Brain Aquaporins (AQPs) expression is associated with sexual dimorphism during hyponatremic encephalopathy.

MASKIN BERNARDO; CESTARI JORGE; STRUCK C; MAJOWICZ MONICA; ZOTTA ELSA; DAMIANO ALICIA E

Berlin

Congreso; 24th ESICM ANNUAL CONGRESS.; 2011

INTRODUCTION. A number of important risk factor for hyponatremic encephalopathy has been described, including sex (women in reproductive age), several hormones such as vasopressin and estrogen, and also hypoxia. These factors could lead to a higher incidence to brain hyponatremic damage in women in reproductive age. AQPs are water-transporting protein, and AQP4 is the most abundant isoform in the blood?brain barrier (BBB). AQP4 is considered as a critical modulator for both water and ion homeostasis in brain. Estrogens tend to impair brain adaptation to hyponatremia affecting the expression of AQP4 [1]. In this study we determine the expression ofAQP4in the brain in a hyponatremic encephalopathy experimental model. METHODS. Experiments were performed on male and female Wistar rats (FFyB Labora- tories, UBA, Buenos Aires) weighing 200?250 g. The animals were divided in four groups. Control normonatremic female (Group A, n = 8) and male (Group B, n = 8) and hyponatremic female (Group C, n = 8) and male (group D, n = 8). Acute hyponatremia was induced in groups C and D by the administration of subcutaneous vasopressin in conjunction with intraperitoneal (IP) glucose/H2O 5%. 4 h after the IP administration of glucose/H2O in subgroups C and D, the animals were sacrificed and the brain immediately removed. Trunk blood was collected to measure plasma sodium concentration. Brain tissue was prepared either for western blot analysis to show the presence of the AQP4 protein or for immunohistochemical investigation on paraffin sections. The data are expressed in mean ± SD RESULTS. Male and female rats from C and D groups had significantly reduced plasma sodium levels (mEq/L): 109.4 ± 12.7 compared to control rats 141.1 ± 2.1. No differences in plasma sodium were observed between both hyponatremic groups: 111.5 ± 13 (male) versus 112.5 ± 13 (female). Semiquantitative Western blot analysis showed that brain non-glycosylated form of AQP4 had a similar expression in male and female normonatremic and hyponatremic rats. While, glycosylated form of AQP4 showed a significantly increase only in female hyponatremic rats. Immunohistochemistry studies detected AQP4 expression at the BBB (endothelium and astrocytes foot processes). Hyponatremic females rats have shown an increased in the expression of AQP4 at both place respect to female controls. Hyponatremic males rats expressed AQP4 only at endothelium level. No difference was detected in males hyponatremic rats respect to male controls. However, the AQP4 expression in male controls was significantly decrease respect to female controls. CONCLUSIONS. Our results suggest that the AQP4 expression in brain present a sexual dimorphism. This condition could be responsible for the poor outcome observed in women with hyponatremic encephalopathy.