title: Hypertonic saline attenuates expression of Notch signaling and proinflammatory mediators in activated microglia in experimentally induced cerebral ischemia and hypoxic BV-2 microglia.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Zeng
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China. yonglih@163.com.
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Han
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Zhu
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
authors.forename: Lin-Qiang
authors.initials: LQ
authors.lastname: Huang
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Deng
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
authors.forename: Qiao-Sheng
authors.initials: QS
authors.lastname: Wang
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
authors.forename: Wen-Qiang
authors.initials: WQ
authors.lastname: Jiang
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
authors.forename: Miao-Yun
authors.initials: MY
authors.lastname: Wen
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
authors.forename: Qian-Peng
authors.initials: QP
authors.lastname: Han
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China. zenghongke@vip.163.com.
authors.forename: Hong-Ke
authors.initials: HK
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D051880:Receptors, Notch; D012462:Saline Solution, Hypertonic; D052247:Nitric Oxide Synthase Type II
keywords: Cerebral ischemia; Hypertonic saline; Microglia; Neuroinflammation; Notch signaling