PA System in the Pathogenesis of Ischemic Stroke

Ischemic stroke remains a leading cause of morbidity and mortality worldwide, driven by complex pathophysiological mechanisms that make finding effective treatments challenging. PAs (plasminogen activators) play a critical role in fibrinolysis and vascular homeostasis and as such are important factors affecting stroke outcome. This review examines the complex relationships between ischemic stroke and PAs, highlighting their physiological, pathological, and therapeutic effects on ischemic stroke. We focus on recombinant tissue-type PA as the only Food and Drug Administration-approved thrombolytic agent, describing its clinical impact and associated obstacles impacting its wide-scale use, such as blood-brain barrier disruption and inflammation. Furthermore, emerging PA-based therapies and combination strategies are explored to address the limitations of recombinant tissue-type PA. By integrating mechanistic information with clinical developments, this review aims to provide insights for the advancement of PA-centered approaches to improve the safety and efficacy of stroke treatments.