Electrical Stimulation of Embryonic Neurons for 1 Hour Improves Axon Regeneration and the Number of Reinnervated Muscles That Function

• Published in: Journal of neuropathology and experimental neurology 2013-07, Vol.72 (7), p.697-707
• Main Authors: Liu, Yang, Grumbles, Robert M, Thomas, Christine K
• Format: Article
• Language: English
• Subjects: Animals; Bladder; Cell Survival; Cells, Cultured; Choline O-Acetyltransferase - metabolism; Disease Models, Animal; Electric Stimulation; Embryo, Mammalian; Evoked Potentials, Motor - physiology; Female; Gene expression; Isometric Contraction - physiology; Male; Motor Neurons - physiology; Motor Neurons - transplantation; Muscle Denervation; Muscle, Skeletal - innervation; Muscular Atrophy - etiology; Muscular Atrophy - therapy; Muscular system; Nerve Regeneration - physiology; Pregnancy; Rats; Rats, Inbred F344; Recovery of Function - physiology; Rodents; Spinal Cord - cytology; Spinal cord injuries; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - therapy; Stem Cell Transplantation - methods; Stem cells; Studies; Time Factors; Transplants & implants
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/NEN.0b013e318299d376

ABSTRACTMotoneuron death after spinal cord injury or disease results in muscle denervation, atrophy, and paralysis. We have previously transplanted embryonic ventral spinal cord cells into the peripheral nerve to reinnervate denervated muscles and to reduce muscle atrophy, but reinnervation was incomplete. Here, our aim was to determine whether brief electrical stimulation of embryonic neurons in the peripheralnerve changes motoneuron survival, axon regeneration, and muscle reinnervation and function because neural depolarization is crucial for embryonic neuron survival and may promote activity-dependent axon growth. At 1 week after denervation by sciatic nerve section, embryonic day 14 to 15 cells were purified for motoneurons, injected into the tibial nerve of adult Fischer rats, and stimulated immediatelyfor up to 1 hour. More myelinated axons were present in tibial nerves 10 weeks after transplantation when transplants had been stimulated acutely at 1 Hz for 1 hour. More muscles were reinnervated if the stimulation treatment lasted for 1 hour. Reinnervation reduced muscle atrophy, with or without the stimulation treatment. These data suggest that brief stimulation of embryonic neurons promotes axon growth, which has a long-term impact on muscle reinnervation and function. Muscle reinnervation is important because it may enable the use of functional electrical stimulation to restore limb movements.