Background: Ischemic cerebrovascular illness deprives the brain tissue of oxygen. Reperfusion, which can occur naturally through thrombus breakup or through therapeutic recanalization, causes the production of reactive oxygen species (ROS) and inflammation, which further destroys brain tissue.

Material and Methods: Rats were given general anesthesia and had their bilateral common carotid arteries occluded for half an hour before being reperfused for an hour, both with and without prior treatment with a combination of Bardoxolone 3 mg/kg and DMF 50 mg/kg intraperitoneally (i.p) for 24 hours. Histopathological scoring and quantification of Nrf2, TLR2 and TLR4 levels were performed on brain tissue samples.

Results: In the combination group, the level of nuclear Nrf2 increased significantly (P<0.05). In rats receiving the combination, brain tissue damage scores TLR2 and TLR4 were considerably reduced (P<0.05). The combination group's histological results showed fewer structural lesions.

Conclusions: Combination Nrf2 activators have a neuroprotective effect against cerebral I/R injury by upregulating nuclear Nrf2 protein and decreasing inflammation.

Keywords— bardoxolone, Cerebral I/R, DMF, Nrf2, and TLR.

DOI: http://doi.org/10.24086/biohs2022/paper.793