American Society for Peripheral Nerve

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The Effect of the Novel Proneurogenic, Neuroprotective Compound P7C3 on Regenerative Properties Following Sciatic Nerve Crush in Neonatal Rats
Stephen W. P. Kemp; Andrew A. Pieper, MD; Matthew D. Wood; Mark Szynkaruk; Tessa Gordon; Gregory H. Borschel
SickKids Hospital and the University of Toronto, Toronto, ON, Canada

Motorneurons of adult rats are able to survive following crush type nerve injuries. However, sciatic nerve injury in neonatal rats results in a significant loss of motorneurons and leads to impaired muscle development and function. The majority of these neurons die rapidly following nerve injury through an apoptotic mechanism. P7C3, a novel aminopropyl carbazole, has been recently shown to display proneurogenic, neuroprotective properties in the subgranular zone of the hippocampus. P7C3 exerts its proneurogenic activity by protecting newborn neurons from apoptosis. However, it is currently unknown what effect P7C3 has on the protection and survival of motorneurons following neonatal nerve injury. In this experiment, we sought to assess the possible neuroprotective effects of daily administration of P7C3 and examined both axonal and Schwann cell (SC) regenerative properties following unilateral sciatic nerve crush at postnatal day 3 (P3) in neonatal rats. Animals were randomly assigned to one of four experimental groups: nerve crush with P7C3 administration for two weeks (Group 1); nerve crush with drug vehicle administration for two weeks (Group 2); sham-operated controls (Group 3), and; sham-operated controls with P7C3 administration for two weeks (Group 4). Following the initial surgery, animals were returned to their home cages and their body weights, and food/water intake were monitored for a one month period. At 1 month, anatomical parameters of both the spinal cord and dorsal root ganglion (DRG) cells were characterized following retrograde labeling of the sciatic nerve with FluorGold (FG). Following nerve injury with vehicle administration, the number of retrogradely labeled motorneurons was reduced to approximately 35%. Preliminary results indicate that animals directly administered P7C3 over a two week period show improved regenerative properties following neonatal sciatic nerve crush. Current studies are analyzing P7C3 mediated anti-apoptotic effects through either a microglia dependant or glutamate excitotoxic preventative mechanism.


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