Fourth International Stroke Summit. Nanjing, China, July 25&amp;ndash;27, 2008

Liu, Xinfeng; Pu, Chuanqiang; Hacke, Werner; Chopp, Michael; Zhang, Suming; Xu, Gelin

doi:10.1159/000146077

Cited by 2 publications

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“…In our previous study, we also showed that intravenous administration of anti-TLR4 antibody 30 min prior to occlusion of the middle cerebral artery attenuated ischemia-reperfusion damage and improved mice behavioral performance [34]. In this study, we were interested in assessing the effect of neutralizing TLR4 using Mts510 in mice with ICH.…”

Section: Resultsmentioning

confidence: 99%

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Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage

Yin

Zhong

et al. 2012

J Neuroinflammation

290

264

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BackgroundInflammatory injury plays a critical role in intracerebral hemorrhage (ICH)-induced neurological deficits; however, the signaling pathways are not apparent by which the upstream cellular events trigger innate immune and inflammatory responses that contribute to neurological impairments. Toll-like receptor 4 (TLR4) plays a role in inflammatory damage caused by brain disorders.MethodsIn this study, we investigate the role of TLR4 signaling in ICH-induced inflammation. In the ICH model, a significant upregulation of TLR4 expression in reactive microglia has been demonstrated using real-time RT-PCR. Activation of microglia was detected by immunohistochemistry, cytokines were measured by ELISA, MyD88, TRIF and NF-κB were measured by Western blot and EMSA, animal behavior was evaluated by animal behavioristics.ResultsCompared to WT mice, TLR4−/− mice had restrained ICH-induced brain damage showing in reduced cerebral edema and lower neurological deficit scores. Quantification of cytokines including IL-6, TNF-α and IL-1β and assessment of macrophage infiltration in perihematoma tissues from TLR4−/−, MyD88−/− and TRIF−/− mice showed attenuated inflammatory damage after ICH. TLR4−/− mice also exhibited reduced MyD88 and TRIF expression which was accompanied by decreased NF-κB activity. This suggests that after ICH both MyD88 and TRIF pathways might be involved in TLR4-mediated inflammatory injury possibly via NF-κB activation. Exogenous hemin administration significantly increased TLR4 expression and microglial activation in cultures and also exacerbated brain injury in WT mice but not in TLR4−/− mice. Anti-TLR4 antibody administration suppressed hemin-induced microglial activation in cultures and in the mice model of ICH.ConclusionsOur findings suggest that heme potentiates microglial activation via TLR4, in turn inducing NF-κB activation via the MyD88/TRIF signaling pathway, and ultimately increasing cytokine expression and inflammatory injury in ICH. Targeting TLR4 signaling may be a promising therapeutic strategy for ICH.

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Section: Resultsmentioning

confidence: 99%

“…Mice in group 4) received class-match control rat anti-mouse mAb (IgG2α, 200 μg/mL, LifeSpan Biosciences, Seattle, WA, USA). The dose of antibodies used was based on our previous findings [34]. Cerebral water content and extent of neurological impairment were measured 3 days after ICH.…”

Section: Methodsmentioning

confidence: 99%

Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage

Yin

Zhong

et al. 2012

J Neuroinflammation

290

264

View full text Add to dashboard Cite

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Fast multimode MRI based emergency assessment of hyperacute stroke thrombolysis

Zhao

Bai

Sui

et al. 2009

Neurological Research

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Patients suffering from hyperacute ischemic cerebral infarction that are strong candidates for intravenous thrombolytic therapy can be identified by multimode MRI, especially for those whose time windows were undefined or beyond 3 hours after symptom onset. Fast multimodal MRI based selection of the hyperacute stroke model is more feasible compared with the traditional diffusion weighted imaging/perfusion weighted imaging mismatch model for the emergency assessment of hyperacute stroke thrombolysis.

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Fourth International Stroke Summit. Nanjing, China, July 25–27, 2008

Cited by 2 publications

References 0 publications

Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage

Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage

Fast multimode MRI based emergency assessment of hyperacute stroke thrombolysis

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