Progress and potential of brain organoids in epilepsy research

Epilepsies are disorders of the brain characterised by an imbalance in electrical activity, linked to a disruption in the excitation and inhibition of neurons. Progress in the epilepsy research field has been hindered by the lack of an appropriate model, with traditionally used 2D primary cell cultu...

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Bibliographic Details
Published in:Stem cell research & therapy 2024-10, Vol.15 (1), p.361-10, Article 361
Main Authors: Brown, Rachel, Rabeling, Alexa, Goolam, Mubeen
Format: Article
Language:English
Subjects:
Animals
Brain
Brain - metabolism
Brain - pathology
Brain development
Brain research
Epilepsy
Epilepsy - genetics
Epilepsy - metabolism
Epilepsy - pathology
Gene expression
Humans
Hyperexcitability
Neurons
Neurons - metabolism
Neurophysiology
Organoids - metabolism
Organoids - pathology
Review
Whole-cell patch-clamp
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Summary:Epilepsies are disorders of the brain characterised by an imbalance in electrical activity, linked to a disruption in the excitation and inhibition of neurons. Progress in the epilepsy research field has been hindered by the lack of an appropriate model, with traditionally used 2D primary cell culture assays and animal models having a number of limitations which inhibit their ability to recapitulate the developing brain and the mechanisms behind epileptogenesis. As a result, the mechanisms behind the pathogenesis of epilepsy are largely unknown. Brain organoids are 3D aggregates of neural tissue formed in vitro and have been shown to recapitulate the gene expression patterns of the brain during development, and can successfully model a range of epilepsies and drug responses. They thus present themselves as a novel tool to advance studies into epileptogenesis. In this review, we discuss the formation of brain organoids, their recent application in studying genetic epilepsies, hyperexcitability dynamics and oxygen glucose deprivation as a hyperexcitability agent, their use as an epilepsy drug testing and development platform, as well as the limitations of their use in epilepsy research and how these can be mitigated.
ISSN:1757-6512
1757-6512
DOI:10.1186/s13287-024-03944-5