UC San Diego

Although our previous studies demonstrate robust regeneration of corticospinal tract (CST) into neural progenitor cell (NPC) grafts placed into spinal cord injury (SCI) site, our recent preliminary data unexpectedly found that only hindlimb CST regenerated and forelimb CST rarely regenerated after mid-cervical SCI. This limited regeneration may be due to small proportional injury of forelimb CST and remaining synaptic connections above SCI, which is consistent with a recent new hypothesis, synaptic suppression of axon regeneration. In order to promote forelimb CST regeneration, we targeted to silence synaptic activity transiently by administration of Gabapentin, a pharmacological agent that blocks the Alpha2delta2 subunit of voltage-gated calcium channels involved in regulation of synaptic activity. Adult rats received mid-cervical SCI and NPC graft-expressing green fluorescent protein (GFP) followed by Gabapentin administration for two weeks. The forelimb-CST were specifically traced by injection of adeno-associated virus (AAV) expressing red fluorescent protein (RFP) and animals survived additional 3 weeks. The experimental group receiving Gabapentin did not show a dramatic increase of forelimb-CST regeneration as hindlimb CST, but a trend toward more regeneration compared to the control group. Further experiment with higher dosage and more frequent administration needs to confirm whether Gabapentin can elicit forelimb CST regeneration and has potential for treatment of SCI.