Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury.

<h4>Background</h4>The blood brain barrier (BBB) and truncated trkB receptor on astrocytes prevent the penetration of brain derived neurotrophic factor (BDNF) applied into the peripheral (PNS) and central nervous system (CNS) thus restrict its application in the treatment of nervous dise...

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Autores principales:	Xing-Yun Song, Fang Li, Feng-He Zhang, Jin-Hua Zhong, Xin-Fu Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8aab18aaca3446bb074817ab29bf9b8
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spelling	oai:doaj.org-article:c8aab18aaca3446bb074817ab29bf9b82021-11-25T06:13:13ZPeripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury.1932-620310.1371/journal.pone.0001707https://doaj.org/article/c8aab18aaca3446bb074817ab29bf9b82008-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18320028/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The blood brain barrier (BBB) and truncated trkB receptor on astrocytes prevent the penetration of brain derived neurotrophic factor (BDNF) applied into the peripheral (PNS) and central nervous system (CNS) thus restrict its application in the treatment of nervous diseases. As BDNF is anterogradely transported by axons, we propose that peripherally derived and/or applied BDNF may act on the regeneration of central axons of ascending sensory neurons.<h4>Methodology/principal findings</h4>The present study aimed to test the hypothesis by using conditioning lesion of the sciatic nerve as a model to increase the expression of endogenous BDNF in sensory neurons and by injecting exogenous BDNF into the peripheral nerve or tissues. Here we showed that most of regenerating sensory neurons expressed BDNF and p-CREB but not p75NTR. Conditioning-lesion induced regeneration of ascending sensory neuron and the increase in the number of p-Erk positive and GAP-43 positive neurons was blocked by the injection of the BDNF antiserum in the periphery. Enhanced neurite outgrowth of dorsal root ganglia (DRG) neurons in vitro by conditioning lesion was also inhibited by the neutralization with the BDNF antiserum. The delivery of exogenous BDNF into the sciatic nerve or the footpad significantly increased the number of regenerating DRG neurons and regenerating sensory axons in the injured spinal cord. In a contusion injury model, an injection of BDNF into the footpad promoted recovery of motor functions.<h4>Conclusions/significance</h4>Our data suggest that endogenous BDNF in DRG and spinal cord is required for the enhanced regeneration of ascending sensory neurons after conditioning lesion of sciatic nerve and peripherally applied BDNF may have therapeutic effects on the spinal cord injury.Xing-Yun SongFang LiFeng-He ZhangJin-Hua ZhongXin-Fu ZhouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 3, p e1707 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xing-Yun Song Fang Li Feng-He Zhang Jin-Hua Zhong Xin-Fu Zhou Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury.
description	<h4>Background</h4>The blood brain barrier (BBB) and truncated trkB receptor on astrocytes prevent the penetration of brain derived neurotrophic factor (BDNF) applied into the peripheral (PNS) and central nervous system (CNS) thus restrict its application in the treatment of nervous diseases. As BDNF is anterogradely transported by axons, we propose that peripherally derived and/or applied BDNF may act on the regeneration of central axons of ascending sensory neurons.<h4>Methodology/principal findings</h4>The present study aimed to test the hypothesis by using conditioning lesion of the sciatic nerve as a model to increase the expression of endogenous BDNF in sensory neurons and by injecting exogenous BDNF into the peripheral nerve or tissues. Here we showed that most of regenerating sensory neurons expressed BDNF and p-CREB but not p75NTR. Conditioning-lesion induced regeneration of ascending sensory neuron and the increase in the number of p-Erk positive and GAP-43 positive neurons was blocked by the injection of the BDNF antiserum in the periphery. Enhanced neurite outgrowth of dorsal root ganglia (DRG) neurons in vitro by conditioning lesion was also inhibited by the neutralization with the BDNF antiserum. The delivery of exogenous BDNF into the sciatic nerve or the footpad significantly increased the number of regenerating DRG neurons and regenerating sensory axons in the injured spinal cord. In a contusion injury model, an injection of BDNF into the footpad promoted recovery of motor functions.<h4>Conclusions/significance</h4>Our data suggest that endogenous BDNF in DRG and spinal cord is required for the enhanced regeneration of ascending sensory neurons after conditioning lesion of sciatic nerve and peripherally applied BDNF may have therapeutic effects on the spinal cord injury.
format	article
author	Xing-Yun Song Fang Li Feng-He Zhang Jin-Hua Zhong Xin-Fu Zhou
author_facet	Xing-Yun Song Fang Li Feng-He Zhang Jin-Hua Zhong Xin-Fu Zhou
author_sort	Xing-Yun Song
title	Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury.
title_short	Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury.
title_full	Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury.
title_fullStr	Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury.
title_full_unstemmed	Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury.
title_sort	peripherally-derived bdnf promotes regeneration of ascending sensory neurons after spinal cord injury.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/c8aab18aaca3446bb074817ab29bf9b8
work_keys_str_mv	AT xingyunsong peripherallyderivedbdnfpromotesregenerationofascendingsensoryneuronsafterspinalcordinjury AT fangli peripherallyderivedbdnfpromotesregenerationofascendingsensoryneuronsafterspinalcordinjury AT fenghezhang peripherallyderivedbdnfpromotesregenerationofascendingsensoryneuronsafterspinalcordinjury AT jinhuazhong peripherallyderivedbdnfpromotesregenerationofascendingsensoryneuronsafterspinalcordinjury AT xinfuzhou peripherallyderivedbdnfpromotesregenerationofascendingsensoryneuronsafterspinalcordinjury
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Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury.

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