Tahamtan Mahshid, Nazari Abbas, Aghaei Iraj, Shabani Mohammad
Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
Basic Clin Neurosci. 2021 Nov-Dec;12(6):789-804. doi: 10.32598/bcn.2021.1941.1. Epub 2021 Nov 1.
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).
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.
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.
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.
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.
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.
急性肾损伤（AKI）是肾衰竭常见的并发症，死亡率高，可导致脑功能障碍。本研究旨在探讨缺血后处理（IPo）对双侧肾缺血（BRI）所致脑功能障碍可能的保护作用。
雄性Wistar大鼠在再灌注后24小时和1周接受BRI、假手术或IPo手术。通过旷场试验、转棒试验和握力试验评估大鼠的探索行为和运动功能。通过被动回避学习和莫里斯水迷宫试验评估认知功能。采用蛋白质免疫印迹法评估海马脑源性神经营养因子（BDNF）的表达。
BRI所致的平衡功能损害未得到逆转；然而，再灌注后24小时进行后处理可逆转被动回避学习障碍。与BRI组相比，IPo增加了肌肉力量；然而，再灌注1周后探索行为和平衡功能无差异。BRI显著降低海马中BDNF蛋白表达，再灌注后24小时进行后处理可使其增加。
所得结果表明BRI在再灌注后24小时对认知和平衡功能具有有害作用。IPo可能通过增强海马中BDNF蛋白表达对认知功能障碍具有治疗作用。
IPo改善了BRI所致的被动回避学习障碍。与BRI组相比，IPo增加了肌肉力量。BRI显著降低海马中BDNF蛋白表达。再灌注后24小时IPo增加了BDNF蛋白表达。
急性肾损伤可能与脑不同区域的多种并发症相关，因为它可能改变血脑屏障的通透性、蓄积毒素、减少脑血流量、增加脑病风险、导致肾衰竭患者出现更严重的精神功能障碍如谵妄、中风、记忆和思维问题（痴呆）。已证明急性肾损伤最常见的死亡原因是脑功能障碍。因此，发现新的治疗方法可减少脑损伤，帮助肾功能不全患者提高生活质量。缺血后处理是指在再灌注后立即在缺血器官部位施加一系列短暂的缺血和再灌注循环，可减轻缺血所致损伤。本研究的目的是调查缺血后处理是否对大鼠肾缺血所致脑功能障碍具有神经保护作用。本研究结果表明急性肾损伤引发远处器官功能障碍，导致肾缺血诱导后24小时出现认知和平衡功能障碍，缺血后处理可保护脑这一远处器官免受肾缺血所致损伤引起的认知功能障碍。
