title: Melatonin Attenuates Early Brain Injury via the Melatonin Receptor/Sirt1/NF-κB Signaling Pathway Following Subarachnoid Hemorrhage in Mice.
abstract: Melatonin (Mel) has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of silent information regulator 1 (Sirt1), a histone deacetylase, has been suggested to be beneficial in SAH. However, the precise role of Sirt1 in Mel-mediated protection against EBI following SAH has not been elucidated. The present study aims to evaluate the role of melatonin receptor/Sirt1/nuclear factor-kappa B (NF-κB) in this process. The endovascular perforation SAH model was used in male C57BL/6J mice, and melatonin was administrated intraperitoneally (150 mg/kg). The mortality, SAH grade, neurological score, brain water content, and neuronal apoptosis were evaluated. The expression of Sirt1, acetylated-NF-κB (Ac-NF-κB), Bcl-2, and Bax were detected by western blot. To study the underlying mechanisms, melatonin receptor (MR) antagonist luzindole and Sirt1 small interfering RNA (siRNA) were administrated to different groups. The results suggest that Mel improved the neurological deficits and reduced the brain water content and neuronal apoptosis. In addition, Mel enhanced the expression of Sirt1 and Bcl-2 and decreased the expression of Ac-NF-κB and Bax. However, the protective effects of Mel were abolished by luzindole or Sirt1 siRNA. In conclusion, our results demonstrate that Mel attenuates EBI following SAH via the MR/Sirt1/NF-κB signaling pathway.
authors: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors: Lei
authors: L
authors: Zhao
authors: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors: Haixiao
authors: H
authors: Liu
authors: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors: Liang
authors: L
authors: Yue
authors: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors: Jingbo
authors: J
authors: Zhang
authors: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors: Xia
authors: X
authors: Li
authors: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors: Bodong
authors: B
authors: Wang
authors: Department of Scientific Research, The Fourth Military Medical University, Xi'an, China.
authors: Yan
authors: Y
authors: Lin
authors: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China. yanqu0123@163.com.|Department of Neurosurgery, Tangdu Hospital, No. 1 Xinsi Road, Xi'an, 710038, China. yanqu0123@163.com.
authors: Yan
authors: Y
authors: Qu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000096:biosynthesis*; D011897:Random Allocation; D044094:Receptors, Melatonin / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D056564:Sirtuin 1 / Q000096:biosynthesis*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D044094:Receptors, Melatonin; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D008550:Melatonin
keywords: Early brain injury; Melatonin receptor; Sirt1/NF-κB signaling; Subarachnoid hemorrhage