title: Improved reperfusion and neuroprotection by creatine in a mouse model of stroke.
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.
authors.affiliation: Department of Experimental Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Prass
authors.forename: Georg
authors.initials: G
authors.lastname: Royl
authors.forename: Ute
authors.initials: U
authors.lastname: Lindauer
authors.forename: Dorette
authors.initials: D
authors.lastname: Freyer
authors.forename: Dirk
authors.initials: D
authors.lastname: Megow
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.forename: Gerda
authors.initials: G
authors.lastname: Stöckler-Ipsiroglu
authors.forename: Theo
authors.initials: T
authors.lastname: Wallimann
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003401:Creatine / Q000378:metabolism*; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D010725:Phosphocreatine / Q000378:metabolism
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003401:Creatine