Botulinum Neurotoxin Application to the Severed Femoral Nerve Modulates Spinal Synaptic Responses to Axotomy and Enhances Motor Recovery in Rats

Botulinum neurotoxin A (BoNT) and brain-derived neurotrophic factor (BDNF) are known for their ability to influence synaptic inputs to neurons. Here, we tested if these drugs can modulate the deafferentation of motoneurons following nerve section/suture and, as a consequence, modify the outcome of p...

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Main Authors: Marcel Irintchev, Orlando Guntinas-Lichius, Andrey Irintchev
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2018/7975013
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author Marcel Irintchev
Orlando Guntinas-Lichius
Andrey Irintchev
author_facet Marcel Irintchev
Orlando Guntinas-Lichius
Andrey Irintchev
author_sort Marcel Irintchev
collection DOAJ
description Botulinum neurotoxin A (BoNT) and brain-derived neurotrophic factor (BDNF) are known for their ability to influence synaptic inputs to neurons. Here, we tested if these drugs can modulate the deafferentation of motoneurons following nerve section/suture and, as a consequence, modify the outcome of peripheral nerve regeneration. We applied drug solutions to the proximal stump of the freshly cut femoral nerve of adult rats to achieve drug uptake and transport to the neuronal perikarya. The most marked effect of this application was a significant reduction of the axotomy-induced loss of perisomatic cholinergic terminals by BoNT at one week and two months post injury. The attenuation of the synaptic deficit was associated with enhanced motor recovery of the rats 2–20 weeks after injury. Although BDNF also reduced cholinergic terminal loss at 1 week, it had no effect on this parameter at two months and no effect on functional recovery. These findings strengthen the idea that persistent partial deafferentation of axotomized motoneurons may have a significant negative impact on functional outcome after nerve injury. Intraneural application of drugs may be a promising way to modify deafferentation and, thus, elucidate relationships between synaptic plasticity and restoration of function.
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spelling doaj-art-1fedefba6636463ca4c954ef1d1581662025-02-03T05:45:39ZengWileyNeural Plasticity2090-59041687-54432018-01-01201810.1155/2018/79750137975013Botulinum Neurotoxin Application to the Severed Femoral Nerve Modulates Spinal Synaptic Responses to Axotomy and Enhances Motor Recovery in RatsMarcel Irintchev0Orlando Guntinas-Lichius1Andrey Irintchev2Department of Otorhinolaryngology, Jena University Hospital, Am Klinikum 1, 07747 Jena, GermanyDepartment of Otorhinolaryngology, Jena University Hospital, Am Klinikum 1, 07747 Jena, GermanyDepartment of Otorhinolaryngology, Jena University Hospital, Am Klinikum 1, 07747 Jena, GermanyBotulinum neurotoxin A (BoNT) and brain-derived neurotrophic factor (BDNF) are known for their ability to influence synaptic inputs to neurons. Here, we tested if these drugs can modulate the deafferentation of motoneurons following nerve section/suture and, as a consequence, modify the outcome of peripheral nerve regeneration. We applied drug solutions to the proximal stump of the freshly cut femoral nerve of adult rats to achieve drug uptake and transport to the neuronal perikarya. The most marked effect of this application was a significant reduction of the axotomy-induced loss of perisomatic cholinergic terminals by BoNT at one week and two months post injury. The attenuation of the synaptic deficit was associated with enhanced motor recovery of the rats 2–20 weeks after injury. Although BDNF also reduced cholinergic terminal loss at 1 week, it had no effect on this parameter at two months and no effect on functional recovery. These findings strengthen the idea that persistent partial deafferentation of axotomized motoneurons may have a significant negative impact on functional outcome after nerve injury. Intraneural application of drugs may be a promising way to modify deafferentation and, thus, elucidate relationships between synaptic plasticity and restoration of function.http://dx.doi.org/10.1155/2018/7975013
spellingShingle Marcel Irintchev
Orlando Guntinas-Lichius
Andrey Irintchev
Botulinum Neurotoxin Application to the Severed Femoral Nerve Modulates Spinal Synaptic Responses to Axotomy and Enhances Motor Recovery in Rats
Neural Plasticity
title Botulinum Neurotoxin Application to the Severed Femoral Nerve Modulates Spinal Synaptic Responses to Axotomy and Enhances Motor Recovery in Rats
title_full Botulinum Neurotoxin Application to the Severed Femoral Nerve Modulates Spinal Synaptic Responses to Axotomy and Enhances Motor Recovery in Rats
title_fullStr Botulinum Neurotoxin Application to the Severed Femoral Nerve Modulates Spinal Synaptic Responses to Axotomy and Enhances Motor Recovery in Rats
title_full_unstemmed Botulinum Neurotoxin Application to the Severed Femoral Nerve Modulates Spinal Synaptic Responses to Axotomy and Enhances Motor Recovery in Rats
title_short Botulinum Neurotoxin Application to the Severed Femoral Nerve Modulates Spinal Synaptic Responses to Axotomy and Enhances Motor Recovery in Rats
title_sort botulinum neurotoxin application to the severed femoral nerve modulates spinal synaptic responses to axotomy and enhances motor recovery in rats
url http://dx.doi.org/10.1155/2018/7975013
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AT orlandoguntinaslichius botulinumneurotoxinapplicationtotheseveredfemoralnervemodulatesspinalsynapticresponsestoaxotomyandenhancesmotorrecoveryinrats
AT andreyirintchev botulinumneurotoxinapplicationtotheseveredfemoralnervemodulatesspinalsynapticresponsestoaxotomyandenhancesmotorrecoveryinrats