Role of adaptor protein MyD88 in TLR-mediated preconditioning and neuroprotection after acute excitotoxicity

Larochelle, Antoine; Bellavance, Marc-André; Rivest, Serge

doi:10.1016/j.bbi.2015.02.019

Cited by 31 publications

(18 citation statements)

References 61 publications

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“…Our results suggest that microglia in the tri-culture play a significant neuroprotective role during excitotoxic events, in line with recent in vivo (Kato et al, 2016;Larochelle et al, 2015;Szalay et al, 2016) and hippocampal slice culture experiments (Masuch et al, 2015;Vinet et al, 2012). We observed significant neuronal cell loss and astrocyte hypotrophy in neuron-astrocyte co-cultures treated with 25 µM glutamate, which is significantly reduced in similarly treated tri-cultures ( Figure 4A).…”

Section: Response To Excitotoxicitysupporting

confidence: 90%

A Primary Neural Cell Culture Model for Neuroinflammation

Goshi

Morgan

Lein

et al. 2020

Preprint

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Interactions between neurons, astrocytes and microglia critically influence neuroinflammatory responses to insult in the central nervous system. Studying neuroinflammation in vitro has been difficult because most primary culture models do not include all three critical cell types. We describe an in vitro model of neuroinflammation comprised of neurons, astrocytes and microglia. Primary rat cortical cells were cultured in a serum-free medium used to co-culture neurons and astrocytes that is supplemented with three factors (IL-34, TGF-β and cholesterol) used to support isolated microglia. This "tri-culture" can be maintained for at least 14 days in vitro while retaining a physiologically-relevant representation of all three cell types. Additionally, we demonstrate that the tri-culture system responds to lipopolysaccharide, mechanical trauma and excitotoxicity with both neurotoxic and neuroprotective aspects of the neuroinflammatory response observed in vivo. We expect the tri-culture model will enable mechanistic studies of neuroinflammation in vitro with enhanced physiological relevance.

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Section: Response To Excitotoxicitysupporting

confidence: 90%

A Primary Neural Cell Culture Model for Neuroinflammation

Goshi

Morgan

Lein

et al. 2020

Preprint

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“…TLR2 is a transmembrane PRR that responds to exogenous and endogenous ligands (3). TLRs are expressed in a variety of immune cells and mediate neuroimmunity (26).…”

Section: Discussionmentioning

confidence: 99%

“…Microglial cells are macrophages specific to the central nervous system (CNS), which serve a crucial role in host defenses against toxins in the CNS (2). Specific stimulators may activate the microglial cells by binding with pattern-recognition receptors (PRR) on their surface (3). Microglial cells may be activated into two distinct types, which are designated as classically activated M1 and alternatively activated M2 cells.…”

Section: Introductionmentioning

confidence: 99%

Anti-neuroinflammatory effect of curcumin on Pam3CSK4-stimulated microglial cells

et al. 2017

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Curcumin is the main curcuminoid present in Curcuma longa and it has been previously reported to exhibit a wide range of pharmacological activities. In the present study, the inhibitory effects of curcumin on the inflammatory mediators released by Pam3CSK4-stimulated BV-2 microglial cells were investigated. The production of pro-inflammatory mediators and cytokines, including tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2), were measured by enzyme‑linked immunosorbent assay (ELISA). The expression of inflammatory genes, including inducible nitric oxide synthase and cyclooxygenase-2, were further investigated using reverse transcription-quantitative polymerase chain reaction. The effects of curcumin on heme oxygenase-1 (HO-1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways were analyzed by western blotting. The results revealed that curcumin dose-dependently inhibited Pam3CSK4-induced nitric oxide, PGE2, and TNF-α secretion. Curcumin suppressed the secretion of inflammatory mediators through an increase in the expression of HO-1. Curcumin induced HO-1 transcription and translation through the Nrf2/antioxidant response element signaling pathway. Inhibitory experiments revealed that HO-1 was required for the anti-inflammatory effects of curcumin. Further mechanistic studies demonstrated that curcumin inhibited neuroinflammation by suppressing NF-κB and MAPK signaling pathways in Pam3CSK4-activated microglial cells. The results of the present study suggest that curcumin may be a novel treatment for neuroinflammation-mediated neurodegenerative disorders.

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“…AIS activates the TLR signaling pathway, leads to the production of a plenty of inflammatory mediators, and triggers secondary inflammation damages. However, a mild ischemic insult can lead to TLR ischemic tolerance and decrease brain injury through the inhibition of the TLR4/NF-κB and TLR2 signaling pathway and the activation of IRF3 signaling: a process points to the beneficial effect of MyD88 signaling pathway [95]. In another word, exposure to a minor cerebral ischemia enhances neuronal tolerance to subsequent injury and shifts cellular signaling from NF-κB pathway to IRF3, which produces IFN-b, one of the final products of IRF3 signaling pathway with neuroprotective effects.…”

Section: The Role Of Toll-like Receptors In Acute Ischemic Strokementioning

confidence: 99%

The role of Toll-like receptor signaling pathways in cerebrovascular disorders: the impact of spreading depolarization

Ahmadabad

Ghadiri

Gorji

2020

J Neuroinflammation

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Cerebral vascular diseases (CVDs) are a group of disorders that affect the blood supply to the brain and lead to the reduction of oxygen and glucose supply to the neurons and the supporting cells. Spreading depolarization (SD), a propagating wave of neuroglial depolarization, occurs in different CVDs. A growing amount of evidence suggests that the inflammatory responses following hypoxic-ischemic insults and after SD plays a double-edged role in brain tissue injury and clinical outcome; a beneficial effect in the acute phase and a destructive role in the late phase. Toll-like receptors (TLRs) play a crucial role in the activation of inflammatory cascades and subsequent neuroprotective or harmful effects after CVDs and SD. Here, we review current data regarding the pathophysiological role of TLR signaling pathways in different CVDs and discuss the role of SD in the potentiation of the inflammatory cascade in CVDs through the modulation of TLRs.

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Role of adaptor protein MyD88 in TLR-mediated preconditioning and neuroprotection after acute excitotoxicity

Cited by 31 publications

References 61 publications

A Primary Neural Cell Culture Model for Neuroinflammation

A Primary Neural Cell Culture Model for Neuroinflammation

Anti-neuroinflammatory effect of curcumin on Pam3CSK4-stimulated microglial cells

The role of Toll-like receptor signaling pathways in cerebrovascular disorders: the impact of spreading depolarization

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