Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke

Intermittent fasting is previously reported to exhibit neuroprotection against experimental ischemic stroke. However, the detailed understanding of protection mechanisms are lacking. By observing the overall transcriptomic changes in each timepoint of ischemic stroke would benefit the understanding of underlying active pathways and mechanisms. Here, we conduct experimental MCAO ischemic stroke on mice exposed to different daily intermittent fasting method to compare not only among the ischemic stroke timepoints but also the efficacy of different intermittent fasting interventions. Our current study presented the transcriptomic changes for the first time in specific timepoints of ischemic stroke as well as under the condition of intermittent fasting. A number of neuroprotective mechanisms-related genes were significantly affected by intermittent fasting conditions in differential manners. Overall design: After 4 months of exposure to daily 12 or 16 h of intermittent fasting, mice were conducted with MCAO for 1 h to induce experimental ischemic stroke on single hemisphere of the brain. Mid-coronal section of ipsilateral cerebrum was dissected after 1 h of ischemia, or at 3, 12, 24, and 72 h after initiation of reperfusion. Total RNA was extracted from collected brain tissue samples and mRNA sequencing was conducted using Illumina HiSeq 4000 system.既往研究表明，间歇性禁食(intermittent fasting)对实验性缺血性脑卒中(ischemic stroke)具有神经保护(neuroprotection)作用，但目前对其具体保护机制仍缺乏深入认知。通过解析缺血性脑卒中各时间点的整体转录组(transcriptome)变化，有助于深入理解其潜在的激活通路与分子机制。本研究对接受不同每日间歇性禁食方案的小鼠构建实验性大脑中动脉闭塞(middle cerebral artery occlusion, MCAO)缺血性脑卒中模型，不仅可对比缺血性脑卒中的不同时间点特征，还能评估不同间歇性禁食干预的保护效力。本研究首次报道了缺血性脑卒中特定时间点以及间歇性禁食干预条件下的转录组变化特征。大量与神经保护机制相关的基因在不同间歇性禁食条件下呈现出显著的差异表达模式。 研究设计：将小鼠每日暴露于12小时或16小时的间歇性禁食环境中，持续4个月后，通过大脑中动脉闭塞1小时构建单侧大脑半球实验性缺血性脑卒中模型。分别在缺血1小时后，以及再灌注开始后的3、12、24和72小时，取同侧大脑的中冠状切片组织。收集脑组织样本后提取总RNA(total RNA)，采用Illumina HiSeq 4000系统进行mRNA测序(messenger RNA sequencing)。