Acute Stimulation of Transplanted Neurons Improves Motoneuron Survival, Axon Growth, and Muscle Reinnervation

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.

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

“…6D). These results contrast with an earlier study in which we showed that motoneuron survival was increased when ventral cell preparations were stimulated at 20 Hz for 1 hour (96). Neural and glial progenitors were abundant in ventral cell preparations.…”

Transplantation of embryonic spinal cord neurons to the injured distal nerve promotes axonal regeneration after delayed nerve repair

“…The muscle atrophy was thereby alleviated. These observations were consistent with those of previous studies (Erb et al ., ; Yohn et al ., ; Casella et al ., ; Grumbles et al ., , ; Su et al ., ; Liu et al ., , ). When the grafted cells were removed and the residual distal stump was cross‐sutured to the proximal end of freshly cut ipsilateral common peroneal (CP) nerve, the axonal regeneration from the proximal stump of the injured CP nerve was promoted, and the muscle function was partially recovered.…”

Regenerative Rehabilitation: Combining Stem Cell Therapies and Activity-Dependent Stimulation

“…59 Based on this cumulative evidence, one of the most successful stem cell transplant studies coupled brief electrical stimulation of the peripheral nerve with motor neuron cell grafts and demonstrated impressive cell survival and muscle re-innervation. 60 This landmark study suggests that the combination of regenerative cell therapies and artificial stimulation may be critical for achieving targeted plasticity and functional recovery following injuries or degeneration of the neuromuscular system.…”