Hypertonic saline ameliorates cerebral edema through downregulation of aquaporin-4 expression in the astrocytes.

Osmotherapy with 10% hypertonic saline (HS) alleviates cerebral edema through osmotic force. Aquaporin-4 (AQP4) has been reported to be implicated in the pathogenesis of cerebral edema resulting from a variety of brain injury. This study aimed to determine if 10% hypertonic saline ameliorates cerebral edema through downregulation of AQP4 expression in the perivascular astrocytes in the ischemic cerebral edema. Adult male Sprague-Dawley (SD) rats were subjected to permanent right-sided middle cerebral artery occlusion (MCAO) and treated with a continuous i.v. infusion of 10% HS. Brain water content (BWC) analyzed by wet-to-dry ratios in the ischemic hemisphere of SD rats was attenuated after 10% HS treatment. This was coupled with the reduction of neuronal apoptosis in the peri-ischemic brain tissue. Concomitantly, downregulated expression of AQP4 in the perivascular astrocytes after 10% HS treatment was observed. Our results suggest that in addition to its osmotic force, 10% HS exerts anti-edema effects possibly through downregulation of AQP4 expression in the perivascular astrocytes. The reduction of brain edema after 10% HS administration can prevent ischemic brain damage.