PMID- 15115607
OWN - NLM
STAT- MEDLINE
DCOM- 20040713
LR  - 20061115
IS  - 0897-7151 (Print)
IS  - 0897-7151 (Linking)
VI  - 21
IP  - 3
DP  - 2004 Mar
TI  - Adenovirus vector-mediated in vivo gene transfer of brain-derived neurotrophic 
      factor (BDNF) promotes rubrospinal axonal regeneration and functional recovery 
      after complete transection of the adult rat spinal cord.
PG  - 329-37
AB  - Neurotrophins have been shown to promote axonal regeneration, but the techniques 
      available for delivering neurotrophins have limited effectiveness. The aim of 
      this study was to evaluate the effect of adenovirus vector mediated gene transfer 
      of brain-derived neurotrophic factor (BDNF) on axonal regeneration after spinal 
      cord injury. We prepared adenovirus vectors encoding either beta-galactosidase 
      (AxCALacZ) or BDNF (AxCABDNF). AxCALacZ was used to assess infection levels of 
      the adenovirus BDNF produced by AxCABDNF was detected by Western blotting and its 
      bioactivity was confirmed by bioassay. As a model of spinal cord injury, the rat 
      spinal cord was completely transected at the T8 level. Immediately after 
      transection, the vectors were injected into both stumps of the spinal cord. 
      Axonal regeneration after transection was assessed by retrograde and anterograde 
      tracing. In AxCALacZ-injected rats, adenovirus-infected cells were observed not 
      only at the injected site but also in brainstem nuclei, as shown by LacZ 
      expression. After the injection of the retrograde tracer fluorogold (FG) distal 
      portion to the transection, AxCABDNF-injected rats showed FG-labeled neurons in 
      the red nucleus. The anterograde tracer biotinylated dextran amine (BDA) injected 
      into the red nucleus was also found in regenerating rubrospinal fibers distal to 
      the transection. These tracing experiments demonstrated the regeneration of 
      descending axons. In addition, rats of the AxCABDNF group showed significant 
      locomotor recovery of hindlimb function, which was completely abolished by 
      re-transection. These results indicate that the recovery was caused by 
      regeneration of rubrospinal axons, not by simple enhancement of the central 
      pattern generator.
FAU - Koda, Masao
AU  - Koda M
AD  - Division of Rehabilitation Medicine, Chiba University Graduate School of 
      Medicine, Chiba, Japan. m-koda@nifty.com
FAU - Hashimoto, Masayuki
AU  - Hashimoto M
FAU - Murakami, Masazumi
AU  - Murakami M
FAU - Yoshinaga, Katsunori
AU  - Yoshinaga K
FAU - Ikeda, Osamu
AU  - Ikeda O
FAU - Yamazaki, Masashi
AU  - Yamazaki M
FAU - Koshizuka, Shuhei
AU  - Koshizuka S
FAU - Kamada, Takahito
AU  - Kamada T
FAU - Moriya, Hideshige
AU  - Moriya H
FAU - Shirasawa, Hiroshi
AU  - Shirasawa H
FAU - Sakao, Seiichiro
AU  - Sakao S
FAU - Ino, Hidetoshi
AU  - Ino H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Adenoviridae
MH  - Animals
MH  - Axons/*physiology
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - *Gene Transfer Techniques
MH  - Genetic Vectors/therapeutic use
MH  - Lac Operon/physiology
MH  - Male
MH  - Nerve Regeneration/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Recovery of Function/physiology
MH  - Spinal Cord Injuries/physiopathology/*therapy
EDAT- 2004/04/30 05:00
MHDA- 2004/07/14 05:00
CRDT- 2004/04/30 05:00
PHST- 2004/04/30 05:00 [pubmed]
PHST- 2004/07/14 05:00 [medline]
PHST- 2004/04/30 05:00 [entrez]
AID - 10.1089/089771504322972112 [doi]
PST - ppublish
SO  - J Neurotrauma. 2004 Mar;21(3):329-37. doi: 10.1089/089771504322972112.