A Near-Infrared Fluorescent\nProbe for Visualization\nof Acetylcholinesterase Flux in the Acute Epileptic Mice Brain

Neurotransmitter imbalance is an important pathological\nbasis for\nepilepsy seizures. Acetylcholinesterase (AChE) as a key hydrolase\nin the cholinergic system directly affects the metabolism of neurotransmitter.\nUnfortunately, owing to the lack of reliable in situ imaging tools\nin the brain, the association between AChE and epilepsy has not been\nfully elucidated yet. Here, we rationally designed a near-infrared\n(NIR) fluorescent probe (<b>QXMC</b>) by employing <i>N</i>,<i>N</i>-dimethyl carbamyl as an AChE sensing group in\nthe quinolinium-xanthene NIR skeleton. <b>QXMC</b> exhibited\nhigh sensitivity, excellent selectivity, and ultrafast response time\n(within 0.5 s) toward AChE. Moreover, <b>QXMC</b> can sensitively\nmonitor the fluctuations of AChE activity in the neuronal cells and\nzebrafish during the apoptosis or oxidative stress process. Significantly,\nusing <b>QXMC</b> with superb blood–brain barrier (BBB)\npermeability, for the first time, we discovered a down-regulated AChE\nlevel in the acute epileptic mice brain through noninvasive NIR in\nvivo imaging. Moreover, the visualization of therapeutic evaluation\nof epilepsy has also been achieved by monitoring AChE with <b>QXMC</b>. This work demonstrated the great potential of <b>QXMC</b> as an effective imaging tool for epilepsy diagnosis, therapeutic\nevaluation, and pathogenesis study.