Lesion Dynamics Under Varying Paracrine PDGF Signaling in Brain Tissue

Susan Christine Massey, Andrea Hawkins-Daarud, Jill Gallaher, Alexander R.A. Anderson, Peter Canoll, Kristin R. Swanson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1645-1664
Number of pages20
JournalBulletin of Mathematical Biology
Volume81
Issue number6
DOIs
StatePublished - Jun 15 2019

Keywords

  • Gliosis
  • Oligodendroglial progenitors
  • Platelet-derived growth factor
  • Scarring

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Mathematics(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Pharmacology
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics

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