TY - JOUR
T1 - Improved reperfusion and neuroprotection by creatine in a mouse model of stroke
AU - Prass, Konstantin
AU - Royl, Georg
AU - Lindauer, Ute
AU - Freyer, Dorette
AU - Megow, Dirk
AU - Dirnagl, Ulrich
AU - Stöckler-Ipsiroglu, Gerda
AU - Wallimann, Theo
AU - Priller, Josef
PY - 2007/3/14
Y1 - 2007/3/14
N2 - 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.
AB - 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.
KW - Cerebral blood flow
KW - Cerebral ischemia
KW - Creatine
KW - Dietary supplementation
KW - Magnetic resonance imaging
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=33847229764&partnerID=8YFLogxK
U2 - 10.1038/sj.jcbfm.9600351
DO - 10.1038/sj.jcbfm.9600351
M3 - Article
C2 - 16773141
AN - SCOPUS:33847229764
SN - 0271-678X
VL - 27
SP - 452
EP - 459
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 3
ER -