Mannino Grant S, Green Tabitha R F, Murphy Sean M, Sierks Michael R, Opp Mark R, Rowe Rachel K
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
University of Glasgow, Glasgow, United Kingdom.
Neurobiol Sleep Circadian Rhythms. 2025 May 15;18:100127. doi: 10.1016/j.nbscr.2025.100127. eCollection 2025 May.
Traumatic brain injury (TBI) is frequently associated with acute and chronic disturbances in sleep architecture. However, the extent to which injury severity and biological sex influence post-traumatic sleep patterns remains underexplored in preclinical models. Here, we used a validated, noninvasive piezoelectric monitoring system to assess sleep in male and female mice following sham (n = 30), mild (n = 32), or moderate (n = 32) midline fluid percussion injury (mFPI). Physiological parameters were recorded non-invasively to determine sleep for 48 h post-injury. Hierarchical mixed-effects models were used to evaluate effects of injury severity and sex on sleep duration, architecture, and fragmentation. We found that sleep increased during the acute post-injury period regardless of TBI severity, but that sleep fragmentation was selectively elevated after moderate injury. Notably, female mice exhibited greater overall sleep disturbances compared to males, highlighting a sex-dependent vulnerability. These effects varied across the light-dark cycle. This study provides the first detailed characterization of sex- and severity-specific changes in sleep architecture and fragmentation following diffuse TBI using a high-throughput, noninvasive method. Importantly, it reveals that injury severity predicts the extent of sleep fragmentation highlighting a direct link between injury severity and disrupted sleep architecture. These findings contribute to the growing recognition of sleep fragmentation as a relevant biomarker in TBI and establish a framework for future mechanistic and interventional studies.
创伤性脑损伤（TBI）常与睡眠结构的急性和慢性紊乱相关。然而，在临床前模型中，损伤严重程度和生物性别对创伤后睡眠模式的影响程度仍未得到充分研究。在此，我们使用经过验证的非侵入性压电监测系统，评估假手术组（n = 30）、轻度（n = 32）或中度（n = 32）中线流体冲击伤（mFPI）后雄性和雌性小鼠的睡眠情况。在损伤后48小时内，通过非侵入性记录生理参数来确定睡眠情况。使用分层混合效应模型评估损伤严重程度和性别对睡眠时间、睡眠结构和睡眠片段化的影响。我们发现，无论TBI严重程度如何，在损伤后的急性期睡眠都会增加，但在中度损伤后睡眠片段化会选择性升高。值得注意的是，与雄性小鼠相比雌性小鼠表现出更严重的整体睡眠障碍，突出了性别依赖性易感性。这些影响在明暗周期中有所不同。本研究首次使用高通量、非侵入性方法详细描述了弥漫性TBI后睡眠结构和睡眠片段化的性别和严重程度特异性变化。重要的是，它揭示了损伤严重程度可预测睡眠片段化程度，突出了损伤严重程度与睡眠结构紊乱之间的直接联系。这些发现有助于人们越来越认识到睡眠片段化是TBI中的一个相关生物标志物，并为未来的机制和干预研究建立了一个框架。
