In VivoNADH Fluorescence Imaging Indicates Effect of Aquaporin-4 Deletion on Oxygen Microdistribution in Cortical Spreading Depression

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.