Project 461880

Peripheral nerve injuries are common and often associated with poor outcomes including incomplete repair, debilitating pain states and compromised function - a reality we aim to change. We can greatly enhance nerve repair by brief electrical nerve stimulation (ES) of the injured nerve at the time of or before surgical repair in rodents and humans, but this approach is invasive. Acute intermittent hypoxia (AIH), breathing alternate cycles of regular air and air with ~50% normal oxygen levels (11% O2) is an emerging, promising non-invasive therapy promoting respiratory and non-respiratory muscle function in spinal cord injured rats and humans. Because the entire body is exposed to this therapy, we believe it has the potential to globally impact the nervous system beyond just controlling respiratory and leg function in spinal cord injured patients. Thus, we hypothesized that an AIH paradigm similar to that used for spinal cord repair will improve peripheral nerve repair in a manner akin to ES, including its impact on expression of regeneration-associated proteins - a predictor of nerve growth states. In recent studies we found this to be the case and now propose to continue these promising studies by: (i) determining the optimal AIH treatments versus ES for nerve repair using a new precise model of graded nerve compression and surgical release to simulate severe carpal tunnel syndrome and release in preclinical models; and (ii) concurrently perform a pilot clinical trial evaluating this form of treatment (using the best parametes identified in our preclinical model) on patients with compromised hand function due to severe nerve compression/entrapment (carpal tunnel syndrome). The latter will translate our bench findings to the patient with the goal of improving nerve repair outcomes in the least invasive and optimal manner.