The Putative Role of Neuroinflammation in the Interaction between Traumatic Brain Injuries, Sleep, Pain and Other Neuropsychiatric Outcomes: A State-of-the-Art Review

Sleep disturbances are widely prevalent following a traumatic brain injury (TBI) and have the potential to contribute to numerous post-traumatic physiological, psychological, and cognitive difficulties developing chronically, including chronic pain. An important pathophysiological mechanism involved in the recovery of TBI is neuroinflammation, which leads to many downstream consequences. While neuroinflammation is a process that can be both beneficial and detrimental to individuals' recovery after sustaining a TBI, recent evidence suggests that neuroinflammation may worsen outcomes in traumatically injured patients, as well as exacerbate the deleterious consequences of sleep disturbances. Additionally, a bidirectional relationship between neuroinflammation and sleep has been described, where neuroinflammation plays a role in sleep regulation and, in turn, poor sleep promotes neuroinflammation. Given the complexity of this interplay, this review aims to clarify the role of neuroinflammation in the relationship between sleep and TBI, with an emphasis on long-term outcomes such as pain, mood disorders, cognitive dysfunctions, and elevated risk of Alzheimer's disease and dementia. In addition, some management strategies and novel treatment targeting sleep and neuroinflammation will be discussed in order to establish an effective approach to mitigate long-term outcomes after TBI.

Automated summary

Sleep disturbances commonly occur after traumatic brain injury (TBI) and can contribute to various chronic physiological, psychological, and cognitive difficulties, including chronic pain. Neuroinflammation, a key pathophysiological mechanism in TBI recovery, may worsen outcomes and exacerbate the consequences of sleep disturbances. There is a bidirectional relationship between neuroinflammation and sleep, where neuroinflammation affects sleep regulation and poor sleep promotes neuroinflammation. This review aims to clarify the role of neuroinflammation in the sleep-TBI relationship and its impact on long-term outcomes, such as pain, mood disorders, cognitive dysfunctions, and increased risk of Alzheimer's disease and dementia. Management strategies and novel treatments targeting sleep and neuroinflammation will also be discussed to mitigate long-term outcomes after TBI.