A Brain-Permeable Selenocyanate Near-Infrared (NIR) Probe Platform for H 2 S Dynamics Imaging: Insights into Redox Homeostasis and Antiepileptic Therapy

The spatiotemporal dynamics of hydrogen sulfide (H2S) in the living brain remain elusive, primarily due to the lack of molecular probes that can concurrently resist biothiol interference, cross the blood-brain barrier (BBB), and yield reliable in vivo signals.This work presents a selenocyanate-based sensing trigger relying on a specific H2S-initiated cascade cyclization that exhibits superior resistance to biothiol degradation. Guided by this rationale, the brain-permeable, ratiometric near-infrared (NIR) fluorescent probe SeCP-3 was developed. It features a large Stokes shift and fast kinetics, enabling high-fidelity imaging of H2S fluctuations in live cells and in a pentylenetetrazole-induced epileptic mouse model. Strikingly, this approach achieves the first direct visualization of H2S downregulation mediated by the antiepileptic drug carbamazepine, correlating this modulation with suppressed seizures and anti-inflammatory effects. These findings offer novel insights into H2S-mediated neuroprotection and redox homeostasis in epilepsy. Beyond this, the established selenocyanate cyclization strategy provides a versatile and robust chemical platform for the development of next-generation in-vivo biosensors with broad applicability in biomedical research and therapeutic monitoring.