Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury.
Scientific interest to find a treatment for spinal cord injuries has led to the development of numerous experimental strategies to promote axonal regeneration across the spinal cord injury site. Although these strategies have been developed in acute injury paradigms and hold promise for individuals with spinal cord injuries in the future, little is known about their applicability for the vast majority of paralyzed individuals whose injury occurred long ago and who are considered to have a chronic injury. Some studies have shown that the effectiveness of these approaches diminishes dramatically within weeks after injury. Here we investigated the regenerative capacity of rat rubrospinal neurons whose axons were cut in the cervical spinal cord 1 year before. Contrary to earlier reports, we found that rubrospinal neurons do not die after axotomy but, rather, they undergo massive atrophy that can be reversed by applying brain-derived neurotrophic factor to the cell bodies in the midbrain. This administration of neurotrophic factor to the cell body resulted in increased expression of growth-associated protein-43 and Talpha1 tubulin, genes thought to be related to axonal regeneration. This treatment promoted the regeneration of these chronically injured rubrospinal axons into peripheral nerve transplants engrafted at the spinal cord injury site. This outcome is a demonstration of the regenerative capacity of spinal cord projection neurons a full year after axotomy.
Kwon
Brian K
BK
CORD (Collaboration on Repair Discoveries), University of British Columbia, Room 2469, Biosciences Building, 6270 University Boulevard, Vancouver, BC, Canada V6T 1Z4.
Liu
Jie
J
Messerer
Corrie
C
Kobayashi
Nao R
NR
McGraw
John
J
Oschipok
Loren
L
Tetzlaff
Wolfram
W
D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D019922:GAP-43 Protein / Q000235:genetics; D015870:Gene Expression; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008867:Microtomy; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010525:Peripheral Nerves / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D012012:Red Nucleus / Q000166:cytology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*; D013131:Spine / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000235:genetics
D019922:GAP-43 Protein; D014404:Tubulin; D020813:Receptor, trkB