Macleod Malcolm R, O'Collins Tori, Horky Laura L, Howells David W, Donnan Georey A
National Stroke Research Institute, Melbourne, Australia.
J Pineal Res. 2005 Jan;38(1):35-41. doi: 10.1111/j.1600-079X.2004.00172.x.
Melatonin is a candidate neuroprotective drug for ischaemic stroke. Any decision to proceed to clinical trial for such drugs should be based on an unbiased assessment of all available data. Such an assessment should include not only the efficacy of a drug but also the in vivo characteristics and limits--in terms of time window, dose, species and model of ischaemia used--to that efficacy. Here we use a systematic approach to establish the limits to and characteristics of the neuroprotective efficacy of melatonin in experimental stroke. We have used systematic review and meta-analysis to assess the evidence for a protective effect of melatonin in animal models of focal cerebral ischaemia. Fourteen studies were identified describing procedures involving 432 animals. The point estimate for the effect of melatonin was a 42.8% (95% CI 39.3-46.3%) improvement in outcome. Efficacy was greater when ketamine anaesthesia was used, and melatonin was equally effective in permanent or temporary ischaemia. Study quality was generally poor by clinical trial standards, and no evidence was found regarding the efficacy of melatonin in focal cerebral ischaemia in aged, hypertensive or diabetic animals, in species other than rats, or at time windows beyond 2 hr. These findings demonstrate a marked efficacy of melatonin in animal models of focal cerebral ischaemia, identify priority areas for future animal research, and suggest melatonin as a candidate neuroprotective drug for human stroke.
褪黑素是一种用于缺血性中风的潜在神经保护药物。对于此类药物是否进行临床试验的任何决定都应基于对所有现有数据的客观评估。这种评估不仅应包括药物的疗效，还应包括其体内特性以及该疗效在时间窗、剂量、所用缺血物种和模型方面的局限性。在此，我们采用系统的方法来确定褪黑素在实验性中风中神经保护作用的局限性和特性。我们使用系统评价和荟萃分析来评估褪黑素在局灶性脑缺血动物模型中保护作用的证据。共鉴定出14项研究，描述了涉及432只动物的实验过程。褪黑素作用效果的点估计值为结局改善42.8%（95%置信区间39.3 - 46.3%）。使用氯胺酮麻醉时疗效更佳，褪黑素在永久性或暂时性缺血中同样有效。按照临床试验标准，研究质量普遍较差，未发现褪黑素在老年、高血压或糖尿病动物、大鼠以外的物种或超过2小时时间窗的局灶性脑缺血中的疗效证据。这些发现证明了褪黑素在局灶性脑缺血动物模型中的显著疗效，确定了未来动物研究的重点领域，并表明褪黑素是人类中风的一种潜在神经保护药物。
