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

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.