Effect of experimental hypoosmolar hyponatremia on the blood brain barrier and brain edema formation.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Blood-Brain Barrier*/metabolism ; Blood-Brain Barrier*/pathology ; Hyponatremia*/metabolism ; Hyponatremia*/complications ; Hyponatremia*/pathology ; Hyponatremia*/chemically induced ; Brain Edema*/metabolism ; Brain Edema*/etiology ; Brain Edema*/pathology; Animals ; Male ; Rats ; Vasopressins ; Claudin-5/genetics ; Claudin-5/metabolism ; Tight Junctions/metabolism ; Deamino Arginine Vasopressin ; Permeability

Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: All animal experiments were performed in accordance with the Law and Regulations on AnimalProtection in Poland (Dz.U. 2015/266) and were approved by the Extramural Second Committee for theCare and Use of Laboratory Animals for Experimental Procedures, National Medicines Institute inWarsaw (WAW2/104/23).
The most frequent cause of hyponatremia is water retention due to the increase in blood levels of antidiuretic hormone (vasopressin, AVP). Hyponatremia is associated with neurological deficits, which are mainly linked to brain edema. Although the cytotoxic mechanism of brain edema in hyponatremia is commonly known, the role of a vasogenic mechanism is ambiguous. The present studies aimed to evaluate the effect of both acute and chronic hyponatremia on brain edema, blood-brain barrier (BBB) permeability, and mRNA expression of the tight junctions. Acute hyponatremia was induced for 5 h by subcutaneous (s.c.) injection of vasopressin or a synthetic analog of vasopressin-desmopressin (dDAVP) with intraperitoneal (i.p.) water loading in the amount of 11% body weight. Chronic hyponatremia was induced for 4 days with the help of AVP or dDAVP released continuously from subcutaneously implanted ALZET mini-osmotic pumps and a liquid diet. Because of the vascular action of vasopressin, either vasopressin or desmopressin was used to induce hyponatremia to assess whether the observed changes were characteristic of AVP-associated hyponatremia or hyponatremia alone. Brain water content was determined using the wet-dry method. BBB permeability was studied using sodium fluorescein. Gene expression of claudin-5, occludin, and zonula occludens (ZO-1) was assessed by real-time PCR (RT-PCR). Osmolarity, Na ⁺ , and Cl ^- concentrations were analyzed using the electrolyte and blood gas analyzer. Hypoosmotic acute hyponatremia led to increased brain water content and downregulation of tight junction gene expression, although leakage of the BBB was not observed. These results, except for the gene expression of claudin-5, were comparable in both groups with acute hyponatremia, regardless of whether AVP or dDAVP induced it. In chronic hyponatremia, irrespective of the mode of induction, there were no changes in the studied parameters. These results demonstrate a new insight into the nature of edema in acute hypoosmotic hyponatremia due to signs of vasogenic edema.
(© 2025. The Author(s).)

