A5087752305- Traumatic Brain Injury and Neurovascular Disturbances
- Traumatic Brain Injury Research
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholesterol and Lipid Metabolism
- S100 Proteins and Annexins
- Drug Transport and Resistance Mechanisms
- Mitochondrial Function and Pathology
- Cardiac Arrest and Resuscitation
- Neuroscience and Neuropharmacology Research
- Peroxisome Proliferator-Activated Receptors
- Immune Response and Inflammation
- Spinal Cord Injury Research
- Hormonal Regulation and Hypertension
- Epilepsy research and treatment
- Neuroscience of respiration and sleep
- Immune cells in cancer
- Sleep and Wakefulness Research
- Cholinesterase and Neurodegenerative Diseases
- Signaling Pathways in Disease
- Circadian rhythm and melatonin
- Cancer, Lipids, and Metabolism
- Lipoproteins and Cardiovascular Health
- Sphingolipid Metabolism and Signaling
- Genetics and Neurodevelopmental Disorders
Georgetown University Medical Center
2015-2025
Georgetown University
2016-2025
Jewish Home
2018
Bruin Biometrics (United States)
2016
The Christie NHS Foundation Trust
2013
New York University
2003-2006
Mayo Clinic in Florida
2005
AstraZeneca (Sweden)
2005
Nathan Kline Institute for Psychiatric Research
2002-2005
Ollscoil na Gaillimhe – University of Galway
2004
Neurofibrillary tangles composed of hyperphosphorylated, aggregated tau are a common pathological feature tauopathies, including Alzheimer's disease. Abnormal phosphorylation by kinases or phosphatases has been proposed as pathogenic mechanism in tangle formation. To investigate whether kinase inhibition can reduce tauopathy and the degeneration associated with it vivo , transgenic mice overexpressing mutant human were treated glycogen synthase kinase-3 (GSK-3) inhibitor lithium chloride....
Abstract The activation of resident microglial cells, alongside the infiltration peripheral macrophages, are key neuroinflammatory responses to traumatic brain injury (TBI) that directly associated with neuronal death. Sexual disparities in response TBI have been previously reported; however it is unclear whether a sex difference exists progression after TBI. We exposed male and female mice moderate‐to‐severe controlled cortical impact studied glial cell acute chronic stages using...
Traumatic brain injury (TBI) can cause a broad array of behavioral problems including cognitive and emotional deficits. Human studies comparing neurobehavioral outcomes after TBI suggest that impairments increase with severity, but such as anxiety depression do not. To determine whether function severity we exposed mice to sham, mild, moderate, or severe controlled cortical impact (CCI) evaluated performance on variety tests in the same animals before assessing lesion volume histological...
Effective team science requires procedural harmonization for rigor and reproducibility. Multicenter studies across experimental modalities (domains) can help accelerate translation. The Translational Outcomes Project in NeuroTrauma (TOP-NT) is a pre-clinical traumatic brain injury (TBI) consortium charged with establishing validating noninvasive TBI assessment tools through science. Here, we present practical approaches of research five centers providing needed vocabulary structure to...
The secondary injury cascade that is activated following traumatic brain (TBI) induces responses from multiple physiological systems, including the immune system. These are not limited to area of injury; they can also alter peripheral organs such as intestinal tract. Gut microbiota play a role in regulation cell populations and microglia activation, microbiome dysbiosis implicated dysregulation behavioral abnormalities. However, changes gut induced after acute TBI remains largely unexplored....
The apolipoprotein E4 (APOE-ε4) allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, and may predispose individuals to Alzheimer's-related cognitive decline by affecting normal brain function early in life. To investigate impact of human APOE alleles on performance mice, we trained 3-mo-old targeted replacement mice (E2, E3, E4) Barnes maze locate enter a target hole along perimeter maze. Long-term spatial memory was probed 24 h 72 after training. We...
Hyperactivity, hypersensitivity to auditory stimuli, and exaggerated fear are common behavioral abnormalities observed in individuals with fragile X syndrome (FXS), a neurodevelopmental disorder that is the most genetic cause of autism. Evidence from studies Fmr1 knockout (KO) mouse model FXS supports notion impaired GABAergic transmission different brain regions such as amygdala, striatum or cerebral cortex central abnormalities. This suggests system might be an intriguing target ameliorate...
