The perivascular pool of aquaporin-4 mediates the effect of osmotherapy in postischemic cerebral edema*
- 1 September 2008
- journal article
- neurologic critical-care
- Published by Ovid Technologies (Wolters Kluwer Health) in Critical Care Medicine
- Vol. 36 (9), 2634-2640
- https://doi.org/10.1097/ccm.0b013e3181847853
Abstract
Targeted disruption of the gene encoding α-syntrophin (α-Syn−/−) that lack the perivascular aquaporin-4 pool but retain the endothelial pool of this protein. Design: Prospective laboratory animal study. Setting: Research laboratory in a university teaching hospital. Measurements and Main Results: Halothane-anesthetized adult male wildtype C57B/6 and α-Syn−/− mice were subjected to 90 min of transient middle cerebral artery occlusion and treated with either a continuous intravenous infusion of 0.9% saline or 3% hypertonic saline (1.5 mL/kg/hr) for 48 hr. In the first series of experiments (n = 59), increased brain water content analyzed by wet-to-dry ratios in the ischemic hemisphere of wildtype mice was attenuated after hypertonic saline (79.9% ± 0.5%; mean ± sem) but not after 0.9% saline (82.3% ± 1.0%) treatment. In contrast in α-Syn−/− mice, hypertonic saline had no effect on the postischemic edema (hypertonic saline: 80.3% ± 0.7%; 0.9% saline: 80.3% ± 0.4%). In the second series of experiments (n = 32), treatment with hypertonic saline attenuated postischemic blood-brain barrier disruption at 48 hr in wildtype mice but not in α-Syn−/− mice; α-Syn deletion alone had no effect on blood-brain barrier integrity. In the third series of experiments (n = 34), α-Syn−/− mice treated with either hypertonic saline or 0.9% saline had smaller infarct volume as compared with their wildtype counterparts. Conclusions: These data demonstrate that 1) osmotherapy with hypertonic saline exerts antiedema effects via the perivascular pool of aquaporin-4, 2) hypertonic saline attenuates blood-brain barrier disruption depending on the presence of perivascular aquaporin-4, and 3) deletion of the perivascular pool of aquaporin-4 alleviates tissue damage after stroke, in mice subjected to osmotherapy and in nontreated mice....This publication has 41 references indexed in Scilit:
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