A5024565293- Neuroinflammation and Neurodegeneration Mechanisms
- Intensive Care Unit Cognitive Disorders
- Tryptophan and brain disorders
- Anesthesia and Neurotoxicity Research
- Alzheimer's disease research and treatments
- Prion Diseases and Protein Misfolding
- Immune Response and Inflammation
- Anesthesia and Sedative Agents
- Stress Responses and Cortisol
- Nuclear Receptors and Signaling
- Neuroscience and Neuropharmacology Research
- Neurological diseases and metabolism
- interferon and immune responses
- Immune cells in cancer
- Dementia and Cognitive Impairment Research
- Birth, Development, and Health
- Toxin Mechanisms and Immunotoxins
- Blood groups and transfusion
- Long-Term Effects of COVID-19
- Cardiovascular Syncope and Autonomic Disorders
- Streptococcal Infections and Treatments
- Mosquito-borne diseases and control
- T-cell and B-cell Immunology
- Viral Infections and Vectors
- Inflammasome and immune disorders
Trinity College Dublin
2016-2025
St. James's Hospital
2011-2022
National University of Ireland, Maynooth
2021
Trinity College
2021
Dementia Collaborative Research Centres
2019
University of Manitoba
2018
St. Boniface Hospital
2018
Virginia Commonwealth University
2013
University of Southampton
2002-2011
Moorgreen Hospital
2009-2011
The contribution of inflammation to the progression neurodegenerative diseases such as Alzheimer's, Parkinson's, and prion is poorly understood. Brain in animal models these dominated by chronic microglial activation with minimal proinflammatory cytokine expression. However, inflammatory cells are “primed” produce exaggerated responses subsequent lipopolysaccharide (LPS) challenges. We show that, using ME7 model disease, intracerebral challenge LPS results dramatic interleukin-1β (IL-1β)...
BackgroundChronic neurodegeneration results in microglial activation, but the contribution of inflammation to progress remains unclear. We have shown that microglia express low levels proinflammatory cytokines during chronic are "primed" produce a more profile after systemic challenge with bacterial endotoxin (lipopolysaccharide [LPS]).MethodsHere, we investigated whether intraperitoneal (IP) LPS, mimic infection, early stages prion disease can 1) exaggerated acute behavioral (n = 9) and...
Recent studies suggest that delirium is associated with risk of dementia and also acceleration decline in existing dementia. However, previous may have been confounded by incomplete ascertainment cognitive status at baseline. Herein, we used a true population sample to determine if factor for incident decline. We examined the effect pathological level determining associations between neuropathological markers patients without history delirium. The Vantaa 85+ study 553 individuals (92% those...
It is increasingly clear that systemic inflammation has both adaptive and deleterious effects on the brain. However, detailed comparisons of brain challenges with different pro-inflammatory cytokines are lacking. In present study, we challenged female C57BL/6 mice intraperitoneally LPS (100 µg/kg), IL-1β (15 or 50 TNF-α (50 250 µg/kg) IL-6 125 µg/kg). We investigated core body temperature, open field activity plasma levels inflammatory markers at 2 hours post injection. also examined...
<h3>Importance</h3> Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they the same as those dementia, independent, or interrelated. <h3>Objective</h3> To examine decline observed after delirium independent processes classic dementia. <h3>Design, Setting, and Participants</h3> Harmonized data from 987 individual brain donors 3 observational cohort studies population-based sampling (Vantaa 85+,...
Dementia prevalence increases with age and Alzheimer's disease (AD) accounts for up to 75% of cases. However, significant variability overlap exists in the extent amyloid-β Tau pathology AD non-demented populations it is clear that other factors must influence progression cognitive decline, perhaps independent effects on amyloid pathology. Coupled failure amyloid-clearing strategies provide benefits patients, seems necessary broaden paradigm dementia research beyond deposition clearance....
Neuroinflammation contributes to Alzheimer's disease (AD) progression. Secondary inflammatory insults trigger delirium and can accelerate cognitive decline. Individual cellular contributors this vulnerability require elucidation. Using APP/PS1 mice AD brain, we studied secondary investigate hypersensitive responses in microglia, astrocytes, neurons, human brain tissue. The NLRP3 inflammasome was assembled surrounding amyloid beta, microglia were primed, facilitating exaggerated...
Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play key role in its management. This update to the 2017 ESAIC Guideline on prevention of POD evidence-based consensus-based considers literature between 01 April 2015, 28 February 2022. search terms broad were identical those used first version guideline published 2017. was defined accordance with DSM-5 criteria. had be measured validated...
Prion diseases are fatal, chronic neurodegenerative of mammals, characterized by amyloid deposition, astrogliosis, microglial activation, tissue vacuolation and neuronal loss. In the ME7 model prion disease in C57BL/6 J mouse, we have shown previously that these animals display behavioural changes indicate onset dysfunction. The current study examines neuropathological correlates early changes. After injection ME7-infected homogenate into dorsal hippocampus, found statistically significant...
Delirium is an acute, severe neuropsychiatric syndrome, characterized by cognitive deficits, that highly prevalent in aging and dementia frequently precipitated peripheral infections. poorly understood the lack of biologically relevant animal models has limited basic research. Here we hypothesized synaptic loss accompanying microglial priming during chronic neurodegeneration ME7 mouse model prion disease predisposes these animals to acute dysfunction region prior pathology upon systemic...
Poor maternal nutrition during pregnancy can alter postnatal phenotype and increase susceptibility to adult cardiovascular metabolic diseases. However, underlying mechanisms are largely unknown. Here, we show that low protein diet (LPD), fed exclusively mouse preimplantation development, leads offspring with increased weight from birth, sustained hypertension, abnormal anxiety-related behavior, especially in females. These adverse outcomes were interrelated perinatal being predictive of...