Abstract：
BACKGROUND: Cilostazol, a phosphodiesterase III inhibitor, appears to be a promising agent for preventing cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Here, the authors perform a systematic review and meta-analysis to quantitatively assess the effects of cilostazol on brain structural and functional outcomes in animal models of cerebral ischemia and subarachnoid hemorrhage-induced cerebral vasospasm.
METHODS: By using the PRISMA guidelines, a search of the PubMed, Scopus, and Web of Science was conducted to identify relevant studies. Study quality of each included study for both systematic reviews were scored by using an adapted 15-item checklist from the Collaborative Approach to Meta-Analysis of Animal Data from Experimental Studies. We calculated a standardized mean difference as effect size for each comparison. For each outcome, comparisons were combined by using random-effects modeling to account for heterogeneity, with a restricted maximum likelihood estimate of between-study variance.
RESULTS: A total of 22 (median [Q1, Q3] quality score of 7 [5, 8]) and 6 (median [Q1, Q3] quality score of 6 [6, 6]) studies were identified for cerebral ischemia and subarachnoid hemorrhage-induced cerebral vasospasm, respectively. Cilostazol significantly reduced the infarct volume in cerebral ischemia models with a pooled standardized mean difference estimate of - 0.88 (95% confidence interval [CI] [- 1.07 to - 0.70], p < 0.0001). Cilostazol significantly reduced neurofunctional deficits in cerebral ischemia models with a pooled standardized mean difference estimate of - 0.66 (95% CI [- 1.06 to - 0.28], p < 0.0001). Cilostazol significantly improved the basilar artery diameter in subarachnoid hemorrhage-induced cerebral vasospasm with a pooled standardized mean difference estimate of 2.30 (95% CI [0.94 to 3.67], p = 0.001). Cilostazol also significantly improved the basilar artery cross-section area with a pooled standardized mean estimate of 1.88 (95% CI [0.33 to 3.43], p < 0.05). Overall, there was between-study heterogeneity and asymmetry in the funnel plot observed in all comparisons.
CONCLUSIONS: Published animal data support the overall efficacy of cilostazol in reducing infarct volume and neurofunctional deficits in cerebral ischemia models and cerebral vasospasm in subarachnoid hemorrhage models.
METHODS: By using the PRISMA guidelines, a search of the PubMed, Scopus, and Web of Science was conducted to identify relevant studies. Study quality of each included study for both systematic reviews were scored by using an adapted 15-item checklist from the Collaborative Approach to Meta-Analysis of Animal Data from Experimental Studies. We calculated a standardized mean difference as effect size for each comparison. For each outcome, comparisons were combined by using random-effects modeling to account for heterogeneity, with a restricted maximum likelihood estimate of between-study variance.
RESULTS: A total of 22 (median [Q1, Q3] quality score of 7 [5, 8]) and 6 (median [Q1, Q3] quality score of 6 [6, 6]) studies were identified for cerebral ischemia and subarachnoid hemorrhage-induced cerebral vasospasm, respectively. Cilostazol significantly reduced the infarct volume in cerebral ischemia models with a pooled standardized mean difference estimate of - 0.88 (95% confidence interval [CI] [- 1.07 to - 0.70], p < 0.0001). Cilostazol significantly reduced neurofunctional deficits in cerebral ischemia models with a pooled standardized mean difference estimate of - 0.66 (95% CI [- 1.06 to - 0.28], p < 0.0001). Cilostazol significantly improved the basilar artery diameter in subarachnoid hemorrhage-induced cerebral vasospasm with a pooled standardized mean difference estimate of 2.30 (95% CI [0.94 to 3.67], p = 0.001). Cilostazol also significantly improved the basilar artery cross-section area with a pooled standardized mean estimate of 1.88 (95% CI [0.33 to 3.43], p < 0.05). Overall, there was between-study heterogeneity and asymmetry in the funnel plot observed in all comparisons.
