Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA.
Ann Neurol. 2010 Jan;67(1):41-52. doi: 10.1002/ana.21798.
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.
年龄和能量摄入过多/肥胖是脑血管疾病的危险因素，但尚不清楚这些因素是否以及如何影响缺血性中风的脑损伤程度和结果。因此，我们确定了年龄和能量摄入对缺血性脑损伤结果的相互作用，并阐明了潜在的机制。
我们利用一种新型基于微芯片的免疫亲和毛细管电泳技术，测量了从小鼠大脑中动脉闭塞和再灌注前接受对照或能量限制饮食的年轻、中年和老年小鼠的脑组织样本中的一系列神经营养因子、细胞因子和细胞应激抗性蛋白。
局灶性缺血性中风的死亡率随着年龄的增长而增加，间歇性禁食（IF）饮食则降低了死亡率。IF 降低了年轻和中年小鼠的脑损伤和功能障碍，但对老年小鼠没有影响。与年轻小鼠相比，老年小鼠大脑皮质和纹状体中的神经营养因子（脑源性神经营养因子和碱性成纤维细胞生长因子）、蛋白伴侣（热休克蛋白 70 和葡萄糖调节蛋白 78）和抗氧化酶血红素加氧酶-1的基础水平和中风后水平降低，而炎症细胞因子的水平升高。IF 可协调增加年轻小鼠的保护蛋白水平并降低炎症细胞因子水平，但不能增加老年小鼠的水平。
减少饮食能量摄入可不同程度地调节神经营养和炎症途径，从而保护神经元免受缺血性损伤，而 IF 的这些有益作用在衰老过程中受到损害，导致脑损伤增加和功能预后较差。
