Abstract 4369451: Critical window post-stroke is influenced by biological sex in mice

Sex differences in stroke outcomes are well documented, but it is unknown how males and females differ in their timing and duration of the critical window– a limited period of heightened plasticity when the brain is most responsive to rehabilitative interventions. While this window is typically defined by motor recovery, the timeline for tactile feedback remains poorly understood and may follow a distinct trajectory. To explore critical windows of tactile recovery, we developed an isolated tactile model of photothrombotic stroke in mice, which allowed us to investigate the effect of various rehabilitation timing on recovery. Mice were trained to perform a whisker-mediated tactile detection task to establish baseline levels of perception. Focal ischemia was induced using photothrombosis, and were given varying periods of rest (1, 7, or 14 days) before resuming training. While animals did not completely recover to pre-lesion levels, earlier retraining led to better recovery. Separating the groups by sex revealed significant differences in timing of the critical window post stroke. Male mice improved in tactile sensation with immediate (1d) training post-stroke, while female mice benefited more from delayed (7d) training. Minimal recovery was observed in the 14d rest group suggesting the tactile critical window occurs within the first week post-stroke for both sexes, but offset in timing. Our work reveals significant differences in the neuroplastic timeline between sexes. These results shed light on an understudied aspect of stroke rehabilitation and motivate future studies that incorporate sex-specific timing strategies for rehabilitation paradigms.