title: Hypertonic saline alleviates experimentally induced cerebral oedema through suppression of vascular endothelial growth factor and its receptor VEGFR2 expression in astrocytes.
abstract: Cerebral oedema is closely related to the permeability of blood-brain barrier, vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) all of which are important blood-brain barrier (BBB) permeability regulatory factors. Zonula occludens 1 (ZO-1) and claudin-5 are also the key components of BBB. Hypertonic saline is widely used to alleviate cerebral oedema. This study aimed to explore the possible mechanisms underlying hypertonic saline that ameliorates cerebral oedema effectively.
  
  
  
  Middle cerebral artery occlusion (MCAO) model in Sprague-Dawley (SD) rats and of oxygen-glucose deprivation model in primary astrocytes were used in this study. The brain water content (BWC) was used to assess the effect of 10 % HS on cerebral oedema. The assessment of Evans blue (EB) extravasation was performed to evaluate the protective effect of 10 % HS on blood-brain barrier. The quantification of VEGF, VEGFR2, ZO-1 and claudin-5 was used to illustrate the mechanism of 10 % HS ameliorating cerebral oedema.
  
  
  
  BWC was analysed by wet-to-dry ratios in the ischemic hemisphere of SD rats; it was significantly decreased after 10 % HS treatment (P < 0.05). We also investigated the blood-brain barrier protective effect by 10 % HS which reduced EB extravasation effectively in the peri-ischemic brain tissue. In parallel to the above notably at 24 h following MCAO, mRNA and protein expression of VEGF and VEGFR2 in the peri-ischemic brain tissue was down-regulated after 10 % HS treatment (P < 0.05). Along with this, in vitro studies showed increased VEGF and VEGFR2 mRNA and protein expression in primary astrocytes under hypoxic condition (P < 0.05), but it was suppressed after HS treatment (P < 0.05). In addition, HS inhibited the down-regulation of ZO-1, claudin-5 effectively.
  
  
  
  The results suggest that 10 % HS could alleviate cerebral oedema possibly through reducing the ischemia induced BBB permeability as a consequence of inhibiting VEGF-VEGFR2-mediated down-regulation of ZO-1, claudin-5.
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: Linqiang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Zhuzhou Central Hospital, Zhuzhou, 412007, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
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: Yiyu
authors.initials: Y
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: Gaofeng
authors.initials: G
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: Yongli
authors.initials: Y
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. zenghongke@vip.163.com.
authors.forename: Hongke
authors.initials: H
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D062507:Claudin-5 / Q000378:metabolism; D004195:Disease Models, Animal; D005947:Glucose / Q000172:deficiency; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D062507:Claudin-5; C491510:Cldn5 protein, rat; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D012462:Saline Solution, Hypertonic; C569044:Tjp1 protein, rat; D042461:Vascular Endothelial Growth Factor A; D062826:Zonula Occludens-1 Protein; C467498:vascular endothelial growth factor A, rat; C000602029:Kdr protein, rat; D040301:Vascular Endothelial Growth Factor Receptor-2; D005947:Glucose
keywords: Astrocyte; Cerebral oedema; Claudin-5; Hypertonic saline; Vascular endothelial growth factor; ZO-1