Abstract：
Ischemic stroke significantly contributes to high mortality and disability rates. Cerebral edema is a common consequence of ischemic stroke and can lead to aggravation or even death. Current treatment strategies are limited to decompressive craniectomy and the intravascular administration of hypertonic drugs, which have significant side effects. Acetazolamide (ACZ) plays a therapeutic role in cerebral edema by inhibiting aquaporin-4 (AQP-4) and improving collateral circulation. This study aimed to perform a meta-analysis and systematic review of ACZ therapy for ischemic stroke and evaluate its efficacy in animal models.
We searched Embase, Cochrane Library, PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature Database until April 2023 for studies on ACZ in ischemic animal models. The quality of the animal trials was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Stroke.
After screening 376 articles, only 5 studies were included. We found that ACZ reduced brain edema in cerebral ischemia 24 hours after onset (standard mean difference, -2.00; 95% confidence interval, -3.57 to -0.43, P = 0.01). ACZ also inhibited AQP-4 expression 24 hours after onset (standard mean difference-1.46; 95% confidence interval, -2.01 to -0.91, P < 0.001). Brain edema and AQP-4 expression also showed a declining trend on the third day after onset, although there were not enough data to support this. The effect of ACZ on brain ischemia in animals\' neurological function is uncertain because of the limited research data.
ACZ inhibited AQP-4 and alleviated brain edema after ischemic stroke in the early stages but seemingly could not improve the neurological function.
We searched Embase, Cochrane Library, PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature Database until April 2023 for studies on ACZ in ischemic animal models. The quality of the animal trials was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Stroke.
After screening 376 articles, only 5 studies were included. We found that ACZ reduced brain edema in cerebral ischemia 24 hours after onset (standard mean difference, -2.00; 95% confidence interval, -3.57 to -0.43, P = 0.01). ACZ also inhibited AQP-4 expression 24 hours after onset (standard mean difference-1.46; 95% confidence interval, -2.01 to -0.91, P < 0.001). Brain edema and AQP-4 expression also showed a declining trend on the third day after onset, although there were not enough data to support this. The effect of ACZ on brain ischemia in animals\' neurological function is uncertain because of the limited research data.
ACZ inhibited AQP-4 and alleviated brain edema after ischemic stroke in the early stages but seemingly could not improve the neurological function.
摘要：
背景：缺血性卒中导致高死亡率和致残率。脑水肿是缺血性中风的常见后果，可导致加重甚至死亡。目前的治疗策略仅限于去骨瓣减压术和高渗药物的血管内给药，有明显的副作用。乙酰唑胺（ACZ）通过抑制水通道蛋白-4（AQP-4）和改善侧支循环而在脑水肿中起治疗作用。本研究旨在对ACZ治疗缺血性卒中的疗效进行Meta分析和系统评价。
方法：我们搜索了Embase，科克伦图书馆,PubMed,WebofScience,中国国家知识基础设施，万方数据库,和中国生物医学文献数据库，直到2023年4月，用于缺血动物模型中的ACZ研究。使用来自实验性中风的动物数据的荟萃分析和审查的协作方法来评估动物试验的质量。
结果：筛选376篇文章后，仅纳入5项研究。我们发现ACZ减轻了脑缺血发作后24小时的脑水肿（SMD，-2.00；95%CI，-3.57至-0.43，p=0.01)。ACZ还在发病后24小时抑制AQP-4的表达(SMD=-1.46,;95%CI,-2.01至-0.91,p<0.001)。脑水肿和AQP-4表达在发病后第3天也呈下降趋势,尽管没有足够的数据来支持这一点。由于研究数据有限，ACZ对动物脑缺血神经功能的影响尚不确定。
结论：ACZ能抑制AQP-4，减轻缺血性脑卒中后早期脑水肿，但似乎不能改善神经功能。
方法：我们搜索了Embase，科克伦图书馆,PubMed,WebofScience,中国国家知识基础设施，万方数据库,和中国生物医学文献数据库，直到2023年4月，用于缺血动物模型中的ACZ研究。使用来自实验性中风的动物数据的荟萃分析和审查的协作方法来评估动物试验的质量。
结果：筛选376篇文章后，仅纳入5项研究。我们发现ACZ减轻了脑缺血发作后24小时的脑水肿（SMD，-2.00；95%CI，-3.57至-0.43，p=0.01)。ACZ还在发病后24小时抑制AQP-4的表达(SMD=-1.46,;95%CI,-2.01至-0.91,p<0.001)。脑水肿和AQP-4表达在发病后第3天也呈下降趋势,尽管没有足够的数据来支持这一点。由于研究数据有限，ACZ对动物脑缺血神经功能的影响尚不确定。
结论：ACZ能抑制AQP-4，减轻缺血性脑卒中后早期脑水肿，但似乎不能改善神经功能。
