Brain Behav. 2026 Jul;16(7):e71588. doi: 10.1002/brb3.71588.
ABSTRACT
INTRODUCTION: Ischemic stroke is a leading cause of mortality and long-term disability, and many survivors develop persistent cognitive deficits that severely affect quality of life. Transient intraluminal filament MCAO models are widely used to study stroke pathophysiology and recovery, yet reported cognitive outcomes are inconsistent. Apparent impairments on spatial tasks such as the Morris water maze (MWM) may reflect residual sensorimotor limitations rather than true mnemonic dysfunction. Here, we performed a post hoc, longitudinal analysis of behavioral data from a 2-h tMCAO cohort to determine whether this model produces measurable deficits in spatial learning, memory, or cognitive flexibility.
MATERIAL AND METHODS: Male Wistar rats underwent Sham surgery or 2-h tMCAO using the intraluminal filament technique with laser Doppler confirmation of adequate occlusion (> 60% cerebral blood flow reduction) and reperfusion. Predefined quality criteria led to exclusion of animals with insufficient occlusion/reperfusion or hemorrhage, yielding final groups of Sham (n = 14) and tMCAO (n = 10). Behavioral testing was conducted by masked assessors across 30 days and included neurological scoring (days 1, 7, and 30), MWM acquisition (days 3-7) with probe testing (Day 8), reversal learning (days 24-28) with probe testing (Day 29), and open field assessments (days 3, 4, 5, and 29). Repeated-measures outcomes were analyzed using linear mixed-effects models.
RESULTS: tMCAO animals exhibited marked acute sensorimotor deficits on Day 1 that improved by Day 7 and largely resolved by Day 30. MWM performance showed intact spatial acquisition, preserved spatial memory on Day 8, and unimpaired reversal learning. Open field testing revealed no locomotor, exploratory, or anxiety-like deficits.
CONCLUSION: Within the testing window of this post hoc analysis (days 3-30), 2-h tMCAO in male Wistar rats produced transient sensorimotor impairment but no detectable spatial cognitive deficits. This exploratory finding raises the possibility that, under stringent quality control, this model may be less well-suited for studying post-stroke cognitive impairment, suggesting consideration of sensorimotor endpoints or alternative paradigms when cognitive dysfunction is the primary target. As a post hoc analysis, this study additionally exemplifies the principle of reduction within the 3Rs framework, deriving scientific value from an existing dataset without additional animals.
PMID:42422886 | DOI:10.1002/brb3.71588