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Craniocerebral trauma (CCT) is the most frequent cause of morbidity–mortality as a result of an accident. 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–wake cycles and toxicity caused by therapeutic agents. These pathogenic factors contribute to the unfavorable development of clinical symptoms as the disease progresses. Melatonin (N-acetyl-5-methoxytryptamine) 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-based reactants, stimulation of the activities of a variety of antioxidative enzymes (e.g. superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase), inhibition of pro-inflammatory cytokines and activation–adhesion 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–brain barrier and reduces contusion volume and stabilizes cellular membranes preventing vasospasm and apoptosis of endothelial cells that occurs as a result of CCT. [ABSTRACT FROM AUTHOR] more...

The functional versatility and diversity of melatonin has exceeded everyone's expectations. The evidence is substantial that melatonin has multiple receptor-mediated and receptor-independent actions. Considering the unexpectedly widespread distribution of cellular membrane receptors as well as the existence of nuclear binding sites/receptors and the fact that some of melatonin's actions are receptor-independent means that melatonin likely functions in every cell with which it comes in contact. This is highlighted by the fact that there are no morphophysiological barriers to melatonin, e.g., the blood-brain barrier. In addition to its widespread actions, melatonin synthesis occurs in widely diverse tissues with its production not being relegated to the pineal gland. This should not be unexpected given that it is present throughout the animal kingdom including species that lack a pineal gland, e.g., insects, and in single cell organisms. In this review, only a few of melatonin's effects that involve the interaction of the indoleamine with receptors are described. These functions include the control of seasonal reproduction, modulation of sleep processes and influences on bone growth and osteoporosis. Among the actions of melatonin that are likely receptor independent and that are reviewed herein include its ability to neutralize free radicals which leads to a reduction in cataract formation, reducing oxidative stress due to exposure to hyperbaric hyperoxia, ameliorating hyperthyroidism and abating the toxicity of sepsis and septic shock. These actions alone speak to the diversity of beneficial effects of melatonin; however, the review is no way near exhaustive in terms of what melatonin is capable of doing. Because of its ubiquitous benefits, the pharmaceutical industry is developing melatonin analogues which interact with melatonin receptors. Clearly, the intent of the drugs is to take advantage of some of melatonin's numerous beneficial effects. [ABSTRACT FROM AUTHOR] more...