Abstract

Introduction

Increased cerebral blood flow (CBF) is positively associated with non-rapid eye movement (NREM) sleep electroencephalogram (EEG) delta power, also known as slow-wave activity (SWA). The pro-inflammatory somnogenic cytokine interleukin-1 beta (IL-1β) can induce vasodilation and increase CBF. Nucleotide leucine-rich protein complex-3 (NLRP3) inflammasomes, which activate IL-1β, are increased in the cortex after sleep deprivation and increase SWA. We aimed to determine the relationship of NLRP3 inflammasomes on sleep loss-induced alterations in vasohemodynamics and SWA.

Methods

NLRP3 knock-out (KO) and wild-type (WT) mice underwent ad libitum sleep, 6 hours of sleep deprivation, or were given 10 ng of IL-1β or the vehicle intracerebroventricularly. SWA and CBF, blood velocity, and blood volume were determined concurrently during sleep/wake states using polysomnography and laser doppler flowmetry. Regional brain changes in CBF were determined using transponders, spectrophotometry, and fluorescent microspheres.

Results

SWA and CBF were significantly increased during the first 6 hours after sleep deprivation in WT but not NLRP3 KO mice. SWA and CBF significantly increased in the first 6 hours after IL-1β in both NLRP3 KO and WT mice. Additionally, alterations in cerebral blood velocity and volume demonstrated state specific changes that varied significantly during the transitions between states. SWA and CBF were significantly positively correlated during both ad libitum sleep and sleep after sleep deprivation in WT mice, although this relationship was not observed in NLRP3 KO mice. We also found significant phase-amplitude frequency coupling between SWA and CBF. Cortical changes CBF were significantly enhanced after sleep deprivation and IL-1β administration in WT mice, although were attenuated in the hypothalamus. NLRP3 KO mice showed these same regional effects in CBF after IL-1β but not sleep deprivation.

Conclusion

Our findings indicate that NLRP3 inflammasomes are involved in neurovascular coupling involving SWA.

Support

Department of Veterans Affairs IBX002823A (MRZ)

中文翻译：

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0133 NLRP3炎性小体调节大脑对睡眠丧失的血管动力反应

摘要

介绍

脑血流量（CBF）的增加与非快速眼动（NREM）睡眠脑电图（EEG）三角肌功能正相关，也称为慢波活动（SWA）。促炎性促细胞因子白细胞介素-1（IL-1β）可以诱导血管舒张并增加CBF。激活IL-1β的富含核苷酸亮氨酸的蛋白质复合物3（NLRP3）炎性小体在睡眠剥夺后皮质中增加并增加SWA。我们旨在确定NLRP3炎性体与睡眠丧失引起的血管血流动力学和SWA改变的关系。

方法

NLRP3基因敲除（KO）和野生型（WT）小鼠进行随意睡眠，剥夺睡眠6小时，或给予10 ngIL-1β或脑室内的媒介物。使用多导睡眠图和激光多普勒血流仪同时测定睡眠/苏醒状态下的SWA和CBF，血流速度和血容量。使用应答器，分光光度法和荧光微球测定CBF的局部大脑变化。

结果

WT的睡眠剥夺后的头6个小时，SWA和CBF显着增加，而NLRP3 KO小鼠没有。在IL-1β后的NLRP3 KO和WT小鼠中，SWA和CBF均在IL-1β后的最初6小时内显着增加。此外，脑血流速度和血容量的变化表明状态间的特定变化在状态之间的转换过程中发生了显着变化。尽管在NLRP3 KO小鼠中未观察到这种关系，但在WT小鼠的随意睡眠和睡眠剥夺后的睡眠中，SWA和CBF均呈显着正相关。我们还发现，SWA和CBF之间存在明显的相位-振幅频率耦合。在WT小鼠中，睡眠剥夺和IL-1β给药后，皮质变化CBF显着增强，尽管在下丘脑中减弱。

结论

我们的发现表明，NLRP3炎性小体参与了涉及SWA的神经血管耦合。

支持

退伍军人事务部IBX002823A（MRZ）