小鼠颅骨视窗及其在光学活体脑成像研究中的应用

摘要

小鼠颅骨视窗作为一种活体光学脑成像辅助工具,以其原位表征、实时观察、长期活体脑成像等优势,成为脑部疾病及神经元突触生长等研究的重要手段之一.小鼠颅骨视窗不仅可以对颅骨下软脑膜血管及血管内红细胞流速、流态变化进行定量分析,在结合荧光标记物与光学显微镜后,还可以对脑部皮层下组织、神经细胞的变化进行清晰成像.过去数十年,科研人员利用小鼠颅骨视窗深入研究了偏头痛、阿尔兹海默症、神经突触等病理生理过程,并取得了大量突破性进展.同时,随着光学成像工具性能的提升,小鼠颅骨视窗的应用也得到了进一步拓展.本文主要介绍颅骨视窗的发展史、构建方法,结合荧光探针及光学成像方法的研究,全面总结了近年来小鼠颅骨视窗在光学脑成像研究中的应用,包括脑内重要生物分子成像、细胞成像、血管及血流成像、神经环路可塑性及神经功能成像、疾病发生机理及药物开发研究等,最后讨论了小鼠颅骨视窗在实际应用中面临的问题,并对其未来应用进行了展望.%Cranial window in mouse,as a kind of in vivo optical imaging aided instrument,with the advantages of in situ representation,real time observation and long-term imaging,has became one of the most important methods for the research of brain diseases and synapse growth.The cranial window can be used to visualize the leptomeningeal vessels and quantitatively analyze the flow velocity and flow regime changes of the erythrocytes in blood vessels.Moreover,combined with the fluorescent markers and optical microscopes,the cranial window can be applied for obtaining the clear images of the brain cortical tissue and the neurons.Over the past few decades,with the aid of cranial window,researchers made lots of breakthroughs on the studies of migraine,Alzheimer's disease and the synapses.Recently,with the development of optical imaging tools,the application of cranial window had been further expanded.Herein,the history of cranial window and construction methods were introduced.We also reviewed the applications of cranial window combined with the fluorescent markers and optical microscopes on optical brain imaging (including imaging for important biological molecules in brain,cells,blood vessels,blood flow,plasticity of neural circuits and neurological functions,and research for pathogenesis and drug screening).Finally,the challenges of different cranial windows in practical application were discussed and the future applications of optical cranial window were prospected.