Article

Age and energy intake interact to modify cell stress pathways and stroke outcome.

Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA.
Annals of Neurology (impact factor: 11.09). 07/2009; 67(1):41-52. DOI:10.1002/ana.21798 pp.41-52
Source: PubMed

ABSTRACT 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.

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Keywords

antioxidant enzyme heme oxygenase-1
 
brain damage
 
brain tissue samples
 
brain-derived neurotrophic factor
 
cellular stress resistance proteins
 
cerebral cortex
 
cerebrovascular disease
 
dietary energy intake differentially modulates neurotrophic
 
energy intake
 
excessive energy intake/obesity
 
focal ischemic stroke
 
heat shock protein 70
 
inflammatory cytokines
 
ischemic brain injury
 
ischemic stroke
 
middle cerebral artery occlusion
 
poorer functional outcome
 
poststroke levels
 
protective proteins
 
protein chaperones