Visualizing Endogenous Sulfur Dioxide Derivatives in Febrile-Seizure-Induced Hippocampal Damage by a Two-Photon Energy Transfer Cassette

Febrile seizure (FS), a frequently encountered seizure disorder in pediatric populations, can cause hippocampus damage. It has been elucidated that sulfur dioxide (SO2) content is overproduced during the development of FS and related brain injury. Thus, monitoring in situ the level of endogenous SO2 in FS-related models is helpful to estimate the pathogenesis of FS-induced brain injury, but the effect detection method remains to be explored. Herein, we developed a two-photon energy transfer cassette based on an acedan–anthocyanidin scaffold, TP-Ratio-SO2, allowing us to achieve this purpose. TP-Ratio-SO2 specifically responds to SO2 derivatives (HSO3–/SO32–) in an ultrafast fashion (less than 3 s), and HSO3–/SO32– can be sensitively determined with a detection limit of 26 nM. Moreover, it exhibits significant changes in two well-resolved fluorescence emissions (Δλ = 140 nm) by reacting with HSO3–/SO32–, behaving as a ratiometric fluorescent sensor. Importantly, ratiometric imaging of endogenous SO2 derivatives generation in hyperpyretic U251 cells and in a rat model of FS-treated hippocampus damage was successfully carried out by TP-Ratio-SO2, demonstrating that it may be a promising tool for studying the role of SO2 in FS-associated neurological diseases