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 language | English |
|---|---|
| Pages (from-to) | 736-746 |
| Number of pages | 11 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 68 |
| Issue number | 7 |
| DOIs | |
| State | Published - 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
Cite this
Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons. / Grumbles, Robert M.; Sesodia, Sanjay; Wood, Patrick; Thomas, Christine K.
In: Journal of Neuropathology and Experimental Neurology, Vol. 68, No. 7, 01.07.2009, p. 736-746.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons
AU - Grumbles, Robert M.
AU - Sesodia, Sanjay
AU - Wood, Patrick
AU - Thomas, Christine K
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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.
AB - 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.
KW - Axon regeneration
KW - Electromyographic activity
KW - Motoneuron death
KW - Motoneuron replacement
KW - Muscle denervation
KW - Muscle reinnervation
KW - Neurotrophic factors
UR - http://www.scopus.com/inward/record.url?scp=68249134222&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68249134222&partnerID=8YFLogxK
U2 - 10.1097/NEN.0b013e3181a9360f
DO - 10.1097/NEN.0b013e3181a9360f
M3 - Article
C2 - 19535998
AN - SCOPUS:68249134222
VL - 68
SP - 736
EP - 746
JO - American Journal of Psychotherapy
JF - American Journal of Psychotherapy
SN - 0002-9564
IS - 7
ER -