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. 1996 Apr 1;492(Pt 1):243–255. doi: 10.1113/jphysiol.1996.sp021305

Effects of hypernatraemia in the central nervous system and its therapy in rats and rabbits.

J C Ayus 1, D L Armstrong 1, A I Arieff 1
PMCID: PMC1158877  PMID: 8730599

Abstract

1. We studied the effects of acute (1 or 4 h) and chronic (1 week) hypernatraemia (plasma [Na+], 170-190 mM) on brain histology, and brain water and solute contents in rats and rabbits. 2. In rabbits with acute hypernatraemia, there was significant loss of intracellular brain water, with increases in brain [Na+ + K+], amino acid concentration, and undetermined solute (idiogenic osmole). After 1 week of recovery, brain intracellular water content had returned to normal. 3. In hypernatraemic rats there was myelinolysis of brain white matter, with karyorrhexis and necrosis of neurons. 4. Hypernatraemic rabbits were treated with 77 mM NaCl (i.v.) to normalize plasma [Na+] over 4-24 h intervals. Therapy of either acute or chronic hypernatraemia resulted in significant brain oedema because brain osmolality failed to decrease at the same rate as plasma osmolality. 5. It is concluded that: (a) untreated hypernatraemia results in brain lesions demonstrating myelinolysis and cellular necrosis; (b) normalization of hypernatraemia over 4-24 h results in cerebral oedema, due primarily to failure of brain amino acids and idiogenic osmoles to dissipate as plasma [Na+] is decreased to normal.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ADAMS R. D., VICTOR M., MANCALL E. L. Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients. AMA Arch Neurol Psychiatry. 1959 Feb;81(2):154–172. [PubMed] [Google Scholar]
  2. Arieff A. I., Doerner T., Zelig H., Massry S. G. Mechanisms of seizures and coma in hypoglycemia. Evidence for a direct effect of insulin on electrolyte transport in brain. J Clin Invest. 1974 Sep;54(3):654–663. doi: 10.1172/JCI107803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arieff A. I., Guisado R. Effects on the central nervous system of hypernatremic and hyponatremic states. Kidney Int. 1976 Jul;10(1):104–116. doi: 10.1038/ki.1976.82. [DOI] [PubMed] [Google Scholar]
  4. Arieff A. I., Kleeman C. R. Cerebral edema in diabetic comas. II. Effects of hyperosmolality, hyperglycemia and insulin in diabetic rabbits. J Clin Endocrinol Metab. 1974 Jun;38(6):1057–1067. doi: 10.1210/jcem-38-6-1057. [DOI] [PubMed] [Google Scholar]
  5. Arieff A. I., Kleeman C. R., Keushkerian A., Bagdoyan H. Brain tissue osmolality: method of determination and variations in hyper- and hypo-osmolar states. J Lab Clin Med. 1972 Feb;79(2):334–343. [PubMed] [Google Scholar]
  6. Arieff A. I., Kleeman C. R. Studies on mechanisms of cerebral edema in diabetic comas. Effects of hyperglycemia and rapid lowering of plasma glucose in normal rabbits. J Clin Invest. 1973 Mar;52(3):571–583. doi: 10.1172/JCI107218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Arieff A. I., Kozniewska E., Roberts T. P., Vexler Z. S., Ayus J. C., Kucharczyk J. Age, gender, and vasopressin affect survival and brain adaptation in rats with metabolic encephalopathy. Am J Physiol. 1995 May;268(5 Pt 2):R1143–R1152. doi: 10.1152/ajpregu.1995.268.5.R1143. [DOI] [PubMed] [Google Scholar]
  8. Ayus J. C., Krothapalli R. K., Arieff A. I. Treatment of symptomatic hyponatremia and its relation to brain damage. A prospective study. N Engl J Med. 1987 Nov 5;317(19):1190–1195. doi: 10.1056/NEJM198711053171905. [DOI] [PubMed] [Google Scholar]
  9. Ayus J. C., Krothapalli R. K., Armstrong D. L., Norton H. J. Symptomatic hyponatremia in rats: effect of treatment on mortality and brain lesions. Am J Physiol. 1989 Jul;257(1 Pt 2):F18–F22. doi: 10.1152/ajprenal.1989.257.1.F18. [DOI] [PubMed] [Google Scholar]
  10. Banister A., Matin-Siddiqi S. A., Hatcher G. W. Treatment of hypernatraemic dehydration in infancy. Arch Dis Child. 1975 Mar;50(3):179–186. doi: 10.1136/adc.50.3.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Clark W. R. Diffuse demyelinating lesions of the brain after the rapid development of hypernatremia. West J Med. 1992 Nov;157(5):571–573. [PMC free article] [PubMed] [Google Scholar]
  12. Cserr H. F., DePasquale M., Nicholson C., Patlak C. S., Pettigrew K. D., Rice M. E. Extracellular volume decreases while cell volume is maintained by ion uptake in rat brain during acute hypernatremia. J Physiol. 1991 Oct;442:277–295. doi: 10.1113/jphysiol.1991.sp018793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. De Villota E. D., Cavanilles J. M., Stein L., Shubin H., Weil M. H. Hyperosmolal crisis following infusion of hypertonic sodium chloride for purposes of therapeutic abortion. Am J Med. 1973 Jul;55(1):116–122. doi: 10.1016/0002-9343(73)90158-7. [DOI] [PubMed] [Google Scholar]
