Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons

Robert M. Grumbles, Sanjay Sesodia, Patrick Wood, Christine K Thomas

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Motoneuron death can occur over several spinal levels with disease or trauma, resulting in muscle denervation. We tested whether cotransplantation of embryonic neurons with 1 or more neurotrophic factors into peripheral nerve improved axon regeneration, muscle fiber area, reinnervation, and function to a greater degree than cell transplantation alone. Sciatic nerves of adult Fischer rats were cut to denervate muscles; 1 week later, embryonic ventral spinal cord cells (days 14-15) were transplanted into the tibial nerve stump as the only source of neurons for muscle reinnervation. Factors that promote motoneuron survival (cardiotrophin 1; fibroblast growth factor 2; glial cell line-derived neurotrophic factor; insulin-like growth factor 1; leukemia inhibitory factor; and hepatocyte growth factor) were added to the transplant individually or in combinations. Inclusion of a single factor with the cells resulted in comparable myelinated axon counts, muscle fiber areas, and evoked electromyographic activity to cells alone 10 weeks after transplantation. Only cell transplantation with glial cell line-derived neurotrophic factor, hepatocyte growth factor, and insulin-like growth factor 1 significantly increased motoneuron survival, myelinated axon counts, muscle reinnervation, and evoked electromyographic activity compared with cells alone. Thus, immediate application of a specific combination of factors to dissociated embryonic neurons improves survival of motoneurons and the long-term function of reinnervated muscle.

Original languageEnglish
Pages (from-to)736-746
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume68
Issue number7
DOIs
StatePublished - Jul 1 2009

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Keywords

  • Axon regeneration
  • Electromyographic activity
  • Motoneuron death
  • Motoneuron replacement
  • Muscle denervation
  • Muscle reinnervation
  • Neurotrophic factors

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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