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 (H 2 S) 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 H 2 S-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 H 2 S fluctuations in live cells and in a pentylenetetrazole-induced epileptic mouse model. Strikingly, this approach achieves the first direct visualization of H 2 S downregulation mediated by the antiepileptic drug carbamazepine, correlating this modulation with suppressed seizures and anti-inflammatory effects. These findings offer novel insights into H 2 S-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.