Establishing the First Posterior Ischemic Stroke Model In Mice

Posterior circulation ischemic stroke is underrepresented in preclinical research despite its clinical importance and diagnostic challenges in the emergency department. Most murine stroke models target anterior circulation territories and do not replicate cerebellar ischemia. We sought to establish and validate a reproducible mouse model of posterior ischemic stroke via microsurgical occlusion of the superior cerebellar artery (SCA) to support translational research relevant to acute patient care.

Adult mice underwent microsurgical exposure and cauterization of the right SCA under ketamine/xylazine anesthesia. Anatomical landmarks were identified using sagittal and lambdoid sutures, followed by a posterior incision behind the right ear and reflection of the trapezius muscle to expose the occipital skull overlying the cerebellum. The SCA was visualized through the translucent skull, accessed via focal drilling, and cauterized under operative microscopy. Sham animals underwent identical procedures without arterial cauterization. Motor coordination was assessed using an accelerating rotarod protocol (0-40 RPM over 180 seconds). Mice were trained pre-operatively (three trials per day for three days) and tested at 24, 48, and 72 hours post-operatively. Brains were harvested for TTC staining to grossly assess infarction. High-definition surgical videos were recorded to document and standardize the operative technique.

Stroke animals demonstrated a decline in rotarod performance relative to baseline, corresponding to a 20.6% reduction in latency to fall (79.4% of baseline; 95% CI 69.1-89.7%). In contrast, sham animals exhibited progressive improvement consistent with continued motor learning, achieving 121.8% of baseline performance (95% CI 57.2-186.4%). TTC staining revealed visually apparent cerebellar infarction in stroke animals, while sham animals showed no evidence of ischemic injury.

This study establishes the first reproducible murine model of posterior circulation ischemic stroke via selective SCA occlusion. The model produces consistent functional deficits and gross evidence of cerebellar infarction, providing a scalable platform for translational posterior stroke research. Future direction will include infarct quantification, immunohistochemistry, expanded behavioral testing, and biomarker identification.