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

• Published in: Advanced science Vol. 6; no. 15; pp. 1900341 - n/a
• Main Authors: Hu, Jiong‐sheng, Shao, Chenwen, Wang, Xueao, Di, Xiaojiao, Xue, Xuling, Su, Zhi, Zhao, Jing, Zhu, Hai‐Liang, Liu, Hong‐Ke, Qian, Yong
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 07-08-2019; John Wiley and Sons Inc; Wiley
• Subjects: brain; Brain research; Communication; Communications; Convulsions & seizures; Design; Epilepsy; FDA approval; fluorescent probe; near‐infrared imaging; Oxidative stress; peroxynitrite; epilepsy; near‐infrared imaging; fluorescent probe; peroxynitrite; brain
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.201900341

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.
The first near‐infrared imaging probe for tracking endogenous peroxynitrite (ONOO−) in brains of kainate‐induced epileptic seizures is developed, which is named ONP. A higher concentration of ONOO− in the epileptic brains associated with severe neuronal damage and epileptogenesis is observed by imaging of hippocampal regions with ONP. By combining high‐content analysis and ONP, a high‐throughput screening method for antiepileptic inhibitors is constructed.