title: Marine compound xyloketal B reduces neonatal hypoxic-ischemic brain injury.
abstract: Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. xaj527@163.com.
authors.forename: Ai-Jiao
authors.initials: AJ
authors.lastname: Xiao
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. wenliang.chen@utoronto.ca.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. liur@jlu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. e.turlova@mail.utoronto.ca.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Turlova
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. andrew.barszczyk@utoronto.ca.
authors.forename: Andrew
authors.initials: A
authors.lastname: Barszczyk
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. christopher.sun@mail.utoronto.ca.
authors.forename: Christopher Lf
authors.initials: CL
authors.lastname: Sun
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. liuling1978@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. marielle.deurloo@gmail.com.
authors.forename: Marielle
authors.initials: M
authors.lastname: Deurloo
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China. wangglei@mail.sysu.edu.cn.
authors.forename: Guan-Lei
authors.initials: GL
authors.lastname: Wang
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. zp.feng@utoronto.ca.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Feng
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. hss.sun@utoronto.ca.
authors.forename: Hong-Shuo
authors.initials: HS
authors.lastname: Sun
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D053148:Caspase 3 / Q000032:analysis; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy*; D051379:Mice; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011714:Pyrans / Q000737:chemistry / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011714:Pyrans; D051028:bcl-2-Associated X Protein; C515343:xyloketal B; D053148:Caspase 3