PMID- 23022460
OWN - NLM
STAT- MEDLINE
DCOM- 20130228
LR  - 20220309
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 239
DP  - 2013 Jan
TI  - Exogenous BDNF enhances the integration of chronically injured axons that 
      regenerate through a peripheral nerve grafted into a chondroitinase-treated 
      spinal cord injury site.
PG  - 91-100
LID - S0014-4886(12)00373-1 [pii]
LID - 10.1016/j.expneurol.2012.09.011 [doi]
AB  - Although axons lose some of their intrinsic capacity for growth after their 
      developmental period, some axons retain the potential for regrowth after injury. 
      When provided with a growth-promoting substrate such as a peripheral nerve graft 
      (PNG), severed axons regenerate into and through the graft; however, they stop 
      when they reach the glial scar at the distal graft-host interface that is rich 
      with inhibitory chondroitin sulfate proteoglycans. We previously showed that 
      treatment of a spinal cord injury site with chondroitinase (ChABC) allows axons 
      within the graft to traverse the scar and reinnervate spinal cord, where they 
      form functional synapses. While this improvement in outgrowth was significant, it 
      still represented only a small percentage (<20%) of axons compared to the total 
      number of axons that regenerated into the PNG. Here we tested whether providing 
      exogenous brain-derived neurotrophic factor (BDNF) via lentivirus in tissue 
      distal to the PNG would augment regeneration beyond a ChABC-treated glial 
      interface. We found that ChABC treatment alone promoted axonal regeneration but 
      combining ChABC with BDNF-lentivirus did not increase the number of axons that 
      regenerated back into spinal cord. Combining BDNF with ChABC did increase the 
      number of spinal cord neurons that were trans-synaptically activated during 
      electrical stimulation of the graft, as indicated by c-Fos expression, suggesting 
      that BDNF overexpression improved the functional significance of axons that did 
      reinnervate distal spinal cord tissue.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Tom, Veronica J
AU  - Tom VJ
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, PA 19129, USA. vtom@drexelmed.edu
FAU - Sandrow-Feinberg, Harra R
AU  - Sandrow-Feinberg HR
FAU - Miller, Kassi
AU  - Miller K
FAU - Domitrovich, Cheryl
AU  - Domitrovich C
FAU - Bouyer, Julien
AU  - Bouyer J
FAU - Zhukareva, Victoria
AU  - Zhukareva V
FAU - Klaw, Michelle C
AU  - Klaw MC
FAU - Lemay, Michel A
AU  - Lemay MA
FAU - Houle, John D
AU  - Houle JD
LA  - eng
GR  - R01 NS026380/NS/NINDS NIH HHS/United States
GR  - R37 NS026380/NS/NINDS NIH HHS/United States
GR  - NS26380/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120927
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 4.2.2.20 (Chondroitin ABC Lyase)
SB  - IM
MH  - Animals
MH  - Axons/*drug effects/metabolism
MH  - Behavior, Animal/drug effects
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Chondroitin ABC Lyase/*therapeutic use
MH  - Electric Stimulation
MH  - Female
MH  - Genetic Vectors
MH  - Lentivirus/genetics
MH  - Locomotion/drug effects
MH  - Nerve Regeneration/*drug effects
MH  - Neuroglia/physiology
MH  - Peripheral Nerves/*drug effects/transplantation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/biosynthesis
MH  - Spinal Cord Injuries/*drug therapy
MH  - Synapses/physiology
MH  - Walking
PMC - PMC4820350
MID - NIHMS768156
EDAT- 2012/10/02 06:00
MHDA- 2013/03/01 06:00
PMCR- 2016/04/04
CRDT- 2012/10/02 06:00
PHST- 2012/02/04 00:00 [received]
PHST- 2012/08/03 00:00 [revised]
PHST- 2012/09/20 00:00 [accepted]
PHST- 2012/10/02 06:00 [entrez]
PHST- 2012/10/02 06:00 [pubmed]
PHST- 2013/03/01 06:00 [medline]
PHST- 2016/04/04 00:00 [pmc-release]
AID - S0014-4886(12)00373-1 [pii]
AID - 10.1016/j.expneurol.2012.09.011 [doi]
PST - ppublish
SO  - Exp Neurol. 2013 Jan;239:91-100. doi: 10.1016/j.expneurol.2012.09.011. Epub 2012 
      Sep 27.