Examining a role for irisin in treating cerebral ischemia

Stroke is a leading cause of death and disability, with ischemic stroke representing most cases. Age is the most significant nonmodifiable risk factor for stroke, and with an aging population, there is an urgent need for effective prevention and treatment strategies. Physical inactivity is a strong risk factor for stroke, and exercise has long been held as a promising approach to improve poststroke outcomes. During exercise, the myokine irisin is released as a product of a type 1 membrane protein cleavage that is encoded by the fibronectin type III domain containing 5 (FNDC5) gene. This review summarizes recent literature on irisin's role in ischemic stroke, examining central effects, stroke risk, poststroke functional outcomes, and exogenous administration. Irisin has value as a prognostic marker for risk stratification. Low levels of irisin correlate with worse outcomes and higher mortality in patients with ischemic stroke. Irisin may also be a key to the benefits of exercise, particularly for high-intensity resistance training, which significantly increases irisin levels. Beyond exercise, exogenous irisin is neuroprotective in murine models, reducing brain edema, inflammation, and apoptosis, and increasing blood-brain barrier integrity and brain-derived neurotrophic factor levels. This underscores irisin's potential to mitigate ischemic damage and promote recovery. Human trials are necessary to validate these findings and explore the feasibility of irisin-based interventions in acute stroke care. This review lays a foundation for future research to clarify irisin's therapeutic benefits, establish optimal exercise protocols, and explore exogenous irisin as a novel intervention for ischemic stroke.