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

Experimental & Translational Stroke Medicine

Fiona E Parkinson⁴  Benedict C Albensi²  Melanie Martin¹  Richard Buist³  Dali Zhang⁴  Hanifi Soylu⁴ 

[1] Department of Physics, University of Winnipeg, Winnipeg, Canada;Division of Neurodegenerative Disorders, St Boniface Hospital Research Centre, Winnipeg, MB, Canada;Departments of Radiology, University of Manitoba, Winnipeg, Canada;Departments of Pharmacology and Therapeutics, University of Manitoba, A404, 753 McDermot Avenue, Winnipeg, MB, Canada R3E 0 T6

关键词: Caffeine;    Adenosine;    Magnetic Resonance Imaging;    Mouse;    CD1;    Human Equilibrative Nucleoside Transporter 1;    Endothelin 1;   

Others  :  861946
DOI  :  10.1186/2040-7378-4-4

 received in 2012-01-09, accepted in 2012-03-12,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Soylu et al; licensee BioMed Central Ltd.

【 图 表 】

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