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在单个传感器中结合活体安培测氧法和电生理学:癫痫研究工具。

Combined in Vivo Amperometric Oximetry and Electrophysiology in a Single Sensor: A Tool for Epilepsy Research.

机构信息

Center for Neuroscience and Cell Biology, University of Coimbra , Rua Larga, 3004-504 Coimbra, Portugal.

BrainSense, Limitada , Biocant Park, 3060-197 Cantanhede, Portugal.

出版信息

Anal Chem. 2017 Nov 21;89(22):12383-12390. doi: 10.1021/acs.analchem.7b03452. Epub 2017 Nov 7.

Abstract

Seizures are paroxysmal events in which increased neuronal activity is accompanied by an increase in localized energetic demand. The ability to simultaneously record electrical and chemical events using a single sensor poses a promising approach to identify seizure onset zones in the brain. In the present work, we used ceramic-based platinum microelectrode arrays (MEAs) to perform high-frequency amperometric recording of local pO and local field potential (LFP)-related currents during seizures in the hippocampus of chronically implanted freely moving rats. Resting levels of O in the rodent brain varied between 6.6 ± 0.7 μM in the dentate gyrus (DG) region of the hippocampus and 22.1 ± 4.9 μM in the cerebral cortex. We also observed an expected increase in hippocampal pO (15 ± 4% from baseline) in response to tail pinch stress paradigm. Finally, induction of status epilepticus by intrahippocampal injection of pilocarpine induced biphasic changes in pO in the hippocampus. The initial dip at seizure onset (ΔO = -4.5 ± 0.7 μM) was followed by a prolonged hyperoxygenation phase (ΔO = +10.4 ± 2.9 μM). By acquiring the amperometry signal with a high sampling rate of 100 Hz we decomposed the raw signal in an oximetry recording (<1 Hz) and LFP recording (>1 Hz), demonstrating that each individual Pt site can simultaneously report changes in local pO and LFP-related currents during pilocarpine-induced seizure activity. This has high potential for translation into the clinical setting supported on intracranial grid or strip electrodes.

摘要

癫痫发作是神经元活动增加伴随局部能量需求增加的阵发性事件。使用单个传感器同时记录电和化学事件的能力为识别大脑中的癫痫发作起始区提供了一种很有前途的方法。在本工作中,我们使用基于陶瓷的铂微电极阵列 (MEA) 在慢性植入的自由移动大鼠的海马体中进行高频安培记录,以记录癫痫发作期间的局部 pO 和局部场电位 (LFP) 相关电流。在啮齿动物大脑中,O 的静息水平在海马体的齿状回 (DG) 区域为 6.6±0.7 μM,在大脑皮层为 22.1±4.9 μM。我们还观察到,在尾夹应激范式下,海马体 pO 预期增加 (与基线相比增加 15±4%)。最后,通过海马内注射匹罗卡品诱导癫痫持续状态,导致海马体 pO 发生双相变化。在癫痫发作开始时出现初始下降 (ΔO = -4.5±0.7 μM),随后是长时间的过度氧合阶段 (ΔO = +10.4±2.9 μM)。通过以 100 Hz 的高采样率获取安培计信号,我们在血氧计记录 (<1 Hz) 和 LFP 记录 (>1 Hz) 中分解原始信号,证明每个单独的 Pt 位点可以在匹罗卡品诱导的癫痫发作活动期间同时报告局部 pO 和 LFP 相关电流的变化。这在颅内网格或条带电极支持下具有很高的转化为临床设置的潜力。

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