@article{73cb6ed0ba5f4f30823d35157e205424,
title = "Astaxanthin mitigates subarachnoid hemorrhage injury primarily by increasing sirtuin 1 and inhibiting the Toll-like receptor 4 signaling pathway",
abstract = "Inflammation plays a key roleinthe progression of subarachnoidhemorrhage(SAH).Here, we examined the effects of astaxanthin (ATX) on the inflammatory response and secondary damage after SAH and the underlying mechanisms of action. In vivo, a prechiasmatic cistern injection model was established in rats and mice. In addition, neuron-microglia cocultures were exposed to oxyhemoglobin to mimic SAH in vitro.Western blotting revealedthat protein expression of TLR4 was markedly increased in microglia at 24 h after SAH, with consequent increases in the downstream molecules myeloid differentiation factor 88 and NF-κB. Treatment withATX significantly inhibitedthe TLR4 activation, increased sirtuin 1 expression, and inhibited the subsequent inflammatory response both in vivo and in vitro. ATX also significantly decreased high-mobility group box 1 nuclear translocation and secretion in neurons, an effect that was reversed by the sirtuin 1-specific inhibitor sirtinol. ATX administered 4 h after SAH ameliorated cerebral inflammation, brain edema, and neuronal death and improved neurologic function. ATX reduced neuronal death but did not improve neurologic function in TLR4 knockout mice. These results suggest that ATX reduces the proinflammatory response and secondary brain injury after SAH, primarily by increasing sirtuin 1 levels and inhibiting the TLR4 signaling pathway.",
keywords = "Early brain injury, Inflammation, Microglia, Neuroprotection",
author = "Xiangsheng Zhang and Yue Lu and Qi Wu and Haibin Dai and Wei Li and Shengyin Lv and Xiaoming Zhou and Xin Zhang and Chunhua Hang and Jian Wang",
note = "Funding Information: This work was supported by the National Natural Science Foundation of China (Grants 81471183 to Xin Zhang, 81501022 to Xiangsheng Zhang, and 81771292 to C.H.), the American Heart Association Grant-in-Aid (17GRNT33660766), and a Stimulating and Advancing Anesthesiology and Critical Care Medicine (ACCM) Research (StAAR) grant from the Department of Anesthesiology and Critical Care Medicine, at Johns Hopkins University. Xiangsheng Zhang is a recipient of the China Scholarship Council Joint Ph.D. training award. The authors declare no conflicts of interest.*%blankline%* Funding Information: The authors thank Dr. Bo Yu and YanLing Han (both from Jinling Hospital) for their generous assistance with pathologic examinations. The authors also thank Claire Levine, M.S., ELS, for assistance with manuscript preparation and the J.W. laboratory team members for insightful input. This work was supported by the National Natural Science Foundation of China (Grants 81471183 to Xin Zhang, 81501022 to Xiangsheng Zhang, and 81771292 to C.H.), the American Heart Association Grant-in-Aid (17GRNT33660766), and a Stimulating and Advancing Anesthesiology and Critical Care Medicine (ACCM) Research (StAAR) grant from the Department of Anesthesiology and Critical Care Medicine, at Johns Hopkins University. Xiangsheng Zhang is a recipient of the China Scholarship Council Joint Ph.D. training award. The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} FASEB.",
year = "2019",
month = jan,
doi = "10.1096/fj.201800642RR",
language = "English (US)",
volume = "33",
pages = "722--737",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "1",
}