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Lesion Dynamics Under Varying Paracrine PDGF Signaling in Brain Tissue

  • Susan Christine MasseyEmail author
  • Andrea Hawkins-Daarud
  • Jill Gallaher
  • Alexander R. A. Anderson
  • Peter Canoll
  • Kristin R. Swanson
Article

Abstract

Paracrine PDGF signaling is involved in many processes in the body, both normal and pathological, including embryonic development, angiogenesis, and wound healing as well as liver fibrosis, atherosclerosis, and cancers. We explored this seemingly dual (normal and pathological) role of PDGF mathematically by modeling the release of PDGF in brain tissue and then varying the dynamics of this release. Resulting simulations show that by varying the dynamics of a PDGF source, our model predicts three possible outcomes for PDGF-driven cellular recruitment and lesion growth: (1) localized, short duration of growth, (2) localized, chronic growth, and (3) widespread chronic growth. Further, our model predicts that the type of response is much more sensitive to the duration of PDGF exposure than the maximum level of that exposure. This suggests that extended duration of paracrine PDGF signal during otherwise normal processes could potentially lead to lesions having a phenotype consistent with pathologic conditions.

Keywords

Platelet-derived growth factor Scarring Gliosis Oligodendroglial progenitors 

Notes

References

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Copyright information

© Society for Mathematical Biology 2019

Authors and Affiliations

  1. 1.Precision Neurotherapeutics Innovation ProgramMayo ClinicPhoenixUSA
  2. 2.Integrative Mathematical OncologyMoffitt Cancer CenterTampaUSA
  3. 3.Division of Neuropathology, Department of Pathology and Cell BiologyColumbia University School of MedicineNew YorkUSA

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