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Open Access Highly Accessed Research

Hypertonic saline reduces lipopolysaccharide-induced mouse brain edema through inhibiting aquaporin 4 expression

Cao C1, Yu X1, Liao Z1, Zhu N1, Huo H1, Wang M1, Ji G1, She H23, Luo Z2* and Yue S1*

Author Affiliations

1 Department of Pediatrics, Xiangya Hospital, Central South University, Xiangya Road, Changsha, Hunan, China 410008

2 Department of Physiology, Xiangya Medical School, Central South University, Xiangya Road, Changsha, Hunan, China 410013

3 Department of Pharmacology, Emory University, 1518 Clifton Road Northeast, Atlanta, GA, USA GA 30322

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Critical Care 2012, 16:R186  doi:10.1186/cc11670

Published: 4 October 2012

Abstract

Introduction

Three percent sodium chloride (NaCl) treatment has been shown to reduce brain edema and inhibited brain aquaporin 4 (AQP4) expression in bacterial meningitis induced by Escherichia coli. Lipopolysaccharide (LPS) is the main pathogenic component of E. coli. We aimed to explore the effect of 3% NaCl in mouse brain edema induced by LPS, as well as to elucidate the potential mechanisms of action.

Methods

Three percent NaCl was used to treat cerebral edema induced by LPS in mice in vivo. Brain water content, IL-1β, TNFα, immunoglobulin G (IgG), AQP4 mRNA and protein were measured in brain tissues. IL-1β, 3% NaCl and calphostin C (a specific inhibitor of protein kinase C) were used to treat the primary astrocytes in vitro. AQP4 mRNA and protein were measured in astrocytes. Differences in various groups were determined by one-way analysis of variance.

Results

Three percent NaCl attenuated the increase of brain water content, IL-1β, TNFα, IgG, AQP4 mRNA and protein in brain tissues induced by LPS. Three percent NaCl inhibited the increase of AQP4 mRNA and protein in astrocytes induced by IL-1β in vitro. Calphostin C blocked the decrease of AQP4 mRNA and protein in astrocytes induced by 3% NaCl in vitro.

Conclusions

Osmotherapy with 3% NaCl ameliorated LPS-induced cerebral edema in vivo. In addition to its osmotic force, 3% NaCl exerted anti-edema effects possibly through down-regulating the expression of proinflammatory cytokines (IL-1β and TNFα) and inhibiting the expression of AQP4 induced by proinflammatory cytokines. Three percent NaCl attenuated the expression of AQP4 through activation of protein kinase C in astrocytes.

Keywords:
hypertonic saline; lipopolysaccharide; brain edema; aquaporin 4; protein kinase C; interleukin-1 beta