Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.
Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey.
Fluids Barriers CNS. 2020 Dec 11;17(1):72. doi: 10.1186/s12987-020-00234-z.
Hydrocephalus, the pathological expansion of the cerebrospinal fluid (CSF)-filled cerebral ventricles, is a common, deadly disease. In the adult, cardiac and respiratory forces are the main drivers of CSF flow within the brain ventricular system to remove waste and deliver nutrients. In contrast, the mechanics and functions of CSF circulation in the embryonic brain are poorly understood. This is primarily due to the lack of model systems and imaging technology to study these early time points. Here, we studied embryos of the vertebrate Xenopus with optical coherence tomography (OCT) imaging to investigate in vivo ventricular and neural development during the onset of CSF circulation.
Optical coherence tomography (OCT), a cross-sectional imaging modality, was used to study developing Xenopus tadpole brains and to dynamically detect in vivo ventricular morphology and CSF circulation in real-time, at micrometer resolution. The effects of immobilizing cilia and cardiac ablation were investigated.
In Xenopus, using OCT imaging, we demonstrated that ventriculogenesis can be tracked throughout development until the beginning of metamorphosis. We found that during Xenopus embryogenesis, initially, CSF fills the primitive ventricular space and remains static, followed by the initiation of the cilia driven CSF circulation where ependymal cilia create a polarized CSF flow. No pulsatile flow was detected throughout these tailbud and early tadpole stages. As development progressed, despite the emergence of the choroid plexus in Xenopus, cardiac forces did not contribute to the CSF circulation, and ciliary flow remained the driver of the intercompartmental bidirectional flow as well as the near-wall flow. We finally showed that cilia driven flow is crucial for proper rostral development and regulated the spatial neural cell organization.
Our data support a paradigm in which Xenopus embryonic ventriculogenesis and rostral brain development are critically dependent on ependymal cilia-driven CSF flow currents that are generated independently of cardiac pulsatile forces. Our work suggests that the Xenopus ventricular system forms a complex cilia-driven CSF flow network which regulates neural cell organization. This work will redirect efforts to understand the molecular regulators of embryonic CSF flow by focusing attention on motile cilia rather than other forces relevant only to the adult.
脑积水是脑脊液（CSF）充满脑室内病理性扩张的一种常见致命疾病。在成人中，心脏和呼吸力是脑室内 CSF 流动的主要驱动力，以清除废物并输送营养物质。相比之下，胚胎大脑中 CSF 循环的力学和功能还知之甚少。这主要是由于缺乏模型系统和成像技术来研究这些早期时间点。在这里，我们使用光学相干断层扫描（OCT）成像研究了脊椎动物非洲爪蟾的胚胎，以研究 CSF 循环开始时脑室和神经发育的体内情况。
光学相干断层扫描（OCT）是一种横截面成像方式，用于研究非洲爪蟾蝌蚪大脑的发育，并实时动态检测体内脑室形态和 CSF 循环，分辨率达到微米级。研究了固定纤毛和心脏消融的影响。
在非洲爪蟾中，我们使用 OCT 成像表明，可以在整个发育过程中跟踪脑室发生，直到变态开始。我们发现，在非洲爪蟾胚胎发育过程中，最初 CSF 充满原始脑室空间并保持静止，随后纤毛驱动 CSF 循环开始，室管膜纤毛产生极化 CSF 流动。在这些尾部芽和早期蝌蚪阶段都没有检测到脉动流。随着发育的进行，尽管非洲爪蟾出现脉络丛，但心脏力并未促进 CSF 循环，纤毛流仍然是腔室间双向流动和近壁流动的驱动力。我们最后表明，纤毛驱动的流动对于正确的头部发育至关重要，并调节了空间神经细胞组织。
我们的数据支持这样一种观点，即非洲爪蟾胚胎脑室发生和头部大脑发育严重依赖于由纤毛驱动的 CSF 流动，而这种流动是独立于心脏搏动产生的。我们的工作表明，非洲爪蟾脑室系统形成了一个复杂的纤毛驱动 CSF 流动网络，调节神经细胞组织。这项工作将通过将注意力集中在运动纤毛上，而不是仅关注与成人相关的其他力，来重新引导人们努力了解胚胎 CSF 流动的分子调节。
