Imaging Dynamic Peroxynitrite Fluxes in Epileptic Brains with a Near‐Infrared Fluorescent Probe

Abstract

Epilepsy is a chronic neurodegenerative disease, and accumulating evidence suggests its pathological progression is closely associated with peroxynitrite (ONOO − ). However, understanding the function remains challenging due to a lack of in vivo imaging probes for ONOO − determination in epileptic brains. Here, the first near‐infrared imaging probe (named ONP) is presented for tracking endogenous ONOO − in brains of kainate‐induced epileptic seizures with high sensitivity and selectivity. Using this probe, the dynamic changes of endogenous ONOO − fluxes in epileptic brains are effectively monitored with excellent temporal and spatial resolution. In vivo visualization and in situ imaging of hippocampal regions clearly reveal that a higher concentration of ONOO − in the epileptic brains associates with severe neuronal damage and epileptogenesis; curcumin administration can eliminate excessively increased ONOO − , further effectively protecting neuronal cells. Moreover, by combining high‐content analysis and ONP, a high‐throughput screening method for antiepileptic inhibitors is constructed, which provides a rapid imaging/screening approach for understanding epilepsy pathology and accelerating antiseizure therapeutic discovery.

Small-molecule fluorescence-based probes for interrogating major organ diseases

“…In 2019, Qian et al reported a NIR fluorescent probe ONP and demonstrated that it could be used to trace endogenous ONOO À signals in kainate (KA)-induced epileptic seizures while providing a means for screening antiepileptic inhibitors. 16 ONP was developed using methylene blue (MB) as the reporter agent with a boronic ester serving as a selective reactive moiety for ONOO À (Fig. 9).…”

Boronate-Based Probes for Biological Oxidants: A Novel Class of Molecular Tools for Redox Biology

“…The typical procedure to introduce such a residue exploits the 4-hydroxymethylphenylboronic acid pinacol ester in which the hydroxyl group is converted, often in situ , into an acid chloride in a reaction with triphosgene (Srikun et al, 2008 ; Chung et al, 2011 ; Zhu D. et al, 2013 ) in the presence of a base in various solvents, which reacts further with the target amino group. There are some examples in which this approach is also used to mask the nitrogen atom on biotin (Chung et al, 2018 ; Wu Y. P. et al, 2018 ) or methylene blue (Hu et al, 2019 ) or in aliphatic systems (Lippert et al, 2010 ; Zhu D. et al, 2013 ; Yik-Sham Chung et al, 2018 ).…”

Changes in Biothiol Levels Are Closely Associated with Alzheimer’s Disease

“…Real-time, in-vivo monitoring of biothiol changes would be bene cial for early diagnosis, prevention and therapeutic development for personalized AD management. Recently, multi-signal uorescent probes have been widely applied to observe and detect biothiols in-situ, due to their high selectivity, sensitivity, and operational simplicity [15,16]. It is of great value to utilized multi-signal uorescent probes to observe and quantify biothiols in AD patients and nerve cells, because this may help to con rm the associations between AD and Hcy levels by direct measurement in real-time.…”