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

Neuroscience. 2015 Jan 22:284:202-216. doi: 10.1016/j.neuroscience.2014.10.005. Epub 2014 Oct 13.


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: P7C3; functional recovery; microglia; neonatal nerve injury; neuroprotection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Carbazoles / therapeutic use*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal / pathology
  • Male
  • Microglia / drug effects
  • Motor Neurons / drug effects
  • Movement Disorders* / drug therapy
  • Movement Disorders* / etiology
  • Movement Disorders* / pathology
  • Muscle Strength / drug effects
  • Nerve Regeneration / drug effects
  • Neuroprotective Agents / therapeutic use*
  • Peripheral Nerve Injuries / complications*
  • Rats
  • Rats, Inbred Lew
  • Sciatic Neuropathy / complications*
  • Sensation / drug effects*
  • Sensory Receptor Cells / drug effects
  • Spinal Cord / pathology


  • Carbazoles
  • Neuroprotective Agents
  • P7C3 compound