A mathematical model of neuroimmune interactions in epileptogenesis for discovering treatment strategies

  • 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.

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Author:Danylo BatulinORCiDGND, Fereshteh LagziORCiDGND, Annamaria VezzaniORCiD, Peter JedličkaORCiDGND, Jochen TrieschORCiD
Parent Title (English):iScience
Place of publication:Amsterdam
Document Type:Article
Date of Publication (online):2022/05/17
Date of first Publication:2022/05/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/11/18
Tag:Biological sciences; Immunology; Mathematical biosciences; Neuroscience
Issue:6, 104343
Article Number:104343
Page Number:26
Institutes:Informatik und Mathematik
Wissenschaftliche Zentren und koordinierte Programme / Frankfurt Institute for Advanced Studies (FIAS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 51 Mathematik / 510 Mathematik
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International