Post Traumatic Sleep: An Individualized Indicator of Severity and Recovery

描述(申请人提供)：睡眠的目的仍在争论中。流行的假说表明，它在恢复能量平衡、允许突触重组或细胞修复方面发挥了作用。在创伤性脑损伤中，机械力和随之而来的细胞信号破坏能量平衡，启动突触去传入，随后发生可塑性，并破坏膜、蛋白质和结构元素。因此，急性创伤后睡眠可能会减轻损伤相关的损害。然而，对于美国每年超过140万脑震荡患者来说，流行的民间传说建议他们不应该被允许睡觉或经常被叫醒，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，而脑损伤后无处不在的炎症反应将促进睡眠的自然修复过程，就像感染时细胞因子信号传递一样。令人惊讶的是，创伤后急性睡眠的益处或危害还有待研究。目前的提议检验了这样一种假设，即睡眠是对弥漫性脑损伤的直接自然反应，可能会促进受损大脑的恢复。目的1将小鼠轻度和中度弥漫性脑损伤后的定量睡眠参数与慢性生理、行为和组织病理学结果密切相关。目的2探讨睡眠障碍对边缘和睡眠结构的认知功能、细胞因子和糖皮质激素水平以及组织病理学的影响。创伤后的睡眠将通过新的非侵入性技术进行监测，这项技术已被证实可用于睡眠-觉醒研究。该系统在笼底上采用了定制设计的压力传感器，当动物处于睡眠姿势时，这些传感器可以持续监测与有节奏的呼吸相关的运动。这些实验首次检验了弥漫性脑损伤对睡眠-觉醒模式的影响。用来干扰睡眠的创伤后干预措施可能会恶化或减轻创伤的行为和组织病理学后果。创伤后睡眠可能成为一种个性化的生物标志物，用来衡量最初损伤的严重程度，并监测恢复过程。对于轻微的脑损伤，睡眠本身可能成为一种看似合理的行为干预，以减轻脑损伤造成的持久的神经后果。 与公共卫生相关：在脑震荡之后，流行的民间传说建议个人不应该被允许睡觉或经常被叫醒。由于睡眠可能负责细胞的修复和重组，损伤后的睡眠障碍可能会推迟甚至阻止恢复。这项建议评估了创伤性脑损伤小鼠模型的损伤后睡眠，以及损伤后不久扰乱睡眠的后果，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.