Sex-dependent investigations of the temporal development of infarct size and blood-brain barrier permeability after photothrombotic stroke in mice - a pilot study.

Stroke is the second leading cause of death worldwide covering two major types: Hemorrhagic and ischemic stroke, with the latter being the most prevalent. The pathogenesis of ischemic stroke is complex including e.g. disruption of the blood-brain barrier (BBB) function of the brain capillaries. Moreover, women are disproportionately more affected by ischemic stroke in terms of mortality rates and disease burden. However, potential sex-dependent differences in the disease pathogenesis remains to be investigated. With this study, we aimed to investigate potential sex differences in infarct size and BBB permeability in a pre-clinical photothrombotic stroke model. Following, the induction of photothrombotic stroke in 9-10-week-old female and male mice, infarct size and BBB permeability were assessed in a temporal manner using magnetic resonance imaging (MRI). Over a time course spanning 2, 6, 24, 48, 72, and 96 h as well as 7 and 14days after photothrombotic stroke, no differences in infarct size between the sexes were observed. However, at 2 and 6 h after stroke, female mice appeared to have a more permeable BBB in the border regions of the infarct compared to the male mice using dynamic contrast enhanced MRI and T1 mapping. At remaining time points, sex-dependent differences in BBB permeability were more inconsistent when assessed by dynamic contrast enhanced MRI and T1 mapping thus challenging definitive conclusions. These findings indicate that BBB permeability, but not infarct size, is influenced by sex in the photothrombotic stroke model. It is the first study of its kind to examine these potential sex-dependent differences following photothrombotic stroke with MRI covering both acute and chronic time points. Therefore, it warrants further investigations into potential sex differences in BBB permeability as well as other potential consequences of stroke, both in additional preclinical ischemic stroke models and in a clinical setting.