Browsing by Author "Walker, Melissa J."

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    Combinational treatment approach for traumatic spinal cord injury
    (2016-03-02) Walker, Melissa J.; Xu, Xiao-Ming
    Spinal cord injury (SCI) is devastating and debilitating, and currently no effective treatments exist. Approximately, 12,000 new cases of SCI occur annually in the United States alone. The central nervous system has very low repair capability after injury, due to the toxic environment in the injured tissue. After spinal cord trauma, ruptured blood vessels cause neighboring cells and tissues to be deprived of oxygen and nutrients, and result in the accumulation of carbon dioxide and waste. New blood vessels form spontaneously after SCI, but then retract as the injured tissue forms a cavity. Thus, the newly formed vasculature likely retracts because it lacks a structural support matrix to extend across the lesion. Currently, in the field of spinal cord injury, combinational treatment approaches appear to hold the greatest therapeutic potential. Therefore, the aim of these studies was to transplant a novel, non-immunogenic, bioengineered hydrogel, into the injured spinal cord to serve as both a structural scaffold (for blood vessels, axons, and astrocytic processes), as well as a functional matrix with a time-controlled release of growth factors (Vascular endothelial growth factor, VEGF; Glial cell line-derived neurotrophic factor, GDNF). The benefit of this hydrogel is that it remains liquid at cooler temperatures, gels to conform to the space surrounding it at body temperature, and was designed to have a similar tensile strength as spinal cord tissue. This is advantageous due to the non-uniformity of lesion cavities following contusive spinal cord injury. Hydrogel alone and combinational treatment groups significantly improved several measures of functional recovery and showed modest histological improvements, yet did not provoke any increased sensitivity to a thermal stimulus. Collectively, these findings suggest that with further investigation, hydrogel along with a combination of growth factors might be a useful therapeutic approach for repairing the injured spinal cord.
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    Functional and Histological Gender Comparison of Age-Matched Rats after Moderate Thoracic Contusive Spinal Cord Injury
    (Mary Ann Liebert, 2019-05-28) Walker, Chandler L.; Fry, Colin M.E.; Wang, Junmei; Du, Xiaolong; Zuzzio, Kirstin; Liu, Nai-Kui; Walker, Melissa J.; Xu, Xiao-Ming; Neurological Surgery, School of Medicine
    Spinal cord injury (SCI) afflicts hundreds of thousands of Americans, and most SCI (∼80%) occurs in males. In experimental animal models, however, many studies used females. Funding agencies like the National Institutes of Health recommend that new proposed studies should include both genders due to variations in gender response to injuries, diseases, and treatments. However, cost and considerations for some animal models, such as SCI, affect investigators in adapting to this recommendation. Research has increased comparing gender effects in various disease and injury models, including SCI. However, most studies use weight-matched animals, which poses issues in comparing results and outcomes. The present study compared histologic and functional outcomes between age-matched male and female Sprague-Dawley rats in a moderate thoracic contusion SCI model. Cresyl violet and eosin staining showed no significant differences in lesion volume between genders after 9 weeks post-SCI (p > 0.05). Luxol fast blue–stained spared myelin was similar between genders, although slightly greater (∼6%) in spared myelin, compared with cord volume (p = 0.044). Glial reactivity and macrophage labeling in the lesion area was comparable between genders, as well. Basso, Beattie, Bresnahan (BBB) functional scores were not significantly different between genders, and Hargreaves thermal hyperalgesia and Gridwalk sensorimotor analyses also were similar between genders, compared with uninjured gender controls. Analysis of covariance showed weight did not influence functional recovery as assessed through BBB (p = 0.65) or Gridwalk assessment (p = 0.63) in this study. In conclusion, our findings suggest age-matched male and female rats recover similarly in a common clinically relevant SCI model.
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    History of Glial Cell Line-Derived Neurotrophic Factor (GDNF) and Its Use for Spinal Cord Injury Repair
    (MDPI, 2018-06-13) Walker, Melissa J.; Xu, Xiao-Ming; Neurological Surgery, School of Medicine
    Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, in combination with other factors and cell transplantations, for repairing the injured spinal cord. As studies of recent decades strongly suggest that combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.
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    A Novel Vertebral Stabilization Method for Producing Contusive Spinal Cord Injury
    (Jove, 2015-01) Walker, Melissa J.; Walker, Chandler L.; Zhang, Y. Ping; Shields, Lisa B. E.; Shields, Christopher B.; Xu, Xiao-Ming; Department of Anatomy & Cell Biology, IU School of Medicine
    Clinically-relevant animal cervical spinal cord injury (SCI) models are essential for developing and testing potential therapies; however, producing reliable cervical SCI is difficult due to lack of satisfactory methods of vertebral stabilization. The conventional method to stabilize the spine is to suspend the rostral and caudal cervical spine via clamps attached to cervical spinous processes. However, this method of stabilization fails to prevent tissue yielding during the contusion as the cervical spinal processes are too short to be effectively secured by the clamps (Figure 1). Here we introduce a new method to completely stabilize the cervical vertebra at the same level of the impact injury. This method effectively minimizes movement of the spinal column at the site of impact, which greatly improves the production of consistent SCIs. We provide visual description of the equipment (Figure 2-4), methods, and a step-by-step protocol for the stabilization of the cervical 5 vertebra (C5) of adult rats, to perform laminectomy (Figure 5) and produce a contusive SCI thereafter. Although we only demonstrate a cervical hemi-contusion using the NYU/MASCIS impactor device, this vertebral stabilization technique can be applied to other regions of the spinal cord, or be adapted to other SCI devices. Improving spinal cord exposure and fixation through vertebral stabilization may be valuable for producing consistent and reliable injuries to the spinal cord. This vertebral stabilization method can also be used for stereotactic injections of cells and tracers, and for imaging using two-photon microscopy in various neurobiological studies.