Impacts of traumatic brain injury severity and sex on sleep architecture, duration, and fragmentation

Abstract

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.