Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury

Abstract Eight weeks post contusive spinal cord injury, we built a peripheral nerve graft bridge (PNG) through the cystic cavity and treated the graft/host interface with acidic fibroblast growth factor (aFGF) and chondroitinase ABC (ChABC). This combinatorial strategy remarkably enhanced integratio...

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Autores principales:	Marc A. DePaul, Ching-Yi Lin, Jerry Silver, Yu-Shang Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/880f0c825b2d4b1c991a2584fd95eaeb
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spelling	oai:doaj.org-article:880f0c825b2d4b1c991a2584fd95eaeb2021-12-02T12:30:18ZCombinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury10.1038/s41598-017-09432-62045-2322https://doaj.org/article/880f0c825b2d4b1c991a2584fd95eaeb2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09432-6https://doaj.org/toc/2045-2322Abstract Eight weeks post contusive spinal cord injury, we built a peripheral nerve graft bridge (PNG) through the cystic cavity and treated the graft/host interface with acidic fibroblast growth factor (aFGF) and chondroitinase ABC (ChABC). This combinatorial strategy remarkably enhanced integration between host astrocytes and graft Schwann cells, allowing for robust growth, especially of catecholaminergic axons, through the graft and back into the distal spinal cord. In the absence of aFGF+ChABC fewer catecholaminergic axons entered the graft, no axons exited, and Schwann cells and astrocytes failed to integrate. In sharp contrast with the acutely bridge-repaired cord, in the chronically repaired cord only low levels of serotonergic axons regenerated into the graft, with no evidence of re-entry back into the spinal cord. The failure of axons to regenerate was strongly correlated with a dramatic increase of SOCS3 expression. While regeneration was more limited overall than at acute stages, our combinatorial strategy in the chronically injured animals prevented a decline in locomotor behavior and bladder physiology outcomes associated with an invasive repair strategy. These results indicate that PNG+aFGF+ChABC treatment of the chronically contused spinal cord can provide a permissive substrate for the regeneration of certain neuronal populations that retain a growth potential over time, and lead to functional improvements.Marc A. DePaulChing-Yi LinJerry SilverYu-Shang LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marc A. DePaul Ching-Yi Lin Jerry Silver Yu-Shang Lee Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury
description	Abstract Eight weeks post contusive spinal cord injury, we built a peripheral nerve graft bridge (PNG) through the cystic cavity and treated the graft/host interface with acidic fibroblast growth factor (aFGF) and chondroitinase ABC (ChABC). This combinatorial strategy remarkably enhanced integration between host astrocytes and graft Schwann cells, allowing for robust growth, especially of catecholaminergic axons, through the graft and back into the distal spinal cord. In the absence of aFGF+ChABC fewer catecholaminergic axons entered the graft, no axons exited, and Schwann cells and astrocytes failed to integrate. In sharp contrast with the acutely bridge-repaired cord, in the chronically repaired cord only low levels of serotonergic axons regenerated into the graft, with no evidence of re-entry back into the spinal cord. The failure of axons to regenerate was strongly correlated with a dramatic increase of SOCS3 expression. While regeneration was more limited overall than at acute stages, our combinatorial strategy in the chronically injured animals prevented a decline in locomotor behavior and bladder physiology outcomes associated with an invasive repair strategy. These results indicate that PNG+aFGF+ChABC treatment of the chronically contused spinal cord can provide a permissive substrate for the regeneration of certain neuronal populations that retain a growth potential over time, and lead to functional improvements.
format	article
author	Marc A. DePaul Ching-Yi Lin Jerry Silver Yu-Shang Lee
author_facet	Marc A. DePaul Ching-Yi Lin Jerry Silver Yu-Shang Lee
author_sort	Marc A. DePaul
title	Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury
title_short	Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury
title_full	Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury
title_fullStr	Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury
title_full_unstemmed	Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury
title_sort	combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/880f0c825b2d4b1c991a2584fd95eaeb
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Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury

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