Sleep-Wake Disturbances After Traumatic Brain Injury: Synthesis of Human and Animal Studies

Abstract

Sleep-wake disturbances following traumatic brain injury (TBI) are increasingly recognized as a serious consequence following injury and as a barrier to recovery. Injury-induced sleep-wake disturbances can persist for years, often impairing quality of life. Recently, there has been a nearly exponential increase in the number of primary research articles published on the pathophysiology and mechanisms underlying sleep-wake disturbances after TBI, both in animal models and in humans, including in the pediatric population. In this review, we summarize over 200 articles on the topic, most of which were identified objectively using reproducible online search terms in PubMed. Although these studies differ in terms of methodology and detailed outcomes; overall, recent research describes a common phenotype of excessive daytime sleepiness, nighttime sleep fragmentation, insomnia, and electroencephalography spectral changes after TBI. Given the heterogeneity of the human disease phenotype, rigorous translation of animal models to the human condition is critical to our understanding of the mechanisms and of the temporal course of sleep-wake disturbances after injury. Arguably, this is most effectively accomplished when animal and human studies are performed by the same or collaborating research programs. Given the number of symptoms associated with TBI that are intimately related to, or directly stem from sleep dysfunction, sleep-wake disorders represent an important area in which mechanistic-based therapies may substantially impact recovery after TBI.

Keywords: BCAA; EEG; TBI; animal models; glutamate; orexin; pediatric; sleep.

Figure 1

Summary table showing the findings from animal and human studies with regard to several levels of analysis: neuropathology, neurophysiology, sleep–wake phenotype, and treatment options. Findings that are shared between animal and human studies are depicted in the center “Shared Findings” column. An absence of any Shared Findings in the Treatment category suggests that there is opportunity to move potential treatments identified in animal studies into the human condition. Abbreviations: EEG, electroencephalography; NREM, nonrapid eye movement sleep; REM, rapid eye movement; MCH, melanin-concentrating hormone; CBT, cognitive–behavioral therapy.