Assessing the effects of aging on the Koizumi’s and Zea Longa’s methods and their suitability as mouse models for evaluating neurodegeneration post-ischemic stroke: A comparative study

Abstract

Koizumi’s and Zea Longa’s middle cerebral artery occlusion (MCAO) models (KMCAO and LMCAO) are commonly used methods in rodent ischemic stroke research. A key distinction between them lies in whether the blood flow through the common carotid artery (CCA) is maintained. Limited evidence exists regarding the systematic comparison of their pathophysiological characteristics, particularly considering the age of experimental mice. In this study, cerebral infarction outcomes were analyzed in mice aged 3, 6, 9, and 12 months. Mice aged 3–6 months exhibited minor cerebral infarction with KMCAO but substantial infarction with LMCAO, whereas differences diminished in 9–12-month-old mice. Comparable infarct severity in 3-month-old mice was achieved by inducing ischemia for 1.5 hours using KMCAO and for 1 hour using LMCAO, suggesting potential mechanistic similarities, subject to further research. LMCAO led to reperfusion injury due to preserved CCA perfusion, whereas KMCAO provided controlled ischemic insult via continuous CCA ligation. Both models confirmed that increased brain damage correlated with decreased neuronal nuclei expression and increased glial fibrillary acidic protein expression. These findings highlight the importance of selecting the MCAO model based on experimental objectives, age, and ischemia duration for the accurate modeling of ischemic and degenerative brain injury.