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Experimental and computational assessment of locomotor coordination and complexity following incomplete spinal cord injury in the rat

Description

Spinal cord injury (SCI) disrupts the communication between supraspinal circuits and spinal circuits distal to the injury. This disruption causes changes in the motor abilities of the affected individual, but it can also be used as an opportunity to study motor control in the absence or limited presence of control from the brain. In the case of incomplete paraplegia, locomotion is impaired and often results in increased incidence of foot drag and decreased postural stability after injury. The overall goal of this work is to understand how changes in kinematics of movement and neural control of muscles effect locomotor coordination following SCI. Toward this end, we examined musculoskeletal parameters and kinematics of gait in rats with and without incomplete SCI (iSCI) and used an empirically developed computational model to test related hypotheses. The first study tested the hypothesis that iSCI causes a decrease in locomotor and joint angle movement complexity. A rat model was used to measure musculoskeletal properties and gait kinematics following mild iSCI. The data indicated joint-specific changes in kinematics in the absence of measurable muscle atrophy, particularly at the ankle as a result of the injury. Kinematic changes manifested as a decrease in complexity of ankle motion as indicated by measures of permutation entropy. In the second study, a new 2-dimensional computational model of the rat ankle combining forward and inverse dynamics was developed using the previously collected data. This model was used to test the hypothesis that altered coordination of flexor and extensor muscles (specifically alteration in burst shape and timing) acting at the ankle joint could be responsible for increases in incidence of foot drag following injury. Simulation results suggest a time course for changes in neural control following injury that begins with foot drag and decreased delay between antagonistic muscle activations. Following this, beneficial adaptations in muscle activation profile and ankle kinematics counteract the decreased delay to allow foot swing. In both studies, small changes in neural control caused large changes in behavior, particularly at the ankle. Future work will further examine the role of neural control of hindlimb in rat locomotion following iSCI.

ContributorsHillen, Brian (Author) / Jung, Ranu (Thesis advisor) / Abbas, James (Committee member) / Muthuswamy, Jit (Committee member) / Jindrich, Devin (Committee member) / Yamaguchi, Gary (Committee member) / Arizona State University (Publisher)

Created2012

Serp-1, a Myxoma Virus-Derived Immune-Modulating Protein, Demonstrates Therapeutic Benefit and Reduces Early Inflammation after Spinal Cord Injury in Rats

Description

Spinal cord injury (SCI) is characterized by severe tissue damage and extreme inflammation involving prolonged invasion of inflammatory cells. Following SCI, there is long-term disability and treatment is limited. We previously demonstrated that sustained subdural infusion of the anti-inflammatory protein, Serp-1, significantly improved functional recovery and reduced inflammatory cell invasion following SCI. We hypothesized that sustained delivery of immune-modulating Serp-1 using a chitosan-collagen hydrogel would demonstrate therapeutic benefits and reduce damage following forceps crush-induced SCI. Following the dorsal column crush injury, we observed that for rats treated with high-dose (100 μg/50 μL) Serp-1, functional motor improvement was observed. There was also a more pronounced neuroprotective effect in comparison to the low-dose (10 μg/50 μL) treatment, which was likely attributable to suppression of local inflammation. Conversely, sustained infusion of low-dose Serp-1 CCH did not enhance recovery. Thus, sustained delivery of immune-modulating Serp-1 through a chitosan-collagen hydrogel exhibits neuroprotective potential following acute SCI.

ContributorsSchutz, Lauren (Author) / Lucas, Alexandra R. (Thesis director) / Yaron, Jordan R. (Committee member) / Karis, John P. (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)

Created2021-05

The effects of exercise on locomotor recovery after partial spinal cord injury in a rat model

Description

This study was conducted to examine the potential effects of exercise training on partial spinal cord injury on locomotor recovery in juvenile rats. Three groups were tested, where three female Long-Evans rats 10-12 weeks of age were studied for their locomotion. All animals underwent a T8-T9 laminectomy and two of the three in each group received a dorsal, partial spinal cord injury. Locomotion was then analyzed every week, over 8-10 weeks. One of the two injured animals was given open access to a wheel after 2 weeks for voluntary exercise training. The results of this study suggested that injured animals displayed more irregular stepping patterns, larger hindlimb bases of support, greater and more variable interpaw distances, slower hindlimb speed, and increased dependency of swing-phase duty cycle on hindlimb speed. Trained animals displayed quicker recovery of stepping patterns, stepping of the hindpaw in relation to the preceding ipsilateral forepaw, and higher swing-duty cycle dependency on hindlimb speed in comparison to injured animals that did not receive exercise training. Due to a small sample size, there was a large amount of variation between individual animals in most parameters. These results are considered to be potential effects that may be seen in further study with a larger sample size. The research team will continue the research project to examine changes in neural pathways in the spinal cord and the effects of exercise on recovery after injury.

ContributorsSleem, Tamara Hatem (Author) / Abbas, James (Thesis director) / Hamm, Thomas (Committee member) / School of Human Evolution and Social Change (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)

Created2018-05