Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling.

Abstract

Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti-inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood-brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-1β (IL-1β), and interleukin-6 (IL-6); these changes were also associated with an increase in the anti-apoptotic factor (Bcl2) and reduction in the pro-apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome-associated apoptosis.

• Authors: Yushu Dong, Chongxi Fan, Wei Hu, Shuai Jiang, Zhiqiang Ma, Xiaolong Yan, Chao Deng, Shouyin Di, Zhenlong Xin, Guiling Wu, Yang Yang, Russel J Reiter, Guobiao Liang
• Journal: Journal of pineal research (J Pineal Res) Vol. 60 Issue 3 Pg. 253-62 (Apr 2016) ISSN: 1600-079X [Electronic] England
• PMID: 26639408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• IL1B protein, mouse
• Inflammasomes
• Interleukin-1beta
• Interleukin-6
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Caspase 1
• Melatonin

Topics

• Animals
• Apoptosis (drug effects)
• Blood-Brain Barrier (metabolism, pathology)
• Brain Hemorrhage, Traumatic (metabolism, pathology)
• Caspase 1 (metabolism)
• Gene Expression Regulation (drug effects)
• Inflammasomes (metabolism)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Male
• Melatonin (pharmacology)
• Mice
• NLR Family, Pyrin Domain-Containing 3 Protein (biosynthesis)
• Signal Transduction (drug effects)
• Subarachnoid Hemorrhage (metabolism, pathology)