Maldonado M D, Murillo-Cabezas F, Terron M P, Flores L J, Tan D X, Manchester L C, Reiter R J
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA, and Center for Rehabilitation and Traumatology of the Hospital University Virgen del Rocio, Seville, Spain.
J Pineal Res. 2007 Jan;42(1):1-11. doi: 10.1111/j.1600-079X.2006.00376.x.
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.
颅脑创伤（CCT）是事故导致发病和死亡的最常见原因。其可能的起源和病因是多因素的，包括自由基形成和氧化应激、非特异性抵抗力的抑制、淋巴细胞减少（细胞黏附和激活紊乱）、机会性感染、局部宏观和微观循环改变、睡眠-觉醒周期紊乱以及治疗药物引起的毒性。随着疾病进展，这些致病因素会导致临床症状的不利发展。褪黑素（N-乙酰-5-甲氧基色胺）是松果体和其他器官内源性产生的一种吲哚胺，是一种针对CCT后损伤的保护剂。褪黑素在CCT后支持其药理学应用的一些作用包括其作为氧和氮基反应物清除剂的作用、刺激多种抗氧化酶（如超氧化物歧化酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和过氧化氢酶）的活性、抑制促炎细胞因子和激活-黏附分子，从而减少淋巴细胞减少和机会性生物体感染。褪黑素的生物钟调节能力还可能重置睡眠和觉醒的自然昼夜节律。褪黑素降低了用于治疗CCT的药物的毒性并提高了它们的疗效。最后，褪黑素可穿过血脑屏障，减少挫伤体积并稳定细胞膜，防止因CCT而发生的血管痉挛和内皮细胞凋亡。