J Am Soc Nephrol. 2017 Jun;28(6):1802-1813. (PMID: 28122966)
Am J Physiol Renal Physiol. 2008 Sep;295(3):F619-24. (PMID: 18448591)
J Neurosci Res. 2010 May 15;88(7):1457-74. (PMID: 20025060)
Folia Neuropathol. 2008;46(4):271-7. (PMID: 19169968)
Clin J Am Soc Nephrol. 2018 Apr 6;13(4):641-649. (PMID: 29295830)
Am J Med. 2006 Jan;119(1):71.e1-8. (PMID: 16431193)
PLoS One. 2013;8(2):e56419. (PMID: 23468865)
Am J Med. 2006 Jul;119(7 Suppl 1):S4-11. (PMID: 16843084)
Am J Physiol. 1995 May;268(5 Pt 2):R1143-52. (PMID: 7771574)
J Clin Neurosci. 2018 Dec;58:192-199. (PMID: 30454689)
Endocr J. 2021 Jan 28;68(1):31-43. (PMID: 32879162)
Physiol Res. 2003;52(5):607-14. (PMID: 14535837)
Int J Mol Sci. 2015 Apr 30;16(5):9949-75. (PMID: 25941935)
J Am Soc Nephrol. 2016 Mar;27(3):766-80. (PMID: 26376860)
Am J Physiol. 1983 May;244(5):R724-32. (PMID: 6846578)
Clin Endocrinol (Oxf). 2006 Aug;65(2):246-9. (PMID: 16886968)
AJNR Am J Neuroradiol. 2001 Jun-Jul;22(6):1068-70. (PMID: 11415899)
Physiol Res. 2022 Dec 31;71(S2):S277-S283. (PMID: 36647915)
Kidney Int. 1991 Jun;39(6):1274-82. (PMID: 1895679)
Am J Physiol. 1987 Apr;252(4 Pt 2):F661-9. (PMID: 3565577)
Endocrinology. 2005 Mar;146(3):1254-67. (PMID: 15591143)
N Engl J Med. 2015 Jan 1;372(1):55-65. (PMID: 25551526)
J Endocrinol. 2010 Jul;206(1):105-11. (PMID: 20392812)
Antiviral Res. 2007 Aug;75(2):104-12. (PMID: 17223204)
J Cereb Blood Flow Metab. 2016 Mar;36(3):513-38. (PMID: 26661240)
J Am Soc Nephrol. 1993 Mar;3(9):1600-6. (PMID: 8507816)
J Clin Endocrinol Metab. 2014 Jan;99(1):291-8. (PMID: 24248182)
Hepatology. 2009 Dec;50(6):1914-23. (PMID: 19821483)
Neurologist. 2003 Nov;9(6):290-300. (PMID: 14629783)
CEN Case Rep. 2013 May;2(1):17-22. (PMID: 28509213)
Sci Rep. 2020 Jan 16;10(1):467. (PMID: 31949182)
Am J Med. 1997 Jan;102(1):67-77. (PMID: 9209203)
Cancer Manag Res. 2016 Aug 22;8:105-14. (PMID: 27578998)
J Neurol Neurosurg Psychiatry. 1981 Mar;44(3):216-9. (PMID: 7229644)
Ann Neurol. 1990 Jan;27(1):106-8. (PMID: 2301918)
Hypertension. 2020 Jan;75(1):237-245. (PMID: 31735081)
Exp Neurol. 2002 Dec;178(2):194-206. (PMID: 12504879)
Microcirculation. 2020 Oct;27(7):e12644. (PMID: 32603523)
Exp Neurol. 2005 Mar;192(1):178-83. (PMID: 15698632)
J Am Geriatr Soc. 2013 Oct;61(10):1838-9. (PMID: 24117308)
Acad Emerg Med. 1997 Jul;4(7):662-73. (PMID: 9223688)
Ann Emerg Med. 1990 Oct;19(10):1113-21. (PMID: 2221516)
Liver Int. 2010 Sep;30(8):1087-90. (PMID: 20536717)
Am J Physiol. 1992 May;262(5 Pt 2):H1557-62. (PMID: 1590460)
Clin Endocrinol (Oxf). 2006 Mar;64(3):250-4. (PMID: 16487432)
J Clin Invest. 1990 Oct;86(4):1023-9. (PMID: 2211999)
J Neurosci. 2001 Sep 1;21(17):6967-77. (PMID: 11517284)
Support Care Cancer. 2015 Jun;23(6):1735-40. (PMID: 25433438)
J Clin Diagn Res. 2017 May;11(5):OD10-OD11. (PMID: 28658832)
NMR Biomed. 1993 Mar-Apr;6(2):119-24. (PMID: 8499241)
Ann Neurol. 1985 Feb;17(2):137-40. (PMID: 3977297)
JA Clin Rep. 2020 Oct 1;6(1):74. (PMID: 33001333)
Biochem Biophys Res Commun. 2000 Apr 13;270(2):495-503. (PMID: 10753653)
J Cereb Blood Flow Metab. 1993 Mar;13(2):304-9. (PMID: 8436623)

2021/43/D/NZ4/03304 National Science Centre of Poland

Keywords: BBB; Cytotoxic edema; Hyponatremia; Tight junctions; Vasogenic edema; Vasopressin

11000-17-2 (Vasopressins)
0 (Claudin-5)
ENR1LLB0FP (Deamino Arginine Vasopressin)

Date Created: 20250702 Date Completed: 20250702 Latest Revision: 20250705

20250705

PMC12222756

10.1038/s41598-025-06320-2

40603486