Cortical spreading depression causes and coincides with tissue hypoxia

Nat Neurosci. 2007 Jun;10(6):754-62. doi: 10.1038/nn1902. Epub 2007 Apr 29.


Cortical spreading depression (CSD) is a self-propagating wave of cellular depolarization that has been implicated in migraine and in progressive neuronal injury after stroke and head trauma. Using two-photon microscopic NADH imaging and oxygen sensor microelectrodes in live mouse cortex, we find that CSD is linked to severe hypoxia and marked neuronal swelling that can last up to several minutes. Changes in dendritic structures and loss of spines during CSD are comparable to those during anoxic depolarization. Increasing O2 availability shortens the duration of CSD and improves local redox state. Our results indicate that tissue hypoxia associated with CSD is caused by a transient increase in O2 demand exceeding vascular O2 supply.

Publication types

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

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Brain Edema / etiology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Cerebrovascular Circulation
  • Cortical Spreading Depression / drug effects
  • Cortical Spreading Depression / physiology*
  • Diagnostic Imaging
  • Electroencephalography / methods
  • Female
  • Hypoxia / pathology*
  • Hypoxia / physiopathology*
  • Laser-Doppler Flowmetry / methods
  • Luminescent Proteins / biosynthesis
  • Male
  • Membrane Potentials / physiology
  • Mice
  • Mice, Transgenic
  • NAD
  • Neurons / metabolism
  • Oxygen / metabolism
  • Oxygen / pharmacology
  • Patch-Clamp Techniques


  • Luminescent Proteins
  • NAD
  • Oxygen