Abstract
BackgroundPrevious 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).MethodsOne 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.ResultsOur 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.ConclusionsThese 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.
Highlights
Previous studies have indicated edema may be involved in the pathophysiology following hypoxicischemic encephalopathy (HIE), and melatonin may exhibit neuro-protection against brain insults
(3) hypoxic-ischemic brain damage (HIBD) induced significant changes of edema related proteins, such as AQP-4, zonula occludens-1 (ZO-1) and occludin, and these changes were partially reversed by melatonin treatment
Because zonula occludens-1 (ZO-1) and occludin are identified within tight junctions (TJ), together they form a virtually impermeable barrier to fluid between closely associated cells, which is very important in the maintenance of the mucosal and vascular endothelial barrier structure [11]
Summary
Previous studies have indicated edema may be involved in the pathophysiology following hypoxicischemic encephalopathy (HIE), and melatonin may exhibit neuro-protection against brain insults. 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). The dynamic changes in edema related proteins, such as AQP-4, ZO-1 and occludin, in the brain and peripheral tissues following HIE and their roles in edema development in central and peripheral tissues have rarely been reported.
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