Improving Outcomes Using Myelotomy with Intramedullary Hemorrhagic Necrosis Removal in Porcine Model of Acute Thoracic Cord Injury
Abstract
Spinal cord injury (SCI) remains one of the leading devastating causes of disability, affecting approximately 1.3 million Americans. Although there have been a number of clinical trials, none have proven efficacy, and to date limited therapeutic options exist for acute SCI. Novel therapeutic strategies are very much needed. 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 is cytotoxic and contributes to the secondary injury cascade after injury. IHN is an autodestructive process, ultimately resulting in a cystic cavitation, scarring of spinal cord with reduction of axonal regeneration. Thus myelotomy (microsurgical incision into spinal cord) with IHN removal (MIHN) has been proposed as a potential therapeutic approach for spinal cord injury. While some previous studies suggested beneficial effects of myelotomy, much remains unknown about its safety and effectiveness in improving locomotor and bladder function recovery after SCI. Previous studies, performed mostly in small animals, have focused primarily on locomotor outcomes without investigation of histopathological correlates of recovery or cystometric studies of effects on bladder function. There is a need for further investigation of MIHN effects prior to widespread translation to humans. The INSPIRE study in humans is an ongoing pilot clinical study of MIHN in combination with scaffold placement. By design, however, the study will not distinguish the benefits of MIHN-alone versus adding a scaffold after MIHN. Thus it remains unclear whether the placement of a scaffold after MIHN has additional beneficial effects on recovery. Further investigation of MIHN effects-alone or with scaffold are needed to fill in critical gaps in our knowledge prior to widespread translation to humans. In the present grant application, we propose to use a large animal model to evaluate the safety and effectiveness of MIHN with or without scaffold as potential treatments for SCI. We will examine the effects of MIHN on locomotor, sensory, and bladder function recovery after a thoracic cord contusion injury. Additionally, we plan to investigate any adverse effects of myelotomy on cord edema or hemorrhage and surgical complications. The effects of MIHN on the areal extent of injury, spared tissue, locomotor, and urodynamic bladder function will be measured. High resolution MRI will be used to assess any adverse impact on spinal cord swelling and damage. The results are expected to significantly enhance potential application of MIHN as a therapeutic strategy for SCI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810117
Entities
People
- Maxwell Boakye
Organizations
- United States Army
- University of Louisville