Acute stimulation of transplanted neurons improves motoneuron survival, axon growth, and muscle reinnervation

Robert M. Grumbles, Yang Liu, Christie M. Thomas, Patrick Wood, Christine K Thomas

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Few options exist for treatment of pervasive motoneuron death after spinal cord injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis. Local transplantation of embryonic motoneurons into an axotomized peripheral nerve is a promising approach to arrest the atrophy of denervated muscles; however, muscle reinnervation is limited by poor motoneuron survival. The aim of the present study was to test whether acute electrical stimulation of transplanted embryonic neurons promotes motoneuron survival, axon growth, and muscle reinnervation. The sciatic nerve of adult Fischer rats was transected to mimic the widespread denervation seen after disease or injury. Acutely dissociated rat embryonic ventral spinal cord cells were transplanted into the distal tibial nerve stump as a neuron source for muscle reinnervation. Immediately post-transplantation, the cells were stimulated at 20 Hz for 1 h. Other groups were used to control for the cell transplantation and stimulation. When neurons were stimulated acutely, there were significantly more neurons, including cholinergic neurons, 10 weeks after transplantation. This led to enhanced numbers of myelinated axons, reinnervation of more muscle fibers, and more medial and lateral gastrocnemius muscles were functionally connected to the transplant. Reinnervation reduced muscle atrophy significantly. These data support the concept that electrical stimulation rescues transplanted motoneurons and facilitates muscle reinnervation.

Original languageEnglish
Pages (from-to)1062-1069
Number of pages8
JournalJournal of Neurotrauma
Volume30
Issue number12
DOIs
StatePublished - Jun 15 2013

Fingerprint

Motor Neurons
Axons
Neurons
Muscles
Growth
Muscular Atrophy
Cell Transplantation
Electric Stimulation
Transplantation
Tibial Nerve
Cholinergic Neurons
Inbred F344 Rats
Amyotrophic Lateral Sclerosis
Denervation
Sciatic Nerve
Spinal Cord Injuries
Peripheral Nerves
Neurodegenerative Diseases
Spinal Cord
Skeletal Muscle

Keywords

  • axon regeneration
  • electrical stimulation
  • motoneuron transplantation
  • muscle denervation

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Acute stimulation of transplanted neurons improves motoneuron survival, axon growth, and muscle reinnervation. / Grumbles, Robert M.; Liu, Yang; Thomas, Christie M.; Wood, Patrick; Thomas, Christine K.

In: Journal of Neurotrauma, Vol. 30, No. 12, 15.06.2013, p. 1062-1069.

Research output: Contribution to journalArticle

Grumbles, Robert M. ; Liu, Yang ; Thomas, Christie M. ; Wood, Patrick ; Thomas, Christine K. / Acute stimulation of transplanted neurons improves motoneuron survival, axon growth, and muscle reinnervation. In: Journal of Neurotrauma. 2013 ; Vol. 30, No. 12. pp. 1062-1069.
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