Coupled NIR-II fluorescence and mass spectrometry imaging of H2S-associated redox dysregulation in Parkinsonian models.

Hydrogen sulfide (H2S) plays an important role in neuronal redox homeostasis and has been implicated in the regulation of dopaminergic neuronal injury, but its transient and reactive nature makes in vivo monitoring challenging. Herein, NIR-II fluorescence imaging coupled with mass spectrometry imaging (MSI) was employed to evaluate H2S-associated redox dysregulation and treatment responses in Parkinsonian models. The H2S-responsive fluorophore CySO3Cl showed fluorescence quenching after reaction with H2S, thereby providing an inverse optical readout of H2S-related changes. In N2a cells, CySO3Cl responded to both exogenous and endogenously modulated H2S and revealed reduced H2S-associated redox status in MPP+-induced neuronal injury. In MPTP-induced Parkinsonian mice, enhanced NIR-II fluorescence signals were observed in the brain region, indicating H2S-associated redox disruption. Treatment with polyphenolic compounds, especially resveratrol and tea polyphenols, decreased the fluorescence signal and improved pathological, behavioral, and oxidative stress-related indices, suggesting partial recovery of H2S-associated redox homeostasis. Furthermore, ex vivo MSI provided complementary spatial molecular information by mapping CySO3Cl, its H2S-responsive product CySO3SH, and dopamine in brain tissues. The MSI results showed reduced dopamine and CySO3SH signals but increased residual CySO3Cl signals in Parkinsonian mice, which were partially reversed after polyphenolic treatment. Together, this study presents a coupled NIR-II fluorescence/MSI imaging strategy for evaluating H2S-associated redox dysregulation and treatment responses in Parkinsonian models.