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Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA

Spinal cord injury (SCI) is a debilitating condition that can cause impaired motor function or full paralysis. In the days to weeks following the initial mechanical injury to the spinal cord, inflammation and apoptosis can cause additional damage to the injured tissues. This secondary injury impairs...

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Autores principales: Crowley, Samuel T., Fukushima, Yuta, Uchida, Satoshi, Kataoka, Kazunori, Itaka, Keiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658833/
https://www.ncbi.nlm.nih.gov/pubmed/31344657
http://dx.doi.org/10.1016/j.omtn.2019.06.016
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author Crowley, Samuel T.
Fukushima, Yuta
Uchida, Satoshi
Kataoka, Kazunori
Itaka, Keiji
author_facet Crowley, Samuel T.
Fukushima, Yuta
Uchida, Satoshi
Kataoka, Kazunori
Itaka, Keiji
author_sort Crowley, Samuel T.
collection PubMed
description Spinal cord injury (SCI) is a debilitating condition that can cause impaired motor function or full paralysis. In the days to weeks following the initial mechanical injury to the spinal cord, inflammation and apoptosis can cause additional damage to the injured tissues. This secondary injury impairs recovery. Brain-derived neurotrophic factor is a secreted protein that has been shown to improve a variety of neurological conditions, including SCI, by promoting neuron survival and synaptic plasticity. This study treated a mouse model of contusion SCI using a single dose of brain-derived neurotrophic factor (BDNF) mRNA nanomicelles prepared with polyethylene glycol polyamino acid block copolymer directly injected into the injured tissue. BDNF levels in the injured spinal cord tissue were approximately doubled by mRNA treatment. Motor function was monitored using the Basso Mouse Scale and Noldus CatWalk Automated Gait Analysis System for 6 weeks post-injury. BDNF-treated mice showed improved motor function recovery, demonstrating the feasibility of mRNA delivery to treat SCI.
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spelling pubmed-66588332019-08-01 Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA Crowley, Samuel T. Fukushima, Yuta Uchida, Satoshi Kataoka, Kazunori Itaka, Keiji Mol Ther Nucleic Acids Article Spinal cord injury (SCI) is a debilitating condition that can cause impaired motor function or full paralysis. In the days to weeks following the initial mechanical injury to the spinal cord, inflammation and apoptosis can cause additional damage to the injured tissues. This secondary injury impairs recovery. Brain-derived neurotrophic factor is a secreted protein that has been shown to improve a variety of neurological conditions, including SCI, by promoting neuron survival and synaptic plasticity. This study treated a mouse model of contusion SCI using a single dose of brain-derived neurotrophic factor (BDNF) mRNA nanomicelles prepared with polyethylene glycol polyamino acid block copolymer directly injected into the injured tissue. BDNF levels in the injured spinal cord tissue were approximately doubled by mRNA treatment. Motor function was monitored using the Basso Mouse Scale and Noldus CatWalk Automated Gait Analysis System for 6 weeks post-injury. BDNF-treated mice showed improved motor function recovery, demonstrating the feasibility of mRNA delivery to treat SCI. American Society of Gene & Cell Therapy 2019-06-29 /pmc/articles/PMC6658833/ /pubmed/31344657 http://dx.doi.org/10.1016/j.omtn.2019.06.016 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Crowley, Samuel T.
Fukushima, Yuta
Uchida, Satoshi
Kataoka, Kazunori
Itaka, Keiji
Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA
title Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA
title_full Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA
title_fullStr Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA
title_full_unstemmed Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA
title_short Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA
title_sort enhancement of motor function recovery after spinal cord injury in mice by delivery of brain-derived neurotrophic factor mrna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658833/
https://www.ncbi.nlm.nih.gov/pubmed/31344657
http://dx.doi.org/10.1016/j.omtn.2019.06.016
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