  14. FINBERG L., KILEY J., LUTTRELL C. N. Mass accidental salt poisoning in infancy. A study of a hospital disaster. JAMA. 1963 Apr 20;184:187–190. doi: 10.1001/jama.1963.03700160063009. [DOI] [PubMed] [Google Scholar]
  15. FINBERG L., LUTTRELL C., REDD H. Pathogenesis of lesions in the nervous system in hypernatremic states. II. Experimental studies of gross anatomic changes and alterations of chemical composition of the tissues. Pediatrics. 1959 Jan;23(1 Pt 1):46–53. [PubMed] [Google Scholar]
  16. Heilig C. W., Stromski M. E., Blumenfeld J. D., Lee J. P., Gullans S. R. Characterization of the major brain osmolytes that accumulate in salt-loaded rats. Am J Physiol. 1989 Dec;257(6 Pt 2):F1108–F1116. doi: 10.1152/ajprenal.1989.257.6.F1108. [DOI] [PubMed] [Google Scholar]
  17. Hogan G. R., Dodge P. R., Gill S. R., Master S., Sotos J. F. Pathogenesis of seizures occurring during restoration of plasma tonicity to normal in animals previously chronically hypernatremic. Pediatrics. 1969 Jan;43(1):54–64. [PubMed] [Google Scholar]
  18. Hogan G. R., Dodge P. R., Gill S. R., Pickering L. K., Master S. The incidence of seizures after rehydration of hypernatremic rabbits with intravenous or ad libitum oral fluids. Pediatr Res. 1984 Apr;18(4):340–345. doi: 10.1203/00006450-198404000-00007. [DOI] [PubMed] [Google Scholar]
  19. LUTTRELL C. N., FINBERG L. Hemorrhagic encephalopathy induced by hypernatremia. I. Clinical, laboratory, and pathological observations. AMA Arch Neurol Psychiatry. 1959 Apr;81(4):424–432. doi: 10.1001/archneurpsyc.1959.02340160022004. [DOI] [PubMed] [Google Scholar]
  20. Levin V. A., Fenstermacher J. D., Patlak C. S. Sucrose and inulin space measurements of cerebral cortex in four mammalian species. Am J Physiol. 1970 Nov;219(5):1528–1533. doi: 10.1152/ajplegacy.1970.219.5.1528. [DOI] [PubMed] [Google Scholar]
  21. Lien Y. H., Shapiro J. I., Chan L. Effects of hypernatremia on organic brain osmoles. J Clin Invest. 1990 May;85(5):1427–1435. doi: 10.1172/JCI114587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lockwood A. H. Acute and chronic hyperosmolality. Effects on cerebral amino acids and energy metabolism. Arch Neurol. 1975 Jan;32(1):62–64. doi: 10.1001/archneur.1975.00490430084018. [DOI] [PubMed] [Google Scholar]
  23. Macaulay D., Watson M. Hypernatraemia in infants as a cause of brain damage. Arch Dis Child. 1967 Oct;42(225):485–491. doi: 10.1136/adc.42.225.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McKee A. C., Winkelman M. D., Banker B. Q. Central pontine myelinolysis in severely burned patients: relationship to serum hyperosmolality. Neurology. 1988 Aug;38(8):1211–1217. doi: 10.1212/wnl.38.8.1211. [DOI] [PubMed] [Google Scholar]
  25. Morris-Jones P. H., Houston I. B., Evans R. C. Prognosis of the neurological complications of acute hypernatraemia. Lancet. 1967 Dec 30;2(7531):1385–1389. doi: 10.1016/s0140-6736(67)93022-x. [DOI] [PubMed] [Google Scholar]
  26. SCHOOLMAN H. M., DUBIN A., HOFFMAN W. S. Clinical syndromes associated with hypernatremia. AMA Arch Intern Med. 1955 Jan;95(1):15–23. doi: 10.1001/archinte.1955.00250070031003. [DOI] [PubMed] [Google Scholar]
  27. Simmons M. A., Adcock E. W., 3rd, Bard H., Battaglia F. C. Hypernatremia and intracranial hemorrhage in neonates. N Engl J Med. 1974 Jul 4;291(1):6–10. doi: 10.1056/NEJM197407042910102. [DOI] [PubMed] [Google Scholar]
  28. Smith R. J., Block M. R., Arieff A. I., Blumenkrantz M. J., Coburn J. W. Hypernatremic, hyperosmolar coma complicating chronic peritoneal dialysis. Proc Clin Dial Transplant Forum. 1974;(4):96–99. [PubMed] [Google Scholar]
  29. Snyder N. A., Feigal D. W., Arieff A. I. Hypernatremia in elderly patients. A heterogeneous, morbid, and iatrogenic entity. Ann Intern Med. 1987 Sep;107(3):309–319. doi: 10.7326/0003-4819-107-2-309. [DOI] [PubMed] [Google Scholar]
  30. Vexler Z. S., Ayus J. C., Roberts T. P., Fraser C. L., Kucharczyk J., Arieff A. I. Hypoxic and ischemic hypoxia exacerbate brain injury associated with metabolic encephalopathy in laboratory animals. J Clin Invest. 1994 Jan;93(1):256–264. doi: 10.1172/JCI116953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. ZIERLER K. L. Hyperosmolarity in adults: a critical review. J Chronic Dis. 1958 Jan;7(1):1–23. doi: 10.1016/0021-9681(58)90180-2. [DOI] [PubMed] [Google Scholar]

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