Treatment with genetically engineered fibroblasts producing NGF or BDNF can accelerate recovery from traumatic spinal cord injury in the adult rat.
We tested the hypothesis that NGF or BDNF can protect damaged neural structures following spinal cord injury. Spinal contusions were produced in adult rats by a weight drop method. Thereafter, unmodified Rat 1 fibroblasts or fibroblasts engineered to secrete NGF or BDNF were injected into the injury site. Weekly assessments of recovery were made for 6 weeks using a locomotor rating scale. All rats were immediately paraplegic, then began to recover. At 1 week after injury, the ratings of locomotor performance in rats implanted with NGF- or BDNF-secreting fibroblasts were significantly increased over those of rats implanted with unmodified fibroblasts. This trend toward enhanced recovery persisted during the duration of the experiment, although the difference became smaller. Histological examination after 6 weeks showed a larger cross-sectional area of spinal cord at the maximal injury site in the animals treated with NGF or BDNF. These results demonstrate a significant biological effect of treatment with neurotrophins in traumatic spinal cord injury.
Kim
D H
DH
Department of Neurosurgery, University of California, San Francisco, USA.
Gutin
P H
PH
Noble
L J
LJ
Nathan
D
D
Yu
J S
JS
Nockels
R P
RP
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D005347:Fibroblasts / Q000637:transplantation; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D008124:Locomotion; D008297:Male; D009043:Motor Activity; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis; D013116:Spinal Cord / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011994:Recombinant Proteins