A5048015906- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Nitric Oxide and Endothelin Effects
- Neurological Disorders and Treatments
- Intracerebral and Subarachnoid Hemorrhage Research
- Barrier Structure and Function Studies
- S100 Proteins and Annexins
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Renin-Angiotensin System Studies
- Acute Ischemic Stroke Management
- Sodium Intake and Health
- Immune cells in cancer
- Neuroscience and Neuropharmacology Research
- Cerebrovascular and Carotid Artery Diseases
- Stress Responses and Cortisol
- Neuroscience of respiration and sleep
- Traumatic Brain Injury and Neurovascular Disturbances
- Tryptophan and brain disorders
- Biochemical effects in animals
- Immune Response and Inflammation
- Inflammatory mediators and NSAID effects
- Advanced Glycation End Products research
- Cerebrospinal fluid and hydrocephalus
- Protease and Inhibitor Mechanisms
MIND Research Institute
2016-2025
Cornell University
2016-2025
Weill Cornell Medicine
2017-2024
McLaughlin Research Institute
2012-2017
Mayo Clinic in Florida
2017
Jacksonville College
2017
Faculty of 1000 (United States)
2015
New York University
2014
Stony Brook University
2012-2014
Institute of Neurobiology
2010
Alterations in cerebrovascular regulation related to vascular oxidative stress have been implicated the mechanisms of Alzheimer's disease (AD), but their role amyloid deposition and cognitive impairment associated with AD remains unclear. We used mice overexpressing Swedish mutation precursor protein (Tg2576) as a model examine reactive oxygen species produced by NADPH oxidase alterations, deposition, behavioral deficits observed these mice. found that 12- 15-month-old Tg2576 lacking...
Increasing evidence indicates that alterations of the cerebral microcirculation may play a role in Alzheimer disease, leading cause late-life dementia. The amyloid-β peptide (Aβ), key pathogenic factor induces profound neurovascular regulation through innate immunity receptor CD36 (cluster differentiation 36), which, turn, activates Nox2-containing NADPH oxidase, to cerebrovascular oxidative stress. Brain perivascular macrophages (PVM) located space, major site brain Aβ collection and...
Aging is associated with cerebrovascular dysregulation, which may underlie the increased susceptibility to ischemic stroke and vascular cognitive impairment occurring in elder individuals. Although it has long been known that oxidative stress responsible for dysfunction, enzymatic system(s) generating reactive oxygen species (ROS) have not identified. In this study, we investigated whether superoxide-producing enzyme NADPH oxidase involved alterations of neurovascular regulation induced by...
Overproduction of the amyloid β (Aβ) peptide is a key factor in pathogenesis Alzheimer's disease (AD), but mechanisms its pathogenic effects have not been defined. Patients with AD cerebrovascular alterations attributable to deleterious Aβ on cerebral blood vessels. We report here that NADPH oxidase, major source free radicals vessels, responsible for dysregulation induced by Aβ. Thus, free-radical production and associated vasoregulation are abrogated oxidase inhibitor gp91ds-tat observed...
The class B scavenger receptor CD36 is involved in the cytotoxicity associated with inflammation, but its role inflammatory reaction that accompanies cerebral ischemia has not been examined. In this study, we investigated whether contributes to brain damage produced by ischemia. middle artery was transiently occluded wild-type mice and deficient CD36. mice, protein expression increased ischemic brain, such it located predominantly cells expressing microglia/macrophage marker CD11b. infarct...
Hypertension (HTN) doubles the risk of Alzheimer’s disease (AD), but mechanisms remain unclear. Amyloid-β (Aβ), a key pathogenic factor in AD, induces cerebrovascular dysfunction. We hypothesized that HTN acts concert with Aβ to amplify its deleterious effects and increase production. Infusion angiotensin II (ANGII; intravenously) elevated blood pressure attenuated cerebral flow (CBF) response whisker stimulation or endothelium-dependent vasodilator acetylcholine (ACh) (P < 0.05)....
