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Mild Intrauterine Hypoperfusion Leads to Lumbar and Cortical Hyperexcitability, Spasticity, and Muscle Dysfunctions in Rats: Implications for Prematurity

Intrauterine ischemia-hypoxia is detrimental to the developing brain and leads to white matter injury (WMI), encephalopathy of prematurity (EP), and often to cerebral palsy (CP), but the related pathophysiological mechanisms remain unclear. In prior studies, we used mild intrauterine hypoperfusion (...

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Autores principales: Coq, Jacques-Olivier, Delcour, Maxime, Ogawa, Yuko, Peyronnet, Julie, Castets, Francis, Turle-Lorenzo, Nathalie, Montel, Valérie, Bodineau, Laurence, Cardot, Phillipe, Brocard, Cécile, Liabeuf, Sylvie, Bastide, Bruno, Canu, Marie-Hélène, Tsuji, Masahiro, Cayetanot, Florence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020763/
https://www.ncbi.nlm.nih.gov/pubmed/29973904
http://dx.doi.org/10.3389/fneur.2018.00423
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author Coq, Jacques-Olivier
Delcour, Maxime
Ogawa, Yuko
Peyronnet, Julie
Castets, Francis
Turle-Lorenzo, Nathalie
Montel, Valérie
Bodineau, Laurence
Cardot, Phillipe
Brocard, Cécile
Liabeuf, Sylvie
Bastide, Bruno
Canu, Marie-Hélène
Tsuji, Masahiro
Cayetanot, Florence
author_facet Coq, Jacques-Olivier
Delcour, Maxime
Ogawa, Yuko
Peyronnet, Julie
Castets, Francis
Turle-Lorenzo, Nathalie
Montel, Valérie
Bodineau, Laurence
Cardot, Phillipe
Brocard, Cécile
Liabeuf, Sylvie
Bastide, Bruno
Canu, Marie-Hélène
Tsuji, Masahiro
Cayetanot, Florence
author_sort Coq, Jacques-Olivier
collection PubMed
description Intrauterine ischemia-hypoxia is detrimental to the developing brain and leads to white matter injury (WMI), encephalopathy of prematurity (EP), and often to cerebral palsy (CP), but the related pathophysiological mechanisms remain unclear. In prior studies, we used mild intrauterine hypoperfusion (MIUH) in rats to successfully reproduce the diversity of clinical signs of EP, and some CP symptoms. Briefly, MIUH led to inflammatory processes, diffuse gray and WMI, minor locomotor deficits, musculoskeletal pathologies, neuroanatomical and functional disorganization of the primary somatosensory and motor cortices, delayed sensorimotor reflexes, spontaneous hyperactivity, deficits in sensory information processing, memory and learning impairments. In the present study, we investigated the early and long-lasting mechanisms of pathophysiology that may be responsible for the various symptoms induced by MIUH. We found early hyperreflexia, spasticity and reduced expression of KCC2 (a chloride cotransporter that regulates chloride homeostasis and cell excitability). Adult MIUH rats exhibited changes in muscle contractile properties and phenotype, enduring hyperreflexia and spasticity, as well as hyperexcitability in the sensorimotor cortex. Taken together, these results show that reduced expression of KCC2, lumbar hyperreflexia, spasticity, altered properties of the soleus muscle, as well as cortical hyperexcitability may likely interplay into a self-perpetuating cycle, leading to the emergence, and persistence of neurodevelopmental disorders (NDD) in EP and CP, such as sensorimotor impairments, and probably hyperactivity, attention, and learning disorders.
