Changes in Neurofilament and Microtubule Distribution following Focal Axon Compression.

Although a number of cytoskeletal derangements have been described in the setting of traumatic axonal injury (TAI), little is known of early structural changes that may serve to initiate a cascade of further axonal degeneration. Recent work by the authors has examined conformational changes in cytos...

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Main Authors: Adam J Fournier, James D Hogan, Labchan Rajbhandari, Shiva Shrestha, Arun Venkatesan, K T Ramesh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4482325?pdf=render
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author Adam J Fournier
James D Hogan
Labchan Rajbhandari
Shiva Shrestha
Arun Venkatesan
K T Ramesh
author_facet Adam J Fournier
James D Hogan
Labchan Rajbhandari
Shiva Shrestha
Arun Venkatesan
K T Ramesh
author_sort Adam J Fournier
collection DOAJ
description Although a number of cytoskeletal derangements have been described in the setting of traumatic axonal injury (TAI), little is known of early structural changes that may serve to initiate a cascade of further axonal degeneration. Recent work by the authors has examined conformational changes in cytoskeletal constituents of neuronal axons undergoing traumatic axonal injury (TAI) following focal compression through confocal imaging data taken in vitro and in situ. The present study uses electron microscopy to understand and quantify in vitro alterations in the ultrastructural composition of microtubules and neurofilaments within neuronal axons of rats following focal compression. Standard transmission electron microscopy processing methods are used to identify microtubules, while neurofilament identification is performed using antibody labeling through gold nanoparticles. The number, density, and spacing of microtubules and neurofilaments are quantified for specimens in sham Control and Crushed groups with fixation at <1 min following load. Our results indicate that the axon caliber dependency known to exist for microtubule and neurofilament metrics extends to axons undergoing TAI, with the exception of neurofilament spacing, which appears to remain constant across all Crushed axon diameters. Confidence interval comparisons between Control and Crushed cytoskeletal measures suggests early changes in the neurofilament spatial distributions within axons undergoing TAI may precede microtubule changes in response to applied loads. This may serve as a trigger for further secondary damage to the axon, representing a key insight into the temporal aspects of cytoskeletal degeneration at the component level, and suggests the rapid removal of neurofilament sidearms as one possible mechanism.
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spelling doaj.art-9d53fce675734d3ebff643ee364782a42022-12-22T03:06:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e013161710.1371/journal.pone.0131617Changes in Neurofilament and Microtubule Distribution following Focal Axon Compression.Adam J FournierJames D HoganLabchan RajbhandariShiva ShresthaArun VenkatesanK T RameshAlthough a number of cytoskeletal derangements have been described in the setting of traumatic axonal injury (TAI), little is known of early structural changes that may serve to initiate a cascade of further axonal degeneration. Recent work by the authors has examined conformational changes in cytoskeletal constituents of neuronal axons undergoing traumatic axonal injury (TAI) following focal compression through confocal imaging data taken in vitro and in situ. The present study uses electron microscopy to understand and quantify in vitro alterations in the ultrastructural composition of microtubules and neurofilaments within neuronal axons of rats following focal compression. Standard transmission electron microscopy processing methods are used to identify microtubules, while neurofilament identification is performed using antibody labeling through gold nanoparticles. The number, density, and spacing of microtubules and neurofilaments are quantified for specimens in sham Control and Crushed groups with fixation at <1 min following load. Our results indicate that the axon caliber dependency known to exist for microtubule and neurofilament metrics extends to axons undergoing TAI, with the exception of neurofilament spacing, which appears to remain constant across all Crushed axon diameters. Confidence interval comparisons between Control and Crushed cytoskeletal measures suggests early changes in the neurofilament spatial distributions within axons undergoing TAI may precede microtubule changes in response to applied loads. This may serve as a trigger for further secondary damage to the axon, representing a key insight into the temporal aspects of cytoskeletal degeneration at the component level, and suggests the rapid removal of neurofilament sidearms as one possible mechanism.http://europepmc.org/articles/PMC4482325?pdf=render
spellingShingle Adam J Fournier
James D Hogan
Labchan Rajbhandari
Shiva Shrestha
Arun Venkatesan
K T Ramesh
Changes in Neurofilament and Microtubule Distribution following Focal Axon Compression.
PLoS ONE
title Changes in Neurofilament and Microtubule Distribution following Focal Axon Compression.
title_full Changes in Neurofilament and Microtubule Distribution following Focal Axon Compression.
title_fullStr Changes in Neurofilament and Microtubule Distribution following Focal Axon Compression.
title_full_unstemmed Changes in Neurofilament and Microtubule Distribution following Focal Axon Compression.
title_short Changes in Neurofilament and Microtubule Distribution following Focal Axon Compression.
title_sort changes in neurofilament and microtubule distribution following focal axon compression
url http://europepmc.org/articles/PMC4482325?pdf=render
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