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Astrocytes in the initiation and progression of epilepsy
Open accessAbstract
Epilepsy affects ~65 million people worldwide. First-line treatment options include >20 antiseizure medications, but seizure control is not achieved in approximately one-third of patients. Antiseizure medications act primarily on neurons and can provide symptomatic control of seizures, but do not alter the onset and progression of epilepsy and can cause serious adverse effects. Therefore, medications with new cellular and molecular targets and mechanisms of action are needed. Accumulating evidence indicates that astrocytes are crucial to the pathophysiological mechanisms of epilepsy, raising the possibility that these cells could be novel therapeutic targets. In this Review, we discuss how dysregulation of key astrocyte functions - gliotransmission, cell metabolism and immune function - contribute to the development and progression of hyperexcitability in epilepsy. We consider strategies to mitigate astrocyte dysfunction in each of these areas, and provide an overview of how astrocyte activation states can be monitored in vivo not only to assess their contribution to disease but also to identify markers of disease processes and treatment effects. Improved understanding of the roles of astrocytes in epilepsy has the potential to lead to novel therapies to prevent the initiation and progression of epilepsy.
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“In other contexts, such as acquired epilepsy, the presence of reactive astrocytes alone is sufficient to drive epileptogenesis54.”
From mTORC1 drives cell-autonomous astrocyte reactivity in tuberous sclerosis (2026) · cites this paper as [54]
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Metadata
- Authors
- Vezzani, A., Ravizza, T., Bedner, P., Aronica, E., Steinhäuser, C., & Boison, D.
- Affiliations
- Mario Negri Institute for Pharmacological Research (IT)
- University of Bonn (DE)
- Amsterdam Neuroscience (NL)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Vezzani, Annamaria
- ORCID
- Venue
- Nature Reviews Neurology
- Published
- 2022-10-24
- Volume
- 18
- Issue
- 12
- Pages
- 707-722
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC10368155
- OpenAlex
- W4307338781
- Cited by
- 272
- References
- 207
- Citations by year
- 2026: 82 · 2025: 96 · 2024: 53 · 2023: 41
- FWCI
- 8.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Pure Amsterdam UMC (acceptedVersion, other-oa)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Funders
- Citizens United for Research in Epilepsy (NS065957, NS103740)
- ZonMw
- Bundesministerium für Bildung und Forschung (16GW0182, 01DN20001 CONNEX, 01DN20001, 16GW0182 CONNEXIN)
- Epilepsy Society
- National Institutes of Health (H2020, NS127846)
- Horizon 2020 Framework Programme (H2020-MSCA, 952455, 722053, H2020-MSCA-ITN)
- National Institute of Neurological Disorders and Stroke (R01NS061844, R01NS103740, R01NS065957, R01NS127846)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- astrocytes, epilepsy, epileptogenesis, hyperexcitability, gliotransmission, astrocyte metabolism, astrocyte activation, antiepileptic drugs, novel therapeutic targets
- MeSH terms
- Astrocytes, Epilepsy, Humans, Neurons, Seizures
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