Recombinant irisin treatment reduced inflammasome complex protein levels and microglial activation in middle-aged female rats post-stroke, promoting neuroprotection.
Does recombinant irisin therapy attenuate post-stroke neuroinflammation and ischemic injury in middle-aged female rats?
Recombinant irisin therapy attenuates neuroinflammation and microglial activation following ischemic stroke in a rat model, suggesting a potential neuroprotective mechanism.
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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<0.05) reduced ASC and caspase-1 levels in irisin-treated rats at 3 days post-tMCAO compared to saline controls, suggesting that irisin suppresses ASC expression or promotes its degradation to limit inflammasome assembly. Sholl analysis demonstrated that irisin-treated rats exhibited significantly (p<0.05) greater branching complexity at distal radii consistent with a more ramified state. Morphometric analysis also revealed 21% smaller soma areas in irisin-treated animals compared to saline. Together, our results indicate that irisin reduces microglial activation into an amoeboid, pro-inflammatory phenotype characterized by retracted processes and enlarged somas. Conclusion: The current findings suggest that irisin promotes neuroprotection by limiting inflammasome complex protein levels and microglial activation, though further studies are needed to clarify the underlying mechanisms.
Patel et al. (Thu,) reported a other. Recombinant irisin treatment reduced inflammasome complex protein levels and microglial activation in middle-aged female rats post-stroke, promoting neuroprotection.