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Project

Treatment of spinal cord injury with an osmotic treatment device

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Spinal cord injury (SCI) causes long-lasting changes in motor, sensory and autonomic function. SCI is characterized by the initial injury due to trauma and by a cascade of cellular events, resulting in a greater degree of secondary injury. Edema, an increase in tissue water content, is responsible for significant morbidity and mortality in many disease states of the central nervous system (CNS), including SCI. Edema formation within the first few hours of injury is thought to worsen neurological outcome due to swelling at the injury site. Our previous work in a mouse SCI contusion model demonstrated that inadequate clearance of tissue water leads to cyst formation and worsens neurological outcome. Despite the contribution of edema to secondary injury and poor neurological outcome, to date no direct tissue-based treatment of edema has been developed and applied to the CNS (brain or spinal cord). It is, however, widely accepted that early intervention may limit the amount of secondary damage. There is therefore a need for new methods to effectively ameliorate edema following SCI in order to decrease tissue swelling at the injury site, improve vascular perfusion, prevent spinal cord compression and improve histological and neurological outcome. Our research group has recently demonstrated that through establishing an external osmotic gradient, water content can be removed from the brain in a controlled manner under normal and pathological brain swelling conditions, resulting in dramatically improved survival and neurological outcome. This approach, utilizing an osmotic transport device (OTD) for direct osmotherapy (DOT), combines the bioengineering principles of fluid transport with in vivo models of edema. The OTD exploits the inevitable osmotic pressure that is generated during transport of concentrated rejected osmolytes (such as proteins or polymers) across a semi-permeable membrane in the presence of aqueous systems. DOT uses osmotic pressure to operate and: (1) removes water from CNS tissue in a controlled fashion; (2) deploys flexibly on the surface of the brain or spinal cord; (3) does not require penetration of the tissue; and (4) causes no histological damage to the underlying tissue. Our results, published in models of brain edema, established a proof-of-principle for DOT treatment of other forms of CNS edema. The objectives of the proposed study are to determine the appropriate OTD configuration and treatment protocol after SCI, while evaluating long-term effects of treatment on histological and neurological outcomes in a standard rodent SCI model. Overall, this novel work has the potential to lead to a new integrated DOT system to detect and reverse post-SCI edema and, thus, reduce tissue damage in individuals with SCI. DOT represents an innovative and controllable bioengineering solution to the devastating clinical problem of CNS injury-associated edema. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • RCDC

    Rare Diseases

  • HRCS HC

    Neurological

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Clinical Medicine and Science