Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms

Skelly, Donal; Griffin, Éadaoin W.; Murray, Carol; Harney, Sarah C.; O’Boyle, Conor; Hennessy, Edel; Rawlins, J. N. P.; Bannerman, David M.; Cunningham, Colm

doi:10.1101/127084

Cited by 5 publications

(2 citation statements)

References 67 publications

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“…In models of three different diseases IL-1 was also found to increase neuronal excitability. In epilepsy, IL-1 suppressed GABA induced inhibitory currents [193]; in a prion disease model, IL-1 depolarized CA1 neurons [194]; and in multiple sclerosis, elevated IL-1 cerebrospinal fluid (CSF) level was correlated with an increased response to transcranial magnetic stimulation, suggesting the neurons are hyperexcitable [195]. The increased neuronal activity can be blocked by IL-1Ra suggesting IL-1R1 signaling mediates the neuronal excitability increase in these diseases [195][196][197].…”

Section: Il-1 and Neuronal Cell Deathmentioning

confidence: 99%

Modulation of Neural Networks by Interleukin-1

Németh

Quan

2021

BPL

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Interleukin-1 (IL-1) is an inflammatory cytokine that has been shown to modulate neuronal signaling in homeostasis and diseases. In homeostasis, IL-1 regulates sleep and memory formation, whereas in diseases, IL-1 impairs memory and alters affect. Interestingly, IL-1 can cause long-lasting changes in behavior, suggesting IL-1 can alter neuroplasticity. The neuroplastic effects of IL-1 are mediated via its cognate receptor, Interleukin-1 Type 1 Receptor (IL-1R1), and are dependent on the distribution and cell type(s) of IL-1R1 expression. Recent reports found that IL-1R1 expression is restricted to discrete subpopulations of neurons, astrocytes, and endothelial cells and suggested IL-1 can influence neural circuits directly through neuronal IL-1R1 or indirectly via non-neuronal neuronal IL-1R1. In this review, we analyzed multiple mechanisms by which IL-1/IL-1R1 signaling might impact neuroplasticity based upon the most up-to-date literature and provided potential explanations to clarify discrepant and confusing findings reported in the past.

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Section: Il-1 and Neuronal Cell Deathmentioning

confidence: 99%

Modulation of Neural Networks by Interleukin-1

Németh

Quan

2021

BPL

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“…Thus, RAW264.7 macrophage is the most generally employed for drug screening for anti-inflammatory activity in vitro [ 9 ]. LPS, toll-like receptor 4 (TLR4) agonist, induces inflammation response on the macrophage, which induces pro-inflammatory cytokines release [ 10 , 11 ]. During pathological inflammation, immune cells are activated first [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Procyanidin A2, a polyphenolic compound, exerts anti-inflammatory and anti-oxidative activity in lipopolysaccharide-stimulated RAW264.7 cells

et al. 2020

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Procyandin A2 (PCA2) is a polyphenolic compound which is isolated from grape seeds. It has been reported that PCA2 exhibits antioxidative and anti-inflammatory effects, but its molecular mechanism is still poorly understood. This study tests the hypothesis that PCA2 suppresses lipopolysaccharide (LPS)-induced inflammation and oxidative stress through targeting the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and NF-E2-related factor 2 (Nrf2) pathways in RAW264.7 cells. PCA2 (20, 40, 80 μM) exhibited no significant cytotoxicity in RAW264.7 cells and showed an inhibitory effect on an LPSinduced nitrite level. Pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO), and reactive oxygen species (ROS) were suppressed by PCA2 with a concentration range of 0-80 μM. The mRNA levels of TNF-α and IL-6 were inhibited by PCA2 (80 μM). The hallmark-protein expression of the NF-κB (p-IKKα/β, p-IκBα, and p-p65) and MAPK (p-p38, p-JNK, and pERK) pathways were decreased by PCA2 in LPS-stimulated RAW264.7 cells. In addition, immunofluorescence results indicated that PCA2 (80 μM) promoted the translocation of NF-κB/p65 from the cytoplasm into the nucleus. PCA2 upregulated the expressions of Nrf2 and HO-1 and downregulated the expression of Keap-1. Simultaneously, PCA2 (80 μM) reversed LPS-induced Nrf2 translocation from the nucleus into the cytoplasm. Collectively, PCA2 protect cells against the damage from inflammation and oxidative injury, which suggest a potential therapeutic strategy for inflammatory and oxidative stress through targeting NF-κB, MAPK, and Nrf2 pathways in RAW264.7 cells.

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The Delirium and Population Health Informatics Cohort study protocol: ascertaining the determinants and outcomes from delirium in a whole population

Davis

Richardson

Hornby

et al. 2018

Preprint

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Background:Delirium affects 25% of older inpatients and is associated with long-term cognitive impairment and future dementia. However, no population studies have systematically ascertained cognitive function before, cognitive deficits during, and cognitive impairment after delirium. Therefore, there is a need to address the following question: does delirium, and its features (including severity, duration, and presumed aetiologies), predict long-term cognitive impairment, independent of cognitive impairment at baseline? Methods:The Delirium and Population Health Informatics Cohort (DELPHIC) study is an observational population-based cohort study based in the London Borough of Camden. It is recruiting 2000 individuals aged ≥ 70 years and prospectively following them for two years, including daily ascertainment of all inpatient episodes for delirium. Daily inpatient assessments include the Memorial Delirium Assessment Scale, the Observational Scale for Level of Arousal, and the Hierarchical Assessment of Balance and Mobility. Data on delirium aetiology is also collected. The primary outcome is the change in the modified Telephone Interview for Cognitive Status at two years. Discussion:DELPHIC is the first population sample to assess older persons before, during and after hospitalisation. The cumulative incidence of delirium in the general population aged ≥ 70 will be described. DELPHIC offers the opportunity to quantify the impact of delirium on cognitive and functional outcomes. Overall, DELPHIC will provide a real-time public health observatory whereby information from primary, secondary, intermediate and social care can be integrated to understand how acute illness is linked to health and social care outcomes.A definitive understanding of the natural history of delirium on risk of long-term cognitive impairment would have implications for identification and follow-up of patients at high risk of dementia, targeting acute treatment strategies, directing further research on mechanisms, and providing prognostic information to patients and carers. Methods AimTo determine the impact of delirium, and its features, on the risk of long-term cognitive impairment in a population sample.

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Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms

Abstract: 283Introduction: 476

Cited by 5 publications

References 67 publications

Modulation of Neural Networks by Interleukin-1

Modulation of Neural Networks by Interleukin-1

Procyanidin A2, a polyphenolic compound, exerts anti-inflammatory and anti-oxidative activity in lipopolysaccharide-stimulated RAW264.7 cells

The Delirium and Population Health Informatics Cohort study protocol: ascertaining the determinants and outcomes from delirium in a whole population

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