A novel Microtus fortis MCAO model for ischemic stroke: surgical validation and transcriptomic insights

Ischemic stroke (IS) is a leading cause of death and long-term disability worldwide. Rodent models, particularly mice and rats, are widely used to investigate its underlying mechanisms. The Microtus fortis (reed vole) represents a promising alternative animal model due to its anatomical similarity to mice and cost-effectiveness; however, a middle cerebral artery occlusion (MCAO) model in this species has not yet been well characterized.

We established an MCAO model in Microtus fortis. Triphenyltetrazolium chloride (TTC) staining, neurological deficit scoring, and cerebral blood flow (CBF) measurements were used to evaluate model establishment. In addition, transcriptomic sequencing was performed on brain tissue from Microtus fortis following cerebral ischemia-reperfusion injury. Gene expression patterns were analyzed using correlation-based classification and functional enrichment analyses. Differentially expressed genes (DEGs) were further validated by quantitative PCR (qPCR).

The model demonstrated a significant reduction in CBF (58.86%, P < 0.001) and clear neurological deficits. A total of 1,707 DEGs were identified, including 1,379 upregulated and 328 downregulated genes, which were primarily enriched in immune and inflammatory pathways. Key genes (CCL4, LIF, IL6, and OSM [upregulated]; LOC126493158 and LOC126489791 [downregulated]) were successfully validated.

Microtus fortis represents a feasible MCAO model, offering both surgical practicality and cost advantages over traditional rodent models. This study provides foundational genomic and functional insights, supporting its potential application in translational stroke research.