Circadian therapy interventions for glymphatic dysfunction in concussions injuries: A narrative review

Abstract

There are two primary threats to the brain after concussion. The first is a buildup of neurotoxic proteins in the brain. The second, a partial consequence of the first, is a sustained neuroinflammatory response that may lead to central sensitization and the development of persistent post-concussive symptoms. These threats make neurotoxin clearance a high clinical priority in the acute period after injury. The glymphatic system is the brain's primary mechanism for clearing neurotoxic waste. The glymphatic system is intimately tied to the sleep cycle and circadian dynamics. However, glymphatic dysfunction and sleep disturbances are nearly ubiquitous in the acute period after concussion injury. Because of this, sleep optimization via circadian therapy is a time-sensitive and critical tool in acute concussion management.

Conservative Management of Acute Sports-Related Concussions: A Narrative Review

“…The central sensitization framework can be used to guide conservative interventions, and clinical researchers have used it to guide treatment in several areas of sports medicine, including chronic low back pain [8][9][10], shoulder pain [11], knee pain [12], chronic myofascial pain [13], tendinopathy [14,15], temporomandibular disorders [16], migraines [17], and post-traumatic headaches [18]. The key insight of the central sensitization model is that chronic pain syndromes can be prevented through early proactive interventions, using the biopsychosocial model of pain as a guide.…”

“…The trend of current research is to recognize prolonged concussion symptoms as a form of nociplastic pain (i.e., pain secondary to central sensitization) [18,[21][22][23]. PPCS follows the typical dynamic sequence of central sensitization: peripheral insult to peripheral sensitization, to prolonged neuroinflammation and neuroplasticity, to centrally-mediated chronic pain [24].…”

“…This is concerning, as cumulative tau deposition around intracerebral vessels is the histological definition of chronic traumatic encephalopathy (CTE) [157]. Therefore, optimizing glymphatic function in the acute period after concussions is an important therapeutic goal [18].…”

“…Finally, because sleep apnea significantly disrupts glymphatic function [165] and is associated with poor outcomes in concussion [166], screening for and treatment of sleep apnea is recommended in concussion injuries. Other interventions along these lines include sleep hygiene, cognitive behavioral therapy (CBT), and prescribed exercise [18].…”

mTBI Biological Biomarkers as Predictors of Postconcussion Syndrome—Review

“…Sleep has an important role in the treatment process. Circadian therapy has been proposed as a form of recovery that includes sleep regulation with melatonin therapy, morning blue light therapy, evening blue light restriction, sleep apnea treatment, and omega oil supplementation [43]. Another method that was proven to be beneficial for improving well-being, psychosocial state, and mental health is cognitive rehabilitation and neurocognitive training [44], which are still being developed as a treatment line in PCS.…”