title: Astaxanthin activates nuclear factor erythroid-related factor 2 and the antioxidant responsive element (Nrf2-ARE) pathway in the brain after subarachnoid hemorrhage in rats and attenuates early brain injury.
abstract: Astaxanthin (ATX) has been proven to ameliorate early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH) by modulating cerebral oxidative stress. This study was performed to assess the effect of ATX on the Nrf2-ARE pathway and to explore the underlying molecular mechanisms of antioxidant properties of ATX in EBI after SAH. A total of 96 male SD rats were randomly divided into four groups. Autologous blood was injected into the prechiasmatic cistern of the rat to induce an experimental SAH model. Rats in each group were sacrificed at 24 h after SAH. Expressions of Nrf2 and heme oxygenase-1 (HO-1) were measured by Western blot and immunohistochemistry analysis. The mRNA levels of HO-1, NAD (P) H: quinone oxidoreductase 1 (NQO-1), and glutathione S-transferase-α1 (GST-α1) were determined by real-time polymerase chain reaction (PCR). It was observed that administration of ATX post-SAH could up-regulate the cortical expression of these agents, mediated in the Nrf2-ARE pathway at both pretranscriptional and posttranscriptional levels. Meanwhile, oxidative damage was reduced. Furthermore, ATX treatment significantly attenuated brain edema, blood-brain barrier (BBB) disruption, cellular apoptosis, and neurological dysfunction in SAH models. This study demonstrated that ATX treatment alleviated EBI in SAH model, possibly through activating the Nrf2-ARE pathway by inducing antioxidant and detoxifying enzymes.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. 18652021010@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. zhangxssp@163.com.
authors.forename: Xiang-Sheng
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. njhdwang@hotmail.com.
authors.forename: Han-Dong
authors.initials: HD
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. njzx@smail.nju.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China. njyuqing@me.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. lwxzlw@gmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. mlzhou1979@hotmail.com.
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. wangxiaoliang1234@hotmail.com.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000187:drug effects*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005982:Glutathione Transferase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D007527:Isoenzymes; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D024341:Xanthophylls; C005948:astaxanthine; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha