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Bull Math Biol. 2019 Jun;81(6):1645-1664. doi: 10.1007/s11538-019-00587-z. Epub 2019 Feb 22.

Lesion Dynamics Under Varying Paracrine PDGF Signaling in Brain Tissue.

Author information

1
Precision Neurotherapeutics Innovation Program, Mayo Clinic, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA. massey.susan@mayo.edu.
2
Precision Neurotherapeutics Innovation Program, Mayo Clinic, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA.
3
Integrative Mathematical Oncology, Moffitt Cancer Center, Tampa, FL, USA.
4
Division of Neuropathology, Department of Pathology and Cell Biology, Columbia University School of Medicine, New York, NY, USA.

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:

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

PMID:
30796683
PMCID:
PMC6494675
[Available on 2020-06-01]
DOI:
10.1007/s11538-019-00587-z

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