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Lactate Administration Reduces Brain Injury and Ameliorates Behavioral Outcomes Following Neonatal Hypoxia-Ischemia.
Neuroscience ( IF 2.9 ) Pub Date : 2020-09-06 , DOI: 10.1016/j.neuroscience.2020.09.006
Isadora D'Ávila Tassinari 1 , Mirella Kielek Galvan Andrade 2 , Luciana Abreu da Rosa 1 , Mariana Leivas Müller Hoff 3 , Ricardo Ribeiro Nunes 1 , Everton Lopes Vogt 3 , Rafael Bandeira Fabres 3 , Eduardo Farias Sanches 4 , Carlos Alexandre Netto 5 , Ana Helena Paz 6 , Luciano Stürmer de Fraga 1
Affiliation  

Neonatal hypoxic-ischemic encephalopathy is a major cause of mortality and disability in newborns and the only standard approach for treating this condition is therapeutic hypothermia, which shows some limitations. Thus, putative neuroprotective agents have been tested in animal models. The present study evaluated the administration of lactate, a potential energy substrate of the central nervous system (CNS) in an animal model of hypoxia-ischemia (HI), that mimics in neonatal rats the brain damage observed in human newborns. Seven-day-old (P7) male and female Wistar rats underwent permanent common right carotid occlusion combined with an exposition to a hypoxic atmosphere (8% oxygen) for 60 minutes. Animals were assigned to four experimental groups: HI, HI+LAC, SHAM, SHAM+LAC. Lactate was administered intraperitoneally 30 minutes and 2 h after hypoxia in HI+LAC and SHAM+LAC groups. HI and SHAM groups received vehicle at the same time points. The volume of brain lesion was evaluated in P9. Animals underwent behavioral assessments: negative geotaxis, righting reflex (P8 and P14), and cylinder test (P20). Lactate administration reduced the volume of brain lesion and improved behavioral parameters after HI in both sexes. Thus, lactate administration could be a neuroprotective strategy for the treatment of neonatal HI, a disorder still affecting a significant percentage of human newborns.



中文翻译:

乳酸盐给药减少了新生儿缺氧缺血后的脑损伤并改善了行为结果。

新生儿缺氧缺血性脑病是新生儿死亡和致残的主要原因,治疗这种疾病的唯一标准方法是治疗性体温过低,这显示出一些局限性。因此,已经在动物模型中测试了推定的神经保护剂。本研究评估了缺氧缺血(HI)动物模型中乳酸盐的施用,乳酸盐是中枢神经系统(CNS)的潜在能量底物,其在新生大鼠中模拟了人类新生儿中观察到的脑损伤。七日龄(P7)雄性和雌性Wistar大鼠经历永久性的常见右颈动脉闭塞,并暴露于低氧气氛(8%氧气)中60分钟。将动物分为四个实验组:HI,HI + LAC,SHAM,SHAM + LAC。缺氧后30分钟和2小时,HI + LAC和SHAM + LAC组腹膜内给予乳酸盐。HI和SHAM组在同一时间接收车辆。在P9中评估脑病变的体积。对动物进行行为评估:负地势,扶正反射(P8和P14)和圆柱体测试(P20)。乳酸给药减少了HI后男女的脑部病变体积并改善了行为参数。因此,乳酸盐的给药可能是治疗新生儿HI的神经保护策略,这种疾病仍影响着很大比例的人类新生儿。和气缸测试(P20)。乳酸给药减少了HI后男女的脑部病变体积并改善了行为参数。因此,乳酸盐的给药可能是治疗新生儿HI的神经保护策略,这种疾病仍影响着很大比例的人类新生儿。和气缸测试(P20)。乳酸给药减少了HI后男女的脑部病变体积并改善了行为参数。因此,乳酸盐的给药可能是治疗新生儿HI的神经保护策略,这种疾病仍影响着很大比例的人类新生儿。

更新日期:2020-09-07
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