Background: Brain damage (myelinolysis) develops in hyponatraemia after a large increase in serum sodium regardless of the currently available methods of correction. However, a preliminary study suggests that treatment of hyponatraemia with urea limits the risks of brain lesions in rats. Benefits of sustained high blood levels of urea and mechanisms of protection remain hypothetical.
Methods: In the first part of the study, hyponatraemic rats received repeated (i.p.) doses of urea (2 g/kg b.w./6 h) leading to sustained blood levels (urea+/-230 mg/dl). Neurologic outcome was compared to correction of hyponatraemia by water diuresis. In the second part of the study, we analysed the adaptative response of the brain to correction of hyponatraemia with either urea or water diuresis, by measurement of cerebral osmolyte contents.
Results: Despite a large correction of the serum sodium (mean Delta SNa=32 mEq/l/24 h), mortality rate (13%) and neurological symptoms were low in the urea-treated group contrary to control groups treated by water diuresis (mortality: 87%). This shows with stronger evidence the protective effect of urea against brain myelinolysis. In the second part, analysis of brain composition shows that, in the urea groups, 24 h after correction, intracerebral hyperionization (NaCl) was avoided and brain water contents remained normal. No significant changes of the major brain organic osmolyte composition were observed after urea administration except reaccumulation of betaine. No difference in brain composition was noted regarding concomitant plasma urea levels (>or<150 mg/dl). In rats treated by water diuresis, the brain remained also significantly depleted in organic osmolytes 24 h after correction, but contrary to administration of urea, this treatment was associated with a high mortality rate.
Conclusions: These comparative results suggest a specific brain-protective effect of urea itself against myelinolysis.