Cerebral ischemic preconditioning or tolerance is a powerful neuroprotective phenomenon by which sublethal injurious stimulus renders the brain resistant to subsequent damaging insult. We used lipopolysaccharide (LPS) as in mouse model of middle cerebral artery occlusion (MCAO) examine whether improvements cerebrovascular function contribute protective effect. Administration LPS 24 h before MCAO reduced infarct 68% and improved blood flow (CBF) 114% areas spared from infarction. In addition,...
Increasing evidence indicates that cerebrovascular dysfunction plays a pathogenic role in Alzheimer's dementia (AD). Amyloid-β (Aβ), peptide central to the pathogenesis of AD, has profound vascular effects mediated, for most part, by reactive oxygen species produced enzyme NADPH oxidase. The mechanisms linking Aβ oxidase-dependent oxidative stress have not been identified, however. We report scavenger receptor CD36, membrane glycoprotein binds Aβ, is essential and neurovascular induced 1–40...
Abstract The ApoE4 allele is associated with increased risk of small vessel disease, which a cause vascular cognitive impairment. Here, we report that mice targeted replacement (TR) the ApoE gene human have reduced neocortical cerebral blood flow compared to ApoE3-TR mice, an effect due density rather than slowing microvascular red cell flow. Furthermore, homeostatic mechanisms matching local delivery brain activity are impaired in ApoE4-TR mice. In model hypoperfusion, these cerebrovascular...
Deposition of amyloid-β (Aβ) in cerebral arteries, known as amyloid angiopathy (CAA), occurs both the setting Alzheimer’s disease and independent it, can cause cerebrovascular insufficiency cognitive deficits. The mechanisms leading to CAA have not been established, no therapeutic targets identified. We investigated role CD36, an innate immunity receptor involved Aβ trafficking, neurovascular dysfunction, deficits, accumulation that mice expressing Swedish mutation precursor protein...
Accumulation of amyloid-β in cerebral blood vessels occurs familial and sporadic forms amyloid angiopathy is a prominent feature Alzheimer disease. However, the functional correlates vascular pathology induced by mechanisms involved have not been fully established.We used male transgenic mice expressing Swedish, Iowa, Dutch mutations precursor protein (Tg-SwDI) to examine effect on cerebrovascular structure function. Somatosensory cortex flow was monitored laser-Doppler flowmetry...
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...
Angiotensin II (AngII) disrupts the regulation of cerebral circulation through superoxide, a reactive oxygen species (ROS) generated by nox2-containing NADPH oxidase. We tested hypothesis that AngII-derived superoxide reacts with nitric oxide (NO) to form peroxynitrite, which, in turn, contributes vascular dysfunction.Cerebral blood flow (CBF) was monitored laser Doppler flowmetry neocortex anesthetized mice equipped cranial window. AngII (0.25+/-0.02 microg/kg/min; intravenous for 30 45...
Objective— Angiotensin II (Ang II) exerts deleterious effect on the cerebral circulation through production of reactive oxygen species (ROS). However, enzymatic source ROS has not been defined. We tested hypothesis that Ang impairs endothelium-dependent responses in microcirculation generated cerebrovascular cells by enzyme NADPH oxidase. Methods and Results— Cerebral blood flow (CBF) was monitored laser Doppler flowmetry anesthetized mice equipped with a cranial window. (0.25±0.02 μg/kg per...
We investigated the role of vascular oxidative stress in mechanisms impairment cerebrovascular regulation produced by amyloid-β peptide (Aβ). In particular, we sought to provide evidence mice overexpressing amyloid precursor protein (APP) and determine whether Aβ-induced attenuation functional hyperemia is mediated free radical overproduction. Oxidative/nitrosative was assessed 3-nitrotyrosine immunoreactivity, while production determined cerebral microvessels hydroethidine...
Hypertension alters cerebrovascular regulation and increases the brain's susceptibility to stroke dementia. We investigated temporal relationships between arterial pressure (AP) elevation induced by "slow pressor" angiotensin II (ANG II) infusion, which recapitulates key features of human hypertension, resulting dysfunction. Minipumps delivering saline or ANG for 14 days were implanted subcutaneously in C57BL/6 mice (n = 5/group). Cerebral blood flow was assessed laser-Doppler flowmetry...