Grant: Operating Grant

Sensory neurons relay information between our body, spinal cord and brain via peripheral nerves. When these nerves are injured, they turn on repair programs that we have shown are critically dependent on signals received from the injury site and a molecule called brain-derived neurotrophic factor (BDNF). However, regeneration of these nerves is a clinically challenging scenario that can result in incomplete repair and/or pain states. We have identified a therapeutic intervention, brief electrical stimulation of the injured nerve/axons that results in more robust and accurate nerve repair, including increases BDNF expression and in preliminary work we show that it also favorably impacts the associated immune response. But, the underlying early cell and molecular events linking electrical stimulation of the injured nerve and to an improved regeneration state are largely unknown and the continued focus of our research, as they will likely provide novel therapeutic targets. More specifically we are trying to (i) understand how early injury signals instruct the injured neuron to begin regrowing an axon, form a growth cone and cope with the cellular stress these events impose; (ii) how electrical stimulation heightens this response and (iii) whether we can exploit what we have learned in a manner that advantages the more clinically challenging delayed nerve repair scenario. We believe that learning how to optimally manipulate the internal repair programs in sensory neurons will vastly improve nerve repair outcomes for Canadians.