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

Abstract

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^-/SO₃^2-) in an ultrafast fashion (less than 3 s), and HSO₃^-/SO₃^2- 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^-/SO₃^2-, 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.