PT  - JOURNAL ARTICLE
AU  - Morgan, M E
AU  - Singhal, D
AU  - Anderson, B D
TI  - Quantitative assessment of blood-brain barrier damage during microdialysis.
DP  - 1996 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1167--1176
VI  - 277
IP  - 2
4099  - http://jpet.aspetjournals.org/content/277/2/1167.short
4100  - http://jpet.aspetjournals.org/content/277/2/1167.full
SO  - J Pharmacol Exp Ther1996 May 01; 277
AB  - In view of the increasing use of microdialysis for monitoring drug uptake into the brain, the consequences of tissue/blood-brain barrier (BBB) damage that occurs on microdialysis probe insertion on the extent and rate of solute uptake need to be more carefully examined. In this study, both microdialysis and a classic method were used to compare the apparent brain uptake of two polar permeants, [3H]sucrose and [14C]urea. The blood-to-brain transfer constants of these compounds differ significantly, with the value of urea exceeding that of sucrose by a factor of approximately 20 when compared by the classic one-point-per-animal method. The BBB selectivity to these nonmetabolized permeants as assessed by microdialysis provides a sensitive measure of the integrity of the BBB to polar nonelectrolytes within the molecular size range of most drugs. The following evidence for blood-brain barrier damage during microdialysis sampling was obtained: (1) the loss of [3H]sucrose from the extracellular fluid in brain on termination of an intravenous infusion is biphasic, with the initial phase evident immediately on termination by the infusion, suggesting that a fraction of the microdialysis probe resides in a region in rapid equilibrium with plasma; (2) complete loss of selectivity in the rate constants for CNS entry of sucrose vs. urea and (3) there were substantially higher area under the concentration vs. time curve AUCECF/AUCplasma ratios for both sucrose and urea generated by microdialysis than the corresponding ratios (AUCCSF/AUCplasma or AUCbrain/AUCplasma) obtained by classic methods. These results suggest that the BBB to small molecule transport likely remains compromised for some time after microdialysis probe insertion.