David S. K. Magnuson, Ph.D.
Friends for Michael Endowed Professor, Departments of Neurological Surgery, Anatomical Sciences & Neurobiology, and Biomedical Engineering
Phone: 502-852-6551; Fax: 502-852-5148
The research in my laboratory is focused on the neurons and pathways in the spinal cord that are responsible for locomotion, and on applying what we learn about locomotor systems to spinal cord injury and repair.
One of our primary investigations is focused on the long propriospinal neurons and pathways in the spinal cord that link the lumbar and cervical enlargements. These circuits are well-suited to participate in locomotion and are thought to mediate forelimb/hindlimb coordination in animals and upper-body/arm movement during walking and running in humans. In collaboration with the Whittemore lab, we use a combination of approaches including electrophysiology and tract-tracing and both the in vitro neonatal rat brainstem/spinal cord preparation, and adult rats, in vivo. We are seeking to determine the roles played by specific descending and ascending pathways in locomotor activity in normal and spinal cord injured rats. The most recent results from this project suggest that local lumbar interneurons (L2 projecting to L5) are important for R-L hindlimb alternation while the long-ascending propriospinals (LAPNs, L2 projecting to C6) are important for R-L alternation of both forelimbs and hindlimbs. Many of the LAPN axons are located in the outermost rim of white matter and are spared following contusion spinal cord injuries, making them excellent potential targets for therapeutic approaches following spinal cord injury.
A second major project in my laboratory is aimed at gaining a better understanding of activity-based rehabilitation, one of the primary rehabilitation strategies used clinically, that usually takes the form of body-weight supported treadmill training. We are currently using several different approaches in animal models including swimming, shallow water walking, and large cages as strategies to enhance recovery and tiny cages or immobilization in a rat wheel-chair to reduce hindlimb movement and recovery after injury. We are investigating the mechanisms underlying functional recovery following activity-based rehabilitation including the role(s) that cutaneous feedback, limb-loading and frequency, timing and duration of training play in a successful rehabilitation program. This project naturally as evolved to include a major focus on cardiovascular and autonomic function and we have discovered that simple approaches like cage size (tiny cages to restrict activity and large cages to enhance activity) are sufficient to make significant changes in key cardiovascular outcomes after a spinal cord injury.
Our third major project is focused on a clinical-modeled physical therapy strategy that mimics the stretching that is applied to lower extremity muscles after a spinal cord injury in an effort to reduce spasticity and to maintain joint range-of-motion. Many patients with spinal cord injury experience severe spasticity and contractures, a severe limitation to joint range of motion that can be debilitating. Currently, the primary non-surgical approach to prevent and reverse contractures is muscle stretch, either manually or using a splint or cast. We have discovered that muscle stretch, when applied either acutely or chronically after an incomplete spinal cord injury has a devastating effect on locomotor function with concomitant evidence for negative spinal plasticity involving nociceptors (pain fibers). In collaboration with the Petruska laboratory we are investigating the physiological mechanisms underlying this phenomenon and trying to determine if stretching might in fact be detrimental to recovery in people with SCI.
In addition, we are working with the laboratories of Drs. Jay Hoying, Amanda LeBlanc and Brad Keller to investigate vascular and cardiovascular changes after injury. We are collaborating with Dr. Michael Voor on bone loss after injury and with Drs. Sujata Saraswat and Cynthia Gomes (Petruska Lab) on vascular and organ inflammation after injury and various levels of activity/exercise.
Amanda M. Pocratsky, Darlene A. Burke, Johnny R. Morehouse, Jason E. Beare, Amberly S. Riegler, Pantelis Tsoulfas, Gregory J. R. States, Scott R. Whittemore & David S. K. Magnuson (2017) Reversible silencing of lumbar spinal interneurons unmasks a task-specific network for securing hindlimb alternation. Nature Communications (in press)
DeVeau KM, Harman KA, Squair JW, Krassioukov AV, Magnuson DSK, West CR. A comparison of passive hind-limb cycling and active upper-limb exercise provides new insights into systolic dysfunction following spinal cord injury. American Journal of Physiology – Heart. (in press).
Magnuson DSK, Dietrich WD. Introduction to the Special Issue on Locomotor Rehabilitation after Spinal Cord Injury. J Neurotrauma 34(9): 1711-1712. 2017. PMID: 28447875
Keller AV, Rees K, Prince D, Morehouse J, Shum-Siu A, Magnuson DSK. Dynamic “range of motion” hindlimb stretching disrupts locomotor function in rats with moderate subacute spinal cord injuries. Journal of Neurotrauma, in press. 2017. PMID: 28288544
DeVeau KM, Martin EK, King NT, Shum-Siu A, Keller BB, West C, Magnuson DSK. Challenging Cardiac Function Post-Spinal Cord Injury with Dobutamine. Autonomic Neuroscience: Basic and Clinical, in press. 2017. PMID 28065654
Keller AV, Wainwright G, Shum-Siu A, Prince D, Hoeper A, Martin E, Magnuson DS. Disruption of locomotion in response to hindlimb muscle stretch at acute and chronic time points after a spinal cord injury in rats. J Neurotrauma 34(3):661-670, 2016. PMID: 27196003
May Z, Fouad K, Shum-Siu A, Magnuson DSK. Challenges of animal models in SCI research: Effects of pre-injury task-specific training in adult rats before lesion. Behavioral Brain Research 291: 26-35, 2015. PMID: 25975172
Caudle KL, Atkinson DA, Brown EH, Donaldson K, Seibt E, Chea T, Smith E, Chung K, Shum-Siu A, Cron C, Magnuson DSK. Hindlimb stretching alters locomotor function post-spinal cord injury in the adult rat. Neurorehab and Neural Repair 29(3): 268-77, 2015. PMID 25106555