Post Traumatic Sleep: An Individualized Indicator of Severity and Recovery

描述（由申请人提供）：睡眠的目的仍然存在争议。流行的假说表明，在恢复能量平衡，允许突触重组，或细胞修复的作用。对于创伤性脑损伤，机械力和随后的细胞信号传导破坏能量平衡，启动突触传入阻滞，随后是可塑性，并破坏膜、蛋白质和结构元件。因此，急性创伤后睡眠可以减轻与伤害有关的损害。然而，对于美国每年超过140万的脑震荡患者来说，流行的民间传说建议他们不应该被允许睡觉或经常醒来，这是没有医学证据支持的。此外，这种睡眠障碍抵消了睡眠的自然修复过程，这将是由脑损伤后普遍存在的炎症反应促进的，就像感染时细胞因子信号传导一样。令人惊讶的是，急性创伤后睡眠的效用或危害尚未被探索。目前的提议测试了这样一个假设，即睡眠是对弥漫性脑损伤的直接自然反应，可能促进受伤大脑的恢复。目的1将小鼠轻度和中度弥漫性脑损伤后急性定量睡眠参数与慢性生理，行为和组织病理学结果相关联。目的2将探讨睡眠障碍对认知功能、细胞因子和糖皮质激素水平以及边缘系统和睡眠结构的组织病理学的影响。创伤后的睡眠将通过睡眠-觉醒研究验证的新型非侵入性技术进行监测。该系统在笼子地板上采用定制设计的压力传感器，当动物处于睡眠姿势时，该压力传感器连续监测与有节奏的呼吸相关的运动。这些实验首次研究了弥漫性脑损伤对睡眠-觉醒模式的影响。破坏睡眠的创伤后干预可能会加重或减轻损伤的行为和组织病理学后果。创伤后睡眠可以作为一种个体化的生物标志物来衡量初始损伤的严重程度并监测恢复过程。对于轻度TBI，睡眠本身可能成为一种合理的行为干预，以减轻TBI的持久神经后果。 公共卫生相关性：脑震荡后，流行的民间传说建议不允许个人睡觉或经常醒来。由于睡眠可能负责细胞修复和重组，因此损伤后睡眠障碍可能会延迟甚至阻止恢复。该提案评估了创伤性脑损伤小鼠模型的损伤后睡眠以及损伤后不久睡眠紊乱的后果，无论是好是坏。

DESCRIPTION (provided by applicant): The purpose of sleep continues to be debated. Prevailing hypotheses suggest a role in restoring energy balance, permitting synaptic reorganization, or cellular repair. With a traumatic brain injury, the mechanical forces and ensuing cellular signaling disrupt energy balance, initiate synaptic deafferentation followed by plasticity, and damage membranes, proteins and structural elements. Thus, acute post-traumatic sleep may mitigate injury-related damage. However, for the more than 1.4 million concussed individuals per year in the United States, prevailing folklore recommends that they should not be allowed to sleep or be awoken regularly, which is unsupported by medical evidence. Moreover, this sleep disturbance counteracts the natural repair processes of sleep that would be promoted by the ubiquitous inflammatory response after brain injury, as occurs with cytokine signaling upon infection. Surprisingly, the utility or detriment of acute post-traumatic sleep has yet to be explored. The current proposal tests the hypothesis that sleep is an immediate natural response to diffuse brain injury likely promoting recovery of the injured brain. Aim 1 will correlate quantitative sleep parameters acutely following mild and moderate diffuse brain injury in the mouse to chronic physiological, behavioral and histopathological outcomes. Aim 2 will explore the consequences of sleep disturbance on cognitive function, cytokine and glucocorticoid levels and histopathology across limbic and sleep structures. Post- traumatic sleep will be monitored by novel non-invasive technology validated for sleep- wake studies. This system employs custom-designed pressure sensors on the cage floor that continuously monitor for the motion associated with rhythmic breathing while animals are in a sleep posture. These experiments examine, for the first time, the effects of diffuse brain injury on sleep-wake patterns. Post-traumatic interventions to disrupt sleep may worsen or mitigate the behavioral and histopathological consequences of injury. Post-traumatic sleep may come to serve as an individualized biomarker to measure the severity of the initial injury and monitor the recovery process. For mild TBI, sleep itself could become a plausible behavioral intervention to mitigate the enduring neurological consequences of TBI. PUBLIC HEALTH RELEVANCE: After a concussion, prevailing folklore recommends that individuals should not be allowed to sleep or be awoken regularly. Since sleep may be responsible for cellular repair and reorganization, post-injury sleep disturbance may delay or even prevent recovery. This proposal evaluates post-injury sleep in a mouse model of traumatic brain injury and the consequences, good or bad, of disturbing sleep shortly after injury.