title: Intracortical injection of endothelin-1 induces cortical infarcts in mice: effect of neuronal expression of an adenosine transporter.
abstract: BACKGROUND
  Activation of adenosine A1 receptors has neuroprotective effects in animal stroke models. Adenosine levels are regulated by nucleoside transporters. In vitro studies showed that neuron-specific expression of human equilibrative nucleoside transporter 1 (hENT1) decreases extracellular adenosine levels and adenosine A1 receptor activity. In this study, we tested the effect of hENT1 expression on cortical infarct size following intracerebral injection of the vasoconstrictor endothelin-1 (ET-1) or saline.
  
  
  METHODS
  Mice underwent stereotaxic intracortical injection of ET-1 (1 μl; 400 pmol) or saline (1 μl). Some mice received the adenosine receptor antagonist caffeine (25 mg/kg, intraperitoneal) 30 minutes prior to ET-1. Perfusion and T2-weighted magnetic resonance imaging (MRI) were used to measure cerebral blood flow (CBF) and subsequent infarct size, respectively.
  
  
  RESULTS
  ET-1 reduced CBF at the injection site to 7.3 ± 1.3% (n = 12) in hENT1 transgenic (Tg) and 12.5 ± 2.0% (n = 13) in wild type (Wt) mice. At 48 hours following ET-1 injection, CBF was partially restored to 35.8 ± 4.5% in Tg and to 45.2 ± 6.3% in Wt mice; infarct sizes were significantly greater in Tg (9 ± 1.1 mm3) than Wt (5.4 ± 0.8 mm3) mice. Saline-treated Tg and Wt mice had modest decreases in CBF and infarcts were less than 1 mm3. For mice treated with caffeine, CBF values and infarct sizes were not significantly different between Tg and Wt mice.
  
  
  CONCLUSIONS
  ET-1 produced greater ischemic injury in hENT1 Tg than in Wt mice. This genotype difference was not observed in mice that had received caffeine. These data indicate that hENT1 Tg mice have reduced ischemia-evoked increases in adenosine receptor activity compared to Wt mice.
authors.affiliation: Departments of Pharmacology and Therapeutics, University of Manitoba, A404, 753 McDermot Avenue, Winnipeg, MB, Canada R3E 0 T6.
authors.forename: Hanifi
authors.initials: H
authors.lastname: Soylu
authors.affiliation: Departments of Pharmacology and Therapeutics, University of Manitoba, A404, 753 McDermot Avenue, Winnipeg, MB, Canada R3E 0 T6.
authors.forename: Dali
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Departments of Radiology, University of Manitoba, Winnipeg, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Buist
authors.affiliation: Departments of Pharmacology and Therapeutics, University of Manitoba, A404, 753 McDermot Avenue, Winnipeg, MB, Canada R3E 0 T6.|Departments of Radiology, University of Manitoba, Winnipeg, Canada.|Department of Physics, University of Winnipeg, Winnipeg, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Martin
authors.affiliation: Departments of Pharmacology and Therapeutics, University of Manitoba, A404, 753 McDermot Avenue, Winnipeg, MB, Canada R3E 0 T6.|Division of Neurodegenerative Disorders, St Boniface Hospital Research Centre, Winnipeg, MB, Canada.
authors.forename: Benedict C
authors.initials: BC
authors.lastname: Albensi
authors.affiliation: Departments of Pharmacology and Therapeutics, University of Manitoba, A404, 753 McDermot Avenue, Winnipeg, MB, Canada R3E 0 T6.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Parkinson