Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury. (22nd January 2015)

• Record Type: Journal Article
• Authors: Kemp, S.W.P.; Szynkaruk, M.; Stanoulis, K.N.; Wood, M.D.; Liu, E.H.; Willand, M.P.; Morlock, L.; Naidoo, J.; Williams, N.S.; Ready, J.M.; Mangano, T.J.; Beggs, S.; Salter, M.W.; Gordon, T.; Pieper, A.A.; Borschel, G.H.
• Is Part Of: Neuroscience. Volume 284(2015)
• Page Start: 202
• Page End: 216
• Publication Date: 2015-01-22
• Subjects: ANOVA analysis of variance -- DRG dorsal root ganglion -- EDL extensor digitorum longus -- LOD limit of detection -- LOQ limit of quantitation -- MUNE motor unit number estimation -- OBPP obstetrical brachial plexus palsy -- P3 postnatal day 3 -- PBS phosphate-buffered saline; neonatal nerve injury -- P7C3 -- neuroprotection -- functional recovery -- microglia; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2014.10.005
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: P7C3 protects neurons from cell death following neonatal nerve injury. P7C3 enhances functional recovery without surgical repair. P7C3 treatment markedly reduced microgliosis after nerve injury. The findings represent a novel basis for future drug development. Abstract: Nerve injuries cause pain, paralysis and numbness that can lead to major disability, and newborns often sustain nerve injuries during delivery that result in lifelong impairment. Without a pharmacologic agent to enhance functional recovery from these injuries, clinicians rely solely on surgery and rehabilitation to treat patients. Unfortunately, patient outcomes remain poor despite application of the most advanced microsurgical and rehabilitative techniques. We hypothesized that the detrimental effects of traumatic neonatal nerve injury could be mitigated with pharmacologic neuroprotection, and tested whether the novel neuroprotective agent P7C3 would block peripheral neuron cell death and enhance functional recovery in a rat neonatal nerve injury model. Administration of P7C3 after sciatic nerve crush injury doubled motor and sensory neuron survival, and also promoted axon regeneration in a dose-dependent manner. Treatment with P7C3 also enhanced behavioral and muscle functional recovery, and reversed pathological mobilization of spinal microglia after injury. Our findings suggest that the P7C3 family of neuroprotective compounds may provide a basis for the development of a new neuroprotective drug to enhance recovery following peripheral nerve injury.