人类脑器官样体具有类似于人脑的三维复杂性，并有潜力加强当前神经系统疾病药物开发流程。癫痫是一种复杂的神经疾病，其特征为反复发作的癫痫发作。三分之一的癫痫患者对当前可用的药物无效，并且没有一种药物能治疗所有亚型；因此，需要更好的癫痫模型来进行药物开发。脑器官样体可以用于解决这一未能满足的需求。在本研究中，使用人类脑器官样体以及电生理方法来探究缺氧葡萄糖供应不足对过度兴奋的作用。同时对该活动对当前的抗癫痫药物的反应进行了研究。此外，还利用qPCR和免疫荧光技术探索了药物候选物的作用机制。研究结果表明，缺氧葡萄糖供应不足诱导了脑器官样体组织中的过度兴奋变化，该变化得到了大麻二酚和布美他尼的治疗。存在NKCC1和KCC2基因表达相关证据，以及参与GABAergic信号复杂发育的其他基因和蛋白质。该研究支持使用器官样体作为建模脑皮质过度兴奋的平台，可扩展到癫痫的建模，并用于药物发现。

Human cerebral organoids resemble the 3D complexity of the human brain and have the potential to augment current drug development pipelines for neurological disease. Epilepsy is a complex neurological condition characterized by recurrent seizures. A third of people with epilepsy do not respond to currently available pharmaceutical drugs, and there is not one drug that treats all subtypes; thus, better models of epilepsy are needed for drug development. Cerebral organoids may be used to address this unmet need. In the present work, human cerebral organoids are used along with electrophysiological methods to explore oxygen-glucose deprivation as a hyperexcitability agent. This activity is investigated in its response to current antiseizure drugs. Furthermore, the mechanism of action of the drug candidates is probed with qPCR and immunofluorescence. The findings demonstrate OGD-induced hyperexcitable changes in the cerebral organoid tissue, which is treated with cannabidiol and bumetanide. There is evidence for NKCC1 and KCC2 gene expression, as well as other genes and proteins involved in the complex development of GABAergic signaling. This study supports the use of organoids as a platform for modelling cerebral cortical hyperexcitability that could be extended to modelling epilepsy and used for drug discovery.