Comparative pathophysiology and pathology of transient ischemic attack, ischemic stroke, and reperfusion injury: Mechanistic and therapeutic perspectives.

Transient ischemic attack (TIA), ischemic stroke, and ischemia-reperfusion (IR) injury represent a continuum of cerebrovascular disorders with distinct clinical and pathophysiological features. While TIA is classically considered benign, recent studies reveal subtle yet potentially deleterious neuronal and glial changes. Ischemic stroke typically results in sustained hypoperfusion, infarction, blood-brain barrier (BBB) disruption, and robust neuroinflammatory cascades. IR injury, though potentially beneficial through vessel recanalization, paradoxically induces oxidative stress, cytokine release, and secondary infarction. This review systematically compares the molecular, histological, and behavioral profiles of these three conditions. Key differences include patterns of neuronal death, glial activation, oxidative damage, and BBB integrity. Human neuroimaging data and animal model histology are integrated to illustrate characteristic features across the spectrum. We also discuss current experimental models and their translational relevance, highlighting challenges in modeling comorbidities and chronic outcomes. Precision medicine strategies considering sex, age, and immune background-are emphasized as essential for advancing diagnostics and optimizing therapeutic efficacy. Emerging multimodal therapies, including pharmacological agents, stem cells, gene editing, and nanomedicine, hold promise but require rigorous validation. A deeper mechanistic understanding of each condition will be crucial for tailoring treatment strategies and bridging the translational gap in ischemic cerebrovascular disease.