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Intracortical injection of endothelin-1 induces cortical infarcts in mice: Effect of neuronal expression of an adenosine transporter

Experimental and Translational Stroke Medicine · Mart 2012

Makale Bilgileri

DergiExperimental and Translational Stroke Medicine
Yayın TarihiMart 2012
Cilt / Sayfa4
Erişim🔓 Açık Erişim
Özet Background: Activation of adenosine A 1 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 A 1 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 T 2-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 mm 3) than Wt (5.4 ± 0.8 mm 3) mice. Saline-treated Tg and Wt mice had modest decreases in CBF and infarcts were less than 1 mm 3. 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. © 2012 Soylu et al; licensee BioMed Central Ltd.

Yazarlar (6)

1
Hanifi Soylu
2
Dali Zhang
3
Richard Buist
4
Melanie Martin
5
Benedict C. Albensi
6
Fiona E. Parkinson

Anahtar Kelimeler

Adenosine Caffeine Cd1 Endothelin 1 Human equilibrative nucleoside transporter 1 Magnetic resonance imaging Mouse

Kurumlar

Hôpital St-Boniface
Winnipeg Canada
The University of Winnipeg
Winnipeg Canada
University of Manitoba
Winnipeg Canada

Metrikler

13
Atıf
6
Yazar
7
Anahtar Kelime