PMID- 15380481
OWN - NLM
STAT- MEDLINE
DCOM- 20041028
LR  - 20061115
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 189
IP  - 2
DP  - 2004 Oct
TI  - Rescue and sprouting of motoneurons following ventral root avulsion and 
      reimplantation combined with intraspinal adeno-associated viral vector-mediated 
      expression of glial cell line-derived neurotrophic factor or brain-derived 
      neurotrophic factor.
PG  - 303-16
AB  - Following avulsion of a spinal ventral root, motoneurons that project through the 
      avulsed root are axotomized. Avulsion between, for example, L2 and L6 leads to 
      denervation of hind limb muscles. Reimplantation of an avulsed root directed to 
      the motoneuron pool resulted in re-ingrowth of some motor axons. However, most 
      motoneurons display retrograde atrophy and subsequently die. Two neurotrophic 
      factors, glial cell line-derived neurotrophic factor (GDNF) and brain-derived 
      neurotrophic factor (BDNF), promote the survival of motoneurons after injury. The 
      long-term delivery of these neurotrophic factors to the motoneurons in the 
      ventral horn of the spinal cord is problematic. One strategy to improve the 
      outcome of the neurosurgical reinsertion of the ventral root following avulsion 
      would involve gene transfer with adeno-associated viral (AAV) vectors encoding 
      these neurotrophic factors near the denervated motoneuron pool. Here, we show 
      that AAV-mediated overexpression of GDNF and BDNF in the spinal cord persisted 
      for at least 16 weeks. At both 1 and 4 months post-lesion AAV-BDNF- and 
      -GDNF-treated animals showed an increased survival of motoneurons, the effect 
      being more prominent at 1 month. AAV vector-mediated overexpression of 
      neurotrophins also promoted the formation of a network of motoneuron fibers in 
      the ventral horn at the avulsed side, but motoneurons failed to extent axons into 
      the reinserted L4 root towards the sciatic nerve nor to improve functional 
      recovery of the hind limbs. This suggests that high levels of neurotrophic 
      factors in the ventral horn promote sprouting, but prevent directional growth of 
      axons of a higher number of surviving motoneurons into the implanted root.
FAU - Blits, Bas
AU  - Blits B
AD  - Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain 
      Research, 1105 AZ Amsterdam, The Netherlands.
FAU - Carlstedt, Thomas P
AU  - Carlstedt TP
FAU - Ruitenberg, Marc Jan
AU  - Ruitenberg MJ
FAU - de Winter, Fred
AU  - de Winter F
FAU - Hermens, Wim T J M C
AU  - Hermens WT
FAU - Dijkhuizen, Paul A
AU  - Dijkhuizen PA
FAU - Claasens, Jill W C
AU  - Claasens JW
FAU - Eggers, Ruben
AU  - Eggers R
FAU - van der Sluis, Ronald
AU  - van der Sluis R
FAU - Tenenbaum, Liliane
AU  - Tenenbaum L
FAU - Boer, Gerard J
AU  - Boer GJ
FAU - Verhaagen, Joost
AU  - Verhaagen J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Gdnf protein, rat)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Gene Transfer Techniques
MH  - Genetic Vectors
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Growth Cones/metabolism/ultrastructure
MH  - Lumbar Vertebrae
MH  - Male
MH  - Motor Neurons/cytology/*metabolism
MH  - Nerve Growth Factors/*genetics
MH  - Nerve Regeneration/*genetics
MH  - Neuronal Plasticity/genetics
MH  - Radiculopathy/metabolism/pathology/*therapy
MH  - Rats
MH  - Rats, Wistar
MH  - Recovery of Function/genetics
MH  - Sciatic Nerve/cytology/physiology
MH  - Spinal Cord/*metabolism/pathology
MH  - Spinal Nerve Roots/injuries/pathology/surgery
EDAT- 2004/09/24 05:00
MHDA- 2004/10/29 09:00
CRDT- 2004/09/24 05:00
PHST- 2003/09/26 00:00 [received]
PHST- 2004/04/29 00:00 [revised]
PHST- 2004/05/11 00:00 [accepted]
PHST- 2004/09/24 05:00 [pubmed]
PHST- 2004/10/29 09:00 [medline]
PHST- 2004/09/24 05:00 [entrez]
AID - S0014488604001979 [pii]
AID - 10.1016/j.expneurol.2004.05.014 [doi]
PST - ppublish
SO  - Exp Neurol. 2004 Oct;189(2):303-16. doi: 10.1016/j.expneurol.2004.05.014.