Abstract WP364: Recombinant irisin therapy attenuates post-stroke neuroinflammation and ischemic injury in middle-aged female rats

Introduction: Irisin, a muscle-derived hormone released during exercise, improves ischemic stroke outcomes, though the mechanisms remain unclear. The current study tests the hypothesis that post-stroke recombinant irisin therapy attenuates neuroinflammation, assessed by inflammasome complex protein levels and microglial reactivity. Methods: Middle-aged female Sprague-Dawley rats underwent transient middle cerebral artery occlusion (tMCAO; 90 min) and were divided into two cohorts. One cohort received saline or irisin (PeproTech, 0.2 µg/g BW) treatment at 4.5 h post-surgery and was survived 1 or 3 days for cortical tissue collection followed by Western blotting for apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1. A second cohort received saline or irisin treatment at 4.5 h post-tMCAO and weekly for 1 month. Following treatment, brains were collected for histological analysis of microglial activation. Two-dimensional morphometric analysis was performed using ImageJ, and Sholl analysis was conducted with the NIH ImageJ Sholl Analysis Plugin (v1.0). Results: Western blotting revealed significantly (p