A5079439108- Neuroinflammation and Neurodegeneration Mechanisms
- S100 Proteins and Annexins
- Acute Ischemic Stroke Management
- Neurological Disease Mechanisms and Treatments
- Immune cells in cancer
- Immune Response and Inflammation
- Barrier Structure and Function Studies
- Protease and Inhibitor Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Lipoproteins and Cardiovascular Health
- Nitric Oxide and Endothelin Effects
- Intracranial Aneurysms: Treatment and Complications
- Cerebrovascular and Carotid Artery Diseases
- Eicosanoids and Hypertension Pharmacology
- Neuropeptides and Animal Physiology
- Calpain Protease Function and Regulation
- Neurogenesis and neuroplasticity mechanisms
- Endoplasmic Reticulum Stress and Disease
- Intracerebral and Subarachnoid Hemorrhage Research
- Alzheimer's disease research and treatments
- Sphingolipid Metabolism and Signaling
- Single-cell and spatial transcriptomics
- Astronomy and Astrophysical Research
- Pharmacological Receptor Mechanisms and Effects
MIND Research Institute
2014-2025
Cornell University
2015-2025
Weill Cornell Medicine
2016-2025
Faculty of 1000 (United States)
2023
New York Proton Center
2021-2023
Mayo Clinic in Florida
2017
McLaughlin Research Institute
2017
Jacksonville College
2017
Vall d'Hebron Institut de Recerca
2008-2014
Universitat Autònoma de Barcelona
2008-2014
Hypertension is a leading risk factor for dementia, but the mechanisms underlying its damaging effects on brain are poorly understood. Due to lack of energy reserves, relies continuous delivery blood flow active regions in accordance with their dynamic metabolic needs. disrupts these vital regulatory mechanisms, neuronal dysfunction and damage cognitive impairment. Elucidating cellular bases impairments essential developing new therapies. Perivascular macrophages (PVMs) represent distinct...
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...
Hypertension is a leading cause of stroke and dementia, effects attributed to disrupting delivery blood flow the brain. also alters blood-brain barrier (BBB), critical component brain health. Although endothelial cells are ultimately responsible for BBB, development maintenance properties depend on interaction with other vascular-associated cells. However, it remains unclear if BBB disruption in hypertension requires cooperative Perivascular macrophages (PVM), innate immune closely...
Regulated phosphorylation of the alpha subunit eukaryotic translation initiation factor 2 (eIF2alpha) by endoplasmic reticulum (ER) stress-activated protein kinase PERK modulates synthesis and couples production ER client proteins with organelle's capacity to fold process them. activation stress is known involve transautophosphorylation, which decorates its unusually long insert loop multiple phosphoserine phosphothreonine residues. We report that selectively enhance affinity for...
Abstract NO produced by inducible synthase (iNOS) contributes to ischemic brain injury, but the cell types expressing iNOS and mediating tissue damage have not been elucidated. To examine relative contribution of in resident cells peripheral leukocytes infiltrating brain, we used bone marrow (BM) chimeric mice which middle cerebral artery was occluded infarct volume determined 3 d later. iNOS−/− engrafted with iNOS+/+ BM exhibited larger infarcts (44 ± 2 mm3; n = 13; mean SE) compared...
Cell therapy with endothelial progenitor cells (EPCs) has emerged as a promising strategy to regenerate the brain after stroke. Here, we aimed investigate if treatment EPCs or their secreted factors could potentiate angiogenesis and neurogenesis permanent focal cerebral ischemia in mouse model of ischemic BALB/C male mice were subjected distal occlusion middle artery, EPCs, cell-free conditioned media (CM) obtained from vehicle administered one day ischemia. Magnetic resonance imaging (MRI)...
Rationale: Cerebrovascular function is critical for brain health, and endogenous vascular protective pathways may provide therapeutic targets neurological disorders. S1P (Sphingosine 1-phosphate) signaling coordinates functions in other organs, 1 (S1P receptor-1) modulators including fingolimod show promise the treatment of ischemic hemorrhagic stroke. However, also lymphocyte trafficking, lymphocytes are currently viewed as principal target modulation Objective: To address roles mechanisms...
