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首页> 美国卫生研究院文献>Frontiers in Neuroengineering >Feasibility Assessment of Micro-Electrode Chip Assay as a Method of Detecting Neurotoxicity in vitro
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Feasibility Assessment of Micro-Electrode Chip Assay as a Method of Detecting Neurotoxicity in vitro

机译：微电极芯片检测作为体外检测神经毒性方法的可行性评估

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Detection and characterization of chemically induced toxic effects in the nervous system represent a challenge for the hazard assessment of chemicals. In vivo, neurotoxicological assessments exploit the fact that the activity of neurons in the central and peripheral nervous system has functional consequences. And so far, no in vitro method for evaluating the neurotoxic hazard has yet been validated and accepted for regulatory purpose. The micro-electrode array (MEA) assay consists of a culture chamber into which an integrated array of micro-electrodes is capable of measuring extracellular electrophysiology (spikes and bursts) from electro-active tissues. A wide variety of electrically excitable biological tissues may be placed onto the chips including primary cultures of nervous system tissue. Recordings from this type of in vitro cultured system are non-invasive, give label free evaluations and provide a higher throughput than conventional electrophysiological techniques. In this paper, 20 substances were tested in a blinded study for their toxicity and dose–response curves were obtained from fetal rat cortical neuronal networks coupled to MEAs. The experimental procedure consisted of evaluating the firing activity (spiking rate) and modification/reduction in response to chemical administration. Native/reference activity, 30 min of activity recording per dilution, plus the recovery points (after 24 h) were recorded. The preliminary data, using a set of chemicals with different mode-of-actions (13 known to be neurotoxic, 2 non-neuroactive and not toxic, and 5 non-neuroactive but toxic) show good predictivity (sensitivity: 0.77; specificity: 0.86; accuracy: 0.85). Thus, the MEA with a neuronal network has the potency to become an effective tool to evaluate the neurotoxicity of substances in vitro.
机译：神经系统中化学诱导的毒性作用的检测和表征对化学物质的危害评估提出了挑战。在体内，神经毒理学评估利用了以下事实：中枢神经系统和周围神经系统中神经元的活动具有功能性后果。到目前为止，还没有一种用于评估神经毒性危害的体外方法得到验证并被接受用于监管目的。微电极阵列（MEA）分析由一个培养室组成，其中集成的微电极阵列能够测量来自电活性组织的细胞外电生理学（尖峰和猝发）。可以将各种各样的可电激发的生物组织放置在芯片上，包括神经系统组织的原代培养物。这种类型的体外培养系统的记录是非侵入性的，可以进行无标签评估，并且比常规电生理技术具有更高的通量。在本文中，在一项盲法研究中测试了20种物质的毒性，并从与MEA结合的胎儿大鼠皮层神经元网络获得了剂量反应曲线。实验程序包括评估烧成活性（加料速率）和响应于化学施用的改性/还原。记录天然/参考活性，每稀释液记录30分钟的活性以及恢复点（24小时后）。使用一组具有不同作用方式的化学物质（13种已知为神经毒性，2种非神经活性且无毒，5种非神经活性但有毒）的初步数据显示出良好的预测性（敏感性：0.77；特异性：0.86） ；准确度：0.85）。因此，具有神经元网络的MEA有潜力成为评估体外物质神经毒性的有效工具。

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