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

Marine Drugs

Qi Wu¹  Xiang-Sheng Zhang¹  Han-Dong Wang¹  Xin Zhang¹  Qing Yu²  Wei Li¹  Meng-Liang Zhou¹  Xiao-Liang Wang¹ 

[1] Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China; E-Mails:;Department of Clinical Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China; E-Mail:

关键词: astaxanthin;    early brain injury;    subarachnoid hemorrhage;    nuclear factor erythroid-related factor 2;   

DOI  :  10.3390/md12126125

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.