Improvement of Motor and Sensory Neuron Survival with N-acetyl cysteine after Peripheral Nerve Injury
Background: Nerve transfers require for the donor nerve to be injured, either partially or completely, in order to guide regenerating axons into new targets. Axon regeneration and recovery after nerve grafting and transfer may be limited by retrograde neuronal death after injury. N-acetyl cysteine (NAC) and acetyl-L-carnitine (ALC) improve survival of neurons after adult nerve injury but it is unknown whether they improve survival after paediatric or neonatal injury when neurons are most susceptible to retrograde neuronal death. Our objective is to examine whether NAC or ALC treatment improves survival of neonatal motor or sensory neurons in a rat model of neonatal nerve injury.
Methods: Rat pups received either a sciatic nerve crush or transection injury at postnatal day 3 and were then randomized to receive either intraperitoneal vehicle (5% dextrose), NAC (750 mg/kg) or ALC (300 mg/kg) once or twice daily. Four weeks after injury, surviving neurons were retrograde-labeled with 4% Fluorogold. The lumbar spinal cord and L4/L5 dorsal root ganglia were then harvested and sectioned to count surviving motor and sensory neurons.
Results: Transection and crush injuries resulted in significant motor and sensory neuron loss, with transection injury resulting in significantly more retrograde neuron death. High-dose NAC (750 mg/kg twice daily) significantly increased motor neuron survival after neonatal sciatic nerve crush and transection injury. Neither NAC nor ALC treatment improved sensory neuron survival.
Conclusions: Proximal neonatal nerve injuries produce significant retrograde neuronal death after injury. Treatments improving motor and sensory neuron survival after nerve injury may improve recovery after nerve transfers or nerve grafting.
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