Motor axonal regeneration after partial and complete spinal cord transection

J Neurosci. 2012 Jun 13;32(24):8208-18. doi: 10.1523/JNEUROSCI.0308-12.2012.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / physiology*
  • Bone Marrow Transplantation / methods
  • Brain-Derived Neurotrophic Factor / administration & dosage
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Brain-Derived Neurotrophic Factor / therapeutic use*
  • Cervical Vertebrae
  • Cyclic AMP / administration & dosage
  • Cyclic AMP / pharmacology
  • Cyclic AMP / therapeutic use*
  • Dependovirus / genetics
  • Female
  • Genetic Vectors / genetics
  • Motor Neurons / drug effects
  • Motor Neurons / physiology*
  • Motor Skills / drug effects
  • Motor Skills / physiology
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology*
  • Rats
  • Rats, Inbred F344
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / physiopathology*
  • Spinal Cord Injuries / therapy*
  • Thoracic Vertebrae
  • Transfection / methods

Substances

  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP