Chronic Decrease in Wakefulness and Disruption of Sleep-Wake Behavior after Experimental Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) can cause sleep-wake disturbances and excessive daytime sleepiness. The pathobiology of sleep disorders in TBI, however, is not well understood, and animal models have been underused in studying such changes and potential underlying mechanisms. We used the rat lateral fluid percussion (LFP) model to analyze sleep-wake patterns as a function of time after injury. Rapid-eye movement (REM) sleep, non-REM (NREM) sleep, and wake bouts during light and dark phases were measured with electroencephalography and electromyography at an early as well as chronic time points after LFP. Moderate TBI caused disturbances in the ability to maintain consolidated wake bouts during the active phase and chronic loss of wakefulness. Further, TBI resulted in cognitive impairments and depressive-like symptoms, and reduced the number of orexin-A-positive neurons in the lateral hypothalamus.

Sleep Disturbances in Traumatic Brain Injury: Associations With Sensory Sensitivity

“…27 Individual items are 5-point Likert scales: 0 = "none," 1 = "mild," 2 = "moderate," 3 = "severe," 4 = "very severe." The total scored can be subdivided into one of four evenly spaced provisional diagnosis categories: no insomnia (0-7); mild insomnia (8)(9)(10)(11)(12)(13)(14); moderate insomnia (15)(16)(17)(18)(19)(20)(21); and severe insomnia (22)(23)(24)(25)(26)(27)(28). In the current study, subjects were categorized as having insomnia with an ISI score of ≥ 15 (ie, moderate to severe insomnia).…”

“…remains unclear, although recent work has implicated a neuroanatomical mechanism based on an impaired orexin/hypocretin system. [8][9][10][11][12][13][14][15] Additionally, sleep disturbances have been implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer disease, a process that may be accelerated by TBI. 16 Light and noise sensitivity are also frequently associated sequelae of TBI.…”

Sleep disruption and the sequelae associated with traumatic brain injury

“…In one study, injured rodents had shortened wake bouts during the normal period of activity (dark phase), indicating that injury produced wake fragmentation (Skopin et al, 2014). These changes were accompanied by a decrease in orexin-A-positive neurons–neurons important for arousal.…”

“…These alterations in the hippocampus, a key brain area for learning and memory, may explain the prominent cognitive deficits seen in post-TBI patients. Indeed, in a rodent model of TBI, sleep disruption has resulted in impaired learning and memory (Skopin et al, 2014). Additionally, in a prospective study of humans with TBI, the duration of daytime sleep partially mediated the positive relationship between the score on the Glasgow Coma Scale and the recovery of cognitive function–controlling for total daytime sleep reduced the relationship (Chiu et al, 2014).…”

Neuroprotection, Photoperiod, and Sleep

“…Hypersomnolence has been associated with a decrease in the number of hypocretin-positive cells in experimental TBI models [50][51][52]. Also, an increased number of awakenings associated with an increase in reactive microglia in thalamic regions have been reported [53].…”