Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
UCT Neuroscience Institute, Cape Town, South Africa.
Stem Cell Res Ther. 2024 Oct 12;15(1):361. doi: 10.1186/s13287-024-03944-5.
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.
癫痫是一种以脑电活动失衡为特征的脑部疾病，与神经元兴奋和抑制的中断有关。由于缺乏合适的模型，癫痫研究领域的进展受到了阻碍，传统使用的 2D 原代细胞培养测定法和动物模型存在许多限制，限制了它们重现发育中大脑和癫痫发生背后机制的能力。因此，癫痫发病机制的背后机制在很大程度上尚不清楚。脑类器官是体外形成的神经组织 3D 聚集体，已被证明可重现大脑在发育过程中的基因表达模式，并且可以成功模拟多种癫痫和药物反应。因此，它们本身就是一种推进癫痫发生研究的新工具。在这篇综述中，我们讨论了脑类器官的形成、它们在研究遗传性癫痫、过度兴奋动力学以及缺氧葡萄糖剥夺作为过度兴奋剂方面的最新应用、它们作为癫痫药物测试和开发平台的用途，以及它们在癫痫研究中的使用限制以及如何减轻这些限制。
