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Project

Ketone body administration to treat spinal cord injury

Funder: Craig H Neilsen Foundation

Funding period
USD 298 K
Funding amount
Abstract
Approximately over 300,000 Americans are living with the typically devastating neurological limitations that are secondary to SCI (http://www.spinalcord.uab.edu). With the exception of the modestly effective methylprednisolone and/or tirilazad, there is presently no clinical pharmacological intervention indicated for SCI that can be administered in the acute stages of trauma to prevent the secondary injury that ultimately limits any potential recovery from paralysis. We have documented that oxidative damage to key mitochondrial enzymes and subsequent mitochondrial dysfunction is pivotal to the neuropathological sequela following SCI. This proposal focuses on targeting mitochondrial dysfunction directly as a novel therapeutic intervention for contusion SCI; the fundamental concept being that SCI-induced excitotoxicity increases mitochondrial Ca2+ cycling/overload and the production of reactive oxygen species (ROS), ultimately leading to mitochondrial dysfunction and glutathione (GSH) depletion. Our approach is two-pronged, aimed at reducing mitochondrial ROS production as well as to provide alternative bio-fuel substrate for energy production utilizing a ketone body, beta-hydroxybutyrate (BHB). Our preliminary data signify that BHB improve mitochondrial bioenergetics following SCI. In this project, we will test the novel hypothesis that reducing oxidative damage to key mitochondrial proteins maintains mitochondrial bioenergetics, thus leading to increased neuroprotection and improved functional recovery following contusion SCI. Therefore, we propose to treat injured patients at the scenes of trauma with a novel antioxidant approach to prevent the spread of damaged spinal cord tissues. Targeting mitochondrial dysfunction and fostering acute neuroprotection may render the greatest functional recovery and independence of affected individuals. (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

  • HRCS HC

    Neurological

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science