Imaging Dynamic Peroxynitrite Fluxes in Epileptic Brains with a Near-Infrared Fluorescent Probe
Hu, JS (Hu, Jiong-sheng)[ 1 ] ; Shao, CW (Shao, Chenwen)[ 2 ] ; Wang, XA (Wang, Xueao)[ 2 ] ; Di, XJ (Di, Xiaojiao)[ 1 ] ; Xue, XL (Xue, Xuling)[ 1 ] ; Su, Z (Su, Zhi)[ 1 ] ; Zhao, J (Zhao, Jing)[ 2 ] ; Zhu, HL (Zhu, Hai-Liang)[ 2 ]*; Liu, HK (Liu, Hong-Ke)[ 1 ]*（刘红科）; Qian, Y (Qian, Yong)[ 1,2 ]*（钱勇）
[ 1 ] Nanjing Normal Univ, Sch Chem & Mat Sci, Wenyuan Rd 1, Nanjing 210046, Jiangsu, Peoples R China
[ 2 ] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Xianlin Rd 163, Nanjing 210023, Jiangsu, Peoples R China
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.