Roles of the Nrf2/HO-1 pathway in the anti-oxidative stress response to ischemia-reperfusion brain injury in rats
Authors: S-M Zhang
Y-C Lu
J-Y Tang
C-W Li
L-J Jiang
F-Y Che
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Nrf2/HO-1 pathway; oxidative stress; ischemia-reperfusion brain injury; rats; neurological functions
Affiliations: Department of Neurology, Linyi People's Hospital Affiliated to Shandong University, Linyi City, Shandong Province, China. .

Abstract:  Objective: The aim of this study was to investigate the roles of the Nrf2/HO-1 pathway in the responses to the oxidative stress created by ischemia-reperfusion brain injury in rats. Materials and methods: 54 healthy, adult, male SD rats were included in the study. Eighteen (18) rats were placed in the sham group. The ischemia-reperfusion model was created in the other 36 rats, among which 18 received injections of Nrf2 agonist before the surgery. The suture method was used to create artery occlusions in the right brain of the rats; and reperfusion was done after 90-minute ischemia (MCAO); while no suture was inserted in the sham group. At 3, 6, 12, 24, 48 and 72 hours after the modeling, their neurological functions were evaluated. Also, at different time points, rats were decapitated, and their fresh brain tissues were used to detect the infarct volume percentages by TTC staining and the brain water contents by the dry-wet weight method. The SOD contents in the brain tissue were measured by Xanthine oxidase assay. RT-PCR was used to detect the mRNA expression of HO-1 in the brain tissues, and western blot method was used to detect the expression level of HO-1 and Nrf-2. Results: The rats in the sham group had no obvious neurological defects; while those in the MCAO group showed significant neurological defects at all time points. The MCAO group had higher neurological evaluation scores than the sham group. TTC staining showed that infarct in the MCAO group kept increasing over time and peaked at 24h. Measurements of SOD found that the sham group had the highest SOD among the three groups, and showed no significant fluctuation over time. The MCAO group had much lower SOD activities than the sham group at all the time points. The higher the level of HO-1mRNA and protein expression in the brain tissue of rats in each group, the higher the degree of brain injury, but the lower the level of Nrf2 protein expression and the lower degree of brain injury. Nrf2 agonist markedly improved all these indicators in the rats which underwent the MCAO surgery. Conclusions: The expression of HO-1 after ischemia-reperfusion brain injury may contribute to the increased infarct volume. Activation of Nrf2 could improve the prognosis of ischemia-reperfusion brain injury. 

Retracted: No

PubPeer comments:
 Figure 3 was brought to my attention by a reader. * Boxes of the same color highlight brains that look more similar than expected. I only marked the left panels, leaving the rest for practice purposes. Cited by 32 other papers.  , 
 Comparing Tables III and IV, which are presented as measurements of very different things, I notice that the parameters in the left-most columns, as well as many numbers are remarkably similar.  , 
 Figure 6 has its own concerns.  ,