Abstract
OBJECTIVE: Osmotherapy with hypertonic saline ameliorates cerebral edema associated with experimental ischemic stroke. We tested the hypothesis that hypertonic saline exerts its antiedema effect by promoting an efflux of water from brain via the perivascular aquaporin-4 pool. We used mice with 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2634-2640 |
| Number of pages | 7 |
| Journal | Critical Care Medicine |
| Volume | 36 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2008 |
| Externally published | Yes |
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Keywords
- Aquaporins
- Astrocyte
- Cerebral edema
- Focal cerebral ischemia
- Infarct
- Osmotherapy
- Reperfusion
- Stroke
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine
Cite this
The perivascular pool of aquaporin-4 mediates the effect of osmotherapy in postischemic cerebral edema. / Zeynalov, Emil; Chen, Chih Hung; Froehner, Stanley C.; Adams, Marvin E.; Ottersen, Ole Petter; Amiry-Moghaddam, Mahmood; Bhardwaj, Anish.
In: Critical Care Medicine, Vol. 36, No. 9, 09.2008, p. 2634-2640.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The perivascular pool of aquaporin-4 mediates the effect of osmotherapy in postischemic cerebral edema
AU - Zeynalov, Emil
AU - Chen, Chih Hung
AU - Froehner, Stanley C.
AU - Adams, Marvin E.
AU - Ottersen, Ole Petter
AU - Amiry-Moghaddam, Mahmood
AU - Bhardwaj, Anish
PY - 2008/9
Y1 - 2008/9
N2 - OBJECTIVE: Osmotherapy with hypertonic saline ameliorates cerebral edema associated with experimental ischemic stroke. We tested the hypothesis that hypertonic saline exerts its antiedema effect by promoting an efflux of water from brain via the perivascular aquaporin-4 pool. We used mice with 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.
AB - OBJECTIVE: Osmotherapy with hypertonic saline ameliorates cerebral edema associated with experimental ischemic stroke. We tested the hypothesis that hypertonic saline exerts its antiedema effect by promoting an efflux of water from brain via the perivascular aquaporin-4 pool. We used mice with 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.
KW - Aquaporins
KW - Astrocyte
KW - Cerebral edema
KW - Focal cerebral ischemia
KW - Infarct
KW - Osmotherapy
KW - Reperfusion
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=53049097949&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53049097949&partnerID=8YFLogxK
U2 - 10.1097/CCM.0b013e3181847853
DO - 10.1097/CCM.0b013e3181847853
M3 - Article
VL - 36
SP - 2634
EP - 2640
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 9
ER -