A5053558414- Neuroinflammation and Neurodegeneration Mechanisms
- S100 Proteins and Annexins
- Acute Ischemic Stroke Management
- Intracerebral and Subarachnoid Hemorrhage Research
- Alzheimer's disease research and treatments
- Cerebrovascular and Carotid Artery Diseases
- Neurological Disease Mechanisms and Treatments
- Protease and Inhibitor Mechanisms
- Advanced Glycation End Products research
- Immune cells in cancer
- Sodium Intake and Health
- Cerebrospinal fluid and hydrocephalus
- Nitric Oxide and Endothelin Effects
- Receptor Mechanisms and Signaling
- Blood Coagulation and Thrombosis Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Stress Responses and Cortisol
- Advanced MRI Techniques and Applications
- Neonatal and fetal brain pathology
- Olfactory and Sensory Function Studies
- Cardiac Imaging and Diagnostics
- Blood properties and coagulation
- High Altitude and Hypoxia
- Aortic Disease and Treatment Approaches
- Atherosclerosis and Cardiovascular Diseases
Weill Cornell Medicine
2020-2025
MIND Research Institute
2020-2025
Cornell University
2020-2025
Washington University in St. Louis
2023
National Cerebral and Cardiovascular Center
2023
Cyceron
2016-2021
Inserm
2016-2021
Université de Caen Normandie
2016-2021
Physiopathologie et imagerie des troubles neurologiques
2018-2021
Normandie Université
2016-2021
Hyperfibrinolysis is a systemic condition occurring in various clinical disorders such as trauma, liver cirrhosis, and leukemia. Apart from increased bleeding tendency, the pathophysiological consequences of hyperfibrinolysis remain largely unknown. Our aim was to develop an experimental model study its effects on homeostasis blood-brain barrier (BBB). We induced sustained hyperfibrinolytic state mice by hydrodynamic transfection plasmid encoding for tissue-type plasminogen activator (tPA)....
Abstract Background Cerebral amyloid angiopathy (CAA) is a devastating condition common in patients with Alzheimer’s disease but also observed the general population. Vascular oxidative stress and neurovascular dysfunction have been implicated CAA cellular source of reactive oxygen species (ROS) related signaling mechanisms remain unclear. We tested hypothesis that brain border-associated macrophages (BAM), yolk sac-derived myeloid cells closely apposed to parenchymal leptomeningeal blood...
Stroke induces a multiphasic systemic immune response, but the consequences of this response on atherosclerosis-a major source recurrent vascular events-have not been thoroughly investigated. We show that stroke exacerbates atheroprogression via alarmin-mediated propagation inflammation. The prototypic brain-released alarmin high-mobility group box 1 protein induced monocyte and endothelial activation receptor for advanced glycation end products (RAGE)-signaling cascade increased plaque load...
The amyloid-β (Aβ) peptide, a key pathogenic factor in Alzheimer's disease, attenuates the increase cerebral blood flow (CBF) evoked by neural activity (functional hyperemia), vital homeostatic response which NMDA receptors (NMDARs) play role through nitric oxide, and CBF produced endothelial factors. Tissue plasminogen activator (tPA), is reduced disease mouse models of Aβ accumulation, required for full expression NMDAR-dependent component functional hyperemia. Therefore, we investigated...
The increase of cerebral blood flow evoked by neuronal activity is essential to ensure enough energy supply the brain. In neurovascular unit, endothelial cells are ideally placed regulate key functions Nevertheless, some outstanding questions remain about their exact role coupling (NVC). Here, we postulated that tissue-type plasminogen activator (tPA) present in circulation might contribute NVC a mechanism dependent its interaction with N-Methyl-D-Aspartate Receptor (NMDAR). To address this...
Neuronal nitric oxide (NO) synthase (nNOS), a Ca 2+ dependent enzyme, is expressed by distinct populations of neocortical neurons. Although neuronal NO well known to contribute the blood flow increase evoked neural activity, relationships between nNOS neurons activity and vascular responses in awake state remain unclear. We imaged barrel cortex awake, head-fixed mice through chronically implanted cranial window. The indicator GCaMP7f was selectively using adenoviral gene transfer cre mice....
