Development of an in situ mouse brain perfusion model and its application to mdr1a P-glycoprotein-deficient mice

J Cereb Blood Flow Metab. 2000 Feb;20(2):381-6. doi: 10.1097/00004647-200002000-00020.


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 approximately 17 mmol/L and Vmax of 310 mmol x 100 g(-1) x 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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics*
  • ATP-Binding Cassette Transporters / genetics*
  • Anesthetics, Intravenous / pharmacokinetics*
  • Animals
  • Blood-Brain Barrier / genetics*
  • Brain / blood supply*
  • Cerebrovascular Circulation / genetics*
  • Colchicine / pharmacokinetics
  • Diazepam / pharmacokinetics*
  • Glucose / pharmacokinetics
  • Inulin / pharmacokinetics
  • Male
  • Mice
  • Mice, Mutant Strains
  • Perfusion
  • Sucrose / pharmacokinetics


  • ATP Binding Cassette Transporter, Subfamily B
  • ATP-Binding Cassette Transporters
  • Anesthetics, Intravenous
  • Sucrose
  • Inulin
  • multidrug resistance protein 3
  • Glucose
  • Diazepam
  • Colchicine