Effect of osmotherapy with hypertonic saline on regional cerebral edema following experimental stroke: a study utilizing magnetic resonance imaging

Abstract

Hypertonic saline (HS) solutions are increasingly being utilized as osmotherapeutic agents for the treatment of cerebral edema associated with brain injury from diverse etiologies. In a rat model of permanent focal ischemia, we (1) determined the effect of HS therapy on regional brain water content with T(1)- and T(2)-weighted magnetic resonance imaging (MRI) and (2) tested the hypothesis that HS therapy modulates the expression of aquaporin-4 (AQP4) in the ischemic brain. Halothane-anesthetized male Wistar rats were subjected to permanent middle cerebral artery occlusion (MCAO) and at 6 hr post-MCAO were treated with either continuous intravenous infusion of 0.9% saline (NS) or 7.5% HS for 18 hr. While lesion size measured on T(2)-weighted imaging did not differ between NS (580 +/- 217 mm(3); mean +/- SD) and HS (460 +/- 86 mm(3)) treatments, there was a correlation between T(2) values and tissue water content as determined by wet-to-dry ratio in the caudoputamen (CP) complex of ischemic core (r = 0.612, P < 0.05). There were significant differences in T(1) values with treatment in the ischemic cortex (NS: 2.08 +/- 0.13; HS: 1.78 +/- 0.20) and CP complex (NS: 2.09 +/- 0.14; HS: 1.77 +/- 0.22), but there was no correlation between T(2) values and regional brain tissue water content in the peri-infarct regions and the non-ischemic hemisphere. There were significant differences in AQP4 protein expression in the ischemic hemisphere between NS and HS-treated rats. These data demonstrate that (1) T(2)-weighted MRI imaging correlates with tissue water content in the ischemic core but not in the peri-infarct regions, and (2) attenuation of ischemia-evoked cerebral edema involves the modulation of AQP4 channels in the brain.