Apolipoprotein-E4 (ApoE4), the strongest genetic risk factor for sporadic Alzheimer's disease, is also a microvascular pathologies leading to cognitive impairment, particularly subcortical white matter injury. These effects have been attributed alterations in regulation of brain blood supply, but cellular source ApoE4 and underlying mechanisms remain unclear. In mice expressing human ApoE3 or we report that border associated macrophages (BAM), myeloid cells closely apposed neocortical...
Solute transport through the brain is of major importance for clearance toxic molecules and metabolites, it plays key roles in pathophysiology central nervous system. This solute notably depends on cerebrospinal fluid (CSF) flow, which circulates subarachnoid spaces, ventricles perivascular spaces. We hypothesized that CSF flow may be different perinatal period compared to adult period. Using vivo magnetic resonance imaging (MRI) near-infrared fluorescence (NIRF), we assessed dynamic rodents...
In humans, spatial cognition and navigation impairments are a frequent situation during physiological pathological aging, leading to dramatic deterioration in the quality of life. Despite discovery neurons with location-specific activity rodents, that is, place cells hippocampus later on grid entorhinal cortex (EC), molecular mechanisms underlying still poorly known. Our present data bring together an unusual combination 2 molecules primary biological importance: major neuronal excitatory...
Preclinical imaging of endothelial activation and mineralization using both positron emission tomography (PET) magnetic resonance (MR) remains scarce. A group uremic ApoE−/− (Ur), non-uremic (NUr), control C57Bl/6 J mice (Ctl) were investigated. Mineralization process was assessed sodium fluoride ([18F]NaF) PET, MR combined with intravenous injection MPIO-αVCAM-1 used to evaluate activation. Micro- macrocalcifications evaluated by flame atomic absorption spectroscopy von Kossa staining,...
In acute ischemic stroke, the only FDA-approved drug; recombinant tissue plasminogen activator (rt-PA) is limited by restricted time-window due to an enhanced risk of hemorrhagic transformation which thought be caused metalloproteinase (MMP). experimental stroke inhibitors mitogen-activated protein kinase extracellular signal-regulated (MEK) 1/2 pathways reduce MMPs. This study evaluated whether a MEK1/2 inhibitor in combination with rt-PA can prevent detrimental effects delayed therapy...
Abstract INTRODUCTION Amyloid beta (Aβ) impairs the cerebral blood flow (CBF) increase induced by neural activity (functional hyperemia). Tissue plasminogen activator (tPA) is required for functional hyperemia, and in mouse models of Aβ accumulation tPA deficiency contributes to neurovascular cognitive impairment. However, it remains unknown if supplementation can rescue Aβ‐induced dysfunction. METHODS Tg2576 mice wild‐type littermates received intranasal (0.8 mg/kg/day) or vehicle 5 days a...
Abstract Background: Cerebral amyloid angiopathy (CAA) is a devastating condition common in patients with Alzheimer’s disease but also observed the general population. Vascular oxidative stress and neurovascular dysfunction have been implicated CAA cellular source of reactive oxygen species (ROS) related signaling mechanisms remain unclear. We tested hypothesis that brain border-associated macrophages (BAM), yolk sac-derived myeloid cells closely apposed to parenchymal leptomeningeal blood...
Abstract Experimental stroke models in rodents are essential for mechanistic studies and therapeutic development. However, these have several limitations negatively impacting their translational relevance. Here we aimed to develop a minimally invasive thrombotic model through magnetic particle delivery that does not require craniotomy, is amenable reperfusion therapy, can be combined with vivo imaging modalities, performed awake mice. We found the results reproducible cortical infarcts...
ABSTRACT Hypertension, a disease afflicting over one billion individuals worldwide, is leading cause of cognitive impairment, the mechanisms which remain poorly understood. In mouse model hypertension, we found that neurovascular and dysfunction depends on IL-17, cytokine elevated in hypertensive individuals. However, neither circulating IL-17 or brain angiotensin signaling could account full for dysfunction. Rather, produced by T-cells dura mater was major culprit reaching cerebrospinal...
Abstract Neuronal nitric oxide (NO) synthase (nNOS), a Ca 2+ dependent enzyme, is expressed by distinct populations of neocortical neurons. Although neuronal NO well known to contribute the blood flow increase evoked neural activity, relationships between nNOS neurons activity and vascular responses in awake state remain unclear. We imaged barrel cortex awake, head-fixed mice through chronically implanted cranial window. The indicator GCaMP7f was selectively using adenoviral gene transfer...