Cortical spreading depression impairs oxygen delivery and metabolism in mice

Izumi Yuzawa, Sava Sakadžić, Vivek Srinivasan, Hwa Kyoung Shin, Katharina Eikermann-Haerter, David A. Boas, Cenk Ayata

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Cortical spreading depression (CSD) is associated with severe hypoperfusion in mice. Using minimally invasive multimodal optical imaging, we show that severe flow reductions during and after spreading depression are associated with a steep decline in cerebral metabolic rate of oxygen. Concurrent severe hemoglobin desaturation suggests that the oxygen metabolism becomes at least in part supply limited, and the decrease in cortical blood volume implicates vasoconstriction as the mechanism. In support of oxygen supply-demand mismatch, cortical nicotinamide adenine dinucleotide (NADH) fluorescence increases during spreading depression for at least 5 minutes, particularly away from parenchymal arterioles. However, modeling of tissue oxygen delivery shows that cerebral metabolic rate of oxygen drops more than predicted by a purely supply-limited model, raising the possibility of a concurrent reduction in oxygen demand during spreading depression. Importantly, a subsequent spreading depression triggered within 15 minutes evokes a monophasic flow increase superimposed on the oligemic baseline, which markedly differs from the response to the preceding spreading depression triggered in naive cortex. Altogether, these data suggest that CSD is associated with long-lasting oxygen supply-demand mismatch linked to severe vasoconstriction in mice.

Original languageEnglish (US)
Pages (from-to)376-386
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume32
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Keywords

  • cerebral metabolic rate of oxygen
  • laser speckle flowmetry
  • mouse
  • multispectral reflectance imaging
  • spreading depression

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

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  • Cite this

    Yuzawa, I., Sakadžić, S., Srinivasan, V., Shin, H. K., Eikermann-Haerter, K., Boas, D. A., & Ayata, C. (2012). Cortical spreading depression impairs oxygen delivery and metabolism in mice. Journal of Cerebral Blood Flow and Metabolism, 32(2), 376-386. https://doi.org/10.1038/jcbfm.2011.148