Lesion Dynamics Under Varying Paracrine PDGF Signaling in Brain Tissue.

TitleLesion Dynamics Under Varying Paracrine PDGF Signaling in Brain Tissue.
Publication TypeJournal Article
Year of Publication2019
AuthorsMassey SC, Hawkins-Daarud A, Gallaher J, Anderson ARA, Canoll P, Swanson KR
JournalBull Math Biol
Date Published2019 Feb 22

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.

Alternate JournalBull. Math. Biol.
PubMed ID30796683
Grant ListU54CA143970 / / National Cancer Institute /
R01CA16437 / / National Cancer Institute /
P01CA42045 / / National Cancer Institute /
U54CA193489 / / National Cancer Institute /
R01NS060752 / / National Institute of Neurological Disorders and Stroke /
DGE-0781824 / / National Science Foundation /
220020264 / / James S. McDonnell Foundation /