Osmotherapy With Hypertonic Saline Attenuates Global Cerebral Edema Following Experimental Cardiac Arrest via Perivascular Pool of Aquaporin-4

Shin Nakayama, Elton Migliati, Mahmood Amiry-Moghaddam, Ole P. Ottersen, Anish Bhardwaj

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

OBJECTIVES:: We tested the hypothesis that osmotherapy with hypertonic saline attenuates cerebral edema following experimental cardiac arrest and cardiopulmonary resuscitation by exerting its effect via the perivascular pool of aquaporin-4. We used mice with targeted disruption of the gene encoding α-syntrophin (α-Syn) that demonstrate diminished perivascular aquaporin-4 pool but retain the non-endfoot and ependymal pools. DESIGN:: Laboratory animal study. SETTING:: University animal research laboratory. INTERVENTIONS:: Isoflurane-anesthetized adult male wild-type C57B/6 or α-Syn mice were subjected to cardiac arrest/cardiopulmonary resuscitation and treated with either a continuous IV infusion of 0.9% saline or various concentrations of hypertonic saline. Serum osmolality, regional brain water content, blood-brain barrier disruption, and aquaporin-4 protein expression were determined at 24 hours after cardiac arrest/cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS:: Hypertonic saline (7.5%) treatment significantly attenuated water content in the caudoputamen complex and cortex compared with 0.9% saline treatment in wild-type mice subjected to cardiac arrest/cardiopulmonary resuscitation. In contrast, in α-Syn mice subjected to cardiac arrest/cardiopulmonary resuscitation, 7.5% hypertonic saline treatment did not attenuate water content. Treatment with 7.5% hypertonic saline attenuated blood-brain barrier disruption at 24 hours following cardiac arrest/cardiopulmonary resuscitation in wild-type mice but not in α-Syn mice. Total aquaporin-4 protein expression was not different between 0.9% saline and hypertonic saline–treated wild-type mice. CONCLUSIONS:: Following experimental cardiac arrest/cardiopulmonary resuscitation: 1) continuous hypertonic saline therapy maintained to achieve serum osmolality of ≈ 350 mOsm/L is beneficial for the treatment of cerebral edema; 2) perivascular pool of aquaporin-4 plays a critical role in water egress from brain; and 3) hypertonic saline attenuates blood-brain barrier disruption via perivascular aquaporin-4 pool.

Original languageEnglish (US)
JournalCritical Care Medicine
DOIs
StateAccepted/In press - Mar 31 2016
Externally publishedYes

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Aquaporin 4
Brain Edema
Cardiopulmonary Resuscitation
Heart Arrest
Blood-Brain Barrier
Water
Osmolar Concentration
Therapeutics
Isoflurane
Brain
Laboratory Animals
Serum

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Osmotherapy With Hypertonic Saline Attenuates Global Cerebral Edema Following Experimental Cardiac Arrest via Perivascular Pool of Aquaporin-4. / Nakayama, Shin; Migliati, Elton; Amiry-Moghaddam, Mahmood; Ottersen, Ole P.; Bhardwaj, Anish.

In: Critical Care Medicine, 31.03.2016.

Research output: Contribution to journalArticle

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title = "Osmotherapy With Hypertonic Saline Attenuates Global Cerebral Edema Following Experimental Cardiac Arrest via Perivascular Pool of Aquaporin-4",
abstract = "OBJECTIVES:: We tested the hypothesis that osmotherapy with hypertonic saline attenuates cerebral edema following experimental cardiac arrest and cardiopulmonary resuscitation by exerting its effect via the perivascular pool of aquaporin-4. We used mice with targeted disruption of the gene encoding α-syntrophin (α-Syn) that demonstrate diminished perivascular aquaporin-4 pool but retain the non-endfoot and ependymal pools. DESIGN:: Laboratory animal study. SETTING:: University animal research laboratory. INTERVENTIONS:: Isoflurane-anesthetized adult male wild-type C57B/6 or α-Syn mice were subjected to cardiac arrest/cardiopulmonary resuscitation and treated with either a continuous IV infusion of 0.9{\%} saline or various concentrations of hypertonic saline. Serum osmolality, regional brain water content, blood-brain barrier disruption, and aquaporin-4 protein expression were determined at 24 hours after cardiac arrest/cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS:: Hypertonic saline (7.5{\%}) treatment significantly attenuated water content in the caudoputamen complex and cortex compared with 0.9{\%} saline treatment in wild-type mice subjected to cardiac arrest/cardiopulmonary resuscitation. In contrast, in α-Syn mice subjected to cardiac arrest/cardiopulmonary resuscitation, 7.5{\%} hypertonic saline treatment did not attenuate water content. Treatment with 7.5{\%} hypertonic saline attenuated blood-brain barrier disruption at 24 hours following cardiac arrest/cardiopulmonary resuscitation in wild-type mice but not in α-Syn mice. Total aquaporin-4 protein expression was not different between 0.9{\%} saline and hypertonic saline–treated wild-type mice. CONCLUSIONS:: Following experimental cardiac arrest/cardiopulmonary resuscitation: 1) continuous hypertonic saline therapy maintained to achieve serum osmolality of ≈ 350 mOsm/L is beneficial for the treatment of cerebral edema; 2) perivascular pool of aquaporin-4 plays a critical role in water egress from brain; and 3) hypertonic saline attenuates blood-brain barrier disruption via perivascular aquaporin-4 pool.",
author = "Shin Nakayama and Elton Migliati and Mahmood Amiry-Moghaddam and Ottersen, {Ole P.} and Anish Bhardwaj",
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T1 - Osmotherapy With Hypertonic Saline Attenuates Global Cerebral Edema Following Experimental Cardiac Arrest via Perivascular Pool of Aquaporin-4

