Mossakowski Medical Research Institute PAS (Polska Akademia Nauk)

The aim of the present studies was to evaluate the effect of acute and chronic hyponatremia on brain edema, BBB permeability, and mRNA expression of the tight junctions. Acute hyponatremia was induced for 5 hours by s.c. injection of vasopressin or synthetic analog of vasopressin-desmopressin (dDAVP) with i.p. water loading in the amount of 11% body weight. Chronic hyponatremia was induced for 4 days with the help of AVP or dDAVP released continuously from subcutaneously implanted ALZET mini-osmotic pumps and a liquid diet. Because of the vascular action of vasopressin, either vasopressin or desmopressin was used to induce hyponatremia to assess whether the observed changes were characteristic of AVP-associated hyponatremia or hyponatremia alone. Brain water content was determined using the wet-dry method. BBB permeability was studied using sodium fluorescein. Gene expression of claudin-5, occludin, and zonula occludens (ZO-1) was assessed by RT-PCR. Osmolarity, Na⁺, and Cl^- concentrations were analyzed using the electrolyte and blood gas analyzer. Hypoosmotic acute hyponatremia led to increased brain water content and downregulation of tight junction gene expression, although the leakage of BBB was not observed. These results were comparable in both groups with acute hyponatremia, regardless of whether AVP or dDAVP induced it. In chronic hyponatremia, irrespective of the mode of induction, there were no changes in the studied parameters.