PMID- 12504875
OWN - NLM
STAT- MEDLINE
DCOM- 20030121
LR  - 20190722
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 178
IP  - 2
DP  - 2002 Dec
TI  - Grafts of BDNF-producing fibroblasts rescue axotomized rubrospinal neurons and 
      prevent their atrophy.
PG  - 150-64
AB  - We have reported that intraspinal transplants of fibroblasts genetically modified 
      to express brain-derived neurotrophic factor (BDNF) promote rubrospinal axon 
      regeneration and functional recovery following subtotal cervical hemisection that 
      completely ablated the rubrospinal tract. In the present study we examined 
      whether these transplants could prevent cell loss and/or atrophy of axotomized 
      Red nucleus neurons. Adult rats received a subtotal spinal cord cervical 
      hemisection followed by a graft of unmodified fibroblasts or fibroblasts 
      producing BDNF into the lesion cavity. One or 2 months later, fluorogold was 
      injected several segments caudal to the lesion-transplant site to retrogradely 
      label those Red nucleus neurons whose axons have regenerated. Unmodified 
      fibroblasts failed to protect against either cell loss or atrophy. Neuron counts 
      and soma-size measurements in Nissl-stained preparations showed a 45% loss of 
      recognizable neurons and 40% atrophy of the surviving neurons in the injured Red 
      nucleus. Grafts of BDNF-producing fibroblasts reduced neuron loss to less than 
      15% and surviving neurons showed only a 20% decrease in mean soma size. Soma size 
      analysis of fluorogold-labeled Red nucleus neurons indicated that the Red nucleus 
      neurons whose axons regenerated caudal to the graft did not atrophy. We conclude 
      that fibroblasts engineered ex vivo to secrete BDNF and grafted into a partial 
      cervical hemisection promote axon regeneration while reducing cell loss and 
      atrophy of neurons in the Red nucleus. These results suggest that transplants of 
      genetically engineered cells could be an important tool for delivery of 
      therapeutic factors that contribute to the repair of spinal cord injury.
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, Pennsylvania 19129, USA.
FAU - Himes, B Timothy
AU  - Himes BT
FAU - Murray, Marion
AU  - Murray M
FAU - Tessler, Alan
AU  - Tessler A
FAU - Fischer, Itzhak
AU  - Fischer I
LA  - eng
GR  - HD07467/HD/NICHD NIH HHS/United States
GR  - NS10090/NS/NINDS NIH HHS/United States
GR  - NS24707/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Atrophy
MH  - Axons/metabolism/pathology/*transplantation
MH  - Axotomy
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/metabolism
MH  - Cell Count/statistics & numerical data
MH  - Cell Survival/physiology
MH  - Female
MH  - Fibroblasts/metabolism/*pathology/*transplantation
MH  - Humans
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Red Nucleus/metabolism/pathology
MH  - *Transplants/statistics & numerical data
EDAT- 2002/12/31 04:00
MHDA- 2003/01/22 04:00
CRDT- 2002/12/31 04:00
PHST- 2002/12/31 04:00 [pubmed]
PHST- 2003/01/22 04:00 [medline]
PHST- 2002/12/31 04:00 [entrez]
AID - S001448860297977X [pii]
AID - 10.1006/exnr.2002.7977 [doi]
PST - ppublish
SO  - Exp Neurol. 2002 Dec;178(2):150-64. doi: 10.1006/exnr.2002.7977.