PMID- 23131414
OWN - NLM
STAT- MEDLINE
DCOM- 20130604
LR  - 20121218
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 239
DP  - 2013 Feb 15
TI  - Synergistic effects of BDNF and rehabilitative training on recovery after 
      cervical spinal cord injury.
PG  - 31-42
LID - S0166-4328(12)00697-3 [pii]
LID - 10.1016/j.bbr.2012.10.047 [doi]
AB  - Promoting the rewiring of lesioned motor tracts following a spinal cord injury is 
      a promising strategy to restore motor function. For instance, axonal collaterals 
      may connect to spared, lesion-bridging neurons, thereby establishing a detour for 
      descending signals and thus promoting functional recovery. In our rat model of 
      cervical spinal cord injury, we attempted to promote targeted rewiring of the 
      unilaterally injured corticospinal tract (CST) via the spared reticulospinal 
      tract (RtST). To promote new connections between the two tracts in the brainstem, 
      we administered viral vectors producing two neurotrophins. Brain-derived 
      neurotrophic factor (BDNF), a known promotor of collateral growth, was expressed 
      in the motor cortex, and neurotrophin 3 (NT-3), which has chemoattractive 
      properties, was expressed in the reticular formation. Because rehabilitative 
      training has proven to be beneficial in promoting functionally meaningful 
      plasticity following injury, we added training in a skilled reaching task. 
      Different neurotrophin or control treatments with or without training were 
      evaluated. As hypothesized, improvements of motor performance with the injured 
      forelimb following neurotrophin treatment alone were absent or modest compared to 
      untreated controls. In contrast, we found a significant synergistic effect on 
      performance when BDNF treatment was combined with training. The mechanism of this 
      recovery remains unidentified, as histological analyses of CST and RtST 
      collateral projections did not reveal differences among treatment groups. In 
      conclusion, we demonstrate that following a cervical spinal lesion, 
      rehabilitative training is necessary to translate effects of BDNF into functional 
      recovery by mechanisms which are likely independent of collateral sprouting of 
      the CST or RtST into the gray matter.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Weishaupt, N
AU  - Weishaupt N
AD  - Centre for Neuroscience, University of Alberta, Edmonton, AB, Canada. 
      weishaup@ualberta.ca
FAU - Li, S
AU  - Li S
FAU - Di Pardo, A
AU  - Di Pardo A
FAU - Sipione, S
AU  - Sipione S
FAU - Fouad, K
AU  - Fouad K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121103
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neurotrophin 3)
SB  - IM
MH  - Adenoviridae
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*therapeutic use
MH  - Cells, Cultured
MH  - Cervical Vertebrae
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression/genetics
MH  - Genetic Vectors/administration & dosage
MH  - Motor Skills/physiology
MH  - Nerve Regeneration/genetics/physiology
MH  - Neurotrophin 3/administration & dosage/*therapeutic use
MH  - Pyramidal Tracts/*physiology
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Recovery of Function/genetics
MH  - Spinal Cord Injuries/*rehabilitation/*therapy
EDAT- 2012/11/08 06:00
MHDA- 2013/06/05 06:00
CRDT- 2012/11/08 06:00
PHST- 2012/09/20 00:00 [received]
PHST- 2012/10/23 00:00 [revised]
PHST- 2012/10/28 00:00 [accepted]
PHST- 2012/11/08 06:00 [entrez]
PHST- 2012/11/08 06:00 [pubmed]
PHST- 2013/06/05 06:00 [medline]
AID - S0166-4328(12)00697-3 [pii]
AID - 10.1016/j.bbr.2012.10.047 [doi]
PST - ppublish
SO  - Behav Brain Res. 2013 Feb 15;239:31-42. doi: 10.1016/j.bbr.2012.10.047. Epub 2012 
      Nov 3.