Speaker
Description
In this talk, I review a class of mathematical models for the early stages of Multiple Sclerosis (MS). A central immunological question concerns the trigger of the immune cascade initiating MS pathology. We compare two scenarios: one based on local microglia activation, recruitment of systemic immune responses, and oligodendrocyte apoptosis \cite{ BBGLPS16,GLRSS24,KhonCal,LBBGPS17}; the other on cytokine-mediated modulation of macrophage activation \cite{MF21}.
We focus on a reaction-diffusion-chemotaxis system for activated macrophages, cytokines, and oligodendrocytes. By varying the parameter governing the effect of cytokines on macrophage activation, the model captures both mechanisms within a unified framework.
Combining analytical results and numerical simulations, we show that the model generates a variety of demyelination patterns. For biologically realistic parameter values, its asymptotic states reproduce pathological features consistent with MRI observations.
Bifurcation analysis highlights marked differences between the two scenarios. The innate-immunity mechanism leads to highly aggressive pathology, with strong focal inflammation and rapid progression, whereas the cytokine-mediated mechanism yields milder inflammation and much slower disease evolution.
Finally, I discuss ongoing extensions including endogenous repair mechanisms active in acute inflammation, with the aim of describing remyelination processes observed in early MS and their failure in chronic lesions.
Bibliography
@ARTICLE{BBGLPS16,
author={Barresi, R. and Bilotta, E. and Gargano, F. and Lombardo, M.C. and Pantano, P. and Sammartino, M.},
title={Wavefront invasion for a chemotaxis model of {M}ultiple {S}clerosis},
journal={Ricerche di Matematica},
year={2016},
volume = {65},
number = {2},
pages = {423 – 434}
}
@ARTICLE{GLRSS24,
author = {Gargano, F. and Lombardo, M.C. and Rizzo, R. and Sammartino, M. and Sciacca, V.},
title = {Cytokine-induced instabilities in a reaction–diffusion-chemotaxis model of Multiple Sclerosis: Bifurcation analysis and well-posedness},
year = {2024},
journal = {International Journal of Non-Linear Mechanics},
volume = {161},
pages = { art.n.104672},
}
@ARTICLE{KhonCal,
author={Khonsari, R.H. and Calvez, V.},
title={The origins of concentric demyelination: Self-organization in the human brain},
journal={PLoS ONE},
year={2007},
volume={2},
number={1},
pages={e150},
}
@ARTICLE{LBBGPS17,
author={Lombardo, M.C. and Barresi, R. and Bilotta, E. and Gargano, F. and Pantano, P. and Sammartino, M.},
title={Demyelination patterns in a mathematical model of multiple sclerosis},
journal={Journal of Mathematical Biology},
year={2017},
volume={75},
number={2},
pages={373-417},
}
@ARTICLE{MF21,
author={Moise, N. and Friedman, A.},
title={A mathematical model of the multiple sclerosis plaque},
journal={Journal of Theoretical Biology},
year={2021},
volume={512},
pages={110532},
}
