title: Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies.
abstract: Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of morbidity and mortality in neonates. Because of high concentrations of sensitive immature cells, metal-catalyzed free radicals, non-saturated fatty acids, and low concentrations of antioxidant enzymes, the brain requires high levels of oxygen supply and is, thus, extremely sensitive to hypoxia. Strong evidence indicates that oxidative stress plays an important role in pathogenesis and progression. Following hypoxia and ischemia, reactive oxygen species (ROS) production rapidly increases and overwhelms antioxidant defenses. A large excess of ROS will directly modify or degenerate cellular macromolecules, such as membranes, proteins, lipids, and DNA, and lead to a cascading inflammatory response, and protease secretion. These derivatives are involved in a complex interplay of multiple pathways (e.g., inflammation, apoptosis, autophagy, and necrosis) which finally lead to brain injury. In this review, we highlight the molecular mechanism for oxidative stress in HIE, summarize current research on therapeutic strategies utilized in combating oxidative stress, and try to explore novel potential clinical approaches.
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital, Central South University, Changsha 410006, China. zhaomingyi1983@aliyun.com.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China. zhupingzggd@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan. nekonagashi@hotmail.com.|National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. nekonagashi@hotmail.com.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujino
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China. zhuangjianzggd@aliyun.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China. guohuiming@vip.tom.cn.
authors.forename: Huiming
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital, Central South University, Changsha 410006, China. Dr_idris99@outlook.com.
authors.forename: IdrisAhmed
authors.initials: I
authors.lastname: Sheikh
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital, Central South University, Changsha 410006, China. llzhao@xy3yy.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital, Central South University, Changsha 410006, China. ri-k@ncchd.go.jp.|National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan. ri-k@ncchd.go.jp.
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D017382:Reactive Oxygen Species
keywords: cell damage; hypoxic-ischemic encephalopathy; oxidative stress; therapeutic strategy