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The probable origins and etiologies are multifactorial and include free radical formation and oxidative stress, the suppression of nonspecific resistance, lymphocytopenia (disorder in the adhesion and activation of cells), opportunistic infections, regional macro and microcirculatory alterations, disruptive sleep\u2013wake cycles and toxicity caused by therapeutic agents. These pathogenic factors contribute to the unfavorable development of clinical symptoms as the disease progresses. Melatonin (N\u2010acetyl\u20105\u2010methoxytryptamine) is an indoleamine endogenously produced in the pineal gland and in other organs and it is protective agent against damage following CCT. Some of the actions of melatonin that support its pharmacological use after CCT include its role as a scavenger of both oxygen and nitrogen\u2010based reactants, stimulation of the activities of a variety of antioxidative enzymes (e.g. superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase), inhibition of pro\u2010inflammatory cytokines and activation\u2013adhesion molecules which consequently reduces lymphocytopenia and infections by opportunistic organisms. The chronobiotic capacity of melatonin may also reset the natural circadian rhythm of sleep and wakefulness. Melatonin reduces the toxicity of the drugs used in the treatment of CCT and increases their efficacy. Finally, melatonin crosses the blood\u2013brain barrier and reduces contusion volume and stabilizes cellular membranes preventing vasospasm and apoptosis of endothelial cells that occurs as a result of CCT.<\/jats:p>","DOI":"10.1111\/j.1600-079x.2006.00376.x","type":"journal-article","created":{"date-parts":[[2006,8,29]],"date-time":"2006-08-29T11:07:19Z","timestamp":1156849639000},"page":"1-11","source":"Crossref","is-referenced-by-count":155,"title":["The potential of melatonin in reducing morbidity\u2013mortality after craniocerebral trauma"],"prefix":"10.1111","volume":"42","author":[{"given":"M.D.","family":"Maldonado","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Murillo\u2010Cabezas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. P.","family":"Terron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. 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