Graduation Semester and Year

2013

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Mario Romero-Ortega

Abstract

Scoliosis corrective surgery requires the application of multidirectional stress forces to the spinal cord, including those of distraction, in addition to the application of fixation rods for correction of the curved spine deformity. If excessive, spine distraction may result in the development of new neurologic deficits, some as severe as permanent paralysis. Intraoperative monitoring is used to alert the surgeon to possible complications; however, the complex nature of spinal cord injury (SCI) involves a primary mechanical insult to the tissue and/or vasculature that may go undetected by monitoring. This is followed by the activation of widespread secondary injury mechanisms. The specific injury mechanisms involved in distraction SCI remain largely unknown, increasing the difficulty of tailoring the selection of possible preventative therapeutics. The majority of animal models used to study the pathobiology of SCI are rat models of transection or contusion, though there have been a few previous models of distraction that have sought to characterize the injury. Deficiencies in the models combined with a lack of functional assessment, however, have limited their ability to effectively elucidate the injury mechanisms. To address such limitations, we designed a novel device that relies on intervertebral grip fixation and linear actuators to induce controllable bidirectional distraction injuries to the spine. The device was tested in three (i.e., 3, 5, and 7–mm) distention paradigms of the rat T9–T11 vertebrae, and the resulting injuries were evaluated through electrophysiological, behavioral, and histological analysis. As expected, animals with 3–mm bidirectional spine distractions showed no neurological deficit. In contrast, those with 5 and 7–mm distractions showed partial and complete paralysis, respectively. The relationship between the severity of the spine distraction and injury to the spinal cord tissue was determined using glial fibrillary acidic protein immunocytochemistry for visualization of reactive astrocytes and labeling of ED1–positive activated macrophages/microglia. These results demonstrate that this device can produce bidirectional spine distraction injuries with high precision and control. To increase the clinical relevance of the model, we further modified the distraction paradigm in which the animal is held in a distracted position for a prolonged period. The observed injury was mild, as evidenced by a lack of reduction in transcranial motor–evoked potential amplitude, intact cords, and a mild behavioral deficit. For the purpose of elucidating the specific injury mechanisms, we then determined the extent to which distraction induces a hypoxic insult through direct measurement of the partial pressure of oxygen (pO2). We recorded a transient sharp decline in pO2 levels in the distal cord parenchyma immediately following the application of distractive force. This sharp decline was followed by a mild hypoxic insult for the duration of the time held in the distracted position. We also observed an acute increase in protein oxidation 30 minutes post–injury. Taken together, these results have led to a greater understanding of the injury mechanisms involved in distraction SCI that will better enable the tailoring of neuroprotective strategies aimed at preventing the onset of neurological deficits during spine deformity surgery.

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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