Elsevier

Neuroscience Letters

Volume 411, Issue 1, 3 January 2007, Pages 1-5
Neuroscience Letters

Decreased blood–brain barrier permeability to fluorescein in streptozotocin-treated rats

https://doi.org/10.1016/j.neulet.2006.09.010Get rights and content

Abstract

Investigations of the blood–brain barrier (BBB) in diabetes have yielded contradictory results. It is possible that diabetes differentially affects paracellular and transcellular permeabilities via modulation of tight junction and transport proteins, respectively. Fluorescein (FL), a marker for paracellular permeability, is a substrate for the transport proteins organic anion transporter (OAT)-3 and multidrug resistance protein (MRP)-2 at the BBB. Furthermore, MRP-2-mediated efflux of FL can be upregulated by glucose. In this study, streptozotocin-induced diabetes led to decreased brain distribution of FL measured by in situ brain perfusion, consistent with activation of an efflux transport system for FL at the BBB. This change was paralleled by increased protein expression of MRP-2, but not OAT-3, in cerebral microvessels. These data indicate that diabetes may lead to changes in efflux transporters at the BBB and have implications for delivery of therapeutics to the central nervous system.

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Acknowledgement

This work was supported by NIDDK grant DK065003 to R.D.E.

References (41)

  • W. Loscher et al.

    Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases

    Prog. Neurobiol.

    (2005)
  • A.T. Nies et al.

    Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain

    Neuroscience

    (2004)
  • E.E. Robertson et al.

    Human renal organic anion transporters: characteristics and contributions to drug and drug metabolite excretion

    Pharmacol. Ther.

    (2006)
  • A. Soontornmalai et al.

    Differential, strain-specific cellular and subcellular distribution of multidrug transporters in murine choroid plexus and blood–brain barrier

    Neuroscience

    (2006)
  • D.H. Sweet et al.

    Impaired organic anion transport in kidney and choroid plexus of organic anion transporter 3 (Oat3 (Slc22a8)) knockout mice

    J. Biol. Chem.

    (2002)
  • B. Bauer et al.

    Modulation of p-glycoprotein transport function at the blood–brain barrier

    Exp. Biol. Med. (Maywood)

    (2005)
  • R.G. Blasberg et al.

    Transport of alpha-aminoisobutyric acid across brain capillary and cellular membranes

    J. Cereb. Blood Flow Metab.

    (1983)
  • M.W. Bradbury et al.

    Permeability of blood–brain and blood–nerve barriers in experimental diabetes mellitus in the anaesthetized rat

    Exp. Physiol.

    (1991)
  • J.M. Chehade et al.

    Diabetes-related changes in rat cerebral occludin and zonula occludens-1 (ZO-1) expression

    Neurochem. Res.

    (2002)
  • S. Dallas et al.

    Multidrug resistance-associated proteins: expression and function in the central nervous system

    Pharmacol. Rev.

    (2006)
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