Melatonin Alleviates Neuronal Damage After Intracerebral Hemorrhage in Hyperglycemic Rats.
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.
['Liang|Feng|F|', 'Wang|Jianli|J|', 'Zhu|Xiangyu|X|0000-0002-9498-7111', 'Wang|Zhen|Z|', 'Zheng|Jingwei|J|0000-0002-9152-6440', 'Sun|Zeyu|Z|', 'Xu|Shenbin|S|', 'Zhang|Jianmin|J|', 'Zhou|Jingyi|J|', 'Shi|Ligen|L|']
D000818:Animals D002543:Cerebral Hemorrhage D004195:Disease Models, Animal D006943:Hyperglycemia D007274:Injections, Intraperitoneal D008297:Male D008550:Melatonin D008928:Mitochondria D009474:Neurons D018696:Neuroprotective Agents D051381:Rats D017207:Rats, Sprague-Dawley
melatonin intracerebral hemorrhage hyperglycemia mitochondria apoptosis