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Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection

Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, v...

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Autores principales: Toomey, Lillian M., Bartlett, Carole A., Gavriel, Nikolas, McGonigle, Terence, Majimbi, Maimuna, Gopalasingam, Gopana, Rodger, Jennifer, Fitzgerald, Melinda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814709/
https://www.ncbi.nlm.nih.gov/pubmed/31653948
http://dx.doi.org/10.1038/s41598-019-51886-3
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author Toomey, Lillian M.
Bartlett, Carole A.
Gavriel, Nikolas
McGonigle, Terence
Majimbi, Maimuna
Gopalasingam, Gopana
Rodger, Jennifer
Fitzgerald, Melinda
author_facet Toomey, Lillian M.
Bartlett, Carole A.
Gavriel, Nikolas
McGonigle, Terence
Majimbi, Maimuna
Gopalasingam, Gopana
Rodger, Jennifer
Fitzgerald, Melinda
author_sort Toomey, Lillian M.
collection PubMed
description Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, vulnerable to secondary degeneration. However, local administration is often not clinically appropriate. This study aimed to compare the efficacy of systemic and local delivery of the ion channel inhibitor combination of lomerizine, brilliant blue G (BBG) and YM872, which inhibits voltage-gated calcium channels, P2X(7) receptors and Ca(2+) permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors respectively. Following a partial optic nerve transection, adult female PVG rats were treated with BBG and YM872 delivered via osmotic mini pump directly to the injury site, or via intraperitoneal injection, both alongside oral administration of lomerizine. Myelin structure was preserved with both delivery modes of the ion channel inhibitor combination. However, there was no effect of treatment on inflammation, either peripherally or at the injury site, or on the density of oligodendroglial cells. Taken together, the data indicate that even at lower concentrations, the combinatorial treatment may be preserving myelin structure, and that systemic and local delivery are comparable at improving outcomes following neurotrauma.
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spelling pubmed-68147092019-10-30 Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection Toomey, Lillian M. Bartlett, Carole A. Gavriel, Nikolas McGonigle, Terence Majimbi, Maimuna Gopalasingam, Gopana Rodger, Jennifer Fitzgerald, Melinda Sci Rep Article Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, vulnerable to secondary degeneration. However, local administration is often not clinically appropriate. This study aimed to compare the efficacy of systemic and local delivery of the ion channel inhibitor combination of lomerizine, brilliant blue G (BBG) and YM872, which inhibits voltage-gated calcium channels, P2X(7) receptors and Ca(2+) permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors respectively. Following a partial optic nerve transection, adult female PVG rats were treated with BBG and YM872 delivered via osmotic mini pump directly to the injury site, or via intraperitoneal injection, both alongside oral administration of lomerizine. Myelin structure was preserved with both delivery modes of the ion channel inhibitor combination. However, there was no effect of treatment on inflammation, either peripherally or at the injury site, or on the density of oligodendroglial cells. Taken together, the data indicate that even at lower concentrations, the combinatorial treatment may be preserving myelin structure, and that systemic and local delivery are comparable at improving outcomes following neurotrauma. Nature Publishing Group UK 2019-10-25 /pmc/articles/PMC6814709/ /pubmed/31653948 http://dx.doi.org/10.1038/s41598-019-51886-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Toomey, Lillian M.
Bartlett, Carole A.
Gavriel, Nikolas
McGonigle, Terence
Majimbi, Maimuna
Gopalasingam, Gopana
Rodger, Jennifer
Fitzgerald, Melinda
Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection
title Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection
title_full Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection
title_fullStr Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection
title_full_unstemmed Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection
title_short Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection
title_sort comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814709/
https://www.ncbi.nlm.nih.gov/pubmed/31653948
http://dx.doi.org/10.1038/s41598-019-51886-3
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