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早期脑胶质瘤与皮质培养物中异常的电活动有关。

Early glioma is associated with abnormal electrical events in cortical cultures.

机构信息

University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77054, USA.

Centenary College of Louisiana, 2911 Centenary Blvd, Shreveport, Louisiana, USA.

出版信息

Med Biol Eng Comput. 2019 Aug;57(8):1645-1656. doi: 10.1007/s11517-019-01980-5. Epub 2019 May 11.

Abstract

The prodromal stages of some neurological diseases have a distinct electrical profile which can potentially be leveraged for early diagnosis, predicting disease recurrence, monitoring of disease progression, and better understanding of the disease pathology. Gliomas are tumors that originate from glial cells present in the brain and spinal cord. Healthy glial cells support normal neuronal function and play an important role in modulating the regular electrical activity of neurons. However, gliomas can disrupt the normal electrical dynamics of the brain. Though experimental and clinical studies suggest that glioma and injury to glial cells disrupt electrical dynamics of the brain, whether these disruptions are present during the earliest stages of glioma and glial injury are unclear. The primary aim of this study is to investigate the effect of early in vitro glial pathology (glioma and glial injury in specific) on neuronal electrical activity. In particular, we investigated the effect of glial pathology on neural synchronization: an important phenomenon that underlies several central neurophysiological processes (ScienceDirect, 2018 ). We used two in vitro disease samples: (a) a sample in which cortical cultures were treated with anti-mitotic agents that deplete glial cells and (b) a glioma sample in which healthy cortical cells were cultured with CRL-2303 (an aggressive glioma cell line). Healthy cortical culture samples were used as controls. Cultures were established over a glass dish embedded with microelectrodes that permits simultaneous measurement of extracellular electrical activity from multiple sites of the culture. We observed that healthy cortical cultures produce spontaneous and synchronized oscillations which were attenuated in the absence of glial cells. The presence of glioma was associated with the emergence of two types of "abnormal electrical activity" each with distinct amplitude and frequency profile. Our results indicate that even early stages of glioma and glial injury are associated with distinct changes in neuronal electrical activity. Graphical abstract.

摘要

一些神经疾病的前驱阶段具有明显的电信号特征,这可能有助于早期诊断、预测疾病复发、监测疾病进展,并更好地了解疾病的病理生理学。神经胶质瘤起源于大脑和脊髓中的神经胶质细胞。健康的神经胶质细胞支持正常的神经元功能,并在调节神经元的正常电活动方面发挥重要作用。然而,神经胶质瘤可能会破坏大脑的正常电动力学。尽管实验和临床研究表明神经胶质瘤和神经胶质细胞损伤会破坏大脑的电动力学,但这些破坏是否存在于神经胶质瘤和神经胶质损伤的最早阶段尚不清楚。本研究的主要目的是研究早期体外神经胶质病理学(特定的神经胶质瘤和神经胶质损伤)对神经元电活动的影响。特别是,我们研究了神经胶质病理学对神经同步的影响:这是一种重要的现象,它是几种中枢神经生理过程的基础(ScienceDirect,2018)。我们使用了两种体外疾病样本:(a)用抗有丝分裂剂处理皮质培养物以耗尽神经胶质细胞的样本,和(b)用 CRL-2303(一种侵袭性神经胶质瘤细胞系)培养健康皮质细胞的神经胶质瘤样本。健康皮质培养样本用作对照。培养物在嵌入微电极的玻璃盘中建立,这允许同时测量培养物多个部位的细胞外电活动。我们观察到,健康皮质培养物产生自发和同步的振荡,而在没有神经胶质细胞的情况下,这些振荡会减弱。神经胶质瘤的存在与两种类型的“异常电活动”的出现有关,每种类型都具有不同的振幅和频率特征。我们的结果表明,即使是神经胶质瘤和神经胶质损伤的早期阶段,也与神经元电活动的明显变化有关。

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