Local and remote growth factor effects after primate spinal cord injury.
Primate models of spinal cord injury differ from rodent models in several respects, including the relative size and functional neuroanatomy of spinal projections. Fundamental differences in scale raise the possibility that retrograde injury signals, and treatments applied at the level of the spinal cord that exhibit efficacy in rodents, may fail to influence neurons at the far greater distances of primate systems. Thus, we examined both local and remote neuronal responses to neurotrophic factor-secreting cell grafts placed within sites of right C7 hemisection lesions in the rhesus macaque. Six months after gene delivery of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) into C7 lesion sites, we found both local effects of growth factors on axonal growth, and remote effects of growth factors reflected in significant reductions in axotomy-induced atrophy of large pyramidal neurons within the primary motor cortex. Additional examination in a rodent model suggested that BDNF, rather than NT-3, mediated remote protection of corticospinal neurons in the brain. Thus, injured neural systems retain the ability to respond to growth signals over the extended distances of the primate CNS, promoting local axonal growth and preventing lesion-induced neuronal degeneration at a distance. Remote cortical effects of spinally administered growth factors could "prime" the neuron to respond to experimental therapies that promote axonal plasticity or regeneration.
Brock
John H
JH
Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
Rosenzweig
Ephron S
ES
Blesch
Armin
A
Moseanko
Rod
R
Havton
Leif A
LA
Edgerton
V Reggie
VR
Tuszynski
Mark H
MH
D000818:Animals; D001284:Atrophy / Q000473:pathology / Q000517:prevention & control; D001369:Axons / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002574:Cervical Vertebrae / Q000293:injuries; D004195:Disease Models, Animal; D005260:Female; D007278:Injections, Spinal; D008253:Macaca mulatta; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D020933:Neurotrophin 3 / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020813:Receptor, trkB / Q000378:metabolism; D020812:Receptor, trkC / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D020813:Receptor, trkB; D020812:Receptor, trkC