The expression of P-glycoprotein is increased in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model

Neuropathol Appl Neurobiol. 2009 Apr;35(2):147-55. doi: 10.1111/j.1365-2990.2008.00966.x.

Abstract

Aims: We previously reported that the blood-brain barrier (BBB) function was impaired in vessels in the hippocampus in 3-month-old stroke-prone spontaneously hypertensive rats (SHRSP). In this study, we examined gene and protein expressions of P-glycoprotein, a representative efflux transporter of cerebral vessels, in the BBB-damaged hippocampal vessels of SHRSP and in the vessels of Wistar Kyoto (WKY) rats as controls, to clarify roles of the efflux transporter in the BBB-damaged vessels.

Methods: The expression of P-glycoprotein in hippocampal and cortical samples was examined by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunoelectron microscopic techniques.

Results: Real-time RT-PCR and Western blotting analyses revealed that the gene and protein expressions of P-glycoprotein were increased in the hippocampal samples of 3-month-old SHRSP compared with hippocampal samples of 3-month-old WKY rats or with cortical samples of SHRSP. The gene expression of P-glycoprotein was also increased in the hippocampal samples of 4-week-old SHRSP. Immunoelectron microscopic examination revealed that immunosignals of P-glycoprotein were seen in the luminal and ab-luminal cytoplasmic membranes of endothelial cells and the basal lamina, that the labelling density of P-glycoprotein in the vessel wall was higher in the hippocampus of 3-month-old SHRSP than in other groups and that the immunosignals of P-glycoprotein were occasionally co-located with those of albumin.

Conclusions: These findings indicate that the expression of P-glycoprotein is increased in BBB-damaged hippocampal vessels in hypertensive SHRSP compared with those in WKY rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Albumins / metabolism
  • Analysis of Variance
  • Animals
  • Basement Membrane / physiology
  • Blood Pressure
  • Blood-Brain Barrier / physiopathology*
  • Blotting, Western
  • Brain / blood supply*
  • Brain / physiopathology*
  • Disease Models, Animal
  • Endothelial Cells / physiology
  • Gene Expression
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Male
  • Microscopy, Immunoelectron
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stroke / physiopathology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Albumins