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Myoneural Studies
The broad area of myoneural control is currently under investigation. One of the primary questions involves neuromuscular junction stability, which is dependent upon the motor neuron, the neuromuscular junction, and the muscle fiber. Current studies encompass all three components that contribute to neuromuscular junction stability.
- Impact of delayed nerve repair on recovery of muscle function –
- This research examines the effect of delayed nerve repair on the stability of the neuromuscular junction. Transection of the tibial nerve in the rat results in changes in the distribution of the five acetylcholine receptor subtypes in the gastrocnemius. Studies suggest that preservation of the subtype ratios present in innervated muscle is an important determinant in whether muscle function returns following delayed reinnervation after nerve transection/repair. There appears to be an interaction between trophic factors released by the motor nerve that maintain the appropriate ratio of acetylcholine receptor subtypes.
- Outcome variables: Muscle force generation following nerve stimulation. ACh receptor subtype expression using RT PCR. Gene array documentation of molecular responses to nerve transection. Nerve electrophysiology (nerve conduction velocity, amplitude of action potential, area under the curve of EMG)
- Time course of recovery of muscle function following intramuscular injection of botulinum toxin –
- Botulinum toxin type A (BoNT-A) injections provide an important management technique for various orthopaedic indications. The time course of muscle/nerve recovery following toxin injection is characterized by transient alterations in the expression of acetylcholine receptor subtypes. Restoration of function following BoNTA is characterized by temporal shifts in the ratios of ACh receptor subtypes.
- Outcome variables: Muscle force generation and myoneural electrophysiology. RT PCR of ACh receptor subtype gene expression.
- Effects of age on restoration of function following nerve repair –
- It is well known that nerve repairs are less successful in aging patients. The mechanism for this impairment is unknown. This research is targeting IGF-1 as a fundamental growth factor responsible for maintaining successful nerve regeneration following injury. These studies use a dwarf rat model of aging; this strain of rats is deficient in GH and IGF-1.
- Outcome variables: Same as above.
- Effects of motor neuron number on nerve recovery following delayed nerve repair –
- This study is being performed in collaboration with Dr. Ron Oppenheim in the Department of Neurobiology and Anatomy. Dr. Oppenheim has a gene-targeted strain of mice (BAX mice) that do not experience the same degree of neuronal apoptosis as normal mice. These mice are characterized by having 30 percent more distal motor fibers in their peripheral nerves. The impact of this genetic alteration on nerve recovery and myofibril innervation is being investigated.
- Outcome variables: Double labeling of neurons is being performed to establish the total number of nerves in the nerve trunk as well as the number of nerves reinnervating the target muscle following nerve transection/repair.
- Effects of distraction frequency on outcomes of limb lengthening –
- These studies were initially performed in rabbits and documented that motorized distraction resulted in superior functional outcomes compared to twice daily distraction during limb-lengthening. Questions of nerve growth factors and muscle functional changes are being pursued in a rat model of limb lengthening.
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