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Melatonin Alleviates Neuronal Damage After Intracerebral Hemorrhage in Hyperglycemic Rats

Authors Liang F, Wang J, Zhu X, Wang Z, Zheng J, Sun Z, Xu S, Zhang J, Zhou J, Shi L

Received 8 April 2020

Accepted for publication 16 June 2020

Published 2 July 2020 Volume 2020:14 Pages 2573—2584

DOI https://doi.org/10.2147/DDDT.S257333

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Georgios D. Panos


Feng Liang,1,* Jianli Wang,1,* Xiangyu Zhu,2,* Zhen Wang,1 Jingwei Zheng,1 Zeyu Sun,1 Shenbin Xu,1 Jianmin Zhang,1,3,4 Jingyi Zhou,1 Ligen Shi1

1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Brain Research Institute, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 4Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ligen Shi 88 Jiefang Road, Hangzhou City, Zhejiang Province 310009, People’s Republic of China
Tel +86-571-87784715
Fax +86-571-87784755
Email slg0904@zju.edu.cn
Jianmin Zhang 88 Jiefang Road, Hangzhou City, Zhejiang Province 310009, People’s Republic of China
Tel +86-571-87784715
Fax +86-571-87784755
Email zjm135@zju.edu.cn

Background: This study sought to investigate a novel effect of melatonin in reducing brain injury in an in vivo hyperglycemic intracerebral hemorrhage (ICH) model and further explore the mechanisms of protection.
Methods: Hyperglycemia ICH was induced in Sprague-Dawley rats by streptozocin injection followed by autologous blood injection into the striatum. A combined approach including RNA-specific depletion, electron microscopy, magnetic resonance, Western blots, and immunohistological staining was applied to quantify the brain injuries after ICH.
Results: Hyperglycemia resulted in enlarged hematoma volume, deteriorated brain edema, and aggravated neuronal mitochondria damage 3 days after ICH. Post-treatment with melatonin 2 hours after ICH dose-dependently improved neurological behavioral performance lasting out to 14 days after ICH. This improved neurological function was associated with enhanced structural and functional integrity of mitochondria. Mechanistic studies revealed that melatonin alleviated mitochondria damage in neurons via activating the PPARδ/PGC-1α pathway. Promisingly, melatonin treatment delayed until 6 hours after ICH still reduced brain edema and improved neurological functions. Melatonin supplementation reduces neuronal damage after hyperglycemic ICH by alleviating mitochondria damage in a PPARδ/PGC-1α-dependent manner.
Conclusion: Melatonin may represent a therapeutic strategy with a wide therapeutic window to reduce brain damage and improve long-term recovery after ICH.

Keywords: melatonin, intracerebral hemorrhage, hyperglycemia, mitochondria, apoptosis

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