Grants Funded

Abstract

Project Summary: Reverse end-to-side (RETS) nerve transfer is a technique to supply injured nerve with a healthy donor nerve by neurorrhaphy of the end of donor nerve to the side of the injured nerve. It is hypothesized to serve two purposes: 1) to provide donor axons to innervate target muscle for functional improvement; and 2) to maintain the health of distal nerve and muscle to support the growth of axons from the injured nerve, also known as the babysitting effect. The concept has been validated in experimental rodent studies and supported by clinical observations; however, the exact mechanism is still controversial since electrophysiological assessment demonstrated lack of contribution from the donor nerve in severe ulnar nerve injury patients as well as rodent studies primarily used acute injury and nerve transfer settings which are not clinically practical. To better understand the mechanism of RETS, we will re-evaluate the contribution of donor axons and babysitting effect using the obturator nerve- femoral nerve combination. To create chronically injured nerve, proximal femoral nerve proper will be ligated for two months before obturator nerve coaptation to the recipient femoral nerve. The motoneuron pools for obturator and femoral nerve will then be retrogradely labelled at six weeks after the transfer. Spinal cords and muscles will be harvested and cleared for whole tissue imaging. To investigate the possible functional connection of the donor axons, donor obturator nerve will be pre-labeled with adeno-associated virus that expresses green fluorescent protein, thereby only donor nerve axons, if any, will be visible in the targeted quadriceps muscle. Electrophysiological recording from donor and native injured nerve will also be assessed to support the findings.

Impact Statement: The speculated mechanisms behind RETS are reasonable and enticing rationale for peripheral nerve reconstructive surgeons to adopt this transfer technique in hope to provide better care to patients. However, it is still early to justify the use without proper control clinical studies and experimental setup. With our proposal that encompasses retrograde tracing, electrophysiological and histological approaches in a clinically relevant rodent RETS model, we will provide a better understanding on whether RETS is successful and by what mechanism it operates in a chronic injury situation, which will eventually inform nerve surgeon to guide their treatment paradigm.

Biography
I am a basic research scientist focusing on spinal cord and peripheral nerve repair. I graduated from the University of Hong Kong with a Ph.D. degree in Neurosciences in 2008. I have worked on multiple medical science projects from beta amyloid deposition to finding a potential drug for spinal cord injury. I am currently working at the University of Calgary as a research associate in Dr. Rajiv Midha's lab and I hold an adjunct faculty position as a Research Assistant Professor. One of my research focus is on harvesting Schwann cells, a supporting glial cell, from human skin and study their therapeutic potential to be used for cell therapy in peripheral nerve and spinal cord injury repair. My another interest is to look at novel surgical approaches for nerve repair, thanks to a stimulating environment working with a multidisciplinary team of cell biologists and neurosurgeons. Together, we are using state-of-the-art imaging equipment and technique to question conventional practices and create novel solutions.