| Co-Investigator(Kenkyū-buntansha) |
SHOJI Masaru Tohoku University, Dept.of Medicine, Research Associate, 医学部, 助手 (10226300)
KIMURA Tokihisa Tohoku University, Dept.of Medicine, Asso.Professor, 医学部, 助教授 (00004945)
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| Research Abstract |
In order to clarify the roles of active amino acid (AA) and nitric oxides (NO) in the osmotic demyelination, which is well known to be occurred in patients with chronic severe hyponatremia and with acute correction of the hyponatremia, we mesured brain AA and NO of the SIADH rat by microdialysis (MD) method.
Materials and Methods : Sprague Dawley rats, aged 10 weeks, were used. DDAVP was continuously given for 7days using osmotic minipump to make SIADH rats. At 6 days, MD probe was inserted into rat striatum. Next day, MD probe was perfused with Ringer's solution in conscious state during hypertonic saline infusion for 60 mm through the femoral vein catheter. 7 days more after, brain was perfused and fixed for histological examination.
Results : At 2nd day, hypotonic hyponatremia was established and continued during 7 days. Hypertonic saline infusion corrected the hyponatremia within 60 min. At the hyponatrmic state, stimulatory AAs, Glutamate and Glycine, and NO were increased in the perfusates, On the other hand, inhibitory AA, GABA, was decreased. After the hypertonic saline infusion, Glutamate and Glycine, and NO were clearly decreased, but GABA was not significantly changed. In histological examination, central myelinolysis in the midbrain and pons was observed in these rats.
Discussion : It is demonstrated that chronic hyponatremia increased stimulatory AAs, Glutamate and Glycine, and neurotoxic NO in the brain. Acute correction of the hypoosmolality reduced these increase. Moreover, inhibitory AA, GABA, was decreased and not changed by osmotic correction. In conclusion, it is suggested that acute changes in the activity of Glutamate and Glycine neuron and neurotoxic NO, at least partly induced by Glutamate through the NMDA receptors, may play active roles in the development of osmotic demyelination during hyponatremic state and its correction.
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