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Protective effect of melatonin against transient global cerebral ischemia-induced neuronal cell damage via inhibition of matrix metalloproteinase-9

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Author(s)
Su-Jin KimSeong-Ryong Lee
Keimyung Author(s)
Lee, Seong Ryong
Department
Dept. of Pharmacology (약리학)
Brain Research Institute (뇌연구소)
Journal Title
Life Science
Issued Date
2014
Volume
94
Issue
1
Keyword
MelatoninGlobal cerebral ischemiaMatrix metalloproteinase
Abstract
Aims

Melatonin possesses various pharmacological effects including neuroprotective effects against brain ischemia. Post-ischemic increases in matrix metalloproteinase-9 (MMP-9) expression and activity mainly contribute to neuronal damage by degradation of the extracellular matrix. This study was designed to examine whether melatonin has a neuroprotective effect and an influence on MMP-9 in transient global brain ischemia.

Main methods

Mice were subjected to 20 min of global brain ischemia and sacrificed 72 h later. Melatonin (30 mg/kg) was administered 30 min before and 2 h after ischemia as well as once daily until sacrifice.

Key findings

Hippocampal pyramidal cell damage after ischemia was significantly decreased by melatonin. As observed by zymography, melatonin inhibited the increase of MMP-9 activity after ischemia. In the brain sections, the increased gelatinase activity was mainly observed in the hippocampus after ischemia and melatonin also reduced gelatinase activity. The laminin and NeuN expression levels were reduced in the hippocampal CA1 and CA2 regions after ischemia, and melatonin reduced laminin degradation and neuronal loss. A TUNEL assay demonstrated that there were TUNEL-positive cells in the hippocampus and the number of TUNEL-positive cells was significantly decreased by melatonin. There was no difference in the ischemia-induced hippocampal neuronal damage between the vehicle- and melatonin-treated groups of MMP-9 knock-out mice.

Significance

These data demonstrate that melatonin suppressed the occurrence of neuronal injury, which might be partly due to its inhibitory effects on MMP-9 in addition to its anti-oxidative effects. MMP-9 may be an important key target of melatonin in neuroprotection against global ischemia.

Keywords
Melatonin;
Global cerebral ischemia;
Matrix metalloproteinase
Keimyung Author(s)(Kor)
이성용
Publisher
School of Medicine
Citation
Su-Jin Kim and Seong-Ryong Lee. (2014). Protective effect of melatonin against transient global cerebral ischemia-induced neuronal cell damage via inhibition of matrix metalloproteinase-9. Life Science, 94(1), 8–16. doi: 10.1016/j.lfs.2013.11.013
Type
Article
ISSN
0024-3205
Source
https://www.sciencedirect.com/science/article/pii/S0024320513007121?via%3Dihub
DOI
10.1016/j.lfs.2013.11.013
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/36305
Appears in Collections:
3. Research Institutues (연구소) > Brain Research Institute (뇌연구소)
1. School of Medicine (의과대학) > Dept. of Pharmacology (약리학)
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