Biomechanics of spinal cord injury: A functional, anatomical, and computational study

Hui Ouyang, Purdue University

Abstract

Traumatic injury to the spinal cord often causes tissue degeneration and functional loss that may lead to permanent paralysis. There are about 12,000 new cases of spinal cord injury (SCI) annually in the U.S., and depending on the severity of injury, the estimated lifetime costs directly attributable to SCI can be more than $3 million per patient. Due to the lack of knowledge about how external mechanical trauma affects the distribution of injury in a spinal cord internally, we are still unable to accurately predict the loss of neural function in specific locations of the cord or to find effective treatments for the injury in a timely fashion. The objective of this thesis work is to elucidate and quantify the relationship between external forces and structural/functional loss in the spinal cord. The investigations were carried out at both tissue and cellular levels. At the tissue level, a multimodal system was developed to record electrophysiological conduction through spinal cord tissue specimens while simultaneously measuring force and deformation. The effects of compression strain, time duration of compression, and compression velocity (strain rate) were investigated in guinea pig spinal cords. A quantitative correlation between injury factors, functional recovery (as measured by compound action potential), and anatomical outcomes (as quantified by horseradish peroxidase uptake) was established. This multimodal system can separate the effects of injury factors, including compression strain, duration, and velocity on neurological deficits in the spinal cord. For the first time, the consequences of each injury factor on spinal cord tissue damage were independently established. On the cellular level, the atomic force microscope (AFM) was utilized to perform mechanical compression on axons from chick embryonic dorsal root ganglia cells. The mechanical stiffness of axons with microtubules, microfilaments, or neurofilaments disrupted separately or simultaneously was investigated for the first time using Hertz contact theory. The elastic modulus of axons with all three elements disrupted was found to be similar to the axons with only microtubules disrupted. This evidence suggests that microtubules not only provide the structure to support the majority of axonal mechanical stiffness, but also offer a scaffold to mechanically sustain microfilaments and neurofilaments inside the axons. Once this scaffold is destroyed by microtubule disruption, the remaining two elements may not be able to maintain physical connections or integrity. Here, we pioneered the use of AFM to measure the stiffness of axons from neural cells ex vivo, and evaluated the relative contribution of each cytoskeletal element to the mechanical properties of axons. Force-deformation data from both tissue and cellular level mechanical tests were collected to build finite element models of the spinal cord. On the tissue level, preliminary results showed that under slow compression (i.e., 0.05 mm/s), there was a higher level of stress generated near the grey matter, which coincided with the axonal damage patterns revealed by histological analysis. At the cellular level, the stresses were found to be highly concentrated at the paranodal junction of axons. Thus, the mechanism of myelin retraction during injury may be associated with stress concentrations that cause debonding at the axoglial interface. Overall, this thesis work provides significant experimental and simulation data that further elucidate the deformation-function relationship in traumatic SCI for both cells and tissues. This information will be helpful in predicting the location and severity of damage in the injured spinal cord. A selective treatment plan that is able to target the needs of individual patients based on their injury conditions can then be developed to maximize the functional recovery in each patient.

Degree

Ph.D.

Advisors

Shi, Purdue University.

Subject Area

Biomedical engineering|Biomechanics

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