Age and energy intake interact to modify cell stress pathways and stroke outcome.
Age and energy intake interact to modify cell stress pathways and stroke outcome.
复制标题
DOI：
10.1002/ana.21798
复制
发表时间：
2010-01
影响因子：
11.2
通讯作者：
Wan, Ruiqian
中科院分区：
文献类型：
--
作者：
Arumugam, Thiruma V.;Phillips, Terry M.;Cheng, Aiwu;Morrell, Christopher H.;Mattson, Mark P.;Wan, Ruiqian
年龄和过量能量摄入/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卒中的脑损伤程度和结局。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。我们利用一种新的基于微芯片的免疫亲和毛细管电泳技术来测量一组神经营养因子，细胞因子和细胞应激抵抗蛋白质的脑组织样本，从年轻，中年和老年小鼠，已保持控制或能量限制饮食之前，大脑中动脉闭塞和再灌注（I/R）。局灶性缺血性卒中的死亡率随着年龄的增长而增加，间歇性禁食（IF）饮食可降低死亡率。IF可以减轻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，老年小鼠大脑皮层和纹状体中神经营养因子（BDNF和bFGF）、蛋白伴侣（HSP 70和GRP 78）和抗氧化酶HO-1的基础和卒中后水平降低，而炎症细胞因子水平升高。IF协调地增加年轻小鼠的保护性蛋白水平并减少炎性细胞因子，但在老年小鼠中则不然。饮食能量摄入的减少差异调节神经营养和炎症途径，以保护神经元免受缺血性损伤，并且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结果变差。
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.
登录
查看更多内容
DOI：
10.1097/00004647-199607000-00006
发表时间：
1996-07-01
影响因子：
6.3
作者：
Chen, J;Graham, SH;Simon, RP
通讯作者：
Simon, RP
DOI：
10.1073/pnas.0536856100
发表时间：
2003-03-04
影响因子：
11.1
作者：
Duan, WZ;Guo, ZH;Mattson, MP
通讯作者：
Mattson, MP
影响因子：
8.3
作者：
Lee, SH;Kim, M;Seo, JS
通讯作者：
Seo, JS
影响因子：
8.3
作者：
Bethel, A;Kirsch, JR;Traystman, RJ
通讯作者：
Traystman, RJ
影响因子：
11.2
作者：
Cheng, Y;Gidday, JM;Holtzman, DM
通讯作者：
Holtzman, DM