Cargando…

A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy

In the brain of full-term newborns, Hypoxic Ischemic Encephalopathy (HIE), a consequence of severe hypoxia and ischemia due to low cardiac output, is frequently observed and results in cerebral injuries with dramatic consequences for life. To investigate the physiopathology of HIE, several animal mo...

Descripción completa

Detalles Bibliográficos
Autores principales: Gotchac, Julien, Cardoit, Laura, Thoby-Brisson, Muriel, Brissaud, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131664/
https://www.ncbi.nlm.nih.gov/pubmed/34025552
http://dx.doi.org/10.3389/fneur.2021.637947
_version_ 1783694748147515392
author Gotchac, Julien
Cardoit, Laura
Thoby-Brisson, Muriel
Brissaud, Olivier
author_facet Gotchac, Julien
Cardoit, Laura
Thoby-Brisson, Muriel
Brissaud, Olivier
author_sort Gotchac, Julien
collection PubMed
description In the brain of full-term newborns, Hypoxic Ischemic Encephalopathy (HIE), a consequence of severe hypoxia and ischemia due to low cardiac output, is frequently observed and results in cerebral injuries with dramatic consequences for life. To investigate the physiopathology of HIE, several animal models have been developed, but none closely replicate human cases, mostly because they are based on a single carotid ligation protocol. In the present study we aimed to develop a novel and more accurate HIE model in juvenile (post-natal days (PND) 14–16) rats. For this, we induced a 9 min hypoxic cardiac arrest (CA) by stopping mechanical ventilation of intubated, ventilated and curarized rats followed by a cardiopulmonary resuscitation. To evaluate the consequences of the CA we performed radiological (cerebral MRI), behavioral (Open Field, Elevated Plus Maze, Fear Conditioning), and histological (Cresyl Violet and Fluoro-Jade B) testing on treated animals. We found that rats in the CA group developed an anxiolytic-like behavioral profile in adulthood without any locomotor impairment, nor memory deficits. However, MRI investigation performed early after CA failed to reveal any change in apparent diffusion coefficient (ADC) in brain tissue (including the hippocampus, striatum, and thalamus), suggesting no massive anatomical lesion had occurred. In contrast, signs of neurodegeneration were found in the Dentate Gyrus and the CA1 region of the hippocampus at day 1 post-CA, suggesting that the anxiolytic-like phenotype observed in adulthood could be related to an abnormal degeneration of this brain region beginning immediately after CA. Thus, our model, despite not representing a severe condition of HIE, nonetheless constitutes a potential model for studying mild, yet persistent and region-specific cerebral injury resulting from an acute oxygen deprivation.
format Online
Article
Text
id pubmed-8131664
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81316642021-05-20 A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy Gotchac, Julien Cardoit, Laura Thoby-Brisson, Muriel Brissaud, Olivier Front Neurol Neurology In the brain of full-term newborns, Hypoxic Ischemic Encephalopathy (HIE), a consequence of severe hypoxia and ischemia due to low cardiac output, is frequently observed and results in cerebral injuries with dramatic consequences for life. To investigate the physiopathology of HIE, several animal models have been developed, but none closely replicate human cases, mostly because they are based on a single carotid ligation protocol. In the present study we aimed to develop a novel and more accurate HIE model in juvenile (post-natal days (PND) 14–16) rats. For this, we induced a 9 min hypoxic cardiac arrest (CA) by stopping mechanical ventilation of intubated, ventilated and curarized rats followed by a cardiopulmonary resuscitation. To evaluate the consequences of the CA we performed radiological (cerebral MRI), behavioral (Open Field, Elevated Plus Maze, Fear Conditioning), and histological (Cresyl Violet and Fluoro-Jade B) testing on treated animals. We found that rats in the CA group developed an anxiolytic-like behavioral profile in adulthood without any locomotor impairment, nor memory deficits. However, MRI investigation performed early after CA failed to reveal any change in apparent diffusion coefficient (ADC) in brain tissue (including the hippocampus, striatum, and thalamus), suggesting no massive anatomical lesion had occurred. In contrast, signs of neurodegeneration were found in the Dentate Gyrus and the CA1 region of the hippocampus at day 1 post-CA, suggesting that the anxiolytic-like phenotype observed in adulthood could be related to an abnormal degeneration of this brain region beginning immediately after CA. Thus, our model, despite not representing a severe condition of HIE, nonetheless constitutes a potential model for studying mild, yet persistent and region-specific cerebral injury resulting from an acute oxygen deprivation. Frontiers Media S.A. 2021-05-05 /pmc/articles/PMC8131664/ /pubmed/34025552 http://dx.doi.org/10.3389/fneur.2021.637947 Text en Copyright © 2021 Gotchac, Cardoit, Thoby-Brisson and Brissaud. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Gotchac, Julien
Cardoit, Laura
Thoby-Brisson, Muriel
Brissaud, Olivier
A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy
title A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy
title_full A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy
title_fullStr A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy
title_full_unstemmed A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy
title_short A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy
title_sort rodent model of mild neonatal hypoxic ischemic encephalopathy
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131664/
https://www.ncbi.nlm.nih.gov/pubmed/34025552
http://dx.doi.org/10.3389/fneur.2021.637947
work_keys_str_mv AT gotchacjulien arodentmodelofmildneonatalhypoxicischemicencephalopathy
AT cardoitlaura arodentmodelofmildneonatalhypoxicischemicencephalopathy
AT thobybrissonmuriel arodentmodelofmildneonatalhypoxicischemicencephalopathy
AT brissaudolivier arodentmodelofmildneonatalhypoxicischemicencephalopathy
AT gotchacjulien rodentmodelofmildneonatalhypoxicischemicencephalopathy
AT cardoitlaura rodentmodelofmildneonatalhypoxicischemicencephalopathy
AT thobybrissonmuriel rodentmodelofmildneonatalhypoxicischemicencephalopathy
AT brissaudolivier rodentmodelofmildneonatalhypoxicischemicencephalopathy