Introduction: Hypertonic saline (HS) solutions are increasingly being utilized as osmotherapeutic agents for the treatment of cerebral edema associated with brain injury from diverse etiologies.
Methods: 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.
Results: 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.
Conclusions: 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.