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

J Cereb Blood Flow Metab. 2013 Jul;33(7):996-9. doi: 10.1038/jcbfm.2013.63. Epub 2013 Apr 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4 / genetics
  • Aquaporin 4 / physiology*
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology
  • Cortical Spreading Depression / drug effects
  • Cortical Spreading Depression / genetics
  • Cortical Spreading Depression / physiology*
  • Female
  • Gene Deletion
  • Hypoxia, Brain / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence, Multiphoton / methods*
  • Models, Biological
  • NAD / chemistry
  • NAD / metabolism*
  • Oxygen / metabolism*
  • Oxygen Consumption / physiology
  • Potassium Chloride / metabolism
  • Potassium Chloride / pharmacology


  • Aqp4 protein, mouse
  • Aquaporin 4
  • NAD
  • Potassium Chloride
  • Oxygen