Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Enhancing Outcomes Following Neonatal Nerve Injury with N-acetyl Cysteine
Daniel Demsey, MD, Joseph Catapano, MD, David Scholl, BSc, Cameron Chiang, BSc, Tessa Gordon, PhD, Gregory Borschel, MD.
The Hospital for Sick Children, Toronto, ON, Canada.

PURPOSE:
Retrograde motor and sensory neuron death may be an overlooked and significant component of disability following neonatal nerve injuries, such as obstetrical brachial plexus injury. Neuronal survival is essential for peripheral nerve regeneration, and pharmaceutical protection of neurons following injury may rescue neurons from retrograde neuronal death and improve the regenerative potential of the peripheral nervous system. N-acetyl cysteine (NAC) and acetyl-L-carnitine (ALC) have a long history of safe clinical use, and both have documented neuronal protection in adult models of peripheral nerve injury. NAC and ALC may, therefore, be ideal targets for development as neuroprotective drugs. This study investigates the efficacy of NAC and ALC in protecting motor and sensory neurons from retrograde neuronal death following neonatal nerve injury in a rat model.
METHODS:
Rats underwent either a sciatic nerve crush or transection and received NAC or ALC at two different doses for a period of either 2 or 4 weeks following injury. Four weeks following injury, surviving cells were retrograde labeled with a fluorescent tracer, and a sample of nerve distal to the site of injury was harvested to assess axon regeneration. Spinal cords and dorsal root ganglia were harvested three days later and samples were serially sectioned for motor and sensory neuron counts.
RESULTS:
Both neonatal sciatic crush and transection injury resulted in significant motor and sensory neuron death. Transection injury was more severe with far fewer neurons surviving injury in comparison to crush. Motoneuron survival following sciatic nerve crush injury was increased following NAC treatment twice daily for four weeks at a dose of 1500 mg/kg/day (558.4 ± 97 vs. 755.1 ± 63) (p<0.01). However, when animals were treated once daily, there were no statistically significant differences in motor or sensory neuron survival. Treatment with ALC did not improve sensory or motor neuron survival in either surgical model and NAC did not demonstrate motor neuron protection following sciatic transection injury. Figure 1:Motoneuron counts from DRGs at 4 weeks with BID dosing for each treatment group. Mean motoneuron counts from uninjured controls shown by 'Naive' line.
CONCLUSION:
Neonatal nerve injury results in profound motor neuron loss, with greater neuron loss following more severe nerve injury. N-acetyl cysteine improves motoneuron survival following neonatal crush injury, and this may translate to improved functional outcomes by preserving neurons crucial to regeneration. Neonatal sciatic nerve transection results in significantly more motor neuron death than crush injury, and therefore improving motoneuron survival may require higher treatment doses or longer treatment duration with NAC.


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