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Mar. Drugs 2015, 13(1), 29-47; doi:10.3390/md13010029

Marine Compound Xyloketal B Reduces Neonatal Hypoxic-Ischemic Brain Injury

1
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
2
Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
3
Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
4
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China
5
Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Keith B. Glaser
Received: 10 September 2014 / Accepted: 11 December 2014 / Published: 24 December 2014
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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. View Full-Text
Keywords: hypoxic-ischemic injury; infarct volume; neuroprotection; oxygen glucose deprivation; primary neuronal cell culture; neonatal stroke; behavioral tests; marine drug hypoxic-ischemic injury; infarct volume; neuroprotection; oxygen glucose deprivation; primary neuronal cell culture; neonatal stroke; behavioral tests; marine drug
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Xiao, A.-J.; Chen, W.; Xu, B.; Liu, R.; Turlova, E.; Barszczyk, A.; Sun, C.L.; Liu, L.; Deurloo, M.; Wang, G.-L.; Feng, Z.-P.; Sun, H.-S. Marine Compound Xyloketal B Reduces Neonatal Hypoxic-Ischemic Brain Injury. Mar. Drugs 2015, 13, 29-47.

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