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...
Main Authors: | , , , , , , , , |
---|---|
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 |
_version_ | 1818142948652482560 |
---|---|
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. |
first_indexed | 2024-12-11T11:23:53Z |
format | Article |
id | doaj.art-0978a36d66a742d09cdac8918dc501c7 |
institution | Directory Open Access Journal |
issn | 1471-2431 |
language | English |
last_indexed | 2024-12-11T11:23:53Z |
publishDate | 2017-03-01 |
publisher | BMC |
record_format | Article |
series | BMC Pediatrics |
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 |
work_keys_str_mv | AT lixiaoxu melatoninalleviatesbrainandperipheraltissueedemainaneonatalratmodelofhypoxicischemicbraindamagetheinvolvementofedemarelatedproteins AT yuanlv melatoninalleviatesbrainandperipheraltissueedemainaneonatalratmodelofhypoxicischemicbraindamagetheinvolvementofedemarelatedproteins AT yanhongli melatoninalleviatesbrainandperipheraltissueedemainaneonatalratmodelofhypoxicischemicbraindamagetheinvolvementofedemarelatedproteins AT xinding melatoninalleviatesbrainandperipheraltissueedemainaneonatalratmodelofhypoxicischemicbraindamagetheinvolvementofedemarelatedproteins AT yingwang melatoninalleviatesbrainandperipheraltissueedemainaneonatalratmodelofhypoxicischemicbraindamagetheinvolvementofedemarelatedproteins AT xinghan melatoninalleviatesbrainandperipheraltissueedemainaneonatalratmodelofhypoxicischemicbraindamagetheinvolvementofedemarelatedproteins AT minghualiu melatoninalleviatesbrainandperipheraltissueedemainaneonatalratmodelofhypoxicischemicbraindamagetheinvolvementofedemarelatedproteins AT binsun melatoninalleviatesbrainandperipheraltissueedemainaneonatalratmodelofhypoxicischemicbraindamagetheinvolvementofedemarelatedproteins AT xingfeng melatoninalleviatesbrainandperipheraltissueedemainaneonatalratmodelofhypoxicischemicbraindamagetheinvolvementofedemarelatedproteins |