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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.01223

Curcumin Mitigates Neuroinflammation by Modulating Microglia Polarization through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid Hemorrhage

 Yongyue Gao1, Zong Zhuang1,  Yue Lu1, Tao Tao1, Yan Zhou1, Guangjie Liu1, Han Wang1,  Dingding Zhang1,  LINGYUN WU1, Haibin Dai1, Wei Li1* and  Chunhua Hang1*
  • 1Department of Neurosurgery, Nanjing Drum Tower Hospital, China

Subarachnoid hemorrhage (SAH) elicits destruction of neuronal cells and neurological function, which is exacerbated by neuro-inflammation in EBI, and toll-like receptor 4 (TLR4) plays an important role in inflammatory cascade via modulation microglia polarization. Curcumin (Cur), as a natural phytochemical compound, has the potential characteristics on anti-inflammatory and microglia phenotype transformation. In this study, we verified the hypothesis curcumin promotes M2 polarization to inhibiting neuro-inflammation, which through suppressing TLR4 signaling pathway after SAH. In tlr4-/- mice and wild type (WT) subjected to prechiasmatic cistern blood injection, Western blotting, brain water content, neurological score, enzyme-linked immunosorbent assay (ELISA) and terminal deoxynucleotidyl transferase dUTP nick endlabeling (TUNEL) staining were performed to investigate the role of TLR4 on neuro-inflammation response and microglia polarization. Curcumin with three different concentrations (50 mg/kg, 100 mg/kg and 200 mg/kg) were injected intraperitoneally (i.p.) at 15 min after SAH. The levels of TLR4, myeloid differentiation factor 88 (MyD88), nuclear factor- κB (NF-κB), Iba-1, CD86, CD206 and pro/anti-inflammation cytokines were measured by Western blotting and immunofluorescence staining at 24 h after SAH. SAH induction increased the protein levels of TLR4, pro-inflammation cytokines and proportion of M1 phenotype. Curcumin with 100 mg/kg treatment dramatically inhibited the release of pro-inflammatory mediators, and elevated the protein levels of anti-inflammatory cytokines and promoted microglia switch to M2. Meanwhile, curcumin treatment also decreased the expressions of TLR4, Myd88 and NF-κB at 24 h post SAH. TLR4 deficiency ameliorated brain water content, neurological deficit and reduced pro-inflammation cytokines after SAH. Moreover, curcumin treatment in tlr4-/- mice further induced M2 polarization, while had no statistic difference on brain water content and neurological score at 24 h post SAH. Our results indicated that curcumin treatment alleviated neuro-inflammation response through promoting microglia phenotype shift toward M2, and which might inhibiting TLR4/MyD88/NF-κB signaling pathway after SAH.

Keywords: Toll-Like Receptor 4, Subarachnoid Hemorrhage, Curcumin, Neuro-inflammation, Microglia polarization

Received: 05 Sep 2019; Accepted: 29 Oct 2019.

Copyright: © 2019 Gao, Zhuang, Lu, Tao, Zhou, Liu, Wang, Zhang, WU, Dai, Li and Hang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Wei Li, Department of Neurosurgery, Nanjing Drum Tower Hospital, Nanjing, China, lvxzlv@126.com
Prof. Chunhua Hang, Department of Neurosurgery, Nanjing Drum Tower Hospital, Nanjing, China, hang_neurosurgery@163.com