AU - Nakayama, Shin

AU - Migliati, Elton

AU - Amiry-Moghaddam, Mahmood

AU - Ottersen, Ole P.

AU - Bhardwaj, Anish

PY - 2016/3/31

Y1 - 2016/3/31

N2 - OBJECTIVES:: We tested the hypothesis that osmotherapy with hypertonic saline attenuates cerebral edema following experimental cardiac arrest and cardiopulmonary resuscitation by exerting its effect via the perivascular pool of aquaporin-4. We used mice with targeted disruption of the gene encoding α-syntrophin (α-Syn) that demonstrate diminished perivascular aquaporin-4 pool but retain the non-endfoot and ependymal pools. DESIGN:: Laboratory animal study. SETTING:: University animal research laboratory. INTERVENTIONS:: Isoflurane-anesthetized adult male wild-type C57B/6 or α-Syn mice were subjected to cardiac arrest/cardiopulmonary resuscitation and treated with either a continuous IV infusion of 0.9% saline or various concentrations of hypertonic saline. Serum osmolality, regional brain water content, blood-brain barrier disruption, and aquaporin-4 protein expression were determined at 24 hours after cardiac arrest/cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS:: Hypertonic saline (7.5%) treatment significantly attenuated water content in the caudoputamen complex and cortex compared with 0.9% saline treatment in wild-type mice subjected to cardiac arrest/cardiopulmonary resuscitation. In contrast, in α-Syn mice subjected to cardiac arrest/cardiopulmonary resuscitation, 7.5% hypertonic saline treatment did not attenuate water content. Treatment with 7.5% hypertonic saline attenuated blood-brain barrier disruption at 24 hours following cardiac arrest/cardiopulmonary resuscitation in wild-type mice but not in α-Syn mice. Total aquaporin-4 protein expression was not different between 0.9% saline and hypertonic saline–treated wild-type mice. CONCLUSIONS:: Following experimental cardiac arrest/cardiopulmonary resuscitation: 1) continuous hypertonic saline therapy maintained to achieve serum osmolality of ≈ 350 mOsm/L is beneficial for the treatment of cerebral edema; 2) perivascular pool of aquaporin-4 plays a critical role in water egress from brain; and 3) hypertonic saline attenuates blood-brain barrier disruption via perivascular aquaporin-4 pool.

AB - OBJECTIVES:: We tested the hypothesis that osmotherapy with hypertonic saline attenuates cerebral edema following experimental cardiac arrest and cardiopulmonary resuscitation by exerting its effect via the perivascular pool of aquaporin-4. We used mice with targeted disruption of the gene encoding α-syntrophin (α-Syn) that demonstrate diminished perivascular aquaporin-4 pool but retain the non-endfoot and ependymal pools. DESIGN:: Laboratory animal study. SETTING:: University animal research laboratory. INTERVENTIONS:: Isoflurane-anesthetized adult male wild-type C57B/6 or α-Syn mice were subjected to cardiac arrest/cardiopulmonary resuscitation and treated with either a continuous IV infusion of 0.9% saline or various concentrations of hypertonic saline. Serum osmolality, regional brain water content, blood-brain barrier disruption, and aquaporin-4 protein expression were determined at 24 hours after cardiac arrest/cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS:: Hypertonic saline (7.5%) treatment significantly attenuated water content in the caudoputamen complex and cortex compared with 0.9% saline treatment in wild-type mice subjected to cardiac arrest/cardiopulmonary resuscitation. In contrast, in α-Syn mice subjected to cardiac arrest/cardiopulmonary resuscitation, 7.5% hypertonic saline treatment did not attenuate water content. Treatment with 7.5% hypertonic saline attenuated blood-brain barrier disruption at 24 hours following cardiac arrest/cardiopulmonary resuscitation in wild-type mice but not in α-Syn mice. Total aquaporin-4 protein expression was not different between 0.9% saline and hypertonic saline–treated wild-type mice. CONCLUSIONS:: Following experimental cardiac arrest/cardiopulmonary resuscitation: 1) continuous hypertonic saline therapy maintained to achieve serum osmolality of ≈ 350 mOsm/L is beneficial for the treatment of cerebral edema; 2) perivascular pool of aquaporin-4 plays a critical role in water egress from brain; and 3) hypertonic saline attenuates blood-brain barrier disruption via perivascular aquaporin-4 pool.

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