The role of Toll-like receptors (TLRs) in stroke

Fadakar, Kaveh; Dadkhahfar, Sahar; Esmaeili, Arash; Rezaei, Nima

doi:10.1515/revneuro-2013-0069

Cited by 31 publications

(23 citation statements)

References 103 publications

(126 reference statements)

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“…Additionally, there is no doubt that inflammation could contribute to EBI and lead to poor outcomes (Miller et al, 2014). As an extremely important part of innate immunity, toll-like receptors (TLRs) are host-cell surface receptors that detect the pathogen-associated molecular patterns (PAMPs) and DAMPSs that correspond to endogenous ligands released after tissue injury or cellular stress, such as ATP, histones, heat-shock proteins, mRNA, high-mobility group box-1 protein (HMGB1), and mitochondrial proteins (Aguirre et al, 2013; Fadakar et al, 2014). During the inflammatory response, activation of TLRs triggers the activation of several transcription factors, such as NF-κB, activator protein-1, and IFN-regulatory factor-3/-7, leading to the upregulation of various cytokines and chemokines at the early stage of SAH (Aguirre et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats

Zhou

et al. 2017

Front. Mol. Neurosci.

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Background: Accumulating evidence suggests that neuroinflammation plays a critical role in early brain injury after subarachnoid hemorrhage (SAH). Pannexin-1 channels, as a member of gap junction proteins located on the plasma membrane, releases ATP, ions, second messengers, neurotransmitters, and molecules up to 1 kD into the extracellular space, when activated. Previous studies identified that the opening of Pannexin-1 channels is essential for cellular migration, apoptosis and especially inflammation, but its effects on inflammatory response in SAH model have not been explored yet.Methods: Adult male Sprague-Dawley rats were divided into six groups: sham group (n = 20), SAH group (n = 20), SAH + LV-Scramble-ShRNA group (n = 20), SAH + LV-ShRNA-Panx1 group (n = 20), SAH + LV-NC group (n = 20), and SAH + LV-Panx1-EGFP group (n = 20). The rat SAH model was induced by injection of 0.3 ml fresh arterial, non-heparinized blood into the prechiasmatic cistern in 20 s. In SAH + LV-ShRNA-Panx1 group and SAH + LV-Panx1-EGFP group, lentivirus was administered via intracerebroventricular injection (i.c.v.) at 72 h before the induction of SAH. The Quantitative real-time polymerase chain reaction, electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, immunofluorescence staining, and western blotting were performed to explore the potential interactive mechanism between Pannexin-1 channels and TLR2/TLR4/NF-κB-mediated signaling pathway. Cognitive and memory changes were investigated by the Morris water maze test.Results: Administration with LV-ShRNA-Panx1 markedly decreased the expression levels of TLR2/4/NF-κB pathway-related agents in the brain cortex and significantly ameliorated neurological cognitive and memory deficits in this SAH model. On the contrary, administration of LV-Panx1-EGFP elevated the expressions of TLR2/4/NF-κB pathway-related agents, which correlated with augmented neuronal apoptosis.Conclusion: Pannexin-1 channels may contribute to inflammatory response and neurobehavioral dysfunction through the TLR2/TLR4/NF-κB-mediated pathway signaling after SAH, suggesting a potential role of Pannexin-1 channels could be a potential therapeutic target for the treatment of SAH.

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Section: Discussionmentioning

confidence: 99%

Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats

Zhou

et al. 2017

Front. Mol. Neurosci.

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“…TLRs are expressed on these endogenous brain cells, as well as the infiltrating immune cells that access lesions due to break down of the blood-brain barrier. The roles of TLRs in stroke and cerebrovascular injury can be classified into two major categories: 1) TLR activation postischemia that mediates neuroinflammation and neurodegeneration and 2) TLRs stimulation before ischemia that is neuroprotective and preconditions the brain to tolerate hypoxia and nutrient deprivation (Fadakar et al, 2014).…”

Section: Stroke/cerebrovascular Injurymentioning

confidence: 99%

Toll-like Receptors in the Vascular System: Sensing the Dangers Within

2015

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“…Other TLRs, such as TLR9, are localized intracellularly within endosomal membranes and primarily recognize nucleic acids. Some TLRs, TLR4 and TLR2 in particular, can recognize DAMPs from ischemic stroke events such as heat shock proteins, fibrinogen, RNA and methylated DNA (Fadakar et al, 2014). While the expression of all TLR orthologues has been reported in mouse microglia, TLR4 and TLR2 are the most predominantly expressed TLRs in the human brain (Nishimura and Naito, 2005; Olson and Miller, 2004).…”

Section: Introductionmentioning

confidence: 99%

Role of microglia in ischemic focal stroke and recovery: focus on Toll-like receptors

Anttila

Whitaker

Wires

et al. 2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Stroke is the leading cause of disability in adults. Drug treatments that target stroke-induced pathological mechanisms and promote recovery are desperately needed. In the brain, an ischemic event triggers major inflammatory responses that are mediated by the resident microglial cells. In this review, we focus on the microglia activation after ischemic brain injury as a target of immunomodulatory therapeutics. We divide the microglia-mediated events following ischemic stroke into three categories: acute, subacute, and long-term events. This division encompasses the spatial and temporal dynamics of microglia as they participate in the pathophysiological changes that contribute to the symptoms and sequela of a stroke. The importance of Toll-like receptor (TLR) signaling in the outcomes of these pathophysiological changes is highlighted. Increasing evidence shows that microglia have a complex role in stroke pathophysiology and they mediate both detrimental and beneficial effects on stroke outcome. So far, most of the pharmacological studies in experimental models of stroke have focused on neuroprotective strategies which are impractical for clinical applications. Post-ischemic inflammation is long lasting and thus, could provide a therapeutic target for novel delayed drug treatment. However, more studies are needed to elucidate the role of microglia in the recovery process from an ischemic stroke and to evaluate the therapeutic potential of modulating post-ischemic inflammation to promote functional recovery.

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The role of Toll-like receptors (TLRs) in stroke

Cited by 31 publications

References 103 publications

Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats

Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats

Toll-like Receptors in the Vascular System: Sensing the Dangers Within

Role of microglia in ischemic focal stroke and recovery: focus on Toll-like receptors

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