A5087624641- Traumatic Brain Injury and Neurovascular Disturbances
- Traumatic Brain Injury Research
- Alzheimer's disease research and treatments
- Sleep and Wakefulness Research
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Computational Drug Discovery Methods
- Stress Responses and Cortisol
- S100 Proteins and Annexins
- Metabolomics and Mass Spectrometry Studies
- Circadian rhythm and melatonin
- Tryptophan and brain disorders
- Spacecraft and Cryogenic Technologies
- Neuroendocrine regulation and behavior
- Acute Ischemic Stroke Management
- Neural dynamics and brain function
- Molecular spectroscopy and chirality
- Protein Interaction Studies and Fluorescence Analysis
- Protein Structure and Dynamics
- Cerebrospinal fluid and hydrocephalus
- Cardiac Arrest and Resuscitation
- Child Abuse and Related Trauma
- Drug Transport and Resistance Mechanisms
- Receptor Mechanisms and Signaling
MaineGeneral Medical Center
2022-2023
Harvard University
2022-2023
Massachusetts General Hospital
2022-2023
The Open University
2016-2020
James A. Haley Veterans' Hospital
2016-2020
Roskamp Institute
2016-2020
Bay Pines VA Healthcare System
2016
Queen Elizabeth University Hospital
2016
University of Pennsylvania
2016
University of Glasgow
2016
Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic encephalopathy, which characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths cortical sulci. We developed an mTBI paradigm explore effects concussive-type over several months mice with human genetic background (hTau). Two injuries were induced hTau weekly period 3 or 4 compared those noninjured sham animals. Behavioral vivo measures detailed...
Abstract Alzheimer’s disease (AD) is characterized by progressive memory loss and cognitive decline. These impairments correlate with early alterations in neuronal network activity AD patients. Disruptions the of individual neurons have been reported mouse models amyloidosis. However, impact amyloid pathology on spontaneous distinct types remains unexplored vivo. Here we use vivo calcium imaging multiphoton microscopy to monitor compare excitatory two inhibitory interneurons cortices APP/PS1...
Abstract Background Alzheimer’s disease (AD) patients exhibit memory disruptions and profound sleep disturbances, including disruption of deep non-rapid eye movement (NREM) sleep. Slow-wave activity (SWA) is a major restorative feature NREM important for consolidation. Methods We generated mouse model where GABAergic interneurons could be targeted in the presence APPswe/PS1dE9 (APP) amyloidosis, APP-GAD-Cre mice. An electroencephalography (EEG) / electromyography (EMG) telemetry system was...
Repetitive mild traumatic brain injury (rmTBI) is a major epigenetic risk factor for Alzheimer’s disease (AD). The precise nature of how rmTBI leads to or precipitates AD pathology currently unknown. Numerous neurological conditions have shown an important role dysfunctional phospholipid metabolism as driving the pathogenesis neurodegenerative diseases. However, in and remains elusive. We hypothesized that detailed characterization would reveal profiles response TBI overlap with...
Incidence of post-traumatic stress disorder (PTSD) ranges from 3 to 30% in individuals exposed traumatic events, with the highest prevalence groups combat, torture, or rape. To date, only a few FDA approved drugs are available treat PTSD, which offer symptomatic relief and variable efficacy. There is, therefore, an urgent need explore new concepts regarding biological responses causing PTSD. Animal models appropriate platform for conducting such studies. Herein, we examined chronic...
Patients with Alzheimer's disease (AD) exhibit non-rapid eye movement (NREM) sleep disturbances in addition to memory deficits. Disruption of NREM slow waves occurs early the progression and is recapitulated transgenic mouse models beta-amyloidosis. However, mechanisms underlying slow-wave disruptions remain unknown. Because astrocytes contribute activity, we used multiphoton microscopy optogenetics investigate whether they APP/PS1 mice. The power but not frequency astrocytic calcium...
Repetitive mild traumatic brain injury (mTBI) is a risk factor for the development of neurodegenerative diseases such as chronic encephalopathy typified by immunoreactive tau aggregates in depths sulci. However, underlying neurobiological mechanisms involved have not been largely explored. Phospholipids are important molecules which form membrane lipid bilayers; they ubiquitous to every cell brain, and carry out host different functions. Imbalance phospholipid metabolism, signaling transport...
