Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Department of Neurology, Miller School of Medicine at the University of Miami, Miami, Florida, USA.
Headache. 2022 May;62(5):577-587. doi: 10.1111/head.14300. Epub 2022 Apr 25.
The objective of this study is to characterize the effects of the sleep-wake cycle on neurovascular and behavioral characteristics of cortical spreading depression (CSD).
There is an important bi-directional relationship between migraine and the sleep-wake cycle, but the basic mechanisms of this relationship are poorly understood.
We have developed a minimally invasive microchip system to continuously monitor cerebral blood volume (CBV) with optical intrinsic signal (OIS), head movement, and multiple other physiological and behavioral parameters in freely behaving mice over weeks. Behavior is also monitored with simultaneous video recording. This system can also be used to intermittently trigger and record CSD and accompanying neurovascular and behavioral responses. CSD was triggered optically in different stages of the sleep-wake cycle.
The optical stimulus threshold to trigger CSD was significantly higher in the wake state compared to sleep (stimulation duration = 16.4 ± 9.7 s vs. 10.8 ± 5.8 s, p = 0.037, n = 6 mice). CSD evoked in the wake versus sleep state produced changes in CBV that were smaller (largest relative change -4.5 ± 5.0% ∆OIS vs. -14.3 ± 8.5% ∆OIS, p = 0.001) and shorter in duration (33:22 ± 6:37 vs. 49:42 ± 8:05 min:s, p = 0.012, n = 6 mice). The threshold for CSD and kinetics of associated CBV changes were correlated with the time since falling asleep or awakening (n = 47 CSDs in 6 mice). CSD triggered in the wake state was associated with a transient freezing behavior. CSD triggered during sleep typically caused a transient awakening and behavioral response. This was followed by a return to sleep until recovery from the sustained phase of decreased CBV that occurred 30-60 min later, at which time there was consistent awakening with behaviors similar to those that occurred at CSD onset. CSD triggered in the wake state evoked a transient decrease in heart rate (from 11.9 ± 0.8 to 9.6 ± 0.8 Hz, p = 0.002, n = 5), whereas when triggered in the sleep state there was a transient increase in HR (from 7.5 ± 0.4 Hz to 9.3 ± 1.1 Hz, p = 0.016, n = 5).
The sleep-wake cycle has significant effects on CSD that may have relevance to the clinical presentations of migraine and brain injury.
本研究旨在描述睡眠-觉醒周期对皮质扩散性抑制（CSD）的神经血管和行为特征的影响。
偏头痛与睡眠-觉醒周期之间存在着重要的双向关系，但这种关系的基本机制尚不清楚。
我们开发了一种微创微芯片系统，可通过光固有信号（OIS）连续监测自由活动小鼠数周内的脑血容量（CBV）、头部运动和其他多种生理和行为参数。同时还通过同步视频记录进行行为监测。该系统还可用于间歇性触发和记录 CSD 及其伴随的神经血管和行为反应。在睡眠-觉醒周期的不同阶段通过光学刺激触发 CSD。
与睡眠状态相比，在觉醒状态下触发 CSD 的光刺激阈值显著升高（刺激持续时间= 16.4 ± 9.7 s 与 10.8 ± 5.8 s，p = 0.037，n = 6 只小鼠）。与睡眠状态相比，在觉醒状态下诱发的 CSD 引起的 CBV 变化较小（最大相对变化-4.5 ± 5.0% ∆OIS 与-14.3 ± 8.5% ∆OIS，p = 0.001），持续时间更短（33:22 ± 6:37 与 49:42 ± 8:05 min:s，p = 0.012，n = 6 只小鼠）。CSD 的阈值和相关 CBV 变化的动力学与入睡或觉醒后的时间有关（n = 6 只小鼠的 47 次 CSD）。在觉醒状态下触发的 CSD 与短暂的冻结行为有关。在睡眠期间触发的 CSD 通常会引起短暂的觉醒和行为反应。随后，CBV 持续下降，持续约 30-60 分钟，在此期间，睡眠恢复，之后持续到 CBV 持续下降阶段结束，此时，心率（从 11.9 ± 0.8 降至 9.6 ± 0.8 Hz，p = 0.002，n = 5）出现一过性下降，与 CSD 发作时类似的行为一致。当在睡眠状态下触发 CSD 时，心率（从 7.5 ± 0.4 Hz 增加到 9.3 ± 1.1 Hz，p = 0.016，n = 5）出现一过性增加。
睡眠-觉醒周期对 CSD 有显著影响，这可能与偏头痛和脑损伤的临床表现有关。
