Cargando…

Spinal Hyper-Excitability and Altered Muscle Structure Contribute to Muscle Hypertonia in Newborns After Antenatal Hypoxia-Ischemia in a Rabbit Cerebral Palsy Model

Rabbit kits after global antenatal hypoxic-ischemic injury exhibit motor deficits similar to humans with cerebral palsy. We tested several mechanisms previously implicated in spinal hyper-excitability after perinatal brain injury that may explain muscle hypertonia in newborns. Stiffness of hind limb...

Descripción completa

Detalles Bibliográficos
Autores principales: Synowiec, Sylvia, Lu, Jing, Yu, Lei, Goussakov, Ivan, Lieber, Richard, Drobyshevsky, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344443/
https://www.ncbi.nlm.nih.gov/pubmed/30705663
http://dx.doi.org/10.3389/fneur.2018.01183
_version_ 1783389426404032512
author Synowiec, Sylvia
Lu, Jing
Yu, Lei
Goussakov, Ivan
Lieber, Richard
Drobyshevsky, Alexander
author_facet Synowiec, Sylvia
Lu, Jing
Yu, Lei
Goussakov, Ivan
Lieber, Richard
Drobyshevsky, Alexander
author_sort Synowiec, Sylvia
collection PubMed
description Rabbit kits after global antenatal hypoxic-ischemic injury exhibit motor deficits similar to humans with cerebral palsy. We tested several mechanisms previously implicated in spinal hyper-excitability after perinatal brain injury that may explain muscle hypertonia in newborns. Stiffness of hind limb muscles during passive stretch, electromyogram, and spinal excitability by Hoffman reflex, were assessed in rabbit kits with muscle hypertonia after global hypoxic-ischemic brain injury and naïve controls. Affected muscle architecture, motoneuron morphology, primary afferents density, gliosis, and KCC2 expression transporter in the spinal cord were also examined. Decrease knee stiffness after anesthetic administration was larger, but residual stiffness was higher in hypertonic kits compared to controls. Hypertonic kits exhibited muscle shortening and atrophy, in both agonists and antagonists. Sarcomere length was longer in tibialis anterior in hypertonic kits than in controls. Hypertonic kits had decreased rate dependent depression and increased H(max)/M(max) in H-reflex. Motor neuron soma sizes, primary afferent density were not different between controls and hypertonic kits. Length of dendritic tree and ramification index were lower in hypertonic group. Gene expression of KCC2 was lower in hypertonic kits, but protein content was not different between the groups. In conclusion, while we found evidence of decreased supraspinal inhibitory control and increased excitability by H-reflex that may contribute to neuronal component in hypertonia, increased joint resistance to stretch was explained predominantly by changes in passive properties of muscles and joints. We did not find structural evidence of increased sensory afferent input or morphological changes in motoneurons that might explain increased excitability. Gliosis, observed in spinal gray matter, may contribute to muscle hypertonia.
format Online
Article
Text
id pubmed-6344443
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-63444432019-01-31 Spinal Hyper-Excitability and Altered Muscle Structure Contribute to Muscle Hypertonia in Newborns After Antenatal Hypoxia-Ischemia in a Rabbit Cerebral Palsy Model Synowiec, Sylvia Lu, Jing Yu, Lei Goussakov, Ivan Lieber, Richard Drobyshevsky, Alexander Front Neurol Neurology Rabbit kits after global antenatal hypoxic-ischemic injury exhibit motor deficits similar to humans with cerebral palsy. We tested several mechanisms previously implicated in spinal hyper-excitability after perinatal brain injury that may explain muscle hypertonia in newborns. Stiffness of hind limb muscles during passive stretch, electromyogram, and spinal excitability by Hoffman reflex, were assessed in rabbit kits with muscle hypertonia after global hypoxic-ischemic brain injury and naïve controls. Affected muscle architecture, motoneuron morphology, primary afferents density, gliosis, and KCC2 expression transporter in the spinal