Development of an In Situ Mouse Brain Perfusion Model and its Application to mdr1a P-Glycoprotein-Deficient Mice
C Dagenais, C Rousselle, GM Pollack… - Journal of Cerebral …, 2000 - journals.sagepub.com
C Dagenais, C Rousselle, GM Pollack, JM Scherrmann
Journal of Cerebral Blood Flow & Metabolism, 2000•journals.sagepub.comAn in situ mouse brain perfusion model predictive of passive and carrier-mediated transport
across the blood-brain barrier (BBB) was developed and applied to mdr1a P-glycoprotein
(Pgp)-deficient mice [mdr1a (−/−)]. Cerebral flow was estimated from diazepam uptake.
Physical integrity of the BBB was assessed with sucrose/inulin spaces; functional integrity
was assessed with glucose uptake, which was saturable with a K m of∼ 17 mmol/L and V
max of 310 mmol· 100 g− 1· min− 1. Brain uptake of a Pgp substrate (colchicine) was …
across the blood-brain barrier (BBB) was developed and applied to mdr1a P-glycoprotein
(Pgp)-deficient mice [mdr1a (−/−)]. Cerebral flow was estimated from diazepam uptake.
Physical integrity of the BBB was assessed with sucrose/inulin spaces; functional integrity
was assessed with glucose uptake, which was saturable with a K m of∼ 17 mmol/L and V
max of 310 mmol· 100 g− 1· min− 1. Brain uptake of a Pgp substrate (colchicine) was …
An in situ mouse brain perfusion model predictive of passive and carrier-mediated transport across the blood-brain barrier (BBB) was developed and applied to mdr1a P-glycoprotein (Pgp)-deficient mice [mdr1a(−/−)]. Cerebral flow was estimated from diazepam uptake. Physical integrity of the BBB was assessed with sucrose/inulin spaces; functional integrity was assessed with glucose uptake, which was saturable with a Km of ∼17 mmol/L and Vmax of 310 mmol · 100 g−1 · min−1. Brain uptake of a Pgp substrate (colchicine) was significantly enhanced (two- to fourfold) in mdr1a(−/−) mice. These data suggest that the model is applicable to elucidating the effects of efflux transporters, including Pgp, on brain uptake.
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