Axonal responses to cellularly delivered NT-4/5 after spinal cord injury.
Neurotrophic factors delivered to the injured spinal cord have been shown to enhance axonal growth, prevent neuronal degeneration and partially improve sensorimotor function. The present study examined the effects of NT-4/5 on growth of spinal and supraspinal axons, glia, and functional outcome after spinal cord injury. Adult Fischer 344 rats received spinal cord dorsal hemisections or complete transections at the midthoracic level. Fibroblasts modified to secrete NT-4/5 or green fluorescent protein as controls were immediately grafted to the lesion site. Axonal growth responses were determined between 3 and 6 months postinjury by retrograde and anterograde tracing and immunohistochemistry. Motor axons, coerulospinal, reticulospinal, and propriospinal axons responded to NT-4/5 delivery after thoracic spinal cord injury with significantly increased axonal penetration into NT-4/5 secreting grafts compared to GFP-expressing control grafts. Axonal growth beyond NT-4/5-producing grafts and functional recovery were not observed. Numerous Schwann cells, but not oligodendrocytes, were present within NT-4/5-secreting grafts and remyelinated axons inside the graft. Thus, NT-4/5 and BDNF appear to be interchangeable to elicit substantial axonal growth in the injured spinal cord.
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA. ablesch@ucsd.edu
Armin
A
Blesch
Hong
H
Yang
Norbert
N
Weidner
An
A
Hoang
Deborah
D
Otero
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D051381:Rats; D011916:Rats, Inbred F344; D017475:Receptors, Nerve Growth Factor / Q000008:administration & dosage* / Q000235:genetics; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D017475:Receptors, Nerve Growth Factor; C089191:neurotrophin 4(5) receptor