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 language | English |
|---|---|
| Pages (from-to) | 1062-1069 |
| Number of pages | 8 |
| Journal | Journal of Neurotrauma |
| Volume | 30 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 15 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Acute stimulation of transplanted neurons improves motoneuron survival, axon growth, and muscle reinnervation
AU - Grumbles, Robert M.
AU - Liu, Yang
AU - Thomas, Christie M.
AU - Wood, Patrick
AU - Thomas, Christine K
PY - 2013/6/15
Y1 - 2013/6/15
N2 - 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.
AB - 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.
KW - axon regeneration
KW - electrical stimulation
KW - motoneuron transplantation
KW - muscle denervation
UR - http://www.scopus.com/inward/record.url?scp=84879328024&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879328024&partnerID=8YFLogxK
U2 - 10.1089/neu.2012.2797
DO - 10.1089/neu.2012.2797
M3 - Article
C2 - 23544978
AN - SCOPUS:84879328024
VL - 30
SP - 1062
EP - 1069
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
SN - 0897-7151
IS - 12
ER -