ROLE OF ORGANIC OSMOLYTES IN MYELINOLYSIS - A TOPOGRAPHIC STUDY IN RATS AFTER RAPID CORRECTION OF HYPONATREMIA

Organic osmolytes have been implicated in the pathogenesis of myelinol ysis because some of them are accumulated slowly during correction of chronic hyponatremia, I investigated whether there was a topographic c orrelation between demyelinative lesions and the regional changes of o rganic osmolytes after rapid correction of chronic hyponatremia, In no rmal female Sprague-Dawley rats, concentrations of glutamate, glutamin e, taurine, and betaine were highest in the cerebral cortex and decrea sed toward the brain stem, Conversely, glycine level was highest in th e brainstem, and decreased toward the cortex, Myoinositol, glycerophos phorylcholine, glycerophosphorylethanolamine, and creatine were distri buted more evenly, In chronic hyponatremic rats (plasma Na 110+/-4 meq /liter), organic osmolytes decreased globally with the total loss rang ing from 13 (medulla) to 24 (cerebellum) mmol/kg H2O. After rapid corr ection with intraperitoneal injection of hypertonic saline, the recove ry of the loss of organic osmolytes was 48% in the cerebral cortex, ce rebellum, and medulla oblongata, 44% in pens, but only 17% in midbrain and 36% in striatum, Histopathology of the brain was examined in nine rats 2-7 d after correction of hyponatremia. Large demyelinative lesi ons were seen persistently in the midbrain and striatum, and smaller l esions in cerebrum, cerebellum, and pens were found less frequently, T his is the first report of regional distribution of brain organic osmo lytes, After rapid correction of chronic hyponatremia, a topographic c orrelation between demyelination lesions and delayed accumulation of o rganic osmolytes exists.