Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury
| Autor: | Tessa Gordon, Noelle S. Williams, Stephen W.P. Kemp, Matthew D. Wood, Joseph M. Ready, Thomas J. Mangano, Michael P. Willand, K. N. Stanoulis, Andrew A. Pieper, Simon Beggs, Mark Szynkaruk, Jacinth Naidoo, Lorraine Morlock, Michael W. Salter, Edward H. Liu, G. H. Borschel |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Sciatic Neuropathy Sensory Receptor Cells Cell Survival Carbazoles Sensation Neuroprotection 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine P7C3 Peripheral Nerve Injuries Ganglia Spinal Paralysis Animals Medicine Muscle Strength Axon Cell Proliferation 030304 developmental biology Motor Neurons 0303 health sciences Movement Disorders Dose-Response Relationship Drug business.industry General Neuroscience Nerve injury Sensory neuron Nerve Regeneration Rats 3. Good health Disease Models Animal Neuroprotective Agents medicine.anatomical_structure Animals Newborn Spinal Cord chemistry Rats Inbred Lew Anesthesia Peripheral nerve injury Microglia medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience. 284:202-216 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2014.10.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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