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 age and old mice that had been maintained on control or energy restricted diets prior to middle cerebral artery occlusion and reperfusion (I/R).
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 age mice, but not in old mice. The basal and post-stroke levels of neurotrophic factors (BDNF and bFGF), protein chaperones (HSP70 and GRP78) and the antioxidant enzyme HO-1 were decreased, while levels of inflammatory cytokines were increased in the cerebral cortex and striatum of old mice compared to younger mice. IF coordinately increased levels of protective proteins and decreases 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.