NT-3 gene delivery elicits growth of chronically injured corticospinal axons and modestly improves functional deficits after chronic scar resection.
Nervous system growth factors promote axonal growth following acute spinal cord injury. In the present experiment, we examined whether delivery of neurotrophic factors after chronic spinal cord injury would also promote axonal growth and influence functional outcomes. Adult Fischer 344 rats underwent mid-thoracic spinal cord dorsal hemisection lesions. Three months later, primary fibroblasts genetically modified to express human neurotrophin-3 (NT-3) were placed in, and distal to, the lesion cavity. Upon sacrifice 3 months later (6 months following the initial lesion), NT-3-grafted animals exhibited significant growth of corticospinal axons up to 15 mm distal to the lesion site and showed a modest but significant 1.5-point improvement in locomotor scores (P < 0.05) on the BBB scale, compared to control-grafted animals. Thus, growth factor gene delivery can elicit growth of corticospinal axons in chronic stages of injury and improves functional outcomes compared to non-growth-factor-treated animals.
Tuszynski
Mark H
MH
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0626, USA. mtuszynski@ucsd.edu
Grill
Ray
R
Jones
Leonard L
LL
Brant
Adam
A
Blesch
Armin
A
Löw
Karin
K
Lacroix
Steve
S
Lu
Paul
P
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D006085:Graft Survival; D006801:Humans; D009043:Motor Activity; D020933:Neurotrophin 3 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D051381:Rats; D013119:Spinal Cord Injuries / Q000628:therapy*; D016896:Treatment Outcome
D020933:Neurotrophin 3