A phenomenological model of neuroimmune interactions in epileptogenesis

  • Epilepsy can have many different causes and its development (epileptogenesis) involves a bewildering complexity of interacting processes. Here, we present a first-of-its-kind computational model to better understand the role of neuroimmune interactions in the development of acquired epilepsy. Our model describes the interactions between neuroinflammation, blood-brain barrier disruption, neuronal loss, circuit remodeling, and seizures. Formulated as a system of nonlinear differential equations, the model is validated using data from animal models that mimic human epileptogenesis caused by infection, status epilepticus, and blood-brain barrier disruption. The mathematical model successfully explains characteristic features of epileptogenesis such as its paradoxically long timescales (up to decades) despite short and transient injuries, or its dependence on the intensity of an injury. Furthermore, stochasticity in the model captures the variability of epileptogenesis outcomes in individuals exposed to identical injury. Notably, in line with the concept of degeneracy, our simulations reveal multiple routes towards epileptogenesis with neuronal loss as a sufficient but non-necessary component. We show that our framework allows for in silico predictions of therapeutic strategies, providing information on 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):bioRxiv
Document Type:Preprint
Date of Publication (online):2021/08/01
Date of first Publication:2021/08/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/03/23
Page Number:34
Institutes:Wissenschaftliche Zentren und koordinierte Programme / Frankfurt Institute for Advanced Studies (FIAS)
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY-NC - Namensnennung - Nicht kommerziell 4.0 International