Abstract Background The ventricular system plays a vital role in blood-cerebrospinal fluid (CSF) exchange and interstitial fluid-CSF drainage pathways. CSF is formed the specialized secretory tissue called choroid plexus, which consists of epithelial cells, fenestrated capillaries highly vascularized stroma. Very little currently known about played by ventricles plexus aging Alzheimer’s disease (AD). Methods In this study, we used our state-of-the-art proteomic platform, liquid...
Clinical studies examining the interaction between traumatic brain injury (TBI) and stress-related disorders (e.g., post-traumatic stress disorder) are often complicated by methodological constraints, such as heterogeneity in type severity, time post-trauma, predisposing risk factors. Developing relevant animal models whereby many variables can be efficiently controlled is thus essential to understanding this elusive relationship. Here, we use our repeated unpredictable (RUS) paradigm,...
Incidences of repetitive mild TBI (r-mTBI), like those sustained by contact sports athletes and military personnel, are thought to be a risk factor for development neurodegenerative disorders. Those suffering from chronic TBI-related illness demonstrate deficits in cerebrovascular reactivity (CVR), the ability cerebral vasculature respond vasoactive stimulus. CVR is thus an important measure traumatic vascular injury (TCVI), possible vivo endophenotype neuropathogenesis. We combined laser...
Objectives: We hypothesized that polypathology is more severe in older than younger mice during the acute phase following repetitive mild traumatic brain injury (r-mTBI).Methods: Young and aged male female transgenic for human tau (hTau) were exposed to r-mTBI or a sham procedure. Twenty-four hours post-last injury, mouse tissue was immunostained alterations astrogliosis, microgliosis, pathology, axonal injury.Results: Quantitative analysis revealed greater percent distribution of glial...
Abstract Alzheimer’s disease (AD) is characterized by synaptic loss and neuronal network dysfunction. These deficits are mediated early alterations in firing rates that coincide with amyloid plaque accumulation. Mounting evidence supports inhibitory networks impaired AD, but the mechanisms driving these poorly understood. Here we use vivo multiphoton calcium imaging to determine relationship between accumulation spontaneous activity of excitatory neurons interneurons an APP/PS1 mouse model...
The relationship between repetitive mild traumatic brain injury (r-mTBI) and Alzheimer’s disease (AD) is well-recognized. However, the precise nature of how r-mTBI leads to or precipitates AD pathogenesis currently not understood. Plasma biomarkers potentially provide non-invasive tools for detecting neurological changes in brain, can reveal overlaps long-term consequences AD. In this study we address by generating time-dependent molecular profiles response mouse models using unbiased...
No concerted investigation has been conducted to explore overlapping and distinct pathobiological mechanisms between repetitive mild traumatic brain injury (r-mTBI) tau/amyloid proteinopathies considering the long history of association TBI Alzheimer's disease. We address this problem by using unbiased proteomic approaches generate detailed time-dependent molecular profiles response mTBI in C57BL/6 mice mouse models amyloidosis (with amyloid precursor protein KM670/671NL (Swedish) Presenilin...
Abstract Patients with Alzheimer’s disease (AD) exhibit non-rapid eye movement (NREM) sleep disturbances in addition to memory deficits. Disruption of NREM slow waves occurs early the progression and is recapitulated transgenic mouse models beta-amyloidosis. However, mechanisms underlying slow-wave disruptions remain unknown. Because astrocytes contribute activity, we used multiphoton microscopy optogenetics investigate whether they APP mice. The power but not frequency astrocytic calcium...
Repetitive mild traumatic brain injury (r-mTBI) is a risk factor for Alzheimer disease (AD). The precise nature of how r-mTBI leads to, or precipitates, AD pathogenesis remains unclear. In this study, we explore subchronic effects chronic (12-impacts) administered over 1-month in aged-PS1/APP mice and littermate controls. We investigate specific mechanisms that may elucidate the molecular link between r-mTBI, focusing primarily on amyloid tau pathology, processing, glial activation states,...
Patients with Alzheimer’s disease (AD) exhibit sleep disturbances, specifically deficits in deep non-rapid eye movement (NREM) sleep. Disruption of NREM slow waves occurs early the progression and is recapitulated transgenic mouse models beta-amyloidosis. However, mechanisms underlying slow-wave disruptions remain unknown. Also, it not clear if these disturbances are a cause or effect AD. Because astrocytes contribute to activity, we used multiphoton microscopy optogenetics investigate...