Ischemic Postconditioning Attenuates Bilateral Renal Ischemia-induced Cognitive Impairments

INTRODUCTION: Acute Kidney Injury (AKI) is a frequent complication of kidney failure with high mortality, leading to brain dysfunction. This study aimed to investigate the possible protective effect of Ischemic Postconditioning (IPo) against brain dysfunction induced by Bilateral Renal Ischemia (BRI). METHODS: Male Wistar rats underwent BRI, sham, or IPo surgery 24h and 1w after reperfusion. The rats’ explorative behaviors and motor function were evaluated by an open field, rotarod, and wire grip tests. The cognitive function was assessed by passive avoidance learning and Morris water maze tests. Western blotting was performed to evaluate hippocampal Brain-Derived Neurotrophic Factor (BDNF) expression. RESULTS: The impairment of balance function induced by BRI was not reversed; however, passive avoidance learning impairment was reversed by postconditioning 24h after reperfusion. IPo increased muscle strength compared to the BRI group; however, explorative behaviors and balance function had no difference 1w after reperfusion. BRI significantly decreased the BDNF protein expression in the hippocampus, and postconditioning increased 24h after reperfusion. CONCLUSION: The obtained results demonstrated the deleterious effect of BRI on cognitive and balance function 24h after reperfusion. IPo indicated a curative effect against cognitive dysfunction probably by enhancing BDNF protein expression in the hippocampus. HIGHLIGHTS: IPo improved passive avoidance learning impairment induced by BRI. IPo increased muscle strength compared to the BRI group. BRI significantly decreased the BDNF protein expression in the hippocampus. IPo increased BDNF protein expression 24h after reperfusion. PLAIN LANGUAGE SUMMARY: Acute kidney injury may be associated with numerous complications in different regions of brain, as it may alter the permeability of the blood-brain barrier, accumulate the toxins, decreased blood flow to the brain, increased risk of encephalopathy, higher mental dysfunctions like delirium, stroke, memory and thinking problems (dementia) in people with kidney failure. It has been demonstrated that the most common causes of mortality in acute kidney injury is brain dysfunction. Therefore, discovering new treatments can decrease the brain injuries and help the patients with kidney dysfunction to have a higher quality of life. Ischemic postconditioning, which refers to a series of brief ischemia and reperfusion cycles applied immediately at the site of the ischemic organ after reperfusion, results in reduced injuries induced by ischemia. The purpose of the current study was designed to investigate whether ischemic postconditioning exerts neuroprotective effects against brain dysfunctions induced by renal ischemia in rats. Results of this study demonstrated that acute kidney injury triggers distant organ dysfunction and leads to cognitive and balance dysfunction 24h after induction of renal ischemia and ischemic postconditioning protects the brain as a remote organ against cognitive dysfunction from the injury induced by renal ischemia.