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 intracelluar 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 [Nae] 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.Hypernatraemia is a common clinical condition which tends to affect individuals at the extremes of age -children and the elderly -and frequently leads to central nervous system damage or death. Plasma Na+ levels associated with brain damage in hypernatraemic patients have been in the range 160-190 mm (Zierler, 1958;Finberg, Kiley & Luttrell, 1963;Morris-Jones, Houston & Evans, 1967; Snyder, Feigal & Arieff, 1987). Previous studies on animals from both our laboratory and others suggest that central nervous system damage or death can occur as a consequence of untreated hypernatraemia (Finberg et al. 1963;Morris-Jones et al. 1967;De Villota, Cavanilles & Stein, 1973; Simmons, Adcock, Bard & Battaglia, 1974;Snyder et al. 1987), but the mechanisms responsible are unclear.Improper therapy of hypernatraemia can also produce brain dysfunction, neurological deterioration and death (Lutrell & Finberg, 1959;Hogan, Dodge & Gill, 1969 METHODS Studies in rabbitsThe experimental protocol was approved by the Animal Studies Subcommittee (Veterans Administration Medical Center, San Francisco, CA, USA). Rabbits were used to study the effects of hypernatraemia on brain water and solute content because in this species grey matter can be readily isolated, and also because of our substantial experience in brain analysis using rabbit models of fluid and electrolyte disorders (Arieff, Doerner, Zelig & Massry, 1974a;Arieff, Kleeman, Keushkerian & Bagdoyan, 1974b). Studies were carried out on New Zealand White rabbits (3-4 kg) of both genders, in which hypernatraemia was induced either acutely for periods of 1 or 4 h, or chronically for 7 days. Hypernatraemic rabbits were then treated over intervals of 4-24 h, to return the plasma [Na+] to normal values (below 150 mM). The following goups of rabbits were studied. Group I: effects of acute untreated hypernatraem...
Hypoxia appears to be a prominent component of brain damage among patients with hyponatremic encephalopathy. Effects of hypoxia on brain in the presence of hyponatremia are not known. In order to evaluate the contributions of hypoxia to brain damage, three separate experiments were conducted in three groups of rodents. Experiment I evaluated the effects of hypoxia and acute (< 4 h) hyponatremia (plasma Na < 120 mmol/l) on brain adaptation in rabbits. Experiment II evaluated the effects of hypoxia and chronic (4 days) hyponatremia on cerebral perfusion in rats. Experiment III evaluated the effects of hypoxia and chronic hyponatremia on brain histology in rats. In experiment I, rabbits with acute hyponatremia demonstrated brain adaptation with significant falls in brain Na content (by 14.2%, P < 0.01) and osmolality (by 8.3%, P < 0.01), and a rise in brain water (by 10.6%, P < 0.05). Rabbits with combined hypoxia and hyponatremia failed to demonstrate brain adaptation. In experiment II, rats with chronic hyponatremia plus hypoxia had a decrease in cerebral perfusion index by more than 50% (P < 0.01). In experiment III, 23% of hypoxic rats had brain lesions, which were in the cerebellum, thalamus, reticular formation, and basal ganglia. Hyponatremia without hypoxia resulted in no brain lesions. Hypoxia in normonatremic animals results in cerebral edema and histopathologic lesions similar to those found in rats whose plasma Na was overcorrected. Hypoxia in hyponatremic animals aggravates cerebral edema, impairs brain adaptation, and decreases cerebral perfusion.
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