Photothrombotic and middle cerebral artery occlusion models produce distinct neurovascular injury and sex-dependent outcomes.

Stroke remains among the top five causes of death and disability in the US. Sex differences in infarct evolution, inflammatory cascades, and functional recovery exist but the mechanisms underlying these differences are not yet well characterized. Preclinical research is needed to bridge these gaps in knowledge and toward this end we set out to clarify some of these differences by providing a systematic comparison of photothrombotic and transient middle cerebral artery occlusion stroke models in both sexes of C57/BL6 mice. We assessed infarct characteristics, vascular protein accumulation, and functional outcomes to generate practical guidance for selecting the most appropriate model for mechanistic or translational studies. Both models yield cortical inflammation and injury, but they interact with sex and diverge in vascular pathology and functional outcomes. MCAO may be the preferred approach where functional outcome is a critical endpoint by generating larger, variable cortical and striatal infarcts with a salvageable penumbra resulting in easy to detect behavioral deficits, particularly in males. PTS produces smaller but denser cortical lesions with sharp borders and marked accumulation of vascular proteins, particularly in female mice.