RGD Reference Report - Hypertonic saline alleviates cerebral edema by inhibiting microglia-derived TNF-alpha and IL-1beta-induced Na-K-Cl Cotransporter up-regulation. - Rat Genome Database

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Hypertonic saline alleviates cerebral edema by inhibiting microglia-derived TNF-alpha and IL-1beta-induced Na-K-Cl Cotransporter up-regulation.

Authors: Huang, LQ  Zhu, GF  Deng, YY  Jiang, WQ  Fang, M  Chen, CB  Cao, W  Wen, MY  Han, YL  Zeng, HK 
Citation: Huang LQ, etal., J Neuroinflammation. 2014 Jun 11;11:102. doi: 10.1186/1742-2094-11-102.
RGD ID: 10450594
Pubmed: PMID:24916922   (View Abstract at PubMed)
PMCID: PMC4080704   (View Article at PubMed Central)
DOI: DOI:10.1186/1742-2094-11-102   (Journal Full-text)

BACKGROUND: Hypertonic saline (HS) has been successfully used clinically for treatment of various forms of cerebral edema. Up-regulated expression of Na-K-Cl Cotransporter 1 (NKCC1) and inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) has been demonstrated to be closely associated with the pathogenesis of cerebral edema resulting from a variety of brain injuries. This study aimed to explore if alleviation of cerebral edema by 10% HS might be effected through down-regulation of inflammatory mediator expression in the microglia, and thus result in decreased NKCC1 expression in astrocytes in the cerebral cortex bordering the ischemic core. METHODS: The Sprague-Dawley (SD) rats that underwent right-sided middle cerebral artery occlusion (MCAO) were used for assessment of NKCC1, TNF-alpha and IL-1beta expression using Western blotting, double immunofluorescence and real time RT-PCR, and the model also was used for evaluation of brain water content (BWC) and infarct size. SB203580 and SP600125, specific inhibitors of the p38 and JNK signaling pathways, were used to treat primary microglia cultures to determine whether the two signaling pathways were required for the inhibition of HS on microglia expressing and secreting TNF-alpha and IL-1beta using Western blotting, double immunofluorescence and enzyme-linked immunosorbent assay (ELISA). The effect of TNF-alpha and IL-1beta on NKCC1 expression in primary astrocyte cultures was determined. In addition, the direct inhibitory effect of HS on NKCC1 expression in primary astrocytes was also investigated by Western blotting, double immunofluorescence and real time RT-PCR. RESULTS: BWC and infarct size decreased significantly after 10% HS treatment. TNF-alpha and IL-1beta immunoexpression in microglia was noticeably decreased. Concomitantly, NKCC1 expression in astrocytes was down-regulated. TNF-alpha and IL-1beta released from the primary microglia subjected to hypoxic exposure and treatment with 100 mM HS were decreased. NKCC1 expression in primary astrocytes was concurrently and progressively down-regulated with decreasing concentration of exogenous TNF-alpha and IL-1beta. Additionally, 100 mM HS directly inhibited NKCC1 up-regulation in astrocytes under hypoxic condition. CONCLUSIONS: The results suggest that 10% HS alleviates cerebral edema through inhibition of the NKCC1 Cotransporter, which is mediated by attenuation of TNF-alpha and IL-1beta stimulation on NKCC1.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Il1b  (interleukin 1 beta)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Il1b  (interleukin 1 beta)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
IL1B  (interleukin 1 beta)
TNF  (tumor necrosis factor)


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