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Project

Evaluating neutrophil extracellular traps in spinal cord injury

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Spinal cord injury (SCI) is a severely debilitating condition that has a profound impact on quality of life. To date, no widely accepted therapeutic has been developed to protect the injured tissue and minimize functional deficits after SCI. Extensive infiltration of immune cells occurs in the acute phase of SCI and corresponds with rapid and progressive tissue loss. However, the mechanisms by which inflammation mediates tissue damage early after SCI are not well known. Neutrophil extracellular traps (NETs) are toxic complexes of DNA and enzymes released by early invading immune cells to help clear infections in the body. While NETs are critical for fighting pathogens, studies in other models of inflammation have implicated NETs as a potent mediator of inflammatory tissue damage. We have identified large increases in NETs in the spinal cord following a pre-clinical contusion injury, but the consequences of NETs in SCI have yet to be determined. The primary objective of the proposed studies is to determine if NETs contribute to acute tissue damage and long-term functional deficits after SCI. The long-term objective of this work is to develop safe and effective neuroprotective strategies to reduce acute tissue damage caused by inflammation and promote long-term recovery in spinal cord injured patients. We will target NETs using pharmacological and genetic means to determine their impact on the injured spinal cord. We will utilize the DNA degrading enzyme, DNase1, to eliminate NETs early after SCI and determine the effect on acute tissue damage and long-term recovery. Furthermore, we will use genetic tools to remove a key enzyme involved in the formation NETs, which may represent an upstream therapeutic target to prevent NETs altogether. Collectively, the proposed studies will determine the impact of NETs in the injured spinal cord and evaluate DNase1 treatment as a readily exploitable therapeutic strategy to reduce tissue damage early after SCI. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1107 Immunology

  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Genetics

  • RCDC

    Neurodegenerative

  • HRCS HC

    Neurological

  • HRCS HC

    Inflammatory and Immune System

  • HRCS HC

    Injuries and Accidents

  • HRCS RAC

    2.1 Biological and endogenous factors

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science