Sumeyye KESKIN, Bahire Beyza YILDIZ, Kevser TANBEK, Suleyman SANDAL, Engin SAHNA
Annals of Medical Research - 2026;33(7):312-317
Aim: Cerebral ischemia-reperfusion (I/R) injury is an unavoidable outcome of reperfusion therapy following a stroke, initiating intricate death mechanisms at both cellular and molecular levels. Comprehending the molecular pathways that result in neuronal death post-stroke is crucial for the development of effective neuroprotective strategies. Ferroptosis is a mechanism of cell death characterized by iron-dependent lipid peroxidation and is believed to contribute to the damage associated with cerebral I/R injury. Materials and Methods: Thirty male Sprague-Dawley rats were randomly assigned to three experimental groups: Control, IR, and IR+REPOSTC (n=10). Cerebral ischemia was induced using the intraluminal filament technique for 60 minutes, and the animals were euthanized after a 24-hour reperfusion period. The femoral artery of the right hind limb of the rat underwent RePostC consisting of three cycles of 5 minutes of ischemia followed by 5 minutes of reperfusion. Triphenyl tetrazolium chloride (TTC) staining was used to measure infarct size. Results: Compared to the control group, the I/R group showed a significant increase in glutathione peroxidase 4 (GPX4) levels, while RePostC treatment significantly decreased GPX4 levels. Compared to the control group, the I/R group showed a significant decrease in hexokinase II (HKII) levels. The RePostC group, however, exhibited a substantial increase in these levels compared with the I/R group. Levels of arachidonic acid 12-lipoxygenase (ALOX12) and lipocalin 2 (LCN2) were significantly increased in the I/R group compared with the control group. No statistically significant difference was observed between the RePostC treatment group and the I/R group. Conclusion: Ferroptotic cell death plays a role in the damage that occurs after cerebral I/R. GPX4, ALOX12, LCN2, and HKII levels may serve as potential targets for the management of cerebral ischemia-reperfusion injury. The RePostC application may help protect against I/R injury by activating the body's own tolerance mechanisms.
