Melatonin in Traumatic Brain Injury and Cognition.

Traumatic brain injury (tbi) is a leading cause of long-term disability and mortality in young adults.The devastating effects of tbi on emotion regulation, executive functioning, and cognition have been well-established, and recent research links tbi as a risk factor for neurodegenerative diseases such as alzheimer's disease.Despite an increased focus on the long-term cognitive dysfunction associated with tbi, research into potential treatments has not yet generated consistent successful results in human subjects.Many foundational studies have analyzed the cellular and molecular events involved in the inflammatory and healing processes following tbi, enhancing our understanding of the mechanisms that may contribute to the progression of dementia and cognitive decline in these patients.In this review, we will discuss the emergent research on melatonin within the framework of neuroinflammation and oxidative stress resulting from tbi and possibly preventing further sequelae such as alzheimer's disease.A literature review was conducted using standard search strategies to query the pub med database.The following search terms were used with qualifiers of various combinations: tbi, traumatic brain injury, melatonin, treatment, dementia, alzheimer's, cognition, and neurodegeneration.Selected studies included meta-analyses, literature reviews, and randomized controlled trials (rct) that evaluated melatonin's role as a potential therapy to prevent post-tbi neurodegeneration, specifically the development of dementia and deficits in memory and cognition.Three independent reviewers assessed all articles for eligibility.After assessment for eligibility, 11 total studies were included.Much of the available data on melatonin in tbi has highlighted its significant neuroprotective and antiinflammatory effects, which can be significant in fighting against the neuroinflammatory processes indicated in neurodegeneration.In animal models, immunohistochemistry and histopathology have allowed researchers to study measures of cell injury such as inflammatory cytokines, edema, and markers of oxidative stress.Though the effects of melatonin in tbi appear to be mediated through mostly indirect mechanisms on inflammatory processes, some research has explored potential mechanisms that could be specific to melatonin.Animal model studies support that melatonin treatment after tbi significantly improves cognition and behavioral outcomes.However, clinical studies with human subjects are scarce.Beyond the apparent general antiinflammatory and antioxidant actions of melatonin, a review of the evidence identified some preliminary research that has suggested the significance of melatonin receptors specifically in tbi.While there is some evidence to suggest that melatonin is able to reduce post-tbi cognitive decline as measured by subject performance on memory tasks, there is a lack of longitudinal data on whether melatonin decreases the risk of developing dementia after tbi.Considering melatonin therapy's promising preclinical data, favorable safety profile, and accessibility, further studies are warranted to assess the effects of melatonin as a post-tbi therapy on human subjects.

Journal: Cureus (2021)
Publication types: Journal Article;Review