The role of TLR4 and HO‐1 in neuroinflammation after subarachnoid hemorrhage

Akamatsu, Yosuke; Pagan, Vicente A.; Hanafy, Khalid A.

doi:10.1002/jnr.24515

Cited by 29 publications

(34 citation statements)

References 96 publications

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“…Activation of TLR4 has been shown to trigger and modulate neuroinflammatory responses and contribute to secondary brain injury after both acute and chronic neurological diseases [ 32 ]. Previous studies using the mouse SAH model showed that activation of TLR4 promoted neuronal apoptosis via microglial- and MyD88-dependent mechanism in the early phase of SAH, whereas the toll receptor-associated activator of interferon (TRIF)-dependent but microglia-independent mechanism was involved in the late phase [ 33 ]. In the present study, the increased expression of TLR4 and MyD88 was detected by western blot after SAH, which was further enhanced by sleep deprivation.…”

Section: Discussionmentioning

confidence: 99%

Sleep deprivation aggravates brain injury after experimental subarachnoid hemorrhage via TLR4-MyD88 pathway

Tao

et al. 2021

Aging

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Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular disease, and most of the SAH patients experience sleep deprivation during their hospital stay. It is well-known that sleep deprivation is one of the key components of developing several neurological disorders, but its effect on brain damage after SAH has not been determined. Therefore, this study was designed to evaluate the effect of sleep deprivation using an experimental SAH model in rats. Induction of sleep deprivation for 24 h aggravated the SAH-induced brain damage, as evidenced by brain edema, neuronal apoptosis and activation of caspase-3. Sleep deprivation also worsened the neurological impairment and cognitive deficits after SAH. The results of immunostaining and western blot showed that sleep deprivation increased the activation of microglial cells. In addition, sleep deprivation differently regulated the expression of anti-inflammatory and pro-inflammatory cytokines. The results of immunofluorescence staining and western blot showed that sleep deprivation markedly increased the activation of Toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein 88 (MyD88). Mechanically, treatment with the TLR4 inhibitor TAK-242 or the MyD88 inhibitor ST2825 significantly attenuated the brain damage and neuroinflammation induced by sleep deprivation after SAH. In conclusion, our results indicate that sleep deprivation aggravates brain damage and neurological dysfunction following experimental SAH in rats. These effects were mediated by the activation of the TLR4-MyD88 cascades and regulation of neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

Sleep deprivation aggravates brain injury after experimental subarachnoid hemorrhage via TLR4-MyD88 pathway

Tao

et al. 2021

Aging

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“…In comparison, hemorrhagic strokes are caused by a ruptured artery or vessel that subsequently enables RBCs to enter the brain, leading to oxidative stress. When looking specifically at a hemorrhagic stroke, free heme- and hemoglobin (Hb)-induced neuroinflammation and cell death been have shown to worsen patient outcomes and exacerbate symptoms the longer they are left untreated [ 14 ]. One potential theory to improve outcomes is to reduce free-circulating RBCs, the haptoglobin and hemoglobin (Hp–Hb) complex, and the heme–hemopexin complex, which, respectively, bind to CD36, CD163, and LRP1 [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Soluble Receptors Affecting Stroke Outcomes: Potential Biomarkers and Therapeutic Tools

Bhattacharya

Ashouri

Fangman

et al. 2021

IJMS

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Soluble receptors are widely understood to be freestanding moieties formed via cleavage from their membrane-bound counterparts. They have unique structures, are found among various receptor families, and have intriguing mechanisms of generation and release. Soluble receptors’ ability to exhibit pleiotropic action by receptor modulation or by exhibiting a dual role in cytoprotection and neuroinflammation is concentration dependent and has continually mystified researchers. Here, we have compiled findings from preclinical and clinical studies to provide insights into the role of soluble/decoy receptors, focusing on the soluble cluster of differentiation 36, the soluble cluster of differentiation 163, and soluble lipoprotein-related protein 1 (sCD36, sCD163, and sLRP1, respectively) and the functions they could likely serve in the management of stroke, as they would notably regulate the bioavailability of the hemoglobin and heme after red blood cell lysis. The key roles that these soluble receptors play in inflammation, oxidative stress, and the related pharmacotherapeutic potential in improving stroke outcomes are described. The precise pleiotropic physiological functions of soluble receptors remain unclear, and further scientific investigation/validation is required to establish their respective role in diagnosis and therapy.

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“…Heme acts as a potent activator of TLR4 as well as the MyD88 and TRIF cascades that lead to neuroinflammation [ 204 ]. This effect may be mediated through the activation of heme oxygenase-1, an enzyme that catalyzes the degradation of heme [ 223 ]. While the activation of the TLR4-MyD88 cascade is mandatory for tissue injury and vasospasm in the early stage of SAH, tissue injury and vasospasm in the late phase of SAH are mediated through the TLR4-TRIF pathway [ 99 ].…”

Section: The Role Of Toll-like Receptors In Cvdsmentioning

confidence: 99%

Toll-Like Receptor Signaling Pathways: Novel Therapeutic Targets for Cerebrovascular Disorders

Ahmadabad

Mirzaasgari

Gorji

et al. 2021

IJMS

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Toll-like receptors (TLRs), a class of pattern recognition proteins, play an integral role in the modulation of systemic inflammatory responses. Cerebrovascular diseases (CVDs) are a group of pathological conditions that temporarily or permanently affect the brain tissue mostly via the decrease of oxygen and glucose supply. TLRs have a critical role in the activation of inflammatory cascades following hypoxic-ischemic events and subsequently contribute to neuroprotective or detrimental effects of CVD-induced neuroinflammation. The TLR signaling pathway and downstream cascades trigger immune responses via the production and release of various inflammatory mediators. The present review describes the modulatory role of the TLR signaling pathway in the inflammatory responses developed following various CVDs and discusses the potential benefits of the modulation of different TLRs in the improvement of functional outcomes after brain ischemia.

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The role of TLR4 and HO‐1 in neuroinflammation after subarachnoid hemorrhage

Cited by 29 publications

References 96 publications

Sleep deprivation aggravates brain injury after experimental subarachnoid hemorrhage via TLR4-MyD88 pathway

Sleep deprivation aggravates brain injury after experimental subarachnoid hemorrhage via TLR4-MyD88 pathway

Soluble Receptors Affecting Stroke Outcomes: Potential Biomarkers and Therapeutic Tools

Toll-Like Receptor Signaling Pathways: Novel Therapeutic Targets for Cerebrovascular Disorders

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