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Photomechanical Wave-Driven Delivery of siRNAs Targeting Intermediate Filament Proteins Promotes Functional Recovery after Spinal Cord Injury in Rats

The formation of glial scars after spinal cord injury (SCI) is one of the factors inhibiting axonal regeneration. Glial scars are mainly composed of reactive astrocytes overexpressing intermediate filament (IF) proteins such as glial fibrillary acidic protein (GFAP) and vimentin. In the current stud...

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Autores principales: Ando, Takahiro, Sato, Shunichi, Toyooka, Terushige, Kobayashi, Hiroaki, Nawashiro, Hiroshi, Ashida, Hiroshi, Obara, Minoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522723/
https://www.ncbi.nlm.nih.gov/pubmed/23272155
http://dx.doi.org/10.1371/journal.pone.0051744
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author Ando, Takahiro
Sato, Shunichi
Toyooka, Terushige
Kobayashi, Hiroaki
Nawashiro, Hiroshi
Ashida, Hiroshi
Obara, Minoru
author_facet Ando, Takahiro
Sato, Shunichi
Toyooka, Terushige
Kobayashi, Hiroaki
Nawashiro, Hiroshi
Ashida, Hiroshi
Obara, Minoru
author_sort Ando, Takahiro
collection PubMed
description The formation of glial scars after spinal cord injury (SCI) is one of the factors inhibiting axonal regeneration. Glial scars are mainly composed of reactive astrocytes overexpressing intermediate filament (IF) proteins such as glial fibrillary acidic protein (GFAP) and vimentin. In the current study, we delivered small interfering RNAs (siRNAs) targeting these IF proteins to SCI model rats using photomechanical waves (PMWs), and examined the restoration of motor function in the rats. PMWs are generated by irradiating a light-absorbing material with 532-nm nanosecond laser pulses from a Q-switched Nd:YAG laser. PMWs can site-selectively increase the permeability of the cell membrane for molecular delivery. Rat spinal cord was injured using a weight-drop device and the siRNA(s) solutions were intrathecally injected into the vicinity of the exposed SCI, to which PMWs were applied. We first confirmed the substantial uptake of fluorescence-labeled siRNA by deep glial cells; then we delivered siRNAs targeting GFAP and vimentin into the lesion. The treatment led to a significant improvement in locomotive function from five days post-injury in rats that underwent PMW-mediated siRNA delivery. This was attributable to the moderate silencing of the IF proteins and the subsequent decrease in the cavity area in the injured spinal tissue.
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spelling pubmed-35227232012-12-27 Photomechanical Wave-Driven Delivery of siRNAs Targeting Intermediate Filament Proteins Promotes Functional Recovery after Spinal Cord Injury in Rats Ando, Takahiro Sato, Shunichi Toyooka, Terushige Kobayashi, Hiroaki Nawashiro, Hiroshi Ashida, Hiroshi Obara, Minoru PLoS One Research Article The formation of glial scars after spinal cord injury (SCI) is one of the factors inhibiting axonal regeneration. Glial scars are mainly composed of reactive astrocytes overexpressing intermediate filament (IF) proteins such as glial fibrillary acidic protein (GFAP) and vimentin. In the current study, we delivered small interfering RNAs (siRNAs) targeting these IF proteins to SCI model rats using photomechanical waves (PMWs), and examined the restoration of motor function in the rats. PMWs are generated by irradiating a light-absorbing material with 532-nm nanosecond laser pulses from a Q-switched Nd:YAG laser. PMWs can site-selectively increase the permeability of the cell membrane for molecular delivery. Rat spinal cord was injured using a weight-drop device and the siRNA(s) solutions were intrathecally injected into the vicinity of the exposed SCI, to which PMWs were applied. We first confirmed the substantial uptake of fluorescence-labeled siRNA by deep glial cells; then we delivered siRNAs targeting GFAP and vimentin into the lesion. The treatment led to a significant improvement in locomotive function from five days post-injury in rats that underwent PMW-mediated siRNA delivery. This was attributable to the moderate silencing of the IF proteins and the subsequent decrease in the cavity area in the injured spinal tissue. Public Library of Science 2012-12-14 /pmc/articles/PMC3522723/ /pubmed/23272155 http://dx.doi.org/10.1371/journal.pone.0051744 Text en © 2012 Ando et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ando, Takahiro
Sato, Shunichi
Toyooka, Terushige
Kobayashi, Hiroaki
Nawashiro, Hiroshi
Ashida, Hiroshi
Obara, Minoru
Photomechanical Wave-Driven Delivery of siRNAs Targeting Intermediate Filament Proteins Promotes Functional Recovery after Spinal Cord Injury in Rats
title Photomechanical Wave-Driven Delivery of siRNAs Targeting Intermediate Filament Proteins Promotes Functional Recovery after Spinal Cord Injury in Rats
title_full Photomechanical Wave-Driven Delivery of siRNAs Targeting Intermediate Filament Proteins Promotes Functional Recovery after Spinal Cord Injury in Rats
title_fullStr Photomechanical Wave-Driven Delivery of siRNAs Targeting Intermediate Filament Proteins Promotes Functional Recovery after Spinal Cord Injury in Rats
title_full_unstemmed Photomechanical Wave-Driven Delivery of siRNAs Targeting Intermediate Filament Proteins Promotes Functional Recovery after Spinal Cord Injury in Rats
title_short Photomechanical Wave-Driven Delivery of siRNAs Targeting Intermediate Filament Proteins Promotes Functional Recovery after Spinal Cord Injury in Rats
title_sort photomechanical wave-driven delivery of sirnas targeting intermediate filament proteins promotes functional recovery after spinal cord injury in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522723/
https://www.ncbi.nlm.nih.gov/pubmed/23272155
http://dx.doi.org/10.1371/journal.pone.0051744
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