Lyckenvik Tim, Forsberg My, Johansson Kalle, Axelsson Markus, Zetterberg Henrik, Blennow Kaj, Illes Sebastian, Wasling Pontus, Hanse Eric
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Department of Neurology, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
Brain Commun. 2025 May 24;7(3):fcaf201. doi: 10.1093/braincomms/fcaf201. eCollection 2025.
Fluctuations of extracellular brain ion concentrations have been associated with transitions between brain states such as sleep and wakefulness, and disturbances have been implicated in a variety of neurological conditions, including dementia, epilepsy and migraine. This study aims to define the normal CSF ion profile and identify key factors influencing its regulation. In this cross-sectional study, we analysed samples from 42 individuals (16 men), including 28 healthy participants and 14 patients with medically unexplained neurological symptoms. Age spanned between 20 and 55 years. Using validated clinical assays, we measured paired CSF and serum concentrations of Ca²⁺, Cl⁻, K⁺, Mg²⁺ and Na⁺. We examined their interrelationships and assessed the impact of blood-brain barrier permeability (the albumin quotient), age, sampling time and sex. CSF ion concentrations were highly stable and maintained within distinct, narrow ranges, separate from serum ranges for all ions measured ( < 0.0001), with no overlapping. Cl (+25%), Na (+5%) and Mg (+37%) concentrations were higher, while K (-30%) and Ca (-50%) concentrations were lower. Consistent with an independent and active CNS homeostatic control, CSF concentrations of K, Cl or Mg showed no significant correlation with their serum counterparts, while Na and Ca displayed moderate associations with serum levels. Moreover, blood-brain barrier permeability had no significant impact on CSF ion concentrations. Small, but significant, age-related declines were observed for Cl, Mg and Ca in CSF, and circadian fluctuations affected K, which increased slightly in the afternoon. Minor sex differences were noted, with men exhibiting slightly higher Mg and Ca levels. Our findings demonstrate that CSF ion concentrations are precisely regulated at the barriers of the CNS, largely independent of serum levels and with low interindividual variation, reinforcing the concept of a highly controlled CNS environment. This distinct ion composition may help modulate neuronal excitability, supporting brain state transitions such as sleep-wake cycling. Identification of hydration status as a potential confounding factor suggests that normalization to CSF-Na may improve the detection of pathological disruptions in CSF ion homeostasis. These insights reinforce the foundation for using CSF ion profiles as biomarkers for neurological disorders.
细胞外脑离子浓度的波动与睡眠和觉醒等脑状态之间的转换有关，而干扰则与包括痴呆、癫痫和偏头痛在内的多种神经系统疾病有关。本研究旨在确定正常的脑脊液离子谱，并确定影响其调节的关键因素。在这项横断面研究中，我们分析了42名个体（16名男性）的样本，包括28名健康参与者和14名有医学上无法解释的神经症状的患者。年龄跨度为20至55岁。我们使用经过验证的临床检测方法，测量了脑脊液和血清中Ca²⁺、Cl⁻、K⁺、Mg²⁺和Na⁺的配对浓度。我们检查了它们之间的相互关系，并评估了血脑屏障通透性（白蛋白商）、年龄、采样时间和性别的影响。脑脊液离子浓度高度稳定，并维持在不同的狭窄范围内，与所有测量离子的血清范围分开（<0.0001），没有重叠。Cl（+25%）、Na（+5%）和Mg（+37%）的浓度较高，而K（-30%）和Ca（-50%）的浓度较低。与独立且活跃的中枢神经系统稳态控制一致，脑脊液中K、Cl或Mg的浓度与其血清对应物无显著相关性，而Na和Ca与血清水平呈中度关联。此外，血脑屏障通透性对脑脊液离子浓度无显著影响。在脑脊液中观察到Cl、Mg和Ca与年龄相关的小幅但显著的下降，昼夜波动影响K，K在下午略有增加。注意到了微小的性别差异，男性的Mg和Ca水平略高。我们的研究结果表明，脑脊液离子浓度在中枢神经系统的屏障处受到精确调节，很大程度上独立于血清水平，个体间差异较小，强化了中枢神经系统环境高度受控的概念。这种独特的离子组成可能有助于调节神经元兴奋性，支持睡眠-觉醒循环等脑状态转换。将水合状态确定为潜在的混杂因素表明，将脑脊液-Na标准化可能会改善脑脊液离子稳态病理破坏的检测。这些见解强化了将脑脊液离子谱用作神经系统疾病生物标志物的基础。
