David S. K. Magnuson, Ph.D. — Kentucky Spinal Cord Injury Research Center

Friends for Michael Endowed Professor, Departments of Neurological Surgery, Anatomical Sciences & Neurobiology, and Biomedical Engineering

Phone: 502-852-6551; Fax: 502-852-5148

E-mail David Magnuson

Research Focus:

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 here at UofL and with Simon Danner and Ilya Rybak at Drexel University, we use a combination of approaches including cutting-edge behavioral analysis, virus-based synaptic silencing and neuronal labeling (including trans-synaptic labeling) and computer modeling. 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 silencing long-ascending or long-descending propriospinal neurons disrupts inter-limb coordination during stepping. Many of the propriospinal 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. Surprisingly, when these neurons were silenced post-spinal cord injury, the locomotor function of the animals actually improved, bringing into question the relationship between spared axons and functional recovery.

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 have a project that focuses on the biomechanics of passive cycling, which is a commonly used approach both clinically and pre-clinically. We have focused on gaining a full understanding of how crank length, cycle frequency, injury location and severity and time post-injury alter the pedal reaction forces that are dictated by muscle activation during this commonly used exercise strategy. This project is a collaboration with Drs. David Rouffet (Exercise Science) and Thomas Roussel (Bioengineering).

Finally, we have an ongoing bioinformatics project focused on enhancing our data analysis and approach to experimental design. This project is in collaboration with Dr. Cynthia Gomes (Petruska Lab) and Drs. Eric Rouchka and Julia Chariker (Computer Science and Engineering).

Key Publications:

Zholudeva LV, Abraira VE, Satkunendrarajah K, McDevitt TC, Goulding MD, Magnuson DSK, Lane MA. 2021 Spinal Interneurons as Gatekeepers to Neuroplasticity after Injury or Disease. J Neurosci. 41(5):845-854. PMID: 33472820.

Pocratsky AM, Shepard CT, Morehouse JR, Burke DA, Riegler AS, et al. 2020. Long ascending propriospinal neurons provide flexible, context-specific control of interlimb coordination. eLife Sep 9;9:e53565. doi: 10.7554/eLife.53565.PMID: 32902379

Hoy KC, Strain MM, Turtle JD, Lee KH, Huie JR, Hartman JJ, Tarbet MM, Harlow ML, Magnuson DSK, Grau JW. 2020 Evidence That the Central Nervous System Can Induce a Modification at the Neuromuscular Junction That Contributes to the Maintenance of a Behavioral Response. J Neurosci. 40(48):9186-9209. PMID: 33097637.

Keller AV, Hainline C, Rees K, Krupp S, Prince D, Wood BD, Shum-Siu A, Burke DA, Petruska JC and Magnuson DSK. 2019. Nociceptor-dependent locomotor dysfunction after clinically-modeled hindlimb muscle stretching in adult rats with spinal cord injury. Exp Neurol 318: 267-276. PMID 30880143

Fouad K, Bixby JL, Callahan A, Grethe JS, Jakeman LB, Lemmon VP, Magnuson DSK, Martone ME, Nielson JL, Schwab JM, Taylor-Burds C, Tetzlaff W, Torres-Espin

A, Ferguson AR; FAIR-SCI Ahead Workshop Participants. 2019 FAIR SCI Ahead: The Evolution of the Open Data Commons for Pre-Clinical Spinal Cord Injury Research. J Neurotrauma. 37(6):831-838. PMID: 31608767.

Chariker JH, Sharp M, Ohri SS, Gomes C, Brabazon F, Harman KA, Whittemore SR, Petruska JC, Magnuson DS, Rouchka EC. 2019 RNA-seq data of soleus muscle tissue after spinal cord injury under conditions of inactivity and applied exercise. Data Brief. 28:105056. PMID: 32226812.

Chariker JH, Gomes C, Brabazon F, Harman KA, Ohri SS, Magnuson DSK, Whittemore SR, Petruska JC, Rouchka EC. 2019 Transcriptome of dorsal root ganglia caudal to a spinal cord injury with modulated behavioral activity. Sci Data. 6(1):83. PMID: 31175296.

Chariker JH, Ohri SS, Gomes C, Brabazon F, Harman KA, DeVeau KM, Magnuson DSK, Hetman M, Petruska JC, Whittemore SR, Rouchka EC. 2019 Activity/exercise-induced changes in the liver transcriptome after chronic spinal cord injury. Sci Data. 6(1):88. PMID: 31197156.

DeVeau KM, Martin EK, King NT, Shum-Siu A, Keller BB, West CR, Magnuson DSK. 2018 Challenging cardiac function post-spinal cord injury with dobutamine. Auton Neurosci. 209:19-24. PMID: 28065654.

Keller AV, Rees KM, Seibt EJ, Wood BD, Wade AD, Morehouse J, Shum-Siu A, Magnuson DSK. 2018 Electromyographic patterns of the rat hindlimb in response to muscle stretch after spinal cord injury. Spinal Cord. 56(6):560-568. PMID: 29459656.

Harman KA, States G, Wade A, Stepp C, Wainwright G, DeVeau K, King N, Shum-Siu A, Magnuson DSK. 2018 Temporal analysis of cardiovascular control and function following incomplete T3 and T10 spinal cord injury in rodents. Physiol Rep. 6(6):e13634. PMID: 29595874.

Pocratsky AM, Burke DA, Morehouse JR, Beare JE, Riegler AS, Tsoulfas P, States GJR, Whittemore SR and Magnuson DSK. 2017. Reversible silencing of lumbar spinal interneurons unmasks a flexible, task-specific network for securing hindlimb alternation. Nat Comms 8(1): 1963. PMID: 29213073.

Keller AV, Wainwright GN, Shum-Siu A, Prince D, Hoeper A, Martin E and Magnuson DSK. 2017 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. PMID: 27196003.

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