In vivo NADH fluorescence imaging indicates effect of aquaporin-4 deletion on oxygen microdistribution in cortical spreading depression

1] Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA [2] Centre for Molecular Biology and Neuroscience, Letten Centre, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway [3] Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism (Impact Factor: 5.41). 04/2013; 33(7). DOI: 10.1038/jcbfm.2013.63
Source: PubMed


Using in vivo two-photon imaging, we show that mice deficient in aquaporin-4 (AQP4) display increased fluorescence of nicotinamide adenine dinucleotide (NADH) when subjected to cortical spreading depression. The increased NADH signal, a proxy of tissue hypoxia, was restricted to microwatershed areas remote from the vasculature. Aqp4 deletion had no effects on the hyperemia response, but slowed [K(+)]o recovery. These observations suggest that K(+) uptake is suppressed in Aqp4(-/-) mice as a consequence of decreased oxygen delivery to tissue located furthest away from the vascular source of oxygen, although increased oxygen consumption may also contribute to our observations.Journal of Cerebral Blood Flow & Metabolism advance online publication, 24 April 2013; doi:10.1038/jcbfm.2013.63.

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Available from: Alexander S Thrane, Sep 16, 2014
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    • "It is now understood that polarity of astrocytes and neurons is critical to their normal function and that loss of polarity plays a role in a number of diseases. Pioneering research on astrocytic membrane transporters and channels has revealed that aquaporin-4 (AQP4) and Kir4.1 potassium channels are concentrated in astrocytic membranes abutting blood vessels (Amiry-Moghaddam and Ottersen, 2003; Nagelhus et al., 1999; Nielsen et al., 1997) and demonstrated their roles in brain extracellular water and K + homeostasis (Amiry-Moghaddam et al., 2003; Haj-Yasein et al., 2011; Thrane et al., 2013) (Fig. 1C). We recently showed that loss of astrocyte polarity occurs in AD, epilepsy and stroke (Alvestad et al., 2013; Eid et al., 2005; Frydenlund et al., 2006; Heuser et al., 2012; Yang et al., 2011). "
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