Melatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence

Abstract

Melatonin (MEL) is a hormone that is produced in the brain and is known to bind to MEL-specific receptors on neuronal membranes in several brain regions. MEL’s documented neuroprotective properties, low toxicity, and ability to cross the blood-brain-barrier have led to its evaluation for patients with traumatic brain injury (TBI), a condition for which there are currently no Food and Drug Administration (FDA)-approved therapies. The purpose of this manuscript is to summarize the evidence surrounding the use of melatonin after TBI, as well as identify existing gaps and future directions. To address this aim, a search of the literature was conducted using Pubmed, Google Scholar, and the Cochrane Database. In total, 239 unique articles were screened, and the 22 preclinical studies that met the a priori inclusion/exclusion criteria were summarized, including the study aims, sample (size, groups, species, strain, sex, age/weight), TBI model, therapeutic details (preparation, dose, route, duration), key findings, and conclusions. The evidence from these 22 studies was analyzed to draw comparisons across studies, identify remaining gaps, and suggest future directions. Taken together, the published evidence suggests that MEL has neuroprotective properties via a number of mechanisms with few toxic effects reported. Notably, available evidence is largely based on data from adult male rats and, to a lesser extent, mice. Few studies collected data beyond a few days of the initial injury, necessitating additional longer-term studies. Other future directions include diversification of samples to include female animals, pediatric and geriatric animals, and transgenic strains.

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“…As shown in Table 3 , GCS was raised in the melatonin group in comparison with the control, which can be credited to the neuroprotective effect of melatonin. This finding was similar to that in Osier and coworker [ 32 ].…”

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“…There is considerable evidence for the existence of such a phenomenon in presymptomatic HD mice that, despite ongoing expression of the mutation that eventually causes disease, are less susceptible to neurotoxins than control mice . Melatonin, with its well‐documented neuroprotective properties, is a prime candidate for playing a role in such autoprotection.…”

Antioxidants and Nanotechnology: Promises and Limits of Potentially Disruptive Approaches in the Treatment of Central Nervous System Diseases

“…The damages caused by the secondary injury can induce neuronal cell death that, in turn, can cause further release of inflammatory factors and ROS, leading to progressive neurodegeneration . Several antioxidant compounds like curcumin, melatonin, and lipoic acid have shown great promise in the treatment of TBI …”