Diffuse Brain Injury Induces Acute Post-Traumatic Sleep

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.

Impact of traumatic brain injury on sleep structure, electrocorticographic activity and transcriptome in mice

“…We observed a specific decrease in the number of long wakefulness bouts after mTBI, indicative of a decreased capacity to maintain wakefulness, which is also consistent with previous rodent literature (Lim et al, 2013;Rowe et al, 2013Rowe et al, , 2014Willie et al, 2012). This difference was only found in the first recorded 24 h, which is reminiscent of a study showing that sleep measured via piezoelectric cages predominates in the first hours after TBI .…”

“…In parallel, secondary injury processes are immediately activated following brain injury. Glial cells release inflammatory mediators, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFa) Helmy et al, 2011;Rowe et al, 2013). These cytokines have specifically been shown to promote sleep and to alter the sleep EEG .…”

A single dose of PPARγ agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats

“…Cell morphology of cortical microglia in the control, sham operated rats, characterized by small spheric cell bodies with several primary, ramified processes, upon LFPI was changed and the signs of the microglia activation, such as swollen cell bodies with fewer, thicker, highly branched processes, appeared. The mentioned result is in accordance with previously described microglia activation obtained in other TBI models (Rowe et al, 2014;Susarla et al, 2014). Moreover, our results demonstrated that single administration of pioglitazone reduced the number of Iba1 positive cells in the cortex of the injured rats close to their number in rats of the control group.…”

Aging with Traumatic Brain Injury: Effects of Age at Injury on Behavioral Outcome following Diffuse Brain Injury in Rats

“…The righting reflex time is the total time from the initial impact until the rat spontaneously rights itself from a supine position. A righting reflex time of 5-10 min for all age groups was indicative of moderate injury and used as inclusion criteria for the study, as previously published [19,23,24,25,26]. In juvenile rats (PND 17), the presence of a seizure shortened the righting reflex times as juveniles consistently righted themselves immediately following injury-induced seizure.…”