CONCLUSIONS: Published animal data support the overall efficacy of cilostazol in reducing infarct volume and neurofunctional deficits in cerebral ischemia models and cerebral vasospasm in subarachnoid hemorrhage models.
摘要：
背景：西洛他唑，磷酸二酯酶III抑制剂，似乎是预防动脉瘤性蛛网膜下腔出血患者脑缺血的有希望的药物。这里,作者进行了系统评价和荟萃分析,以定量评估西洛他唑对脑缺血和蛛网膜下腔出血诱导的脑血管痉挛动物模型中脑结构和功能结局的影响.
方法：通过使用PRISMA指南，搜索PubMed,Scopus,和WebofScience进行了相关研究。通过使用从合作方法到来自实验研究的动物数据的荟萃分析的适应性15项清单,对两个系统评价的每个纳入研究的研究质量进行评分。我们计算了标准化的平均差作为每次比较的效应大小。对于每个结果，通过使用随机效应模型来解释异质性，具有研究间方差的受限最大似然估计。
结果：总共22项（中位数[Q1，Q3]质量评分为7[5，8]）和6项（中位数[Q1，Q3]质量评分为6[6，6]）研究被确定为脑缺血和蛛网膜下腔出血引起的脑血管痉挛，分别。西洛他唑显著减少脑缺血模型的梗死体积，合并的标准化均差估计值为-0.88（95％置信区间[CI][-1.07至-0.70]，p<0.0001)。西洛他唑可显着降低脑缺血模型的神经功能缺损，合并的标准化平均差估计值为-0.66（95％CI[-1.06至-0.28]，p<0.0001)。西洛他唑显著改善蛛网膜下腔出血引起的脑血管痉挛的基底动脉直径，合并的标准化平均差值估计值为2.30(95%CI[0.94,3.67],p=0.001)。西洛他唑还显著改善了基底动脉横截面面积，合并的标准化平均估计值为1.88(95%CI[0.33,3.43],p<0.05)。总的来说,在所有比较中观察到的漏斗图中存在研究间异质性和不对称性.
结论：已发表的动物数据支持西洛他唑在减少脑缺血模型的梗死体积和神经功能缺损以及蛛网膜下腔出血模型的脑血管痉挛方面的总体疗效。
方法：通过使用PRISMA指南，搜索PubMed,Scopus,和WebofScience进行了相关研究。通过使用从合作方法到来自实验研究的动物数据的荟萃分析的适应性15项清单,对两个系统评价的每个纳入研究的研究质量进行评分。我们计算了标准化的平均差作为每次比较的效应大小。对于每个结果，通过使用随机效应模型来解释异质性，具有研究间方差的受限最大似然估计。
结果：总共22项（中位数[Q1，Q3]质量评分为7[5，8]）和6项（中位数[Q1，Q3]质量评分为6[6，6]）研究被确定为脑缺血和蛛网膜下腔出血引起的脑血管痉挛，分别。西洛他唑显著减少脑缺血模型的梗死体积，合并的标准化均差估计值为-0.88（95％置信区间[CI][-1.07至-0.70]，p<0.0001)。西洛他唑可显着降低脑缺血模型的神经功能缺损，合并的标准化平均差估计值为-0.66（95％CI[-1.06至-0.28]，p<0.0001)。西洛他唑显著改善蛛网膜下腔出血引起的脑血管痉挛的基底动脉直径，合并的标准化平均差值估计值为2.30(95%CI[0.94,3.67],p=0.001)。西洛他唑还显著改善了基底动脉横截面面积，合并的标准化平均估计值为1.88(95%CI[0.33,3.43],p<0.05)。总的来说,在所有比较中观察到的漏斗图中存在研究间异质性和不对称性.
结论：已发表的动物数据支持西洛他唑在减少脑缺血模型的梗死体积和神经功能缺损以及蛛网膜下腔出血模型的脑血管痉挛方面的总体疗效。
