Epilepsy is a chronic neurological disorder characterized by recurrent seizures, which poses a significant threat to human health. Increasing evidence indicates that the pathological mechanism of epilepsy is closely related to the presence of peroxynitrite (ONOO-). To address this issue, we have developed a dual-molecule release precursor, DVN, with different functional components, which consists of a responsive group, a reporter segment, and a drug molecule, for monitoring peroxynitrite. Based on in vitro assays, DVN exhibits several advantages, including high specificity, a rapid response time (120 s), and a dual release function, and is not affected by other reactive oxygen species. When this precursor is activated by peroxynitrite, valproic acid (VPA) is released, which is a broad-spectrum antiepileptic drug that can reduce seizure occurrences; a near-infrared (NIR) reporter unit is formed synchronously using DVN, and we successfully tracked the fluctuations of endogenous and exogenous ONOO- in SH-SY5Y cells and achieved significant spatiotemporal resolution. Moreover, DVN can clearly display the changes of endogenous ONOO- in SH-SY5Y cells. Crucially, DVN helps to perform fluorescence imaging of the ONOO- concentration in epilepsy models, while also reducing the seizure levels in mice and shortening their seizure latency, for the first time. These findings indicate that DVN provides a promising tool for the diagnosis and treatment of epilepsy by imaging the fluctuations of ONOO-, and offers a reliable method for studying the treatment of epilepsy.
Li et al. (Tue,) studied this question.
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