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.