TY  - JOUR
A1  - Batulin, Danylo
A1  - Lagzi, Fereshteh
A1  - Vezzani, Annamaria
A1  - Jedlička, Peter
A1  - Triesch, Jochen
T1  - A mathematical model of neuroimmune interactions in epileptogenesis for discovering treatment strategies
T2  - iScience
N2  - The development of epilepsy (epileptogenesis) involves a complex interplay of neuronal and immune processes. Here, we present a first-of-its-kind mathematical model to better understand the relationships among these processes. Our model describes the interaction between neuroinflammation, blood-brain barrier disruption, neuronal loss, circuit remodeling, and seizures. Formulated as a system of nonlinear differential equations, the model reproduces the available data from three animal models. The model successfully describes characteristic features of epileptogenesis such as its paradoxically long timescales (up to decades) despite short and transient injuries or the existence of qualitatively different outcomes for varying injury intensity. In line with the concept of degeneracy, our simulations reveal multiple routes toward epilepsy with neuronal loss as a sufficient but non-necessary component. Finally, we show that our model allows for in silico predictions of therapeutic strategies, revealing injury-specific therapeutic targets and optimal time windows for intervention.
KW  - Biological sciences
KW  - Neuroscience
KW  - Immunology
KW  - Mathematical biosciences
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76108
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-761081
SN  - 2589-0042
VL  - 25
IS  - 6, 104343
PB  - Elsevier
CY  - Amsterdam
ER  -