Promoting Recovery by Inhibiting PDE10A-Mediated Inflammation

Abstract

The first goal was to determine the effects of TP-10 treatment in nerve and muscle recovery after sciatic nerve injury. Using sciatic nerve crush injury, we obtained reproducible damage as measured by muscle force and CatWalk gait analyses. To find the optimal dose of PDE10A inhibitor to improve these parameters, we used two different PDE10A specific inhibitors, MP-10 and TP-10. We optimized the dose using an in vitro macrophage model. Specifically, we stimulated inflammasome activation and pyroptosis to show the importance of PDE10A in macrophage mediated inflammation, inflammasome activation and pyroptosis (a specific type of programmed cell death that releases high amounts of inflammatory cytokines such as IL-b and IL-18. To stimulate pyroptosis, we incubated macrophages with lipopolysaccharide (LPS) and nigericin.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2022
Accession Number
AD1190407

Entities

People

  • Bradford C. Berk

Organizations

  • University of Rochester

Tags

DTIC Thesaurus Topics

  • Arteries
  • Biomedical Research
  • Cardiovascular System
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Cytokines
  • Department Of Defense
  • Inhibition
  • Inhibitors
  • Macrophages
  • Medical Personnel
  • Nerves
  • Nervous System
  • Proteins
  • Sciatic Nerve
  • Standards
  • Training

Fields of Study

  • Medicine

Readers

  • Immunology and Pathology
  • Microbial Pathology
  • Rehabilitation and Prosthetic Care for Military Service Members and Veterans with Limb Loss or Disability.