Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, CAS Research/Education Center for Excellence in Molecule Science, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
J Am Chem Soc. 2020 Nov 11;142(45):19012-19016. doi: 10.1021/jacs.0c09011. Epub 2020 Oct 27.
Cytotoxic edema is the initial and most important step in the sequence that almost inevitably leads to brain damage. Exploring the neurochemical disturbances in this process is of great significance in providing a measurable biological parameter for signaling specific pathological conditions. Here, we present an electrochemical system that pinpoints a critical neurochemical involved in cytotoxic edema. Specially, we report a molecularly tailored brain-implantable ascorbate sensor (CFE) featuring excellent selectivity and spatiotemporal resolution that assists the first observation of release of ascorbate induced by cytotoxic edema in vivo. Importantly, we reveal that this release is associated with an increase in the amount of cytotoxic edema-inducing agent and that blockage of cytotoxic edema abolishes ascorbate release, further supporting that ascorbate efflux is cytotoxic edema-dependent. Our study holds the promise for understanding the molecular basis of cytotoxic edema that can lead to the discovery of biomarkers or potential therapeutic strategies of brain diseases.
细胞毒性水肿是几乎不可避免地导致脑损伤的一系列过程中的初始和最重要的步骤。探索该过程中的神经化学紊乱对于提供可测量的生物参数以指示特定的病理状况具有重要意义。在这里，我们提出了一种电化学系统，可以精确定位与细胞毒性水肿相关的关键神经化学物质。具体来说，我们报告了一种分子定制的脑内可植入抗坏血酸传感器（CFE），具有出色的选择性和时空分辨率，有助于首次观察到细胞毒性水肿在体内诱导的抗坏血酸释放。重要的是，我们揭示了这种释放与细胞毒性水肿诱导剂数量的增加有关，并且阻断细胞毒性水肿可消除抗坏血酸的释放，这进一步支持了抗坏血酸外排是细胞毒性水肿依赖性的。我们的研究有望深入了解细胞毒性水肿的分子基础，从而为发现脑疾病的生物标志物或潜在治疗策略提供依据。
