These authors made equal contributions to this work.
Age and energy intake interact to modify cell stress pathways and stroke outcome
Article first published online: 7 JUL 2009
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 67, Issue 1, pages 41–52, January 2010
How to Cite
Arumugam, T. V., Phillips, T. M., Cheng, A., Morrell, C. H., Mattson, M. P. and Wan, R. (2010), Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neurol., 67: 41–52. doi: 10.1002/ana.21798
- Issue published online: 23 FEB 2010
- Article first published online: 7 JUL 2009
- Accepted manuscript online: 7 JUL 2009 12:00AM EST
- Manuscript Accepted: 26 JUN 2009
- Manuscript Revised: 16 JUN 2009
- Manuscript Received: 22 APR 2009
- National Institute on Aging Intramural Research Program
- National Institute of Biomedical Imaging and Bioengineering Intramural Research Program of the National Institutes of Health
Age and excessive energy intake/obesity are risk factors for cerebrovascular disease, but it is not known if and how these factors affect the extent of brain damage and outcome in ischemic stroke. We therefore determined the interactions of age and energy intake on the outcome of ischemic brain injury, and elucidated the underlying mechanisms.
We utilized a novel microchip-based immunoaffinity capillary electrophoresis technology to measure a panel of neurotrophic factors, cytokines, and cellular stress resistance proteins in brain tissue samples from young, middle-aged, and old mice that had been maintained on control or energy-restricted diets prior to middle cerebral artery occlusion and reperfusion.
Mortality from focal ischemic stroke was increased with advancing age and reduced by an intermittent fasting (IF) diet. Brain damage and functional impairment were reduced by IF in young and middle-aged mice, but not in old mice. The basal and poststroke levels of neurotrophic factors (brain-derived neurotrophic factor and basic fibroblast growth factor), protein chaperones (heat shock protein 70 and glucose regulated protein 78), and the antioxidant enzyme heme oxygenase-1 were decreased, whereas levels of inflammatory cytokines were increased in the cerebral cortex and striatum of old mice compared with younger mice. IF coordinately increased levels of protective proteins and decreased inflammatory cytokines in young, but not in old mice.
Reduction in dietary energy intake differentially modulates neurotrophic and inflammatory pathways to protect neurons against ischemic injury, and these beneficial effects of IF are compromised during aging, resulting in increased brain damage and poorer functional outcome. ANN NEUROL 2010;67:41–52