Electrochemically Probing Dynamics of Ascorbate during Cytotoxic Edema in Living Rat Brain

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_AA2.0) 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.