Postoperative intermittent fasting prevents hippocampal oxidative stress and memory deficits in a rat model of chronic cerebral hypoperfusion
Postoperative intermittent fasting prevents hippocampal oxidative stress and memory deficits in a rat model of chronic cerebral hypoperfusion
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DOI：
10.1007/s00394-018-1606-4
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发表时间：
2019-02-01
影响因子：
5
通讯作者：
Zhang, Jun-Jian
中科院分区：
文献类型：
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作者：
Hu, Yuan;Zhang, Miao;Zhang, Jun-Jian
目的卒中后的间歇性禁食(IF)治疗是否能预防其长期有害影响尚不清楚。在此，我们研究了IF对永久性双血管闭塞(2VO)血管性痴呆大鼠模型认知功能障碍的影响及其可能的机制。术后8周采用新型目标再认(NOR)任务和Morris水迷宫(MWM)评估大鼠的认知功能。通过行为学测试，检测大鼠海马丙二醛(MDA)和谷胱甘肽(GSH)含量、超氧化物歧化酶(SOD)活性、抗氧化酶基因表达、炎性蛋白水平和小胶质细胞密度。结果术后IF可显著改善NOR和MWM大鼠的认知功能。认知增强与2VO大鼠海马区PSD95和BDNF水平的保持是平行的。从机制上讲，IF可减轻2VO大鼠海马区的氧化应激，表现为降低了MDA浓度、mRNA和活性氧产生酶烟酰胺腺嘌呤二核苷酸磷酸氧化酶1的蛋白水平。IF处理还保留了GSH水平和SOD活性及其上游调节酶的水平，从而保持了抗氧化能力。此外，术后IF还可抑制2VO大鼠海马神经细胞小胶质细胞的激活和1-磷酸鞘氨醇受体1及炎性细胞因子的升高。结论术后IF可抑制慢性脑缺血所致的神经炎症和氧化应激，从而保护血管性痴呆大鼠的认知功能。
PurposeWhether intermittent fasting (IF) treatment after stroke can prevent its long-term detrimental effects remains unknown. Here, we investigate the effects of postoperative IF on cognitive deficits and its underlying mechanisms in a permanent two-vessel occlusion (2VO) vascular dementia rat model.MethodsRats were subjected to either IF or ad libitum feeding 1week after 2VO surgery. The cognition of rats was assessed using the novel object recognition (NOR) task and Morris water maze (MWM) 8 weeks after surgery. After behavioral testing, hippocampal malondialdehyde (MDA) and glutathione (GSH) concentrations, superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes, inflammatory protein levels, and microglia density were determined.ResultsPostoperative IF significantly ameliorated the cognitive performance of 2VO rats in the NOR and MWM tests. Cognitive enhancement paralleled preservation of the PSD95 and BDNF levels in the 2VO rat hippocampus. Mechanistically, postoperative IF mitigated hippocampal oxidative stress in 2VO rats, as indicated by the reduced MDA concentration and mRNA and the protein levels of the reactive oxygen species-generating enzyme nicotinamide adenine dinucleotide phosphate oxidase 1. IF treatment also preserved the GSH level and SOD activity, as well as the levels of their upstream regulating enzymes, resulting in preserved antioxidative capability. In addition, postoperative IF prevented hippocampal microglial activation and elevation of sphingosine 1-phosphate receptor 1 and inflammatory cytokines in 2VO rats.ConclusionsOur results suggest that postoperative IF suppresses neuroinflammation and oxidative stress induced by chronic cerebral ischemia, thereby preserving cognitive function in a vascular dementia rat model.