Sam Poore

Hello. Since coming to Brown as a student in the MD/PhD program I have had the pleasure of working in Ted Goslow’s lab on a variety of projects with a variety of individuals-undergraduates and graduate students alike. As I became involved and engaged in several studies on the evolution of bird flight, an interest emerged in how to apply the techniques we were using to a problem in medical science-animal movement and locomotion after peripheral nerve injury and how to best assess recovery of function. While the sciatic nerve crush is the most widely used model in the world and is at the forefront of peripheral nerve research, at the time there existed no rigorous model to analyze functional recovery. With advancements in the fields of biotechnology and genetic engineering, functional analysis of recovery of peripheral nerve injury with a high degree of resolution is paramount. To this end, over the past four years we have developed a rigorous model to analyze functional recovery during peripheral nerve regeneration in rats.

The Basic Science. We used an integrative approach that utilizes advances in high-speed videography and gait analysis, force-platform technology and in situ physiological measurement. Rats were trained to run on a treadmill (movie link here) and over a force platform (movie link here) and data was collected every seven days, at discrete 'observation windows,' during a 28 day regeneration period. Physiological measurements of the medial gastrocnemius muscle were also made at each observation window. Several findings will prove to be very useful in future studies on peripheral nerve regeneration.
First, two sensitive indicators of functional nerve regeneration have emerged including 1) the foot-horizontal angle as rats walked on the treadmill, and 2) the location of the center of pressure of the foot on a force-platform during stepping. Second, in all functional assays there was a striking pattern of functional reinnervation bracketed by post-operative days 14 and 21, presumably coincident with reinnervation of limb musculature. Third, our results demonstrate a fundamental difference between nerve regrowth/elongation and the time to achieve some measurable degree of functional recovery. To obtain an accurate analysis of regeneration, the concept of regeneration must be partitioned into nerve regrowth and functional recovery and techniques designed to assess regeneration should follow similar lines of partitioning.

The Clinical Correlation. Ted and I worked closely with Dr. Edward Akelman (Department of Orthopaedics, Brown University) who, with years of experience as a hand surgeon dealing with peripheral nerve injury every day (ranging from transected nerves in the hand to carpal tunnel syndrome), guided the project down a more clinical pathway. Since returning to medical school and my clinical electives I have had the opportunity to work with Dr. Akelman in the operating room where I have seen first-hand how our findings translate from the bench to clinical setting. The next logical step is to further this collaboration and try to devise strategies to augment peripheral nerve regeneration in humans with conditions affecting the peripheral nervous system such as carpal tunnel syndrome or peripheral neuropathies from a range of disease processes.

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