Human Brain Organoid Models of Developmental Epilepsies.
Human Brain Organoid Models of Developmental Epilepsies.
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DOI：
10.1177/1535759720949254
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发表时间：
2020-09
影响因子：
3.6
通讯作者：
Hsieh J
中科院分区：
文献类型：
--
作者：
Nieto-Estévez V;Hsieh J
癫痫是一种常见的神经系统疾病，其特征是由于神经元过度活跃引起的反复和无端发作。很大一部分癫痫病例始于儿童时期。癫痫的病因包括中风、感染、脑损伤、遗传因素或改变大脑结构和发育的其他因素，但高达50%的病例病因不明。大约35%的患者有难治性癫痫发作，对药物治疗无效。动物模型和体外培养有助于我们对癫痫的理解，但显然需要更好的模型来探索正常和病理状态下的人类大脑。人类多能干细胞（PSC）技术为分析大脑发育和疾病，特别是具有遗传成分的疾病的新模型打开了大门。最初，将PSCs分化为均匀的神经细胞群的二维培养物，如谷氨酸能兴奋性或γ-氨基丁酸能抑制性神经元，以及胶质细胞。然而，这些文化缺乏人类大脑的结构和复杂性。在过去的十年里，PSC技术通过被称为类器官的三维培养的发展已经发展到一个新的水平。这些类器官概括了动物模型中缺失的人类大脑特征，使人类大脑的深入研究成为可能。本文就类器官的研究现状及其在癫痫中的应用作一综述。
Epilepsy is a common neurological disorder characterized by recurrent and unprovoked seizures due to neuronal hyperactivity. A large proportion of epilepsy cases begin during childhood. Causes of epilepsy include stroke, infections, brain injury, genetic factors, or other factors that alter brain structure and development, but in up to 50% of cases the cause is unknown. Approximately 35% of patients have refractory seizures that do not respond to medication. Animal models and in vitro cultures have contributed to our understanding of epilepsy, but there is a clear need for better models to explore the human brain in normal and pathological conditions. Human pluripotent stem cell (PSC) technologies opened the door for new models for analyzing brain development and disease, especially conditions with a genetic component. Initially, PSCs were differentiated into 2-dimensional cultures of a homogenous population of neural cells, such as glutamatergic excitatory or γ-aminobutyric acidergic inhibitory neurons, as well as glial cells. Nevertheless, these cultures lacked the structure and complexity of a human brain. In the last decade, PSC technology has advanced to the next level through the development of 3-dimensional culture, called organoids. These organoids recapitulate features of the human brain that are missing in animal models, enabling a deeper study of the human brain. In this review, we will summarize the current status of organoid research and its application to epilepsy.
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影响因子：
16.2
作者：
Cadwell, Cathryn R.;Bhaduri, Aparna;Mostajo-Radji, Mohammed A.;Keefe, Matthew G.;Nowakowski, Tomasz J.
通讯作者：
Nowakowski, Tomasz J.
影响因子：
23.9
作者：
Bershteyn M;Nowakowski TJ;Pollen AA;Di Lullo E;Nene A;Wynshaw-Boris A;Kriegstein AR
通讯作者：
Kriegstein AR
影响因子：
82.9
作者：
Blanchard JW;Bula M;Davila-Velderrain J;Akay LA;Zhu L;Frank A;Victor MB;Bonner JM;Mathys H;Lin YT;Ko T;Bennett DA;Cam HP;Kellis M;Tsai LH
通讯作者：
Tsai LH
影响因子：
5.1
作者：
DOBYNS, WB;STRATTON, RF;LEDBETTER, DH
通讯作者：
LEDBETTER, DH
影响因子：
64.8
作者：
Birey F;Andersen J;Makinson CD;Islam S;Wei W;Huber N;Fan HC;Metzler KRC;Panagiotakos G;Thom N;O'Rourke NA;Steinmetz LM;Bernstein JA;Hallmayer J;Huguenard JR;Paşca SP
通讯作者：
Paşca SP