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N-acetyl cysteine enhances motor neuron survival in a rat model of neonatal nerve injury
Joseph Catapano, MD; Cameron Chiang; David Scholl, PhD; Tessa Gordon, PhD; Gregory H. Borschel, MD
Division of Plastic and Reconstructive Surgery, University of Toronto, Toronto, ON, Canada
Introduction: Motor and sensory neuron death may be an overlooked component of disability following neonatal nerve injuries, such as obstetrical brachial plexus injury. Previously, we have demonstrated that increasing motor and sensory neuron survival with a novel neuroprotective agent, P7C3, improves functional recovery in a rat model of neonatal nerve injury. However, P7C3 is not approved for clinical use. N-acetyl cysteine (NAC) has demonstrated neuroprotective properties in adult models of peripheral nerve injury and has a long history of safe clinical use in pediatric populations. This study investigates the efficacy of NAC in protecting motor and sensory neurons from cell death following neonatal nerve injury in a rat model.
Materials and Methods: Animals were injured 3 days after birth with either a crush or transection injury of the sciatic nerve and treated with intraperitoneal injections of NAC at a dose of 750mg/kg/day for 2 weeks. 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 serially sectioned for motor and sensory neuron counts.
Results: Motor neuron survival following sciatic nerve crush injury was increased with NAC treatment in comparison to vehicle treated animals (505.4 ± 39 vs. 403.7 ± 57) (p<0.05). NAC treated animals did not significantly improve axon regeneration distal to the site of injury in comparison to vehicle treated animals (6224 ± 620 vs 5508 ± 908). Transection injury resulted in significantly more motor and sensory neuron death than crush injury, however NAC did not improve motor neuron survival following transection injury.
Conclusions: N-acetyl cysteine demonstrated motor neuron protection following neonatal crush injury. Neonatal sciatic nerve transection results in significantly more motor neuron death than crush injury, and therefore improving motor neuron survival may require higher treatment doses or longer treatment duration with NAC.
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