Distinctions between the Koizumi and Zea Longa methods for middle cerebral artery occlusion (MCAO) model: a systematic review and meta-analysis of rodent data

Ischemic stroke in rodents is usually induced by intraluminal middle cerebral artery occlusion (MCAO) via the common carotid artery plugging filament invented by Koizumi et al. (MCAO-KM), or the external carotid artery plugging filament created by Zea Longa et al. (MCAO-LG). A systematic review of the distinctions between them is currently lacking. Here, we performed a meta-analysis in terms of model establishment, cerebral blood flow (CBF), and cerebral ischemia-reperfusion injury (CIRI) between them, Weighted Mean Differences and Standardized Mean Difference were used to analyze the combined effects, Cochrane's Q test and the I-2 statistic were applied to determine heterogeneity, sensitivity analysis and subgroup analysis were performed to explore the source of heterogeneity. Literature mining suggests that MCAO-KM brings shorter operation time (p = 0.007), higher probability of plugging filament (p < 0.001) and molding establishment (p = 0.006), lower possibility of subarachnoid hemorrhage (p = 0.02), larger infarct volume (p = 0.003), severer brain edema (p = 0.002), and neurological deficits (p = 0.03). Nevertheless, MCAO-LG shows a more adequate CBF after ischemia-reperfusion (p < 0.001), a higher model survival rate (p = 0.02), and a greater infarct rate (p = 0.007). In conclusion, the MCAO-KM method is simple to operate with a high modeling success rate, and is suitable for the study of brain edema under long-term hypoperfusion, while the MCAO-LG method is highly challenging for novices, and is suitable for the study of CIRI caused by complete ischemia-reperfusion. These findings are expected to benefit the selection of intraluminal filament MCAO models before undertaking ischemic stroke preclinical effectiveness trials.