Lactate administration causes long-term neuroprotective effects following neonatal hypoxia-ischemia.

Autor: Tassinari ID; Departamento de Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil; Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil., Zang J; Departamento de Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil; Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil., Ribeiro NH; Departamento de Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil., Martins BB; Departamento de Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil., Tauffer JVM; Departamento de Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil., Nunes RR; Departamento de Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil; Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil., Sanches EF; Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland., Sizonenko S; Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, Switzerland., Netto CA; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil; Departamento de Bioquímica, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil., Paz AH; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil; Departamento de Ciências Morfológicas, Federal University of Rio Grande do Sul (UFRGS), Sarmento Leite, 500, Porto Alegre 90050-170, Brazil; Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil., de Fraga LS; Departamento de Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos, 2600, Porto Alegre 90035-003, Brazil; Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil. Electronic address: lucianof@ufrgs.br.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2024 Nov; Vol. 381, pp. 114929. Date of Electronic Publication: 2024 Aug 20.
DOI: 10.1016/j.expneurol.2024.114929
Abstrakt: Neonatal hypoxia-ischemia (HI) is one of the main causes of mortality and long-term disabilities in newborns, and the only clinical approach to treat this condition is therapeutic hypothermia, which shows some limitations. Thus, putative neuroprotective agents have been tested in animal models of HI. Lactate is a preferential metabolic substrate of the neonatal brain and has already been shown to produce beneficial neuroprotective outcomes in neonatal animals exposed to HI. Here, we administered lactate as a treatment in neonatal rats previously exposed to HI and evaluated the impact of this treatment in adulthood. 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 one of 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, whereas HI and SHAM groups received vehicle. Animals were tested in the behavioral tasks of negative geotaxis and righting reflex (P8), cylinder test (P24), and the modified neurological severity score was calculated (P25). Open field (OF), and novel object recognition (NOR) were evaluated in adulthood. Animals were killed at P60, and the brains were harvested and processed to evaluate the volume of brain injury. Our results showed that lactate administration reduced the volume of brain lesion and improved sensorimotor and cognitive behaviors in neonatal, juvenile, and adult life in HI animals from both sexes. Thus, lactate administration might be considered as a potential neuroprotective strategy for the treatment of neonatal HI, which is a prevalent disorder affecting newborns.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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