Abstract

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 marked by iron-dependent lipid peroxidation, believed to play a role in 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 via the intraluminal filament technique for 60 minutes; the animals were euthanized after the 24-hour reperfusion period. The right hind paw femoral artery of the rat underwent RePostC in three cycles of 5 minutes of ischemia followed by 5 minutes of reperfusion. Triphenyl tetrazolium chloride (TTC) staining was used to measure the size of the infarct.

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, on the other hand, recorded a large increase in these levels compared to the I/R group. There was a significant increase in arachidonic acid 12-lipoxygenase (ALOX12) and lipocalin 2 (LCN2) levels between the I/R group and the control group. There was no statistically significant difference between the RePostC treatment group and the I/R group.

Key words: Cerebral I/R, Ferroptosis, GPX4, ALOX12