Curcumin Mitigates Neuro-Inflammation by Modulating Microglia Polarization Through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid Hemorrhage

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 phytoc...

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Main Authors: YongYue Gao, Zong Zhuang, Yue Lu, Tao Tao, Yan Zhou, GuangJie Liu, Han Wang, DingDing Zhang, LingYun Wu, HaiBin Dai, Wei Li, ChunHua Hang
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-11-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnins.2019.01223/full
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author YongYue Gao
Zong Zhuang
Yue Lu
Tao Tao
Yan Zhou
GuangJie Liu
Han Wang
DingDing Zhang
LingYun Wu
HaiBin Dai
Wei Li
ChunHua Hang
author_facet YongYue Gao
Zong Zhuang
Yue Lu
Tao Tao
Yan Zhou
GuangJie Liu
Han Wang
DingDing Zhang
LingYun Wu
HaiBin Dai
Wei Li
ChunHua Hang
author_sort YongYue Gao
collection DOAJ
description 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 end labeling (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.
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spelling doaj.art-c45179ed9f084d1ebb822ffb2736a9982022-12-22T02:05:44ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-11-011310.3389/fnins.2019.01223496029Curcumin Mitigates Neuro-Inflammation by Modulating Microglia Polarization Through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid HemorrhageYongYue Gao0Zong Zhuang1Yue Lu2Tao Tao3Yan Zhou4GuangJie Liu5Han Wang6DingDing Zhang7LingYun Wu8HaiBin Dai9Wei Li10ChunHua Hang11Department of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital Nanjing University Medicine School, Nanjing, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital Nanjing University Medicine School, Nanjing, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital Nanjing University Medicine School, Nanjing, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital Nanjing University Medicine School, Nanjing, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital Nanjing University Medicine School, Nanjing, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Clinical Medical College of Southern Medical University, Guangzhou, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital Nanjing University Medicine School, Nanjing, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital Nanjing University Medicine School, Nanjing, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital Nanjing University Medicine School, Nanjing, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital Nanjing University Medicine School, Nanjing, ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital Nanjing University Medicine School, Nanjing, ChinaSubarachnoid 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 end labeling (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.https://www.frontiersin.org/article/10.3389/fnins.2019.01223/fulltoll-like receptor 4subarachnoid hemorrhagecurcuminneuro-inflammationmicroglia polarization
spellingShingle YongYue Gao
Zong Zhuang
Yue Lu
Tao Tao
Yan Zhou
GuangJie Liu
Han Wang
DingDing Zhang
LingYun Wu
HaiBin Dai
Wei Li
ChunHua Hang
Curcumin Mitigates Neuro-Inflammation by Modulating Microglia Polarization Through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid Hemorrhage
Frontiers in Neuroscience
toll-like receptor 4
subarachnoid hemorrhage
curcumin
neuro-inflammation
microglia polarization
title Curcumin Mitigates Neuro-Inflammation by Modulating Microglia Polarization Through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid Hemorrhage
title_full Curcumin Mitigates Neuro-Inflammation by Modulating Microglia Polarization Through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid Hemorrhage
title_fullStr Curcumin Mitigates Neuro-Inflammation by Modulating Microglia Polarization Through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid Hemorrhage
title_full_unstemmed Curcumin Mitigates Neuro-Inflammation by Modulating Microglia Polarization Through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid Hemorrhage
title_short Curcumin Mitigates Neuro-Inflammation by Modulating Microglia Polarization Through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid Hemorrhage
title_sort curcumin mitigates neuro inflammation by modulating microglia polarization through inhibiting tlr4 axis signaling pathway following experimental subarachnoid hemorrhage
topic toll-like receptor 4
subarachnoid hemorrhage
curcumin
neuro-inflammation
microglia polarization
url https://www.frontiersin.org/article/10.3389/fnins.2019.01223/full
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