1. N-Acetylcysteine Prevents Retrograde Motor Neuron Death after Neonatal Peripheral Nerve Injury
- Author
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Jennifer Y. Zhang, Cameron D. Chiang, David Scholl, Joseph Catapano, Tessa Gordon, and Gregory H. Borschel
- Subjects
0301 basic medicine ,Cell Survival ,Sensory system ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,Peripheral Nerve Injuries ,medicine ,Animals ,Motor Neurons ,Cell Death ,business.industry ,Motor neuron ,Nerve injury ,medicine.disease ,Sensory neuron ,Acetylcysteine ,Rats ,Lumbar Spinal Cord ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Brachial plexus injury ,Rats, Inbred Lew ,Anesthesia ,Peripheral nerve injury ,Crush injury ,Female ,Surgery ,medicine.symptom ,Acetylcarnitine ,business ,030217 neurology & neurosurgery - Abstract
Background Neuronal death may be an overlooked and unaddressed component of disability following neonatal nerve injuries, such as obstetric brachial plexus injury. N-acetylcysteine and acetyl-L-carnitine improve survival of neurons after adult nerve injury, but it is unknown whether they improve survival after neonatal injury, when neurons are most susceptible to retrograde neuronal death. The authors' objective was to examine whether N-acetylcysteine or acetyl-L-carnitine 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), N-acetylcysteine (750 mg/kg), or acetyl-L-carnitine (300 mg/kg) once or twice daily. Four weeks after injury, surviving neurons were retrograde-labeled with 4% Fluoro-Gold. 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 less neuron survival. High-dose N-acetylcysteine (750 mg/kg twice daily) significantly increased motor neuron survival after neonatal sciatic nerve crush and transection injury. Neither N-acetylcysteine nor acetyl-L-carnitine treatment improved sensory neuron survival. Conclusions Proximal neonatal nerve injuries, such as obstetric brachial plexus injury, produce significant retrograde neuronal death after injury. High-dose N-acetylcysteine significantly increases motor neuron survival, which may improve functional outcomes after obstetrical brachial plexus injury.
- Published
- 2017
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