Simultaneous microdialysis in brain and blood of the mouse: extracellular and intracellular brain colchicine disposition

Brain Research
P A EvrardJ M Scherrmann

Abstract

A simultaneous brain and blood microdialysis system was developed to study the passage of colchicine through the blood-brain barrier in the mouse. Colchicine was administered as a bolus in the jugular vein (1.5 mg kg-1) and its hippocampal extracellular fluid (ECF) and blood kinetics were determined over a 4 h period using two microdialysis probes, one in the dorsal hippocampus, the other in the inferior vena cava. Colchicine rapidly diffused into the hippocampus (maximum concentration in the first dialysate sample) and brain and blood concentrations declined in parallel, suggesting rapid equilibration between these two compartments. However, only 6. 7% of total blood colchicine, 14% of unbound colchicine was present in the hippocampus suggesting that the P-glycoprotein efflux pump limits colchicine uptake by the brain. We also found, using conventional tissue homogenate analysis in parallel, that the concentration of colchicine in the hippocampal ECF was 10 times less than that in the intracellular space and that the hippocampus colchicine concentration was 2.8 times higher than that of the rest of the brain. This study shows that the simultaneous brain and blood microdialysis can be used to measure the passage of colchicine t...Continue Reading

References

Mar 25, 1992·Analytical Chemistry·S MenacherryJ B Justice
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May 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·R B Goldschmidt, O Steward
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Citations

Jun 14, 2001·Alzheimer Disease and Associated Disorders·P S AisenM Fusco
Dec 4, 2012·Journal of Biomolecular Screening·István SzirákiPéter Krajcsi
Sep 7, 2016·International Journal of Molecular Sciences·Sandeep Vasant MoreDong-Kug Choi
May 18, 2016·Molecular Neurobiology·Chun Min KhoNorazharuddin Shah Abdullah

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