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 journalArticlepeer-review

22 Scopus citations


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)
Pages (from-to)e702-e710
JournalCritical care medicine
Issue number8
StatePublished - Aug 1 2016
Externally publishedYes


  • aquaporins
  • cardiac arrest
  • cerebral edema
  • global cerebral ischemia
  • hypertonic saline
  • osmotherapy

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine


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