Ion Concentrations in CSF and Serum are Differentially and Precisely Regulated

Background Disturbances in brain ion concentrations have been implicated in the regulation of brain states such as sleep and wakefulness, as well as in a variety of neurological conditions, including dementia, epilepsy, and migraine. Despite this, studies specifically characterizing normal cerebrospinal fluid (CSF) ion composition are generally lacking. Methods We quantify the normal human CSF ion composition in this non-interventional, cross-sectional, retrospective study using paired CSF and serum concentrations of Ca²⁺, Cl⁻, K⁺, Mg²⁺, and Na⁺ measured in healthy young to middle-aged volunteers (n = 28) and patients without neurological disease (n = 14). Relationships with variables such as albumin quotient, age, sampling time, and sex were analyzed. Group differences were assessed using the Kruskal-Wallis and Mann-Whitney U tests, while correlations were examined with Spearman's rank correlation coefficient. Results CSF ion concentrations were significantly different from serum for all ions measured (P < 0.0001). Cl ⁻ (+ 25%), Na ⁺ (+ 5%) and Mg ²⁺ (+ 37%) concentrations were higher, while K ⁺ (-30%) and Ca ²⁺ (-50%) concentrations were lower. These differences were consistent with no overlap between serum and CSF concentrations. There was a trend toward higher ion concentrations in samples collected later in the day and in men, but no significant correlation with the albumin quotient. Conclusions The distinct ion composition of CSF, compared to serum, may establish a low baseline neuronal excitability, allowing for controlled modulation by neuromodulators without leading to pathological hyperexcitability. This might offer new insights for targeting neurological diseases associated with disrupted ion homeostasis.