Prophylactic Creatine Administration Mediates Neuroprotection in Cerebral Ischemia in Mice
Open Access
- 30 June 2004
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 24 (26), 5909-5912
- https://doi.org/10.1523/jneurosci.1278-04.2004
Abstract
Creatine mediates remarkable neuroprotection in experimental models of amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and traumatic brain injury. Because caspase-mediated pathways are shared functional mechanistic components in these diseases, as well as in ischemia, we evaluated the effect of creatine supplementation on an experimental stroke model. Oral creatine administration resulted in a remarkable reduction in ischemic brain infarction and neuroprotection after cerebral ischemia in mice. Postischemic caspase-3 activation and cytochromecrelease were significantly reduced in creatine-treated mice. Creatine administration buffered ischemia-mediated cerebral ATP depletion. These data provide the first direct correlation between the preservation of bioenergetic cellular status and the inhibition of activation of caspase cell-death pathwaysin vivo. An alternative explanation to our findings is that creatine is neuroprotective through other mechanisms that are independent of mitochondrial cell-death pathways, and therefore postischemic ATP preservation is the result of tissue spearing. Given its safety record, creatine might be considered as a novel therapeutic agent for inhibition of ischemic brain injury in humans. Prophylactic creatine supplementation, similar to what is recommended for an agent such as aspirin, may be considered for patients in high stroke-risk categories.This publication has 26 references indexed in Scilit:
- Apoptosis and Caspases in Neurodegenerative DiseasesThe New England Journal of Medicine, 2003
- Additive neuroprotective effects of minocycline with creatine in a mouse model of ALSAnnals of Neurology, 2003
- Protective effects of oral creatine supplementation on spinal cord injury in ratsSpinal Cord, 2002
- BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemiaProceedings of the National Academy of Sciences of the United States of America, 2001
- Amyotrophic Lateral SclerosisThe New England Journal of Medicine, 2001
- Protective Effect of the Energy Precursor Creatine Against Toxicity of Glutamate and β‐Amyloid in Rat Hippocampal NeuronsJournal of Neurochemistry, 2000
- Creatine and Cyclocreatine Attenuate MPTP NeurotoxicityExperimental Neurology, 1999
- Attenuation of Transient Focal Cerebral Ischemic Injury in Transgenic Mice Expressing a Mutant ICE Inhibitory ProteinJournal of Cerebral Blood Flow & Metabolism, 1997
- Expression of a Dominant Negative Mutant of Interleukin-1β Converting Enzyme in Transgenic Mice Prevents Neuronal Cell Death Induced by Trophic Factor Withdrawal and Ischemic Brain InjuryThe Journal of Experimental Medicine, 1997
- Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemiaNeuron, 1994