Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury

S. W P Kemp, M. Szynkaruk, K. N. Stanoulis, M. D. Wood, E. H. Liu, M. P. Willand, L. Morlock, J. Naidoo, N. S. Williams, J. M. Ready, T. J. Mangano, S. Beggs, M. W. Salter, T. Gordon, A. A. Pieper, G. H. Borschel

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)202-216
Number of pages15
JournalNeuroscience
Volume284
DOIs
StatePublished - Jan 2 2015

Fingerprint

Wounds and Injuries
Neuroprotective Agents
Nerve Crush
Peripheral Nerve Injuries
Hypesthesia
Microglia
Motor Neurons
Sensory Receptor Cells
Sciatic Nerve
Paralysis
Axons
P7C3 compound
Regeneration
Cell Death
Rehabilitation
Newborn Infant
Neurons
Pain
Muscles
Therapeutics

Keywords

  • Functional recovery
  • Microglia
  • Neonatal nerve injury
  • Neuroprotection
  • P7C3

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kemp, S. W. P., Szynkaruk, M., Stanoulis, K. N., Wood, M. D., Liu, E. H., Willand, M. P., ... Borschel, G. H. (2015). Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury. Neuroscience, 284, 202-216. https://doi.org/10.1016/j.neuroscience.2014.10.005

Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury. / 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.

In: Neuroscience, Vol. 284, 02.01.2015, p. 202-216.

Research output: Contribution to journalArticle

Kemp, SWP, Szynkaruk, M, Stanoulis, KN, Wood, MD, Liu, EH, Willand, MP, Morlock, L, Naidoo, J, Williams, NS, Ready, JM, Mangano, TJ, Beggs, S, Salter, MW, Gordon, T, Pieper, AA & Borschel, GH 2015, 'Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury', Neuroscience, vol. 284, pp. 202-216. https://doi.org/10.1016/j.neuroscience.2014.10.005
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. / Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury. In: Neuroscience. 2015 ; Vol. 284. pp. 202-216.
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