Motor axonal regeneration after partial and complete spinal cord transection.
We subjected rats to either partial midcervical or complete upper thoracic spinal cord transections and examined whether combinatorial treatments support motor axonal regeneration into and beyond the lesion. Subjects received cAMP injections into brainstem reticular motor neurons to stimulate their endogenous growth state, bone marrow stromal cell grafts in lesion sites to provide permissive matrices for axonal growth, and brain-derived neurotrophic factor gradients beyond the lesion to stimulate distal growth of motor axons. Findings were compared with several control groups. Combinatorial treatment generated motor axon regeneration beyond both C5 hemisection and T3 complete transection sites. Yet despite formation of synapses with neurons below the lesion, motor outcomes worsened after partial cervical lesions and spasticity worsened after complete transection. These findings highlight the complexity of spinal cord repair and the need for additional control and shaping of axonal regeneration.
Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
Paul
P
Lu
Armin
A
Blesch
Lori
L
Graham
Yaozhi
Y
Wang
Ramsey
R
Samara
Karla
K
Banos
Verena
V
Haringer
Leif
L
Havton
Nina
N
Weishaupt
David
D
Bennett
Karim
K
Fouad
Mark H
MH
Tuszynski
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002574:Cervical Vertebrae; D000242:Cyclic AMP / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000229:Dependovirus / Q000235:genetics; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology* / Q000628:therapy*; D013904:Thoracic Vertebrae; D014162:Transfection / Q000379:methods
D019208:Brain-Derived Neurotrophic Factor; D000242:Cyclic AMP