Hyponatremia is among the most comon conditions found in clinical medicine. The main goal of this project is to study the effect on the brain of the adaptation to acute and chronic hyponatremia, and the brain's response to correction of hyponatremia. We have shown in a rat model that rapid increases in plasma sodium concentration or plasma osmolality can disrupt the blood-brain barrier (BBB); that this disruption occurs at a lower plasma osmolality in chronic hyponatremic rats than in normonatremic controls; that a rapid increase in plasma sodium and plasma osmolality causes a marked global increase in cerebral perfusion in both hyponatremic and normonatremic rats; and that disruption of BBB appears to be related to the subsequent development of brain demylenation. This year we assessed the effect of DPSPX, an adenosine ~ and 2 receptor blocker on osmolar induced increases in cerebral perfusion. Eight rats were administered DPSPX prior to receiving hypertonic sodium intravenously. DPSPX did not prevent the increase in cerebral perfusion showing that adenosine probably is not involved in the alterations in cerebral perfusion induced by rapid correction of CHN. Our future experiments will focus on how alterations in BBB permeability and the changes in cerebral perfusion which follow rapid changes in plasma osmolality relate to the subsequent development of neurologic symptoms and brain demylenation which often follow rapid correction of hyponatremia. Specifically, we hope to identify (i) the mechanisms responsible for the osmolar induced increase in cerebral perfusion, and to determine whether and how such changes in perfusion influence osmotic disruption of the brain and subsequent development of demylenation following rapid correction of hyponatremia, (ii) the mediators responsible for the changes in cerebral perfusion during correction ofhyponatremia, and (iii) to identify the mechanisms responsible for the osmotic opening of the BBB and how this might cause subsequent demylenation.
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