Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration beyond sites of spinal cord injury

J Neurosci. 2004 Jul 14;24(28):6402-9. doi: 10.1523/JNEUROSCI.1492-04.2004.

Abstract

Previous attempts to promote regeneration after spinal cord injury have succeeded in stimulating axonal growth into or around lesion sites but rarely beyond them. We tested whether a combinatorial approach of stimulating the neuronal cell body with cAMP and the injured axon with neurotrophins would propel axonal growth into and beyond sites of spinal cord injury. A preconditioning stimulus to sensory neuronal cell bodies was delivered by injecting cAMP into the L4 dorsal root ganglion, and a postinjury stimulus to the injured axon was administered by injecting neurotrophin-3 (NT-3) within and beyond a cervical spinal cord lesion site grafted with autologous bone marrow stromal cells. One to 3 months later, long-projecting dorsal-column sensory axons regenerated into and beyond the lesion. Regeneration beyond the lesion did not occur after treatment with cAMP or NT-3 alone. Thus, clear axonal regeneration beyond spinal cord injury sites can be achieved by combinatorial approaches that stimulate both the neuronal soma and the axon, representing a major advance in strategies to enhance spinal cord repair.

Publication types

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

MeSH terms

  • Animals
  • Axons / drug effects*
  • Axons / physiology
  • Bone Marrow Transplantation
  • Bucladesine / administration & dosage
  • Bucladesine / therapeutic use*
  • Combined Modality Therapy
  • Drug Evaluation
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Female
  • Ganglia, Spinal
  • Injections, Intralesional
  • Nerve Regeneration / drug effects*
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology
  • Neurotrophin 3 / administration & dosage
  • Neurotrophin 3 / therapeutic use*
  • Rats
  • Rats, Inbred F344
  • Spinal Cord Injuries / drug therapy*
  • Stromal Cells / transplantation
  • Transplantation, Autologous

Substances

  • Neurotrophin 3
  • Bucladesine