■在脑梗塞的核心,灌注严重受阻,神经元死亡发生在几分钟内。在半影,核心附近有更多剩余灌注的区域,细胞最初保持活力,但活性显著降低。原则上,如果按时建立再灌注,可以保存半影,使其成为有希望的治疗目标。在微电极阵列(MEAs)上培养神经元的体外模型为研究缺血性中风如何影响神经元功能提供了有用的工具。这些模型往往是统一的,专注于孤立的半影,并且通常缺少诸如核心和未受影响的区域(正常灌注)的相邻区域。然而,这些区域的过程可能会影响半影区的神经元功能和存活。
■这里,我们设计的,制作,并表征了一种细胞相容性装置,该装置在体外神经元培养物中产生氧气梯度,以使细胞暴露于从缺氧到缺氧附近的各种深度的缺氧。这标志着在模仿核心的道路上迈出了一步,半影,和健康的组织,并将有助于更好的缺血性中风的体外建模。
■发生器在30分钟内形成稳定且可再现的梯度。极端情况下的氧浓度可在生理相关范围内调节。发生器的应用不会对电生理记录或培养物的活力产生负面影响,从而证实了该装置的细胞相容性。
■开发的装置能够对神经元培养物施加氧梯度,并可能丰富体外中风模型。
UNASSIGNED: In the core of a brain infarct, perfusion is severely impeded, and neuronal death occurs within minutes. In the penumbra, an area near the core with more remaining perfusion, cells initially remain viable, but activity is significantly reduced. In principle, the penumbra can be saved if reperfusion is established on time, making it a promising target for treatment. In vitro models with cultured neurons on microelectrode arrays (MEAs) provide a useful tool to investigate how ischemic stroke affects neuronal functioning. These models tend to be uniform, focusing on the isolated penumbra, and typically lack adjacent regions such as a core and unaffected regions (normal perfusion). However, processes in these regions may affect neuronal functioning and survival in the penumbra.
UNASSIGNED: Here, we designed, fabricated, and characterized a cytocompatible device that generates an oxygen gradient across in vitro neuronal cultures to expose cells to hypoxia of various depths from near anoxia to near normoxia. This marks a step in the path to mimic core, penumbra, and healthy tissue, and will facilitate better in vitro modeling of ischemic stroke.
UNASSIGNED: The generator forms a stable and reproducible gradient within 30 min. Oxygen concentrations at the extremes are adjustable in a physiologically relevant range. Application of the generator did not negatively affect electrophysiological recordings or the viability of cultures, thus confirming the cytocompatibility of the device.
UNASSIGNED: The developed device is able to impose an oxygen gradient on neuronal cultures and may enrich in vitro stroke models.