IMR Press / FBE / Volume 3 / Issue 1 / DOI: 10.2741/E222

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Inhibiting the Na+/H+ exchanger reduces reperfusion injury: a small animal MRI study
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1 Department of Pediatrics, University of Wisconsin, Madison, WI 53792
2 Department of Neurological Surgery, University of Wisconsin, Madison, WI 53792
3 Department of Medical Physics, University of Wisconsin, Madison, WI 53792
4 Neuroscience Training Program, University of Wisconsin, Madison, WI 53792
5 Waisman Center, University of Wisconsin, Madison, WI 53792

*Author to whom correspondence should be addressed.


Front. Biosci. (Elite Ed) 2011, 3(1), 81–88;
Published: 1 January 2011

We used magnetic resonance imaging (MRI) to assess the efficacy of Na+/H+ exchanger isoform 1 (NHE-1) inhibition following cerebral ischemia. Transient focal cerebral ischemia was induced in wild-type controls (NHE-1+/+), NHE-1 genetic knockdown mice (NHE-1+/-), and NHE-1+/+ mice treated with the selective NHE-1 inhibitor HOE642. Diffusion weighted imaging (DWI) revealed a brain lesion as early as 1 hour following reperfusion and illustrated significant protection in NHE-1+/- mice (16.2 +/- 7.9 mm3 in NHE-1+/- mice vs. 47.5 +/- 16.6 mm3 in NHE-1+/+ mice). Knockdown of NHE-1 showed significantly smaller infarct at 72 hours on T2 imaging (21.2 +/- 12.6 mm3 in NHE-1+/- mice vs. 64.6 +/- 2.5 mm3 in NHE-1+/+ mice). Administration of HOE642 prior to reperfusion or during early reperfusion reduced ischemic damage. Thus, high resolution T2 images can be used for consistent and precise calculation of lesion volumes, while changes of DWI are a sensitive early marker of ischemic injury. The results of this study demonstrate the therapeutic potential for inhibition of NHE-1 in treating cerebral ischemia.

Ionic Homeostasis
Neuronal Death
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