{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:32:39Z","timestamp":1790742759858,"version":"4.1.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":143,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 Ca\u00b2\u207a, Cl\u207b, K\u207a, Mg\u00b2\u207a and Na\u207a. We examined their interrelationships and assessed the impact of blood\u2013brain 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 (P &amp;lt; 0.0001), with no overlapping. Cl\u2212 (+25%), Na+ (+5%) and Mg2+ (+37%) concentrations were higher, while K+ (\u221230%) and Ca2+ (\u221250%) concentrations were lower. Consistent with an independent and active CNS homeostatic control, CSF concentrations of K+, Cl\u2212 or Mg2+ showed no significant correlation with their serum counterparts, while Na+ and Ca2+ displayed moderate associations with serum levels. Moreover, blood\u2013brain barrier permeability had no significant impact on CSF ion concentrations. Small, but significant, age-related declines were observed for Cl\u2212, Mg2+ and Ca2+ in CSF, and circadian fluctuations affected K+, which increased slightly in the afternoon. Minor sex differences were noted, with men exhibiting slightly higher Mg2+ and Ca2+ 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\u2013wake 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.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf201","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T09:42:13Z","timestamp":1747993333000},"source":"Crossref","is-referenced-by-count":18,"title":["Ion concentrations in CSF and serum are differentially and precisely regulated"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6769-4575","authenticated-orcid":false,"given":"Tim","family":"Lyckenvik","sequence":"first","affiliation":[{"name":"Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg , SE-405 30 Gothenburg ,","place":["Sweden"]},{"name":"Department of Neurology, Sahlgrenska University Hospital , SE-413 45 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"My","family":"Forsberg","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg , SE-405 30 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalle","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg , SE-413 45 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Axelsson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sahlgrenska University Hospital , SE-413 45 Gothenburg ,","place":["Sweden"]},{"name":"Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg , SE-413 45 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg , SE-413 45 Gothenburg ,","place":["Sweden"]},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53792 ,","place":["USA"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , SE-431 41 M\u00f6lndal ,","place":["Sweden"]},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"UK Dementia Research Institute at UCL , London NW1 3BT ,","place":["UK"]},{"name":"Hong Kong Center for Neurodegenerative Diseases , Clear Water Bay, Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg , SE-413 45 Gothenburg ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , SE-431 41 M\u00f6lndal ,","place":["Sweden"]},{"name":"Paris Brain Institute, ICM, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Sorbonne University , FR-75013 Paris ,","place":["France"]},{"name":"Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC , Hefei 230001 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2328-5382","authenticated-orcid":false,"given":"Sebastian","family":"Illes","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg , SE-405 30 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontus","family":"Wasling","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sahlgrenska University Hospital , SE-413 45 Gothenburg ,","place":["Sweden"]},{"name":"Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg , SE-413 45 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hanse","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of 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