Cargando…

Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats

After spinal cord injury (SCI), secondary injury results in an expanding area of glial cell apoptosis. Oligodendrocyte precursor cells (OPCs) actively proliferate after SCI, but many of these cells undergo apoptosis. One of the factors that exacerbates secondary injury is endoplasmic reticulum (ER)...

Descripción completa

Detalles Bibliográficos
Autores principales: Imai, Takeshi, Katoh, Hiroyuki, Suyama, Kaori, Kuroiwa, Masahiro, Yanagisawa, Sho, Watanabe, Masahiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867572/
https://www.ncbi.nlm.nih.gov/pubmed/29510579
http://dx.doi.org/10.3390/jcm7030046
_version_ 1783308989930405888
author Imai, Takeshi
Katoh, Hiroyuki
Suyama, Kaori
Kuroiwa, Masahiro
Yanagisawa, Sho
Watanabe, Masahiko
author_facet Imai, Takeshi
Katoh, Hiroyuki
Suyama, Kaori
Kuroiwa, Masahiro
Yanagisawa, Sho
Watanabe, Masahiko
author_sort Imai, Takeshi
collection PubMed
description After spinal cord injury (SCI), secondary injury results in an expanding area of glial cell apoptosis. Oligodendrocyte precursor cells (OPCs) actively proliferate after SCI, but many of these cells undergo apoptosis. One of the factors that exacerbates secondary injury is endoplasmic reticulum (ER) stress. In this study, we tested the effects of amiloride treatment on the fate of OPCs during secondary injury in rats. Amiloride is an FDA-approved diuretic for treating hypertension, which in rats enhances ER stress response and suppresses the apoptosis of glial cells after SCI. A severe contusive SCI was induced in Sprague-Dawley rats using an infinite horizon (IH)-impactor (200 kdyne). Beginning 24 h after SCI, 10 mg/kg of amiloride or phosphate buffered saline (PBS) was intraperitoneally administered daily for a period of 14 days. At 7, 14, 28, and 56 days after SCI, animals were subsequently euthanized in order to analyze the injured spinal cord. We labeled proliferating OPCs and demonstrated that amiloride treatment led to greater numbers of OPCs and oligodendrocytes in the injured spinal cord. Increased myelin basic protein (MBP) expression levels were observed, suggesting that increased numbers of mature oligodendrocytes led to improved remyelination, significantly improving motor function recovery.
format Online
Article
Text
id pubmed-5867572
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-58675722018-04-09 Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats Imai, Takeshi Katoh, Hiroyuki Suyama, Kaori Kuroiwa, Masahiro Yanagisawa, Sho Watanabe, Masahiko J Clin Med Article After spinal cord injury (SCI), secondary injury results in an expanding area of glial cell apoptosis. Oligodendrocyte precursor cells (OPCs) actively proliferate after SCI, but many of these cells undergo apoptosis. One of the factors that exacerbates secondary injury is endoplasmic reticulum (ER) stress. In this study, we tested the effects of amiloride treatment on the fate of OPCs during secondary injury in rats. Amiloride is an FDA-approved diuretic for treating hypertension, which in rats enhances ER stress response and suppresses the apoptosis of glial cells after SCI. A severe contusive SCI was induced in Sprague-Dawley rats using an infinite horizon (IH)-impactor (200 kdyne). Beginning 24 h after SCI, 10 mg/kg of amiloride or phosphate buffered saline (PBS) was intraperitoneally administered daily for a period of 14 days. At 7, 14, 28, and 56 days after SCI, animals were subsequently euthanized in order to analyze the injured spinal cord. We labeled proliferating OPCs and demonstrated that amiloride treatment led to greater numbers of OPCs and oligodendrocytes in the injured spinal cord. Increased myelin basic protein (MBP) expression levels were observed, suggesting that increased numbers of mature oligodendrocytes led to improved remyelination, significantly improving motor function recovery. MDPI 2018-03-05 /pmc/articles/PMC5867572/ /pubmed/29510579 http://dx.doi.org/10.3390/jcm7030046 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Imai, Takeshi
Katoh, Hiroyuki
Suyama, Kaori
Kuroiwa, Masahiro
Yanagisawa, Sho
Watanabe, Masahiko
Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats
title Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats
title_full Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats
title_fullStr Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats
title_full_unstemmed Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats
title_short Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats
title_sort amiloride promotes oligodendrocyte survival and remyelination after spinal cord injury in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867572/
https://www.ncbi.nlm.nih.gov/pubmed/29510579
http://dx.doi.org/10.3390/jcm7030046
work_keys_str_mv AT imaitakeshi amiloridepromotesoligodendrocytesurvivalandremyelinationafterspinalcordinjuryinrats
AT katohhiroyuki amiloridepromotesoligodendrocytesurvivalandremyelinationafterspinalcordinjuryinrats
AT suyamakaori amiloridepromotesoligodendrocytesurvivalandremyelinationafterspinalcordinjuryinrats
AT kuroiwamasahiro amiloridepromotesoligodendrocytesurvivalandremyelinationafterspinalcordinjuryinrats
AT yanagisawasho amiloridepromotesoligodendrocytesurvivalandremyelinationafterspinalcordinjuryinrats
AT watanabemasahiko amiloridepromotesoligodendrocytesurvivalandremyelinationafterspinalcordinjuryinrats