Seifman Marc A, Adamides Alexios A, Nguyen Phuong N, Vallance Shirley A, Cooper David James, Kossmann Thomas, Rosenfeld Jeffrey V, Morganti-Kossmann M Cristina
National Trauma Research Institute, The Alfred, Melbourne, Victoria, Australia.
J Cereb Blood Flow Metab. 2008 Apr;28(4):684-96. doi: 10.1038/sj.jcbfm.9600603. Epub 2008 Jan 9.
Oxidative stress plays a significant role in secondary damage after severe traumatic brain injury (TBI); and melatonin exhibits both direct and indirect antioxidant effects. Melatonin deficiency is deleterious in TBI animal models, and its administration confers neuroprotection, reducing cerebral oedema, and improving neurobehavioural outcome. This study aimed to measure the endogenous cerebrospinal fluid (CSF) and serum melatonin levels post-TBI in humans and to identify relationships with markers of oxidative stress via 8-isoprostaglandin-F2alpha (isoprostane), brain metabolism and neurologic outcome. Cerebrospinal fluid and serum samples of 39 TBI patients were assessed for melatonin, isoprostane, and various metabolites. Cerebrospinal fluid but not serum melatonin levels were markedly elevated (7.28+/-0.92 versus 1.47+/-0.35 pg/mL, P<0.0005). Isoprostane levels also increased in both CSF (127.62+/-16.85 versus 18.28+/-4.88 pg/mL, P<0.0005) and serum (562.46+/-50.78 versus 126.15+/-40.08 pg/mL (P<0.0005). A strong correlation between CSF melatonin and CSF isoprostane on day 1 after injury (r=0.563, P=0.002) suggests that melatonin production increases in conjunction with lipid peroxidation in TBI. Relationships between CSF melatonin and pyruvate (r=0.369, P=0.049) and glutamate (r=0.373, P=0.046) indicate that melatonin production increases with metabolic disarray. In conclusion, endogenous CSF melatonin levels increase after TBI, whereas serum levels do not. This elevation is likely to represent a response to oxidative stress and metabolic disarray, although further studies are required to elucidate these relationships.
氧化应激在重度创伤性脑损伤(TBI)后的继发性损伤中起重要作用;褪黑素具有直接和间接的抗氧化作用。在TBI动物模型中,褪黑素缺乏是有害的,给予褪黑素可提供神经保护作用,减轻脑水肿,并改善神经行为结果。本研究旨在测量人类TBI后脑脊液(CSF)和血清中内源性褪黑素水平,并通过8-异前列腺素-F2α(异前列腺素)、脑代谢和神经学结果确定与氧化应激标志物的关系。对39例TBI患者的脑脊液和血清样本进行褪黑素、异前列腺素和各种代谢物的评估。脑脊液中的褪黑素水平显著升高(7.28±0.92对1.47±0.35 pg/mL,P<0.0005),而血清中的褪黑素水平未升高。脑脊液(127.62±16.85对18.28±4.88 pg/mL,P<0.0005)和血清(562.46±50.78对126.15±40.08 pg/mL,P<0.0005)中的异前列腺素水平也升高。损伤后第1天脑脊液褪黑素与脑脊液异前列腺素之间存在强相关性(r=0.563,P=0.002),表明TBI中褪黑素的产生与脂质过氧化同时增加。脑脊液褪黑素与丙酮酸(r=0.369,P=0.049)和谷氨酸(r=0.373,P=0.046)之间的关系表明,褪黑素的产生随着代谢紊乱而增加。总之,TBI后脑脊液中内源性褪黑素水平升高,而血清水平未升高。这种升高可能代表对氧化应激和代谢紊乱的反应,尽管需要进一步研究来阐明这些关系。