cord were also examined. Decrease knee stiffness after anesthetic administration was larger, but residual stiffness was higher in hypertonic kits compared to controls. Hypertonic kits exhibited muscle shortening and atrophy, in both agonists and antagonists. Sarcomere length was longer in tibialis anterior in hypertonic kits than in controls. Hypertonic kits had decreased rate dependent depression and increased H(max)/M(max) in H-reflex. Motor neuron soma sizes, primary afferent density were not different between controls and hypertonic kits. Length of dendritic tree and ramification index were lower in hypertonic group. Gene expression of KCC2 was lower in hypertonic kits, but protein content was not different between the groups. In conclusion, while we found evidence of decreased supraspinal inhibitory control and increased excitability by H-reflex that may contribute to neuronal component in hypertonia, increased joint resistance to stretch was explained predominantly by changes in passive properties of muscles and joints. We did not find structural evidence of increased sensory afferent input or morphological changes in motoneurons that might explain increased excitability. Gliosis, observed in spinal gray matter, may contribute to muscle hypertonia. Frontiers Media S.A. 2019-01-17 /pmc/articles/PMC6344443/ /pubmed/30705663 http://dx.doi.org/10.3389/fneur.2018.01183 Text en Copyright © 2019 Synowiec, Lu, Yu, Goussakov, Lieber and Drobyshevsky. 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(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
Synowiec, Sylvia
Lu, Jing
Yu, Lei
Goussakov, Ivan
Lieber, Richard
Drobyshevsky, Alexander
Spinal Hyper-Excitability and Altered Muscle Structure Contribute to Muscle Hypertonia in Newborns After Antenatal Hypoxia-Ischemia in a Rabbit Cerebral Palsy Model
title Spinal Hyper-Excitability and Altered Muscle Structure Contribute to Muscle Hypertonia in Newborns After Antenatal Hypoxia-Ischemia in a Rabbit Cerebral Palsy Model
title_full Spinal Hyper-Excitability and Altered Muscle Structure Contribute to Muscle Hypertonia in Newborns After Antenatal Hypoxia-Ischemia in a Rabbit Cerebral Palsy Model
title_fullStr Spinal Hyper-Excitability and Altered Muscle Structure Contribute to Muscle Hypertonia in Newborns After Antenatal Hypoxia-Ischemia in a Rabbit Cerebral Palsy Model
title_full_unstemmed Spinal Hyper-Excitability and Altered Muscle Structure Contribute to Muscle Hypertonia in Newborns After Antenatal Hypoxia-Ischemia in a Rabbit Cerebral Palsy Model
title_short Spinal Hyper-Excitability and Altered Muscle Structure Contribute to Muscle Hypertonia in Newborns After Antenatal Hypoxia-Ischemia in a Rabbit Cerebral Palsy Model
title_sort spinal hyper-excitability and altered muscle structure contribute to muscle hypertonia in newborns after antenatal hypoxia-ischemia in a rabbit cerebral palsy model
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344443/
https://www.ncbi.nlm.nih.gov/pubmed/30705663
http://dx.doi.org/10.3389/fneur.2018.01183
work_keys_str_mv AT synowiecsylvia spinalhyperexcitabilityandalteredmusclestructurecontributetomusclehypertoniainnewbornsafterantenatalhypoxiaischemiainarabbitcerebralpalsymodel
AT lujing spinalhyperexcitabilityandalteredmusclestructurecontributetomusclehypertoniainnewbornsafterantenatalhypoxiaischemiainarabbitcerebralpalsymodel
AT yulei spinalhyperexcitabilityandalteredmusclestructurecontributetomusclehypertoniainnewbornsafterantenatalhypoxiaischemiainarabbitcerebralpalsymodel
AT goussakovivan spinalhyperexcitabilityandalteredmusclestructurecontributetomusclehypertoniainnewbornsafterantenatalhypoxiaischemiainarabbitcerebralpalsymodel
AT lieberrichard spinalhyperexcitabilityandalteredmusclestructurecontributetomusclehypertoniainnewbornsafterantenatalhypoxiaischemiainarabbitcerebralpalsymodel
AT drobyshevskyalexander spinalhyperexcitabilityandalteredmusclestructurecontributetomusclehypertoniainnewbornsafterantenatalhypoxiaischemiainarabbitcerebralpalsymodel