Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/110824
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Type: Journal article
Title: Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma
Author: O'Hare Doig, R.
Chiha, W.
Giacci, M.
Yates, N.
Bartlett, C.
Smith, N.
Hodgetts, S.
Harvey, A.
Fitzgerald, M.
Citation: BMC Neuroscience, 2017; 18(1):62
Publisher: BioMed Central
Issue Date: 2017
ISSN: 1471-2202
1471-2202
Statement of
Responsibility: 
Ryan L. O, Hare Doig, Wissam Chiha, Marcus K. Giacci, Nathanael J. Yates, Carole A. Bartlett, Nicole M. Smith, Stuart I. Hodgetts, Alan R. Harvey and Melinda Fitzgerald
Abstract: Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca2+ channel inhibitor Lomerizine (Lom), the Ca2+ permeable AMPA receptor inhibitor YM872 and the P2X7 receptor inhibitor oxATP. Results: Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. Conclusions: Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs.
Keywords: Axonal degeneration; Ion channel inhibitor; Lipid peroxidation; Neurotrauma; Node of Ranvier; Oligodendrocyte precursor cells; Oxidative stress; Secondary degeneration; Traumatic injury
Rights: © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
RMID: 0030076290
DOI: 10.1186/s12868-017-0380-1
Grant ID: http://purl.org/au-research/grants/nhmrc/1061791
http://purl.org/au-research/grants/nhmrc/1087114
Appears in Collections:Medicine publications

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