Astaxanthin mitigates subarachnoid hemorrhage injury primarily by increasing sirtuin 1 and inhibiting the Toll-like receptor 4 signaling pathway

Xiangsheng Zhang, Yue Lu, Qi Wu, Haibin Dai, Wei Li, Shengyin Lv, Xiaoming Zhou, Xin Zhang, Chunhua Hang, Jian Wang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)722-737
Number of pages16
JournalFASEB Journal
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • Early brain injury
  • Inflammation
  • Microglia
  • Neuroprotection

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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