Department of Pathology, Rush University Medical Center, Chicago, Illinois, USA.
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
NMR Biomed. 2024 Sep;37(9):e5149. doi: 10.1002/nbm.5149. Epub 2024 Apr 7.
The central nervous system (CNS) lacks traditionally defined lymphatic vasculature. However, CNS tissues and barriers compartmentalize the brain, spinal cord, and adjacent spaces, facilitating the transmittal of fluids, metabolic wastes, immune cells, and vital signals, while more conventional lymphatic pathways in the meninges, cervicofacial and paraspinal regions transmit efflux fluid and molecules to peripheral lymph and lymph nodes. Thus, a unique and highly organized fluid circulation network encompassing intraparenchymal, subarachnoid, dural, and extradural segments functions in unison to maintain CNS homeostasis. Pathways involved in this system have been under investigation for centuries and continue to be the source of considerable interest and debate. Modern imaging and microscopy technologies have led to important breakthroughs pertaining to various elements of CNS fluid circuitry and exchange over the past decade, thus enhancing knowledge on mechanisms of mammalian CNS maintenance and disease. Yet, to better understand precise anatomical routes, the physiology and clinical significance of these CNS pathways, and potential therapeutic targets in humans, fluid conduits, flow-regulating factors, and tissue effects must be analyzed systematically and in a global manner in persons across age, demographical factors, and disease states. Here, we illustrate the system-wide nature of intermixing CNS fluid networks, summarize historical and clinical studies, and discuss anatomical and physiological similarities and differences that are relevant for translation of evidence from mice to humans. We also review Cushing's classical model of cerebrospinal fluid flow and present a new framework of this "third circulation" that emphasizes previously unexplained complexities of CNS fluid circulation in humans. Finally, we review future directions in the field, including emerging theranostic techniques and MRI studies required in humans.
中枢神经系统（CNS）缺乏传统定义的脉管系统。然而，CNS 组织和屏障将大脑、脊髓和相邻空间分隔开，促进了流体、代谢废物、免疫细胞和重要信号的传递，而脑膜、颈面部和脊柱旁区域的更传统的淋巴途径则将流出液和分子输送到外周淋巴和淋巴结。因此，一个独特而高度组织化的流体循环网络，包括脑实质内、蛛网膜下腔、硬脑膜和硬膜外段，协同作用以维持 CNS 内环境稳定。该系统涉及的途径已经研究了几个世纪，并且仍然是相当大的兴趣和争论的来源。在过去十年中，现代成像和显微镜技术在 CNS 流体电路和交换的各个方面取得了重要突破，从而增强了对哺乳动物 CNS 维持和疾病机制的认识。然而，为了更好地了解这些 CNS 途径的精确解剖途径、生理学和临床意义以及人类中的潜在治疗靶点，必须系统地和全面地分析流体导管、流量调节因子和组织效应。在这里，我们展示了 CNS 混合流体网络的系统性质，总结了历史和临床研究，并讨论了与将证据从小鼠转化为人类相关的解剖学和生理学上的相似性和差异。我们还回顾了库欣（Cushing）关于脑脊液流动的经典模型，并提出了一个新的框架，强调了人类 CNS 流体循环以前未被解释的复杂性。最后，我们回顾了该领域的未来方向，包括新兴的治疗技术和人类所需的 MRI 研究。
