Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins

Abstract Background 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...

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Main Authors: Li-Xiao Xu, Yuan Lv, Yan-Hong Li, Xin Ding, Ying Wang, Xing Han, Ming-Hua Liu, Bin Sun, Xing Feng
Format: Article
Language:English
Published: BMC 2017-03-01
Series:BMC Pediatrics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12887-017-0824-x
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author Li-Xiao Xu
Yuan Lv
Yan-Hong Li
Xin Ding
Ying Wang
Xing Han
Ming-Hua Liu
Bin Sun
Xing Feng
author_facet Li-Xiao Xu
Yuan Lv
Yan-Hong Li
Xin Ding
Ying Wang
Xing Han
Ming-Hua Liu
Bin Sun
Xing Feng
author_sort Li-Xiao Xu
collection DOAJ
description Abstract Background 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). Methods 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. Results 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. Conclusions 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.
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spelling doaj.art-0978a36d66a742d09cdac8918dc501c72022-12-22T01:09:04ZengBMCBMC Pediatrics1471-24312017-03-0117111310.1186/s12887-017-0824-xMelatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteinsLi-Xiao Xu0Yuan Lv1Yan-Hong Li2Xin Ding3Ying Wang4Xing Han5Ming-Hua Liu6Bin Sun7Xing Feng8Institute of Pediatric Research, Children’s Hospital of Soochow UniversityDepartment of Neonatology, Northern Jiangsu People’s HospitalInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityDepartment of Neonatology, Children’s Hospital of Soochow UniversityDepartment of Neonatology, Children’s Hospital of Soochow UniversityDepartment of Neonatology, Children’s Hospital of Soochow UniversityDepartment of Neonatology, Children’s Hospital of Soochow UniversityDepartment of Neonatology, Children’s Hospital of Soochow UniversityDepartment of Neonatology, Children’s Hospital of Soochow UniversityAbstract Background 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). Methods 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s12887-017-0824-xMelatoninHypoxic-ischemic encephalopathyEdemaAquaporin-4Zonula occludens-1Occludin
spellingShingle Li-Xiao Xu
Yuan Lv
Yan-Hong Li
Xin Ding
Ying Wang
Xing Han
Ming-Hua Liu
Bin Sun
Xing Feng
Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins
BMC Pediatrics
Melatonin
Hypoxic-ischemic encephalopathy
Edema
Aquaporin-4
Zonula occludens-1
Occludin
title Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins
title_full Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins
title_fullStr Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins
title_full_unstemmed Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins
title_short Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins
title_sort melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic ischemic brain damage the involvement of edema related proteins
topic Melatonin
Hypoxic-ischemic encephalopathy
Edema
Aquaporin-4
Zonula occludens-1
Occludin
url http://link.springer.com/article/10.1186/s12887-017-0824-x
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