In recent days，the research group led by Prof. Yong Qian and Prof. Hongke Liu from the School of Chemistry and Materials Science at NNU has made a significant breakthrough in the field of biochemistry. Their achievement was published online by Advanced Science, Wiley-VCH, titled Imaging Dynamic Peroxynitrite Fluxes in the Brain of Epilepsy with a Near-Infrared Fluorescent Probe. Advanced Science is a world-class comprehensive academic journal, and its impact factor in 2018 was 15.804.
Brain injury resulting from epileptic seizure is a complex dynamic process associated with excitotoxicity‐induced mitochondrial dysfunction and oxidative stress. During the initiation and progression of epilepsy, as the defense capability of antioxidase wears down, numerous reactive oxygen species (ROS) are continuously generated that further reacts with nitric oxide (NO) to produce reactive nitrogen species (RNS) such as peroxynitrite (ONOO−), a critical neurotoxic factor that plays an important role in the pathogenesis of epilepsy and other neurodegenerative diseases. Overexpressed ONOO- is found in the progression of epilepsy, Alzheimer's disease and Parkinson's disease, which can serve as a potential biomarker to confirm these diseases. Nevertheless, the potential biological roles of ONOO− in epileptogenesis have not yet been fully understood. Thus, to explore the pathophysiological mechanism of in vivo ONOO− and investigate its role in epilepsy, it is crucial to develop effective imaging tools for monitoring ONOO− in the brain.
The research group led by Prof. Yong Qian and Prof. Hongke Liu from the School of Chemistry and Materials Sciences at NNU constructed a NIR fluorescent probe that can effectively trace endogenous ONOO−signals in kainate (KA)‐induced epileptic seizure. This probe ONP, judiciously designed with a methylene blue (MB)‐based near‐infrared fluorophore, enables efficient and selective imaging of ONOO− in vitro and in vivo. Importantly, it can effectively cross the blood–brain barrier (BBB) with the brain‐targeted characteristic. Using this probe, the dynamic changes of endogenous ONOO− fluxes in KA‐induced 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. Moreover, for the first time, their studies have shown that a high‐throughput screening method for antiepileptic inhibitors has been constructed by combining high‐content analysis (HCA) with ONP, which provides a simple and effective approach for investigating ONOO− in biosystems and for further screening antiepileptic drugs.
This research was sponsored by the international cooperation key project of the National Natural Science Foundation of China, a general program of the National Natural Science Foundation of China and the Distinguished Professor Plan in Jiangsu Province. Prof. Yong Qian and Prof. Hongke Lian from the School of Chemistry and Material Science at Nanjing Normal University and Prof. Hailiang Zhu from the School of Life Sciences at Nanjing University are co-corresponding authors. Graduate student Jiongsheng Hu from NNU and Ph.D student Chenwen Shao from NJU are joint first authors.