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Neuroinflammatory mediators in acquired epilepsy: an update

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Abstract

Epilepsy is a group of chronic neurological disorders that have diverse etiologies but are commonly characterized by spontaneous seizures and behavioral comorbidities. Although the mechanisms underlying the epileptic seizures mostly remain poorly understood and the causes often can be idiopathic, a considerable portion of cases are known as acquired epilepsy. This form of epilepsy is typically associated with prior neurological insults, which lead to the initiation and progression of epileptogenesis, eventually resulting in unprovoked seizures. A convergence of evidence in the past two decades suggests that inflammation within the brain may be a major contributing factor to acquired epileptogenesis. As evidenced in mounting preclinical and human studies, neuroinflammatory processes, such as activation and proliferation of microglia and astrocytes, elevated production of pro-inflammatory cytokines and chemokines, blood–brain barrier breakdown, and upregulation of inflammatory signaling pathways, are commonly observed after seizure-precipitating events. An increased knowledge of these neuroinflammatory processes in the epileptic brain has led to a growing list of inflammatory mediators that can be leveraged as potential targets for new therapies of epilepsy and/or biomarkers that may provide valued information for the diagnosis and prognosis of the otherwise unpredictable seizures. In this review, we mainly focus on the most recent progress in understanding the roles of these inflammatory molecules in acquired epilepsy and highlight the emerging evidence supporting their candidacy as novel molecular targets for new pharmacotherapies of acquired epilepsy and the associated behavioral deficits.

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Acknowledgements

This work was supported by the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) grants R01NS100947 (J.J.), R21NS109687 (J.J.), and R61NS124923 (J.J.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors apologize for not being able to cite and discuss all publications that are relevant to the broad topics in this review because of the space limitation.

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  1. Yu Chen and Marwa M. Nagib have contributed equally to this work.

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN, USA

    Yu Chen, Marwa M. Nagib, Nelufar Yasmen, Madison N. Sluter, Taylor L. Littlejohn, Ying Yu & Jianxiong Jiang

  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo, Egypt

    Marwa M. Nagib

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Conceptualization: YC, MMN, YY, and JJ; literature search, data collection, and writing: YC and MMN; review and editing: NY, MNS, TLL, YY, and JJ. All authors have read and approved the final version of the manuscript.

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Chen, Y., Nagib, M.M., Yasmen, N. et al. Neuroinflammatory mediators in acquired epilepsy: an update. Inflamm. Res. 72, 683–701 (2023). https://doi.org/10.1007/s00011-023-01700-8

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