Altered Expression of Aquaporin 4 (AQP4) in Hippocampal Formation after Systemic Hyponatremia / 대한해부학회지

ABSTRACT

The expression of aquaporin-4 (AQP4) protein, bi-directional water channel, in the blood-brain barrier of the hippocampal formation (HF) was studied in the rat to determine the role of AQP4 in the pathophysiology of systemic hyponatremia. Systemic hyponatremia was induced by coadministration of 30 ml (~12% body weight) dextrose solution (140 mM) intraperitoneally and a 3-microg subcutaneous dose of 1-deamino-8-D-arginine vasopressin (dDAVP). Two and six hours after the drug administration, there were significant reductions in the serum osmolarity (252+/-5.1 and 252+/-6.4 mOsm/L) and in Na+/- concentration (117+/-1.7 and 97.2 mM) from the control values (296+/-5.2 mOsm/L, 140+/-4.7 mM). Brain injury in the HF and the expression of AQP4 were determined by using TUNEL, immunohistochemistry and quantitative immunoblotting. TUNEL revealed apoptotic cell death in the dentate gyrus (DG), presumably resulting from brain edema and a subsequent elevation of intracranial pressure after 2 h of systemic hyponatremia. However, AQP4 expression was decreased by 82%+/-6% after 2 h of systemic hyponatremia and then normalized after 6 h (108%+/-9%) compared with that of the control. Therefore, apoptotic cell death in the DG from brain swelling in this systemic hyponatremic model is likely associated with decrease of excessive brain water elimination because reincreased AQP4 expression/function accelerates the elimination of apoptotic cells from the DG.