Abstract
Traumatic brain injury (TBI) and Alzheimer’s disease (AD) are diseases during which the fine-tuned autoregulation of the brain is lost. Despite the stark contrast in their causal mechanisms, both TBI and AD are conditions which elicit a neuroinflammatory response that is coupled with physical, cognitive, and affective symptoms. One commonly reported symptom in both TBI and AD patients is disturbed sleep. Sleep is regulated by circadian and homeostatic processes such that pathological inflammation may disrupt the chemical signaling required to maintain a healthy sleep profile. In this way, immune system activation can influence sleep physiology. Conversely, sleep disturbances can exacerbate symptoms or increase the risk of inflammatory/neurodegenerative diseases. Both TBI and AD are worsened by a chronic pro-inflammatory microenvironment which exacerbates symptoms and worsens clinical outcome. Herein, a positive feedback loop of chronic inflammation and sleep disturbances is initiated. In this review, the bidirectional relationship between sleep disturbances and inflammation is discussed, where chronic inflammation associated with TBI and AD can lead to sleep disturbances and exacerbated neuropathology. The role of microglia and cytokines in sleep disturbances associated with these diseases is highlighted. The proposed sleep and inflammation-mediated link between TBI and AD presents an opportunity for a multifaceted approach to clinical intervention.
Highlights
In diseased states affecting the central nervous system (CNS), the fine-tuned autoregulation of the brain is lost, which contributes to the affective and cognitive symptoms seen in psychiatric, neurological, and mental health disorders (Charrier et al, 2017)
It was hypothesized that this fusion event was to create a barrier between healthy and injured tissue (Davalos et al, 2005). These findings suggest that microglia may be the first line of defense following Traumatic brain injury (TBI) (Kumar and Loane, 2012)
These data support that the orexinergic system may be involved in long-term sleep-wake alterations that persist after the acute inflammatory response to TBI has subsided
Summary
In diseased states affecting the central nervous system (CNS), the fine-tuned autoregulation of the brain is lost, which contributes to the affective and cognitive symptoms seen in psychiatric, neurological, and mental health disorders (Charrier et al, 2017). Unregulated release of pro-inflammatory cytokines following an injury can cause pathological functions that lead to detrimental inflammation and progressive tissue damage (Kumar and Loane, 2012; Morganti-Kossmann et al, 2018). Unregulated cytokine release sustains microglial activation and priming which results in a chronic pro-inflammatory microenvironment. The movement of amyloid-β (Aβ) and Tau through the breach in the BBB could potentially seed protein oligomerization and aggregation, thereby acting as possible drivers of central plaque and tangle pathology Such aggregates in the brain further contribute to microglial activation, the pro-inflammatory microenvironment, and neuronal apoptosis. We highlight the role of microglia and cytokines in sleep disturbances associated with these diseases
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