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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.
- Source :
-
BMC neuroscience [BMC Neurosci] 2017 Mar 14; Vol. 18 (1), pp. 32. Date of Electronic Publication: 2017 Mar 14. - Publication Year :
- 2017
-
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.<br />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.<br />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.
- Subjects :
- Animals
Brain Ischemia immunology
Brain Ischemia pathology
Cell Hypoxia physiology
Cell Line
Disease Models, Animal
Drug Evaluation, Preclinical
Male
Mice
Microglia immunology
Microglia pathology
Nitric Oxide Synthase Type II metabolism
Random Allocation
Rats, Sprague-Dawley
Reperfusion Injury drug therapy
Reperfusion Injury immunology
Reperfusion Injury pathology
Signal Transduction drug effects
Brain Ischemia drug therapy
Cell Hypoxia drug effects
Microglia drug effects
Neuroprotective Agents pharmacology
Receptors, Notch metabolism
Saline Solution, Hypertonic pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2202
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 28288585
- Full Text :
- https://doi.org/10.1186/s12868-017-0351-6