title: 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.affiliation: Department of Neurosurgery, General Hospital of Shenyang Military Area Command, Shenyang, China.
authors.forename: Yushu
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, China.|Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Chongxi
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Aerospace Medicine, The Fourth Military Medical University, Xi'an, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Shouyin
authors.initials: S
authors.lastname: Di
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, China.
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Xin
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, China.
authors.forename: Guiling
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA.
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.affiliation: Department of Neurosurgery, General Hospital of Shenyang Military Area Command, Shenyang, China.
authors.forename: Guobiao
authors.initials: G
authors.lastname: Liang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D020201:Brain Hemorrhage, Traumatic / Q000378:metabolism* / Q000473:pathology; D020170:Caspase 1 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects*; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology
chemical_list: C587672:IL1B protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D015850:Interleukin-6; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D020170:Caspase 1; D008550:Melatonin
keywords: early brain injury; inflammasome; melatonin; nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3; subarachnoid hemorrhage