Electrochemical sensing of transient ascorbate fluctuation under hypoxic stress in live rat brain.

Hypoxia, a common cause of programmed cell death or apoptosis, represents a neuropathological process. Although certain response proteins to hypoxic stress and their effects on cell status and fate have been identified, the real-time quantification of smaller neurochemicals to understand pathogenic mechanism in live rat brain during such stress remains unexplored. In this study, by employing a cutting-edge electrochemical tool developed with carbon nanotube-sheathed carbon fiber microelectrode that offers remarkable selectivity and temporal/spatial resolution for monitoring ascorbate, we observed a substantial efflux of ascorbate in response to hypoxic stress in live rat brain. Furthermore, using a small molecule compound as channel inhibitor to investigate the behavior of ascorbate efflux, we found that this efflux is closely correlated with N-methyl-D-aspartic acid receptor-induced neuronal excitability. Notably, antagonistic actions on volume-sensitive anion channel can suppress ascorbate efflux evoked by hypoxic stress, further revealing that ascorbate fluctuation is volume-sensitive anion channel-dependent. This research not only facilitates a greater understanding of the neurochemical mechanism in hypoxia but also uncovers a potential biomarker for future closed-loop therapies.