Pre-treatment with erythropoietin attenuates bilateral renal ischemia-induced cognitive impairments

Document Type: Research article

Authors

1 Intracellular Recording Lab, Kerman Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.

2 Physiology Department, Shiraz University of Medical Sciences, Shiraz, Iran.

3 ntracellular Recording Lab, Kerman Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.

4 Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.

5 Department of Neuroscience, Neuroscience Research Center, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran.

6 Department of Physiology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Kerman, Iran.

Abstract

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 (24h) 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 24h 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 24h 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 decreased significantly the BDNF protein expression in the hippocampus and EPO increased that 24h after operation.
These observations showed protective effect of EPO against cognitive dysfunctions following BRI 24h after reperfusion through increase in BDNF protein expression.

Keywords

Main Subjects