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Project

Myelotomy with Hemorrhagic Necrosis Removal in a Porcine SCI Model

Funder: Craig H Neilsen Foundation

Funding period
USD 600 K
Funding amount
Abstract
Spinal cord injury (SCI) remains one of the leading devastating causes of disability affecting approximately 1.3 million Americans. In U.S., there are nearly 17,000 new SCI cases each year. The costs associated with SCI are staggering. The lifetime cost of care for a tetraplegic patient can reach USD 2.5 million. To date there is no effective treatment for SCI.Scientific endeavors to develop SCI treatments have depended on animal models. In the past 30 years, rodents have been the most commonly used SCI model in preclinical studies. However, the successful translation of effective therapies from rodent models to human patients is lacking. This may be partially attributed to anatomical, physiological, and scale differences between humans and rodents. In recent years, there has been an emerging interest in the large animal models of SCI to evaluate various treatments. During past 2 years, in collaboration with Dr. Brian Kwon’s group at University of British Columbia, Vancouver, Canada, we have established a large animal model of SCI in Yucatan miniature pigs. The porcine SCI model is valuable because of the comparable spinal cord size between pigs and humans, and is an intermediary between rodent and human SCI for preclinical evaluation of novel therapies. We have developed a comprehensive set of porcine SCI model evaluation parameters, including (i) magnetic resonance imaging (MRI) to measure cord microstructural integrity, lesion size, and perilesional cerebrospinal fluid (CSF) flow, (ii) gait kinematics to measure behavioral outcome, (iii) electromyography (EMG) to measure muscle response, (iv) cystometric testing to assess bladder function, and (v) histology to evaluate the injury volume and motor fiber tracts plasticity. In the present grant application, we propose to evaluate the effect of a microsurgical treatment, i.e., myelotomy (incision of the spinal cord) with intramedullary hemorrhagic necrosis removal (MIHN) in the porcine SCI model. Following SCI, there is often a liquefied hemorrhagic necrotic tissue, termed intramedullary hemorrhagic necrosis (IHN), at the injury site. Besides exerting a mass effect on surrounding tissue, IHN was reported to be cytotoxic and to contribute to secondary injury cascade that follows the initial primary injury and reduce axonal regeneration.MIHN was reported to exert beneficial effects on functional recovery in rodent SCI models, and can be a potential therapeutic approach in human SCI, if can be done safely. Here we propose to perform detailed locomotor, neuroimaging, electrophysiological, histological, and urodynamic analyses to evaluate beneficial effects of MIHN on cord edema, CSF physiology, cavity formation, axon and cell body sparing, and behavioral outcomes. Simultaneously, we will identify and mitigate any potential detrimental effects of this treatment. The results of this study may help develop an effective ‘translatable’ therapy that can improve functional outcome in SCI patients. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1103 Clinical Sciences

  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Bioengineering

  • RCDC

    Regenerative Medicine

  • RCDC

    Neurosciences

  • RCDC

    Rehabilitation

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • HRCS HC

    Neurological

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Clinical Medicine and Science