Exploring the Nexus: How Ferroptosis, Microglia, and Neuroinflammation Converge in Ischemic Stroke Pathogenesis.

Abstract

Ischemic stroke ranks as a leading cause of significant morbidity, mortality, and disability globally, with currently available therapeutic options remaining constrained. Prior research has elucidated that neuroinflammatory processes and pronounced microglial activation constitute critical underpinnings of ischemic stroke, precipitating neural system dysfunctions and facilitating disease exacerbation. Ferroptosis, an emergent paradigm, plays a pivotal role in this context. Defined by an iron-dependent cell death pathway, ferroptosis is distinguished by marked iron accumulation, lipid peroxidation, and the concomitant irreversible destruction of the plasma membrane, thereby contributing to the propagation of ischemic stroke through the accelerated neuronal dysfunction and aberrant microglial activation. Within this review, we initially delineate the constructs of ferroptosis, microglia, ischemic stroke, and their interconnections. Subsequently, we delve into the quintessential involvement of ferroptosis in the aberrant microglial activation associated with ischemic stroke's neuroinflammatory milieu, paving the path for the exploration of novel potential therapeutic targets against ischemic stroke.