Traumatic Brain Injury (TBI) is a major cause of disability and mortality, to which there currently no comprehensive treatment. Blood Barrier (BBB) dysfunction well documented in human TBI patients, yet the molecular mechanisms that underlie this neurovascular unit (NVU) pathology remains unclear. The apolipoprotein-E (apoE) protein has been implicated controlling BBB integrity an isoform dependent manner, via suppression Cyclophilin A (CypA)–Matrix metallopeptidase-9 (MMP-9) signaling...
Traumatic brain injury (TBI) has long been a leading cause of death and disability, yet research failed to successfully translate findings from the pre-clinical, animal setting into clinic. One factor that contributes significantly this struggle is heterogeneity observed in clinical where patients present with injuries varying types, severities, comorbidities. Modeling highly varied population laboratory remains challenging. Given feasibility constraints, individual laboratories often focus...
Epidemiology, in vitro , and vivo studies strongly implicate a role for cholesterol the pathogenesis of Alzheimer's disease (AD). We have examined impact aberrant intracellular transport on processing amyloid precursor protein (APP) mouse model Niemann-Pick type C (NPC) disease. In NPC brain, accumulates late endosomes/lysosomes. This was associated with accumulation β-C-terminal fragments (CTFs) APP, but level β-secretase its activity were not affected. α-Secretase secreted APPα generation...
Soluble amyloid-beta (Aβ) oligomers are hypothesized to be the pathogenic species in Alzheimer's disease (AD), and increased levels of brain subsequent traumatic injury (TBI) may exacerbate secondary pathways underlie risk developing AD later life. To determine whether TBI causes Aβ aggregation oligomerization brain, we exposed triple transgenic model mice controlled cortical impact measured soluble, insoluble, oligomeric by enzyme-linked immunosorbent assay (ELISA) at 1, 3, 7 days...
The clinical manifestations that occur after traumatic brain injury (TBI) include a wide range of cognitive, emotional, and behavioral deficits. loss excitatory synapses could potentially explain why such diverse symptoms TBI, recent preclinical study has demonstrated dendritic spines, the postsynaptic site synapse, fluid percussion injury. objective this was to determine if controlled cortical impact (CCI) also resulted in spine retraction probe underlying mechanisms loss. We used...
NADPH oxidase (NOX2) is an enzyme system that generates reactive oxygen species (ROS) in microglia and macrophages. Excessive ROS production linked with neuroinflammation chronic neurodegeneration following traumatic brain injury (TBI). Redox signaling regulates macrophage/microglial phenotypic responses (pro-inflammatory versus anti-inflammatory), NOX2 inhibition moderate-to-severe TBI markedly reduces pro-inflammatory activation of macrophages/microglia resulting concomitant increases...
ABCA1 promotes cholesterol efflux from cells and is required for maintaining plasma levels. Cholesterol homeostasis important in the production of beta-amyloid (Abeta), a peptide that overproduced Alzheimer's disease (AD). Overexpression can be achieved by stimulating Liver X Receptors (LXR), changes Abeta have been reported after LXR stimulation vitro. To determine whether could alter endogenous levels, we used two different vivo systems. We first examined effects an agonist (TO-901317) on...
Abstract Apolipoprotein E (apoE) has been implicated in modulating the central nervous system (CNS) inflammatory response. However, molecular mechanisms involved apoE‐dependent immunomodulation are poorly understood. We hypothesize that apoE alters CNS response by signaling via low‐density lipoprotein (LDL) receptors glia. To address this hypothesis, we used a small bioactive peptide formed from receptor‐binding domain of apoE, (EP), to study LDL receptor microglia. model glial activation,...
Alzheimer's disease and Parkinson's are common neurodegenerative diseases that may share some underlying mechanisms of pathogenesis. Aβ 1–42 fragments found intracellularly, extracellularly as amyloid plaques, in dementia with Lewy Bodies. Parkin is an E3-ubiquitin ligase involved proteasomal degradation intracellular proteins. Mutations parkin, which result loss parkin function, lead to early onset Parkinsonism. Here we tested whether the ubiquitin activity could reduction human ....