by changing PaC02' The PS of water, however, was unaltered by hypocapnia or hypercapnia. In similar experiments, Raichle et al (1976) reproduced the same pattern of Et responses to changes in Paco2 when measuring the extraction fractions of llC-labeled methanol, ethanol, and isopropanol. The method used in their studies is notable in that it measured Et and F independently, but the Et and F values measured at different P aC02 levels defined a constant PS when substituted into Eq.…”

Two-Day Starvation Does Not Alter the Kinetics of Blood-Brain Barrier Transport and Phosphorylation of Glucose in Rat Brain

“…First, we assume that [14C]butanol is freely cleared across the BBB, as suggested by the work of Raichle et al (1976), , and Van Vitert et al (1981). However, Goldman et al (1980) have shown that the extraction of [14C]_ butanol is only 74% in the conscious animal and 88% in the pentobarbital-anesthetized animal, indicating some diffusion limitation to the BBB clearance of butanol.…”