Selection of Experimental Conditions for the Accurate Determination of Blood-Brain Transfer Constants from Single-Time Experiments: A Theoretical Analysis

Reliable blood–brain transfer constants can be determined from data obtained in single-time experiments (i.e., a single experimental time for tissue sampling). The accuracy of such measurements depends on factors such as the test molecule used and the experimental time chosen; therefore, the selecti...

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Bibliographic Details
Published in:Journal of cerebral blood flow and metabolism 1983-06, Vol.3 (2), p.215-225
Main Authors: Blasberg, Ronald G., Patlak, Clifford S., Fenstermacher, Joseph D.
Format: Article
Language:English
Subjects:
Aminoisobutyric Acids - metabolism
Animals
Biological Transport
Blood-Brain Barrier
Capillary Permeability
Models, Biological
Pentetic Acid - metabolism
Research Design
Tissue Distribution
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Summary:Reliable blood–brain transfer constants can be determined from data obtained in single-time experiments (i.e., a single experimental time for tissue sampling). The accuracy of such measurements depends on factors such as the test molecule used and the experimental time chosen; therefore, the selection of optimal experimental conditions is important. In this presentation, a model of transport across the blood–brain barrier (BBB) was developed and used to determine appropriate experimental protocols for single-time experiments. Transfer numbers derived from published data with α-aminoisobutyric acid (AIB; a compound of low BBB permeability that is readily taken up by brain cells) and diethylenetriaminepentaacetic acid (DTPA; a compound of very low BBB permeability that is not taken up by brain cells) were inserted into the model and apparent blood-to-brain transfer constants (K1) were obtained. In addition, the two basic sets of transfer numbers were altered to mimic various experimental and pathological changes in blood–brain transport. The results of this analysis indicate that moderate to large transfer rates across the BBB (0.01–1.0 ml g−1 min−1) are more easily and reliably measured by AIB-like compounds. In contrast, compounds like DTPA are better test-molecules for measuring small changes in the BBB transfer rate (0.0001–0.001 ml g−1 min−1), provided an appropriate experimental time is chosen.
ISSN:0271-678X
1559-7016
DOI:10.1038/jcbfm.1983.29