Al Omran Alzahra J, Saternos Hannah C, Liu Tongyu, Nauli Surya M, AbouAlaiwi Wissam A
Department of Pharmacology and Experimental Therapeutics, University of Toledo, College of Pharmacy and Pharmaceutical Sciences.
Life Sciences Institute, University of Michigan.
J Vis Exp. 2015 Jun 1(100):e52853. doi: 10.3791/52853.
Multiciliated ependymal cells line the ventricles in the adult brain. Abnormal function or structure of ependymal cilia is associated with various neurological deficits. The current ex vivo live imaging of motile ependymal cilia technique allows for a detailed study of ciliary dynamics following several steps. These steps include: mice euthanasia with carbon dioxide according to protocols of The University of Toledo's Institutional Animal Care and Use Committee (IACUC); craniectomy followed by brain removal and sagittal brain dissection with a vibratome or sharp blade to obtain very thin sections through the brain lateral ventricles, where the ependymal cilia can be visualized. Incubation of the brain's slices in a customized glass-bottom plate containing Dulbecco's Modified Eagle's Medium (DMEM)/High-Glucose at 37 °C in the presence of 95%/5% O2/CO2 mixture is essential to keep the tissue alive during the experiment. A video of the cilia beating is then recorded using a high-resolution differential interference contrast microscope. The video is then analyzed frame by frame to calculate the ciliary beating frequency. This allows distinct classification of the ependymal cells into three categories or types based on their ciliary beating frequency and angle. Furthermore, this technique allows the use of high-speed fluorescence imaging analysis to characterize the unique intracellular calcium oscillation properties of ependymal cells as well as the effect of pharmacological agents on the calcium oscillations and the ciliary beating frequency. In addition, this technique is suitable for immunofluorescence imaging for ciliary structure and ciliary protein localization studies. This is particularly important in disease diagnosis and phenotype studies. The main limitation of the technique is attributed to the decrease in live motile cilia movement as the brain tissue starts to die.
多纤毛室管膜细胞排列在成人大脑的脑室中。室管膜纤毛的功能或结构异常与各种神经功能缺损有关。目前用于活动的室管膜纤毛的体外实时成像技术,经过几个步骤后可对纤毛动力学进行详细研究。这些步骤包括:根据托莱多大学机构动物护理和使用委员会(IACUC)的方案,用二氧化碳对小鼠实施安乐死;然后进行颅骨切除术,接着取出大脑,并用振动切片机或锋利刀片进行矢状脑解剖,以获得穿过脑侧脑室的非常薄的切片,在此处可观察到室管膜纤毛。将脑切片置于定制的玻璃底板培养皿中,该培养皿含有杜氏改良 Eagle 培养基(DMEM)/高糖培养基,于 37℃、95%/5% O₂/CO₂ 混合气体环境下孵育,这对于在实验过程中保持组织存活至关重要。然后使用高分辨率微分干涉对比显微镜记录纤毛摆动的视频。接着逐帧分析该视频以计算纤毛摆动频率。这使得能够根据室管膜细胞的纤毛摆动频率和角度将其明确分为三类或三种类型。此外,该技术允许使用高速荧光成像分析来表征室管膜细胞独特的细胞内钙振荡特性,以及药理试剂对钙振荡和纤毛摆动频率的影响。此外,该技术适用于纤毛结构和纤毛蛋白定位研究的免疫荧光成像。这在疾病诊断和表型研究中尤为重要。该技术的主要局限性在于随着脑组织开始死亡,活动的纤毛运动会减少。