Pre-Treatment with Erythropoietin Attenuates Bilateral Renal Ischemia-Induced Cognitive Impairments

Iran J Pharm Res. 2018 Spring;17(2):601-612.


One of the most common causes of mortality in acute kidney injury is brain dysfunction. Here we investigated the possible protective effect of erythropoietin (EPO) on cognitive impairments induced by bilateral renal ischemia (BRI). Eighty male Wistar rats were allocated into 8 groups: 1, 2) Sham +V (Vehicle), 3, 4) Sham+EPO, 5, 6) BRI+V, 7, 8) BRI+EPO. The groups followed by the reperfusion periods of 24hours (24 h) and 1week (1w). EPO or saline was administrated 30 min before surgery (1000 IU/kg, i.p). The cognitive function was assessed by passive avoidance learning and Morris water maze tests. Hippocampal brain-derived neurotrophic factor (BDNF) protein expression was assessed by western blotting. BUN (blood urea nitrogen) and creatinine (Cr) concentrations were significantly increased in BRI+V group 24 h after reperfusion. BRI+V rats had just an increased level of BUN but not Cr 1w after reperfusion. EPO reversed passive avoidance learning impairments observed in BRI+V group 24 h after reperfusion. There were no significant differences in spatial and passive avoidance learning between experimental groups 1w after reperfusion and histological evaluation confirmed the behavioral data. BRI significantly decreased the BDNF protein expression in the hippocampus and EPO increased that 24 h after operation. These observations showed protective effect of EPO against cognitive dysfunctions following BRI 24 h after reperfusion through increase in BDNF protein expression.

Keywords: Acute Kidney Injury; Bilateral Renal Ischemia; Cognitive Impairments; Erythropoietin; Memory.