Wang Peng-Fei, Zhou Yu, Fang Huang, Lin Sen, Wang Yan-Chun, Liu Yong, Xia Jun, Eslick Guy D, Yang Qing-Wu
Department of Neurology, Xinqiao Hospital, The Second Affiliated Hospital, The Third Military Medical University, Chongqing, China.
Department of Development and Regeneration Key Laboratory of Sichuan Province, Department of Histoembryology and Neurobiology, Chengdu Medical College, Chengdu, China.
Transl Neurosci. 2015 Feb 11;6(1):47-58. doi: 10.1515/tnsci-2015-0006. eCollection 2015.
There are numerous potential treatments assessed for acute cerebral ischemia using animal models. This study aimed to assess the effect of these treatments in terms of infarct size and neurobehavioral change. This meta-analysis was conducted to determine if any of these treatments provide a superior benefit so that they might be used on humans.
A systematic search was conducted using several electronic databases for controlled animal studies using only nonsurgical interventions for acute cerebral ischemia. A random-effects model was used.
After an extensive literature search, 145 studies were included in the analysis. These studies included 1408 treated animals and 1362 control animals. Treatments that had the most significant effect on neurobehavioral scales included insulin, various antagonists, including N-methyl-D-aspartate (NMDA) receptor antagonist ACEA1021, calmodulin antagonist DY-9760e, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist YM872, and antiviral agents. Treatments providing the greatest effect on infarct size included statins, sphingosine-1-phosphate agonist (fingolimod), alcohol, angiotensin, and leukotrienes. Treatments offering the greatest reduction in brain water content included various agonists, including sphingosine-1-phosphate agonist fingolimod, statins, and peroxisome proliferator-activated receptor gamma (PPAR-γ). Treatment groups with more than one study all had high heterogeneity (I > 80%), however, using meta-regression we determined several sources of heterogeneity including sample size of the treatment and control groups, the occlusion time, but not the year when the study was conducted.
Some treatments stand out when compared to others for acute cerebral ischemia in animals. Greater replication of treatment studies is required before any treatments are selected for future human trials.
利用动物模型对急性脑缺血评估了众多潜在治疗方法。本研究旨在从梗死面积和神经行为变化方面评估这些治疗方法的效果。进行这项荟萃分析以确定这些治疗方法中是否有任何一种能带来更显著的益处，从而可应用于人类。
使用多个电子数据库对仅采用非手术干预治疗急性脑缺血的对照动物研究进行系统检索。采用随机效应模型。
经过广泛的文献检索，145项研究纳入分析。这些研究包括1408只接受治疗的动物和1362只对照动物。对神经行为量表影响最显著的治疗方法包括胰岛素、各种拮抗剂，包括N - 甲基 - D - 天冬氨酸（NMDA）受体拮抗剂ACEA1021、钙调蛋白拮抗剂DY - 9760e、α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）受体拮抗剂YM872以及抗病毒药物。对梗死面积影响最大的治疗方法包括他汀类药物、鞘氨醇 - 1 - 磷酸激动剂（芬戈莫德）、酒精、血管紧张素和白三烯。脑含水量降低最显著的治疗方法包括各种激动剂，包括鞘氨醇 - 1 - 磷酸激动剂芬戈莫德、他汀类药物和过氧化物酶体增殖物激活受体γ（PPAR - γ）。有多项研究的治疗组均具有高度异质性（I>80%），然而，通过荟萃回归我们确定了几个异质性来源，包括治疗组和对照组的样本量、闭塞时间，但不包括研究开展的年份。
在动物急性脑缺血治疗中，某些治疗方法比其他方法更为突出。在选择任何治疗方法进行未来人体试验之前，需要对治疗研究进行更多的重复验证。