A key feature of the inflammatory response after cerebral ischemia is brain infiltration blood monocytes. There are two main monocyte subsets in mouse blood: CCR2+Ly6Chi "inflammatory" monocytes involved acute inflammation, and CX3CR1+Ly6Clo "patrolling" monocytes, which may play a role repair processes. We hypothesized that recruited early phase transdifferentiate into "repair" macrophages brain. CX3CR1GFP/+CCR2RFP/+ bone marrow (BM) chimeric mice underwent transient middle artery occlusion...
Loss-of-function mutations of progranulin (PGRN) have been linked to frontotemporal dementia, but little is known about the effects PGRN deficiency on brain in health and disease. has implicated neurovascular development, inflammation, Wnt signaling, a pathway involved formation blood–brain barrier (BBB). Because BBB alterations inflammation contribute ischemic injury, we examined role damage produced by ischemia-reperfusion. +/− −/− mice underwent middle cerebral artery occlusion (MCAO)...
Exposure to low-dose lipopolysaccharide (LPS) before cerebral ischemia is neuroprotective in stroke models, a phenomenon termed preconditioning (PC). Although it well established that LPS-PC induces central and peripheral immune responses, the cellular mechanisms modulating ischemic injury remain unclear. Here, we investigated role of cells brain protection afforded by PC tested whether monocytes may be reprogrammed ex vivo LPS exposure, thus inflammatory after male mice. We found systemic...
The scavenger receptor CD36 is a critical factor initiating ischemic brain injury, but the cell type(s) expressing and responsible for its harmful effects remain unknown. Using bone marrow (BM) chimeras subjected to transient middle cerebral artery occlusion, we found that −/− mice transplanted with wild-type (WT) BM (WT→CD36 ) have smaller infarcts (−67%), comparable those of lacking both in hematogenous cells (CD36 →CD36 ; − 72%). Conversely, WT receiving →WT) similar WT→WT mice,...
Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of ischemic stroke. In this study, we investigated time course gelatinolytic activation a rat model permanent ischemia. We observed an MMPs as early 30 mins after insult, mainly nuclei brain cells. Besides, explored MMP-13 expression samples animal and stroke deceased patients. upregulation active brains ( P< 0.05) 90 cerebral Human infarct/periinfarct also showed higher levels compared with contralateral ones....
Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme involved in recruitment of lymphocytes neutrophils through its semicarbazide-sensitive amine oxidase (SSAO) activity. We aimed to study plasma VAP-1/SSAO activity relation the risk for intracranial bleeding complications patients with stroke treated tissue plasminogen activator (tPA), greatest safety concern this treatment.In 141 ischemic stroke, we measured taken before tPA administration. Hemorrhagic events were...
Rodent experimental models are essential for in vivo study of stroke. Our aim was to develop a reproducible method mouse transient focal cerebral ischaemia by distal artery compression.The middle (dMCA) occluded compression with blunted needle, and blood flow monitored laser Doppler flowmetry ensure appropriate occlusion reperfusion Balb/c mice. The ischaemic lesion evaluated 24 h after TTC staining immunolabelling (NeuN, CD31, GFAP Iba-1) while the established permanent dMCA (dMCAO) model...
<i>Background:</i> Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme that belongs to the semicarbazide-sensitive amine oxidase (SSAO) family, which oxidatively deaminates primary amines implicated in leukocyte extravasation. Our aim was investigate alteration of soluble VAP-1/SSAO activity plasma samples after acute intracerebral hemorrhage (ICH) its presence human ICH brain tissue. <i>Methods:</i> determined 66 patients 58 healthy controls....
ABSTRACT High dietary salt intake has powerful effects on cerebral blood vessels and emerged as a risk factor for stroke cognitive impairment. In mice, high diet (HSD) leads to reduced flow (CBF), tau hyperphosphorylation dysfunction. However, it is still unclear whether the CBF responsible of HSD cognition. Capillary stalling cause reduction impairment in models Alzheimer’s disease diabetes. Therefore, we tested hypothesis that capillary also contributes HSD. Using two-photon imaging, found...