| Title: |
Anti-inflammatory Strategies for Disease Modification ; Focus on Therapies Close to Clinical Translation |
| Authors: |
Vezzani, Annamaria; Balosso, Silvia; Varvel, Nicholas H.; Dingledine, Ray |
| Contributors: |
Rogawski, Michael A. |
| Source: |
Jasper's Basic Mechanisms of the Epilepsies ; page 1535-1554 ; ISBN 0197549462 9780197549469 9780197549490 |
| Publisher Information: |
Oxford University PressNew York |
| Publication Year: |
2024 |
| Description: |
Clinical and preclinical studies have confirmed that neuroinflammation is a salient feature of the epileptic brain. The engagement of several neuroinflammatory pathways has been documented after epileptogenic injuries and in the aftermath of ongoing seizure activity. Preclinical research over the past decade has demonstrated that the ensuing neuroinflammation after epileptogenic triggers promotes seizures, neuronal injury, blood–brain barrier dysfunction, and behavioral comorbidities. Thus, successful modulation of the neuroinflammatory cascade is a potential therapeutic strategy. An overarching goal of anti-inflammatory approaches is to quench pathogenic neuroinflammation while maintaining, or promoting, the homeostatic effects. In this chapter we focus on treatments that are close to clinical translation, outlining the experimental evidence supporting the use of the anti-inflammatory therapy for both reducing drug-resistant seizures and for providing disease-modification effects. Approaches targeting IL-1β-IL-1R1 signaling, COX-2 pathways, immune-endothelial cell interations, statins, and dexamethasone are discussed. Recent combinatorial approaches with disease-modifying effects are highlighted. Successful development of anti-inflammatory therapies for epilepsy faces hurdles. The timing of therapeutic administration after epileptogenic triggers should, ideally, preserve the physiological roles of inflammation while opposing pathological ones. Biomarkers and consideration of epilepsy etiology can help identify patients who will best benefit from anti-inflammatory drugs. Clinical studies of anti-inflammatory treatments are underway in patients with drug-resistant seizures, and the results are described here. New clinical trial designs are likely needed to take into account the differences in mechanism of action between anti-inflammatory and conventional antiseizure medications. |
| Document Type: |
book part |
| Language: |
English |
| ISBN: |
978-0-19-754946-9; 978-0-19-754949-0; 0-19-754946-2; 0-19-754949-7 |
| DOI: |
10.1093/med/9780197549469.003.0074 |
| Availability: |
https://doi.org/10.1093/med/9780197549469.003.0074; https://academic.oup.com/book/57972/chapter/476213421 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.3C4BA719 |
| Database: |
BASE |