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Project

Restoring motor axon circuits after spinal cord injury

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Motor function depends on intact motor axon circuits, which are interrupted after spinal cord injury (SCI). Promoting regeneration of severed descending motor axons after SCI may support the restoration of damaged motor circuits. An intraspinal Schwann cell (SC) transplant elicits regeneration of motor axons, but these do not exit the transplant environment unless additional interventions are introduced. Facilitating motor axon growth from a SC transplant into the contiguous spinal cord may enable their integration into axon circuits that are either are directly involved in, or can be recruited for, motor function, which would support recovery after SCI. Here, we aim to facilitate growth of descending motor axons from a SC transplant into the contiguous spinal cord by promoting migration of transplanted SCs into the adjacent astrocytic scar and beyond thereby providing the axons with a cellular, growth-conducive, terrain. Transplanted SC motility is prevented at least in part by astrocytes. We propose to use 6-aminonicotinamide (6-AN) to specifically target astrocytes in the spinal cord adjacent to a SC transplant to enable SC migration. We have exciting preliminary data showing that 6-AN treatment just caudal from a SC transplant results in considerable exit of SCs into the adjacent spinal cord. Thus we now have in our hands a pharmacological, non-viral, glia-specific, tool to elicit SC migration and thus providing a growth-conducive trajectory to regenerating motor axons that may guide them out of a SC transplant into the contiguous spinal cord. Our central hypothesis is that the limited recovery in motor function after spinal cord injury is in part due to the lack of restoration of axonal circuits involved in motor function. The main objectives are to: 1) enhance our mechanistic knowledge of the effects of 6-AN on astrocyte and Schwann cell intermingling; and 2) develop an effective 6-AN-based approach to maximize SC migration from a SC transplant into the contiguous spinal cord. (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

    Regenerative Medicine

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • RCDC

    Transplantation

  • HRCS HC

    Neurological

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science