Department of Neurosurgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China.
School of Pharmacy, China Medical University, Shenyang, 110122, China.
Fluids Barriers CNS. 2022 Dec 15;19(1):101. doi: 10.1186/s12987-022-00382-4.
Cerebrospinal fluid (CSF) is an essential and critical component of the central nervous system (CNS). According to the concept of the "third circulation" originally proposed by Cushing, CSF is mainly produced by the choroid plexus and subsequently leaves the cerebral ventricles via the foramen of Magendie and Luschka. CSF then fills the subarachnoid space from whence it disperses to all parts of the CNS, including the forebrain and spinal cord. CSF provides buoyancy to the submerged brain, thus protecting it against mechanical injury. CSF is also transported via the glymphatic pathway to reach deep interstitial brain regions along perivascular channels; this CSF clearance pathway promotes transport of energy metabolites and signaling molecules, and the clearance of metabolic waste. In particular, CSF is now intensively studied as a carrier for the removal of proteins implicated in neurodegeneration, such as amyloid-β and tau. Despite this key function of CSF, there is little information about its production rate, the factors controlling CSF production, and the impact of diseases on CSF flux. Therefore, we consider it to be a matter of paramount importance to quantify better the rate of CSF production, thereby obtaining a better understanding of CSF dynamics. To this end, we now review the existing methods developed to measure CSF production, including invasive, noninvasive, direct, and indirect methods, and MRI-based techniques. Depending on the methodology, estimates of CSF production rates in a given species can extend over a ten-fold range. Throughout this review, we interrogate the technical details of CSF measurement methods and discuss the consequences of minor experimental modifications on estimates of production rate. Our aim is to highlight the gaps in our knowledge and inspire the development of more accurate, reproducible, and less invasive techniques for quantitation of CSF production.
脑脊液（CSF）是中枢神经系统（CNS）的重要关键组成部分。根据 Cushing 最初提出的“第三循环”概念，CSF 主要由脉络丛产生，随后通过 Magendie 和 Luschka 孔离开侧脑室。CSF 随后充满蛛网膜下腔，从那里分散到 CNS 的所有部位，包括大脑前脑和脊髓。CSF 为浸没的大脑提供浮力，从而保护其免受机械损伤。CSF 还通过神经胶质途径运输，以沿着血管周围通道到达深部脑间质区域；这种 CSF 清除途径促进能量代谢物和信号分子的运输，以及代谢废物的清除。特别是，CSF 现在作为一种载体被深入研究，用于清除与神经退行性变有关的蛋白质，如淀粉样β和 tau。尽管 CSF 具有这种关键功能，但关于其产生率、控制 CSF 产生的因素以及疾病对 CSF 流量的影响的信息很少。因此，我们认为更好地量化 CSF 产生率是至关重要的，从而更好地了解 CSF 动力学。为此，我们现在回顾了用于测量 CSF 产生的现有方法，包括侵入性、非侵入性、直接和间接方法以及基于 MRI 的技术。根据方法学，在给定物种中 CSF 产生率的估计值可以相差十倍。在本综述中，我们检查了 CSF 测量方法的技术细节，并讨论了实验修改对产生率估计的影响。我们的目的是突出我们知识中的差距，并激发开发更准确、可重复和侵入性较小的 CSF 产生定量技术。
