Cortical spreading depression causes and coincides with tissue hypoxia.
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.
Takano
Takahiro
T
Center for Aging and Developmental Biology, Department of Neurosurgery, University of Rochester Medical Center, 601 Elmwood Avenue, Box 645, Rochester, New York 14642, USA. takahiro_takano@urmc.rochester.edu
Tian
Guo-Feng
GF
Peng
Weiguo
W
Lou
Nanhong
N
Lovatt
Ditte
D
Hansen
Anker J
AJ
Kasischke
Karl A
KA
Nedergaard
Maiken
M
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D003952:Diagnostic Imaging; D004569:Electroencephalography / Q000379:methods; D005260:Female; D000860:Hypoxia / Q000473:pathology* / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008164:Luminescent Proteins / Q000096:biosynthesis; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009243:NAD; D009474:Neurons / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D018408:Patch-Clamp Techniques
D008164:Luminescent Proteins; D009243:NAD; D010100:Oxygen