title: Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins.
abstract: Previous studies have indicated edema may be involved in the pathophysiology following hypoxic-ischemic encephalopathy (HIE), and melatonin may exhibit neuro-protection against brain insults. However, little is known regarding the mechanisms that involve the protective effects of melatonin in the brain and peripheral tissues after HIE. The present study aimed to examine the effects of melatonin on multiple organs, and the expression of edema related proteins in a neonatal rat model of hypoxic-ischemic brain damage (HIBD).
  
  
  
  One hundred ninety-two neonatal rats were randomly divided into three subgroups that underwent a sham surgery or HIBD. After the HIBD or sham-injury, the rats received an intraperitoneal injection of melatonin or an equal volume vehicle, respectively. We investigated the effects of melatonin on brain, kidney, and colon edema via histological examination and the expression of edema related proteins, including AQP-4, ZO-1 and occludin, via qPCR and western blot.
  
  
  
  Our data indicated (1) Melatonin reduced the histological injury in the brain and peripheral organs induced by HIBD as assessed via H-E staining and transmission electron microscopy. (2) Melatonin alleviated the HIBD-induced cerebral edema characterized by increased brain water content. (3) HIBD induced significant changes of edema related proteins, such as AQP-4, ZO-1 and occludin, and these changes were partially reversed by melatonin treatment.
  
  
  
  These findings provide substantial evidence that melatonin treatment has protective effects on the brain and peripheral organs after HIBD, and the edema related proteins, AQP4, ZO-1, and occludin, may indirectly contribute tothe mechanism of the edema protection by melatonin.
authors.affiliation: Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Li-Xiao
authors.initials: LX
authors.lastname: Xu
authors.affiliation: Department of Neonatology, Northern Jiangsu People's Hospital, Yangzhou, 225001, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Neonatology, Children's Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Neonatology, Children's Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neonatology, Children's Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Neonatology, Children's Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Liu
authors.affiliation: Department of Neonatology, Children's Hospital of Soochow University, Suzhou, 215006, China. sunyu0628@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Neonatology, Children's Hospital of Soochow University, Suzhou, 215006, China. xing_feng66@suda.edu.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001929:Brain Edema / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003108:Colonic Diseases / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004487:Edema / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D007674:Kidney Diseases / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008550:Melatonin / Q000627:therapeutic use*; D046529:Microscopy, Electron, Transmission; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D008550:Melatonin
keywords: Aquaporin-4; Edema; Hypoxic-ischemic encephalopathy; Melatonin; Occludin; Zonula occludens-1