Activation of TLR4-Mediated NFB Signaling in Hemorrhagic Brain in Rats

Weiyu Teng,Lishu Wang,Chao Guan,Weishuang Xue

doi:10.1155/2009/473276

Weiyu Teng, Lishu Wang + Show 2 more

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https://doi.org/10.1155/2009/473276

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Abstract

Inflammation and immunity play a crucial role in the pathogenesis of Intracerebral hemorrhage (ICH). Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa-B (NFκB) signaling plays critical roles in the activation and regulation of inflammatory responses in injured brain. However, the involvement of TLR4-mediated NFκB signaling in the pathogenesis of ICH remains unknown. The present study was to evaluate the temporal profile of the expression of TLR4 and the activation of TLR4-mediated NFκB signaling in brain tissues of Wistar rats after ICH. TLR4 mRNA and protein, the phosphorylation of inhibitors of kappa B (p-IκBα), and the activity of NFκB were examined in hemorrhagic cerebral tissue by Rt-PCR, Western blots, immunohistochemistry staining, and EMSA. Compared with saline control, the TLR4 mRNA and protein significantly increased starting at 6 hours after ICH, peaked on the 3rd day after ICH, and then decreased but still maintained at a higher level on the 7th day after ICH (P < .05). The level of p-IκBα and the activity of NFκB also increased in the brain after ICH compared with saline control. The present study firstly suggests that TLR4-mediated NFκB signaling participates in the pathogenesis of ICH, which may become a therapeutic target for ICH-induced brain damage.

Highlights

Intracerebral hemorrhage (ICH) represents 10%–15% of all strokes and occurs with increasing frequency as a complication of the thrombolytic treatment of ischemic stroke, which is associated with high mortality and severe disability in survivors [1, 2]
TLR4 mRNA Increased in Brain Tissue after ICH
The low level of TLR4 mRNA was observed in normal rat brain tissue

Summary

Introduction

Intracerebral hemorrhage (ICH) represents 10%–15% of all strokes and occurs with increasing frequency as a complication of the thrombolytic treatment of ischemic stroke, which is associated with high mortality and severe disability in survivors [1, 2]. Local brain tissue deformation induces primary brain damage after ICH; more importantly, the excitotoxicity and inflammatory responses in the brain tissue induced by ICH result in further brain damage following ICH [3]. Both innate and adaptive immunological/inflammatory mechanisms have been clearly shown to participate in the progression of brain injury after ischemic stroke. Activation of TLRs recruits downstream signaling proteins and results in transcription of genes encoding inflammation-associated molecules and cytokines [5, 6]. We detected the transcription of TLR4 gene and the activation of TLR4-mediated signaling in the rat brains subjected to experimental ICH. Our data firstly provided the knowledge about the distribution of TLR4 and the temporal profile of the activation of TLR4-mediated signaling in rat brain tissue after ICH

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