1. ¹Department of Experimental Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany
2. ²Department of Neonatology and General Pediatrics, University Hospital of Vienna, Vienna, Austria
3. ³Institute of Cell Biology, ETH-Hönggerberg, Zurich, Switzerland
4. ⁴Laboratory of Molecular Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany

Correspondence: Dr J Priller, Departments of Psychiatry and Experimental Neurology, Charité Universitätsmedizin Berlin, Schumannstrasse 20/21, D-10117 Berlin, Germany. E-mail: josef.priller@charite.de

⁵These authors contributed equally to this work.

Received 29 January 2006; Revised 24 April 2006; Accepted 10 May 2006; Published online 14 June 2006.

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.