文章基本信息

标题：A mathematical model of neuroimmune interactions in epileptogenesis for discovering treatment strategies
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作者：Danylo Batulin ; Fereshteh Lagzi ; Annamaria Vezzani 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：6
页码：1-26
DOI：10.1016/j.isci.2022.104343
语种：English
出版社：Elsevier
摘要：SummaryThe 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 forin silicopredictions of therapeutic strategies, revealing injury-specific therapeutic targets and optimal time windows for intervention.Graphical abstractDisplay OmittedHighlights•A dynamical systems model describes the development of epilepsy after different injuries•Simulation results are in agreement with data from three animal models•Model shows degeneracy: multiple distinct but linked mechanisms cause epileptogenesis•Framework permits studying the effects of therapeutic interventionsin silicoBiological sciences; Neuroscience; Immunology; Mathematical biosciences