Improved reperfusion and neuroprotection by creatine in a mouse model of stroke

Konstantin Prass, Georg Royl, Ute Lindauer, Dorette Freyer, Dirk Megow, Ulrich Dirnagl, Gerda Stöckler-Ipsiroglu, Theo Wallimann, Josef Priller

Research output: Contribution to journalArticlepeer-review

Abstract

Stroke leads to energy failure and subsequent neuronal cell loss. Creatine and phosphocreatine constitute a cellular energy buffering and transport system, and dietary creatine supplementation was shown to protect neurons in several models of neurodegeneration. Although creatine has recently been found to reduce infarct size after cerebral ischemia in mice, the mechanisms of neuroprotection remained unclear. We provide evidence for augmented cerebral blood flow (CBF) after stroke in creatine-treated mice using a magnetic resonance imaging (MRI)-based technique of CBF measurement (flow-sensitive alternating inversion recovery-MRI). Moreover, improved vasodilatory responses were detected in isolated middle cerebral arteries obtained from creatine-treated animals. After 3 weeks of dietary creatine supplementation, minor changes in brain creatine, phosphocreatine, adenosine triphosphate, adenosine diphosphate and adenosine monophosphate levels were detected, which did not reach statistical significance. However, we found a 40% reduction in infarct volume after transient focal cerebral ischemia. Our data suggest that creatine-mediated neuroprotection can occur independent of changes in the bioenergetic status of brain tissue, but may involve improved cerebrovascular function.

Original languageEnglish
Pages (from-to)452-9
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue number3
DOIs
Publication statusPublished - Mar 2007

Keywords

  • Adenosine Triphosphate
  • Animals
  • Brain
  • Brain Ischemia
  • Cerebrovascular Circulation
  • Creatine
  • Disease Models, Animal
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Phosphocreatine
  • Journal Article
  • Research Support, Non-U.S. Gov't

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