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Cerebrospinal fluid sodium rhythms

Harrington, Michael G. and Salomon, Ronald M. and Pogoda, Janice M. and Oborina, Elena and Okey, Neil and Johnson, Benjamin and Schmidt, Dennis and Fonteh, Alfred N. and Dalleska, Nathan F. (2010) Cerebrospinal fluid sodium rhythms. Cerebrospinal Fluid Research, 7 . Art. No. 3. ISSN 1743-8454. PMCID PMC2822736.

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Background: Cerebrospinal fluid (CSF) sodium levels have been reported to rise during episodic migraine. Since migraine frequently starts in early morning or late afternoon, we hypothesized that natural sodium chronobiology may predispose susceptible persons when extracellular CSF sodium increases. Since no mammalian brain sodium rhythms are known, we designed a study of healthy humans to test if cation rhythms exist in CSF. Methods: Lumbar CSF was collected every ten minutes at 0.1 mL/min for 24 h from six healthy participants. CSF sodium and potassium concentrations were measured by ion chromatography, total protein by fluorescent spectrometry, and osmolarity by freezing point depression. We analyzed cation and protein distributions over the 24 h period and spectral and permutation tests to identify significant rhythms. We applied the False Discovery Rate method to adjust significance levels for multiple tests and Spearman correlations to compare sodium fluctuations with potassium, protein, and osmolarity. Results: The distribution of sodium varied much more than potassium, and there were statistically significant rhythms at 12 and 1.65 h periods. Curve fitting to the average time course of the mean sodium of all six subjects revealed the lowest sodium levels at 03.20 h and highest at 08.00 h, a second nadir at 09.50 h and a second peak at 18.10 h. Sodium levels were not correlated with potassium or protein concentration, or with osmolarity. Conclusion: These CSF rhythms are the first reports of sodium chronobiology in the human nervous system. The results are consistent with our hypothesis that rising levels of extracellular sodium may contribute to the timing of migraine onset. The physiological importance of sodium in the nervous system suggests that these rhythms may have additional repercussions on ultradian functions.

Item Type:Article
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URLURL TypeDescription CentralArticle
Harrington, Michael G.0000-0002-7923-8032
Dalleska, Nathan F.0000-0002-2059-1587
Additional Information:© 2010 Harrington et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 22 September 2009; Accepted: 20 January 2010; Published: 20 January 2010. This research was supported at HMRI by the NIH, the Norris, Lucas Brothers, Glide, and Hezlep foundations. GCRC work was supported in part by Vanderbilt CTSA grant 1 UL1 RR024975 from the National Center for Research Resources, National Institutes of Health. We are indebted to our study participants for their altruism. Authors’ contributions: MGH conceived and designed the project, analyzed all data, and wrote the initial manuscript. RMS designed the CSF collections, analyzed all data, and participated in manuscript revisions. JMP oversaw all statistical analyses, and participated in manuscript revisions. NFD and EO designed the ion chromatography methods and performed cation analyses. NO carried out cation analyses. BJ performed all intrathecal cannulations. DS carried out all preliminary CSF retrievals. ANF contributed to manuscript revisions. All authors read and approved the final manuscript. The authors declare that they have no competing interests.
Funding AgencyGrant Number
Norris FoundationUNSPECIFIED
Hezlep FoundationUNSPECIFIED
NIH1 UL1 RR024975
Lucas Brothers FoundationUNSPECIFIED
Glide FoundationUNSPECIFIED
PubMed Central ID:PMC2822736
Record Number:CaltechAUTHORS:20131107-141916099
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Official Citation:Harrington et al.: Cerebrospinal fluid sodium rhythms. Cerebrospinal Fluid Research 2010 7:3
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:42313
Deposited By: Tony Diaz
Deposited On:07 Nov 2013 22:34
Last Modified:03 Oct 2019 05:57

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