Ischemia-reperfusion injury signaling pathway (IRI pathway)

Ischemia-reperfusion injury (IRI) is tissue damage occurring when blood supply returns to tissue after a period of ischemia (lack of oxygen). Restoration of blood flow paradoxically exacerbates the initial injury through mechanisms involving oxidative stress, calcium overload, inflammation, mitochondrial dysfunction, and activation of multiple cell death pathways. IRI is a central process in myocardial infarction, stroke, organ transplantation, and other acute tissue injuries. Molecularly, it involves ROS release, mitochondrial permeability transition pore opening, activation of inflammatory cytokines, and complex interplay among pathways such as Wnt, NF-κB, Notch, and Toll-like receptor signaling. Despite extensive study, no single molecular target defines the IRI pathway, and therapeutic strategies aim to modulate various nodes within these interconnected signaling networks [1][3][4][5][6][7].

Other names

Ischemia-reperfusion injuryReperfusion injuryIRIReoxygenation injury

Mechanisms include reduction of reactive oxygen species, inhibition of calcium overload, modulation of inflammatory pathways (e.g., NF-κB, Toll-like receptor 4), inhibition of mitochondrial permeability transition pore opening, and suppression of cytokine release.