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spelling pubmed-60207632018-07-04 Mild Intrauterine Hypoperfusion Leads to Lumbar and Cortical Hyperexcitability, Spasticity, and Muscle Dysfunctions in Rats: Implications for Prematurity Coq, Jacques-Olivier Delcour, Maxime Ogawa, Yuko Peyronnet, Julie Castets, Francis Turle-Lorenzo, Nathalie Montel, Valérie Bodineau, Laurence Cardot, Phillipe Brocard, Cécile Liabeuf, Sylvie Bastide, Bruno Canu, Marie-Hélène Tsuji, Masahiro Cayetanot, Florence Front Neurol Neurology Intrauterine ischemia-hypoxia is detrimental to the developing brain and leads to white matter injury (WMI), encephalopathy of prematurity (EP), and often to cerebral palsy (CP), but the related pathophysiological mechanisms remain unclear. In prior studies, we used mild intrauterine hypoperfusion (MIUH) in rats to successfully reproduce the diversity of clinical signs of EP, and some CP symptoms. Briefly, MIUH led to inflammatory processes, diffuse gray and WMI, minor locomotor deficits, musculoskeletal pathologies, neuroanatomical and functional disorganization of the primary somatosensory and motor cortices, delayed sensorimotor reflexes, spontaneous hyperactivity, deficits in sensory information processing, memory and learning impairments. In the present study, we investigated the early and long-lasting mechanisms of pathophysiology that may be responsible for the various symptoms induced by MIUH. We found early hyperreflexia, spasticity and reduced expression of KCC2 (a chloride cotransporter that regulates chloride homeostasis and cell excitability). Adult MIUH rats exhibited changes in muscle contractile properties and phenotype, enduring hyperreflexia and spasticity, as well as hyperexcitability in the sensorimotor cortex. Taken together, these results show that reduced expression of KCC2, lumbar hyperreflexia, spasticity, altered properties of the soleus muscle, as well as cortical hyperexcitability may likely interplay into a self-perpetuating cycle, leading to the emergence, and persistence of neurodevelopmental disorders (NDD) in EP and CP, such as sensorimotor impairments, and probably hyperactivity, attention, and learning disorders. Frontiers Media S.A. 2018-06-15 /pmc/articles/PMC6020763/ /pubmed/29973904 http://dx.doi.org/10.3389/fneur.2018.00423 Text en Copyright © 2018 Coq, Delcour, Ogawa, Peyronnet, Castets, Turle-Lorenzo, Montel, Bodineau, Cardot, Brocard, Liabeuf, Bastide, Canu, Tsuji and Cayetanot. http://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 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
Coq, Jacques-Olivier
Delcour, Maxime
Ogawa, Yuko
Peyronnet, Julie
Castets, Francis
Turle-Lorenzo, Nathalie
Montel, Valérie
Bodineau, Laurence
Cardot, Phillipe
Brocard, Cécile
Liabeuf, Sylvie
Bastide, Bruno
Canu, Marie-Hélène
Tsuji, Masahiro
Cayetanot, Florence
Mild Intrauterine Hypoperfusion Leads to Lumbar and Cortical Hyperexcitability, Spasticity, and Muscle Dysfunctions in Rats: Implications for Prematurity
title Mild Intrauterine Hypoperfusion Leads to Lumbar and Cortical Hyperexcitability, Spasticity, and Muscle Dysfunctions in Rats: Implications for Prematurity
title_full Mild Intrauterine Hypoperfusion Leads to Lumbar and Cortical Hyperexcitability, Spasticity, and Muscle Dysfunctions in Rats: Implications for Prematurity
title_fullStr Mild Intrauterine Hypoperfusion Leads to Lumbar and Cortical Hyperexcitability, Spasticity, and Muscle Dysfunctions in Rats: Implications for Prematurity
title_full_unstemmed Mild Intrauterine Hypoperfusion Leads to Lumbar and Cortical Hyperexcitability, Spasticity, and Muscle Dysfunctions in Rats: Implications for Prematurity
title_short Mild Intrauterine Hypoperfusion Leads to Lumbar and Cortical Hyperexcitability, Spasticity, and Muscle Dysfunctions in Rats: Implications for Prematurity
title_sort mild intrauterine hypoperfusion leads to lumbar and cortical hyperexcitability, spasticity, and muscle dysfunctions in rats: implications for prematurity
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020763/
https://www.ncbi.nlm.nih.gov/pubmed/29973904
http://dx.doi.org/10.3389/fneur.2018.00423
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