Treatment Effects of Acetazolamide on Ischemic Stroke: Meta-Analysis and Systematic Review

Background 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. Methods 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. Results After screening 376 articles, only five studies were included. We found that ACZ reduced brain edema in cerebral ischemia 24 h after onset(SMD,-2.00 ;95% CI,-3.57 to -0.43 ,p=0.01). ACZ also inhibited AQP-4 expression 24 h after onset( SMD=-1.46,;95% CI, -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. Conclusions ACZ inhibited AQP-4 and alleviated brain edema after ischemic stroke in the early stages but seemingly couldn’t improve the neurological function.