The impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.

Peripheral nerve transection and neuroma-in-continuity injuries are associated with permanent functional deficits, often despite successful end-organ reinnervation. Axonal misdirection with non-specific reinnervation, frustrated regeneration and axonal attrition are believed to be among the anatomic...

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Autores principales:	Jacob Daniel de Villiers Alant, Ferry Senjaya, Aleksandra Ivanovic, Joanne Forden, Antos Shakhbazau, Rajiv Midha
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/56a7a5bad1364580a67b977a7c4b3c62
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spelling	oai:doaj.org-article:56a7a5bad1364580a67b977a7c4b3c622021-11-18T08:44:45ZThe impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.1932-620310.1371/journal.pone.0082546https://doaj.org/article/56a7a5bad1364580a67b977a7c4b3c622013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24282624/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Peripheral nerve transection and neuroma-in-continuity injuries are associated with permanent functional deficits, often despite successful end-organ reinnervation. Axonal misdirection with non-specific reinnervation, frustrated regeneration and axonal attrition are believed to be among the anatomical substrates that underlie the poor functional recovery associated with these devastating injuries. Yet, functional deficits associated with axonal misdirection in experimental neuroma-in-continuity injuries have not yet been studied. We hypothesized that experimental neuroma-in-continuity injuries would result in motor axon misdirection and attrition with proportional persistent functional deficits. The femoral nerve misdirection model was exploited to assess major motor pathway misdirection and axonal attrition over a spectrum of experimental nerve injuries, with neuroma-in-continuity injuries simulated by the combination of compression and traction forces in 42 male rats. Sciatic nerve injuries were employed in an additional 42 rats, to evaluate the contribution of axonal misdirection to locomotor deficits by a ladder rung task up to 12 weeks. Retrograde motor neuron labeling techniques were utilized to determine the degree of axonal misdirection and attrition. Characteristic histological neuroma-in-continuity features were demonstrated in the neuroma-in-continuity groups and poor functional recovery was seen despite successful nerve regeneration and muscle reinnervation. Good positive and negative correlations were observed respectively between axonal misdirection (p<.0001, r(2)=.67), motor neuron counts (attrition) (p<.0001, r(2)=.69) and final functional deficits. We demonstrate prominent motor axon misdirection and attrition in neuroma-in-continuity and transection injuries of mixed motor nerves that contribute to the long-term functional deficits. Although widely accepted in theory, to our knowledge, this is the first experimental evidence to convincingly demonstrate these correlations with data inclusive of the neuroma-in-continuity spectrum. This work emphasizes the need to focus on strategies that promote both robust and accurate nerve regeneration to optimize functional recovery. It also demonstrates that clinically relevant neuroma-in-continuity injuries can now also be subjected to experimental investigation.Jacob Daniel de Villiers AlantFerry SenjayaAleksandra IvanovicJoanne FordenAntos ShakhbazauRajiv MidhaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e82546 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jacob Daniel de Villiers Alant Ferry Senjaya Aleksandra Ivanovic Joanne Forden Antos Shakhbazau Rajiv Midha The impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.
description	Peripheral nerve transection and neuroma-in-continuity injuries are associated with permanent functional deficits, often despite successful end-organ reinnervation. Axonal misdirection with non-specific reinnervation, frustrated regeneration and axonal attrition are believed to be among the anatomical substrates that underlie the poor functional recovery associated with these devastating injuries. Yet, functional deficits associated with axonal misdirection in experimental neuroma-in-continuity injuries have not yet been studied. We hypothesized that experimental neuroma-in-continuity injuries would result in motor axon misdirection and attrition with proportional persistent functional deficits. The femoral nerve misdirection model was exploited to assess major motor pathway misdirection and axonal attrition over a spectrum of experimental nerve injuries, with neuroma-in-continuity injuries simulated by the combination of compression and traction forces in 42 male rats. Sciatic nerve injuries were employed in an additional 42 rats, to evaluate the contribution of axonal misdirection to locomotor deficits by a ladder rung task up to 12 weeks. Retrograde motor neuron labeling techniques were utilized to determine the degree of axonal misdirection and attrition. Characteristic histological neuroma-in-continuity features were demonstrated in the neuroma-in-continuity groups and poor functional recovery was seen despite successful nerve regeneration and muscle reinnervation. Good positive and negative correlations were observed respectively between axonal misdirection (p<.0001, r(2)=.67), motor neuron counts (attrition) (p<.0001, r(2)=.69) and final functional deficits. We demonstrate prominent motor axon misdirection and attrition in neuroma-in-continuity and transection injuries of mixed motor nerves that contribute to the long-term functional deficits. Although widely accepted in theory, to our knowledge, this is the first experimental evidence to convincingly demonstrate these correlations with data inclusive of the neuroma-in-continuity spectrum. This work emphasizes the need to focus on strategies that promote both robust and accurate nerve regeneration to optimize functional recovery. It also demonstrates that clinically relevant neuroma-in-continuity injuries can now also be subjected to experimental investigation.
format	article
author	Jacob Daniel de Villiers Alant Ferry Senjaya Aleksandra Ivanovic Joanne Forden Antos Shakhbazau Rajiv Midha
author_facet	Jacob Daniel de Villiers Alant Ferry Senjaya Aleksandra Ivanovic Joanne Forden Antos Shakhbazau Rajiv Midha
author_sort	Jacob Daniel de Villiers Alant
title	The impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.
title_short	The impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.
title_full	The impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.
title_fullStr	The impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.
title_full_unstemmed	The impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.
title_sort	impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/56a7a5bad1364580a67b977a7c4b3c62
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The impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.

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