Shin Nakayama1, Elton Migliati, Mahmood Amiry-Moghaddam, Ole P Ottersen, Anish Bhardwaj. 1. 1Departments of Neurology, Neurological Surgery and Anesthesiology and Peri-Operative Medicine, Oregon Health and Science University, Portland, OR. 2Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
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.
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-Synmice 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-Synmice 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-Synmice. 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.
Authors: Mahmood Amiry-Moghaddam; Anne Williamson; Maria Palomba; Tore Eid; Nihal C de Lanerolle; Erlend A Nagelhus; Marvin E Adams; Stanley C Froehner; Peter Agre; Ole P Ottersen Journal: Proc Natl Acad Sci U S A Date: 2003-11-03 Impact factor: 11.205
Authors: Zachary L Fuller; John W Faro; Clifton W Callaway; Patrick J Coppler; Jonathan Elmer Journal: Resuscitation Date: 2021-03-01 Impact factor: 5.262
Authors: Ryan L Hoiland; Philip N Ainslie; Cheryl L Wellington; Jennifer Cooper; Sophie Stukas; Sonny Thiara; Denise Foster; Nicholas A Fergusson; Edward M Conway; David K Menon; Peter Gooderham; Veronica Hirsch-Reinshagen; Donald E Griesdale; Mypinder S Sekhon Journal: Circ Res Date: 2021-07-21 Impact factor: 17.367