Sleep Is Critical for Remote Preconditioning-Induced Neuroprotection
Sleep Is Critical for Remote Preconditioning-Induced Neuroprotection
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DOI：
10.5665/sleep.6238
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发表时间：
2016-11-01
期刊：
影响因子：
5.6
通讯作者：
Paul, Ketema N.
中科院分区：
文献类型：
--
作者：
Brager, Allison J.;Yang, Tao;Paul, Ketema N.
研究目标：小鼠短暂肢体缺血（远程预处理）的发作诱导对模型缺血性中风（局灶性脑缺血）的耐受。由于中风结果部分取决于睡眠-觉醒史，我们试图确定睡眠对于肢体缺血的神经保护作用是否至关重要。方法：将脑电图/肌电图记录电极植入小鼠体内。 24 小时基线记录后，通过收紧左侧股四头肌周围的松紧带 10 分钟，然后放松 10 分钟，两个周期诱导肢体缺血。远程预处理两天后，完成第二次 24 小时 EEG/EMG 记录，随后立即对大脑中动脉进行 60 分钟缝合闭塞（模拟缺血性中风）。然后在昼夜节律和睡眠异常模型中重复该实验（Bmal1 敲除 [KO] 小鼠比野生型同窝小鼠多睡 2 小时）。通过活体染料染色确定脑梗塞，并通过训练有素的脑电图/肌电图记录识别来评估睡眠。结果：肢体缺血两天后，野生型小鼠又睡了 2.4 小时。这种额外的睡眠主要包括浅阶段中间的非快速眼动 (NREM) 睡眠（即小睡）。重复该实验，但在肢体缺血后阻止睡眠增加，从而消除了对缺血性中风的耐受性。在 Bmal1 敲除小鼠中，远程预处理不会增加每日睡眠，也不会提供对随后局灶性缺血的耐受性。结论：这些结果表明，远程预处理诱导的睡眠对于其对中风结果的神经保护作用来说既是充分的也是必要的。
Study Objectives: Episodes of brief limb ischemia (remote preconditioning) in mice induce tolerance to modeled ischemic stroke (focal brain ischemia). Since stroke outcomes are in part dependent on sleep-wake history, we sought to determine if sleep is critical for the neuroprotective effect of limb ischemia.Methods: EEG/EMG recording electrodes were implanted in mice. After a 24 h baseline recording, limb ischemia was induced by tightening an elastic band around the left quadriceps for 10 minutes followed by 10 minutes of release for two cycles. Two days following remote preconditioning, a second 24 h EEG/EMG recording was completed and was immediately followed by a 60-minute suture occlusion of the middle cerebral artery (modeled ischemic stroke). This experiment was then repeated in a model of circadian and sleep abnormalities (Bmal1 knockout [KO] mice sleep 2 h more than wild-type littermates). Brain infarction was determined by vital dye staining, and sleep was assessed by trained identification of EEG/EMG recordings.Results: Two days after limb ischemia, wild-type mice slept an additional 2.4 h. This additional sleep was primarily comprised of non-rapid eye movement (NREM) sleep during the middle of the light-phase (i.e., naps). Repeating the experiment but preventing increases in sleep after limb ischemia abolished tolerance to ischemic stroke. In Bmal1 knockout mice, remote preconditioning did not increase daily sleep nor provide tolerance to subsequent focal ischemia.Conclusions: These results suggest that sleep induced by remote preconditioning is both sufficient and necessary for its neuroprotective effects on stroke outcome.