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Int. J. Mol. Sci. 2018, 19(5), 1539; https://doi.org/10.3390/ijms19051539

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

1
School of Nursing, University of Texas at Austin, Holistic Adult Health, Austin, TX 78712, USA
2
Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX 78705, USA
3
School of Nursing, University of Pittsburgh, Pittsburgh, PA 15213, USA
4
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15260, USA
5
Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA
6
School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
7
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15213, USA
8
V.A. Pittsburgh Healthcare System, Pittsburgh, PA 15240, USA
*
Author to whom correspondence should be addressed.
Received: 19 April 2018 / Revised: 4 May 2018 / Accepted: 7 May 2018 / Published: 22 May 2018
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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. View Full-Text
Keywords: melatonin; therapy; traumatic brain injury (TBI); neurotrauma; preclinical; review melatonin; therapy; traumatic brain injury (TBI); neurotrauma; preclinical; review
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Osier, N.; McGreevy, E.; Pham, L.; Puccio, A.; Ren, D.; Conley, Y.P.; Alexander, S.; Dixon, C.E. Melatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence. Int. J. Mol. Sci. 2018, 19, 1539.

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