Lactate Administration Reduces Brain Injury and Ameliorates Behavioral Outcomes Following Neonatal Hypoxia–Ischemia. (10th November 2020)

• Record Type: Journal Article
• Authors: Tassinari, Isadora D'Ávila; Andrade, Mirella Kielek Galvan; da Rosa, Luciana Abreu; Hoff, Mariana Leivas Müller; Nunes, Ricardo Ribeiro; Vogt, Everton Lopes; Fabres, Rafael Bandeira; Sanches, Eduardo Farias; Netto, Carlos Alexandre; Paz, Ana Helena; de Fraga, Luciano Stürmer
• Is Part Of: Neuroscience. Volume 448(2020)
• Page Start: 191
• Page End: 205
• Publication Date: 2020-11-10
• Subjects: HI hypoxia–ischemia -- TH therapeutic hypothermia -- TBI traumatic brain injury; neurodevelopment -- lactate -- neuroprotection -- neonatal hypoxia–ischemia; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.09.006
• Languages: English
• ISSNs: 0306-4522

Abstract

Graphical abstract: Highlights: Neonatal hypoxia–ischemia is a main cause of mortality and disability in human newborns. Lactate is a potential energy substrate for the neonatal brain. An intraperitoneal injection of lactate is able to elevate the cerebral levels of lactate. Administration of lactate reduces the volume of brain lesion caused by neonatal hypoxia–ischemia. Neonatal hypoxia–ischemia causes behavioral deficits that are ameliorated by lactate administration. Abstract: 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 min. Animals were assigned to four experimental groups: HI, HI + LAC, SHAM, SHAM + LAC. Lactate was administered intraperitoneally 30 min 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.