Diffuse Brain Injury Induces Acute Post-Traumatic Sleep

Rachel K Rowe,Linda J Van Eldik,Martin Striz,Bruce F O'Hara,Kevin D Donohue,Jonathan Lifshitz,Adam D Bachstetter,Fernando De Castro

doi:10.1371/journal.pone.0082507

Abstract

ObjectiveClinical observations report excessive sleepiness immediately following traumatic brain injury (TBI); however, there is a lack of experimental evidence to support or refute the benefit of sleep following a brain injury. The aim of this study is to investigate acute post-traumatic sleep.MethodsSham, mild or moderate diffuse TBI was induced by midline fluid percussion injury (mFPI) in male C57BL/6J mice at 9:00 or 21:00 to evaluate injury-induced sleep behavior at sleep and wake onset, respectively. Sleep profiles were measured post-injury using a non-invasive, piezoelectric cage system. In separate cohorts of mice, inflammatory cytokines in the neocortex were quantified by immunoassay, and microglial activation was visualized by immunohistochemistry.ResultsImmediately after diffuse TBI, quantitative measures of sleep were characterized by a significant increase in sleep (>50%) for the first 6 hours post-injury, resulting from increases in sleep bout length, compared to sham. Acute post-traumatic sleep increased significantly independent of injury severity and time of injury (9:00 vs 21:00). The pro-inflammatory cytokine IL-1β increased in brain-injured mice compared to sham over the first 9 hours post-injury. Iba-1 positive microglia were evident in brain-injured cortex at 6 hours post-injury.ConclusionPost-traumatic sleep occurs for up to 6 hours after diffuse brain injury in the mouse regardless of injury severity or time of day. The temporal profile of secondary injury cascades may be driving the significant increase in post-traumatic sleep and contribute to the natural course of recovery through cellular repair.

Highlights

Traumatic brain injury (TBI) is a major cause of death and disability throughout the world with little pharmacological treatment for the individuals who suffer from lifelong neurological morbidities associated with TBI
Injury-induced inflammation is mediated by the production of cytokines, such as pro-inflammatory interleukin-1 beta (IL-1b), which can have dual roles as sleep regulatory substances (SRSs) [10,11]
After diffuse TBI, mean percent sleep was significantly increased in brain-injured animals compared to sham for the first 6 hours post-injury (F(1, 45) = 6.545, p = 0.00007) (Figure 2A)

Summary

Introduction

Traumatic brain injury (TBI) is a major cause of death and disability throughout the world with little pharmacological treatment for the individuals who suffer from lifelong neurological morbidities associated with TBI. Brain injury can lead to both short and long-term impairment, including cognitive [1], and behavioral [2] deficits as well as increasing the risk for developing neurodegenerative disease [3] and/or psychiatric disorders [4]. Little can be done to mitigate the mechanical disruption associated with the primary insult and the biochemical cascades initiated shortly after the time of injury can impair physiological function and worsen long-term outcome [5]. After TBI, secondary injury mechanisms may impair physiological functions associated with the homeostatic regulation of sleep. Injury-induced inflammation is mediated by the production of cytokines, such as pro-inflammatory interleukin-1 beta (IL-1b), which can have dual roles as sleep regulatory substances (SRSs) [10,11]. Cytokines which are SRSs can modulate sleep-wake behavior, primarily enhancing sleep by acting on sleep circuits of the brain [11,16]

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