@article{aa8cc3bf4941480285c1bef095d4558f,
title = "Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury",
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.",
keywords = "Functional recovery, Microglia, Neonatal nerve injury, Neuroprotection, P7C3",
author = "Kemp, {S. W.P.} and M. Szynkaruk and Stanoulis, {K. N.} and Wood, {M. D.} and Liu, {E. H.} and Willand, {M. P.} and L. Morlock and J. Naidoo and Williams, {N. S.} and Ready, {J. M.} and Mangano, {T. J.} and S. Beggs and Salter, {M. W.} and T. Gordon and Pieper, {A. A.} and Borschel, {G. H.}",
note = "Funding Information: The authors are grateful to Jennifer Zhang and Cameron Chiang for expert technical assistance, Dr. Graham Pitcher for the use of the von Frey apparatus, and to Amy Tan for help with immunohistochemical protocols. This research was supported by grants from the Canadian Institute of Health Research (CIHR), the National Institute of Health (NIH), the Plastic Surgery Foundation (PSF), and National Institutes of Mental Health (NIMH) 1R01MH087986 to A.A.P. and Steven L. McKnight. At no time did any funding source have an involvement in either the design of the research, preparation of the manuscript, or the decision to submit the manuscript to a scientific journal. Dr. Kemp was supported through postdoctoral fellowship grants from the IAMGOLD Corporation and the Hospital for Sick Children RESTRACOMP program. The authors thank the National Institute of Mental Health{\textquoteright}s Psychoactive Drug Screening Program for K i determinations of receptor binding (contract # HHSN-271-2008-00025-C (NIMH PDSP), directed by Bryan L. Roth MD, PhD at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscol at NIMH, Bethesda MD, USA. Funding Information: K i determinations were provided by the National Institute of Mental Health{\textquoteright}s Psychoactive Drug Screening Program, Contract # HHSN-271-2008-00025-C (NIMH PDSP). The NIMH PDSP is directed by Bryan L. Roth MD, PhD at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscol at NIMH, Bethesda MD, USA. For experimental details please refer to the PDSP web site http://pdsp.med.unc.edu/ and click on “Binding Assay” on the menu bar. Publisher Copyright: {\textcopyright} 2014 IBRO.",
year = "2015",
month = jan,
day = "2",
doi = "10.1016/j.neuroscience.2014.10.005",
language = "English",
volume = "284",
pages = "202--216",
journal = "Neuroscience",
issn = "0306-4522",
}