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Hypertonic saline attenuates expression of Notch signaling and proinflammatory mediators in activated microglia in experimentally induced cerebral ischemia and hypoxic BV-2 microglia
Hypertonic saline attenuates expression of Notch signaling and proinflammatory mediators in activated microglia in experimentally induced cerebral ischemia and hypoxic BV-2 microglia
- Source :
- BMC Neuroscience
- Publisher :
- Springer Nature
-
Abstract
- Background Ischemic stroke is a major disease that threatens human health in ageing population. Increasing evidence has shown that neuroinflammatory mediators play crucial roles in the pathophysiology of cerebral ischemia injury. Notch signaling is recognized as the cell fate signaling but recent evidence indicates that it may be involved in the inflammatory response in activated microglia in cerebral ischemia. Previous report in our group demonstrated hypertonic saline (HS) could reduce the release of interleukin-1 beta and tumor necrosis factor-alpha in activated microglia, but the underlying molecular and cellular mechanisms have remained uncertain. This study was aimed to explore whether HS would partake in regulating production of proinflammatory mediators through Notch signaling. Results HS markedly attenuated the expression of Notch-1, NICD, RBP-JK and Hes-1 in activated microglia both in vivo and in vitro. Remarkably, HS also reduced the expression of iNOS in vivo, while the in vitro levels of inflammatory mediators Phos-NF-κB, iNOS and ROS were reduced by HS as well. Conclusion Our results suggest that HS may suppress of inflammatory mediators following ischemia/hypoxic through the Notch signaling which operates synergistically with NF-κB pathway in activated microglia. Our study has provided the morphological and biochemical evidence that HS can attenuate inflammation reaction and can be neuroprotective in cerebral ischemia, thus supporting the use of hypertonic saline by clinicians in patients with an ischemia stroke. Electronic supplementary material The online version of this article (doi:10.1186/s12868-017-0351-6) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
0301 basic medicine
Drug Evaluation, Preclinical
Ischemia
Notch signaling pathway
Nitric Oxide Synthase Type II
Inflammation
Pharmacology
Neuroprotection
Brain Ischemia
Cell Line
Proinflammatory cytokine
Rats, Sprague-Dawley
Mice
Random Allocation
03 medical and health sciences
Cellular and Molecular Neuroscience
Hypertonic saline
0302 clinical medicine
Neuroinflammation
medicine
Animals
Notch signaling
Saline Solution, Hypertonic
Receptors, Notch
Microglia
business.industry
General Neuroscience
Cerebral ischemia
medicine.disease
Cell Hypoxia
Disease Models, Animal
Neuroprotective Agents
030104 developmental biology
medicine.anatomical_structure
Reperfusion Injury
Immunology
medicine.symptom
business
030217 neurology & neurosurgery
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 14712202
- Volume :
- 18
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Neuroscience
- Accession number :
- edsair.doi.dedup.....9716efe1318298f828e5bc855d9f3f79
- Full Text :
- https://doi.org/10.1186/s12868-017-0351-6