A5080067331- Barrier Structure and Function Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological Disease Mechanisms and Treatments
- Neonatal and fetal brain pathology
- Immune cells in cancer
- Advanced Neuroimaging Techniques and Applications
- MRI in cancer diagnosis
- Neuroscience and Neuropharmacology Research
- Cerebrospinal fluid and hydrocephalus
- Alzheimer's disease research and treatments
- Neonatal Respiratory Health Research
- Angiogenesis and VEGF in Cancer
- Neuroscience of respiration and sleep
- Traumatic Brain Injury and Neurovascular Disturbances
- Stress Responses and Cortisol
- Drug Transport and Resistance Mechanisms
- Fetal and Pediatric Neurological Disorders
- Erythrocyte Function and Pathophysiology
- Ion Transport and Channel Regulation
- Single-cell and spatial transcriptomics
- Anesthesia and Neurotoxicity Research
- Extracellular vesicles in disease
- Intracerebral and Subarachnoid Hemorrhage Research
- Caveolin-1 and cellular processes
- Traditional Chinese Medicine Analysis
University of Coimbra
2012-2025
Seattle Children's Hospital
2019-2024
University of Washington
2019-2024
Children’s Institute
2022
Seattle University
2021
University of Chemistry and Technology, Prague
2018
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2018
Association for Innovation and Biomedical Research on Light and Image
2017
Institute of Pharmacology
2017
Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide results from an obstruction in blood supply to a region heart. In attempt replenish oxygen nutrients deprived area, affected cells release signals promote development new vessels confer protection against MI. However, mechanisms underlying growth ischaemic scenario remain poorly understood. Here, we show that cardiomyocytes subjected ischaemia exosomes elicit angiogenic response endothelial (ECs).Exosomes...
Abstract Deterioration of brain capillary flow and architecture is a hallmark aging dementia. It remains unclear how loss pericytes in these conditions contributes to dysfunction. Here, we conduct cause-and-effect studies by optically ablating adult aged mice vivo. Focal pericyte induces dilation without blood-brain barrier disruption. These abnormal dilations are exacerbated the brain, result increased heterogeneity networks. A subset affected capillaries experience reduced perfusion due...
Significance The distribution of blood throughout the brain is facilitated by highly interconnected capillary networks. However, steps involved in construction these networks has remained unclear. We used vivo two-photon imaging through noninvasive cranial windows to study engineering cerebral cortex mouse neonates. find that angiogenic activity originates at ascending venules, which undergo a burst sprouting second postnatal week. This first establishes long paths connect venules input from...
Abstract Proper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth function throughout life, ensuring the continuous supply of nutrients oxygen. This involves crucial events during pre- postnatal stages through key pathways, including vascular endothelial factor (VEGF) Wnt signaling. These pathways pivotal growth, expansion, blood–brain barrier (BBB) maturation. Interestingly, fetal neonatal formation coincides with early peak activity...
Methamphetamine (METH) is a psychostimulant that causes neurologic and psychiatric abnormalities. Recent studies have suggested its neurotoxicity may also result from ability to compromise the blood–brain barrier (BBB). Herein, we show METH rapidly increased vesicular transport across endothelial cells (ECs), followed by an increase of paracellular transport. Moreover, triggered release tumor necrosis factor-alpha (TNF- α), blockade this cytokine or inhibition nuclear factor-kappa B (NF- κB)...
It is well known that methamphetamine (METH) neurotoxic and recent studies have suggested the involvement of neuroinflammatory processes in brain dysfunction induced by misuse this drug. Indeed, glial cells seem to be activated response METH, but its effects on microglial are not fully understood. Moreover, it has been shown cytokines, which normally released microglia, may a dual role injury. This led us study toxic effect METH looking cell death alterations tumor necrosis factor-alpha...
Nervous tissue homeostasis requires the regulation of microglia activity. Using conditional gene targeting in mice, we demonstrate that genetic ablation small GTPase Rhoa adult is sufficient to trigger spontaneous activation, producing a neurological phenotype (including synapse and neuron loss, impairment long-term potentiation [LTP], formation β-amyloid plaques, memory deficits). Mechanistically, loss triggers Src activation Src-mediated tumor necrosis factor (TNF) production, leading...
Worldwide, millions of people are exposed to dietary imbalance that impacts in health and quality life. In developing countries, like Brazil, poor settings, habits, traditionally hypoproteic, changing rapidly western-type high-fat foods. These habits imposing new challenges human there many questions the field remain be answered. Accordingly, we currently do not know if chronic consumption hypoproteic (regional basic diet, RBD) or diets (HFD) may impact brain physiology, contributing...
Pericytes and endothelial cells share membranous interdigitations called “peg-and-socket” interactions that facilitate their adhesion biochemical crosstalk during vascular homeostasis. However, the morphology distribution of these ultrastructures have remained elusive. Using a combination 3D electron microscopy techniques, we examined peg-and-socket in mouse brain capillaries. We found pegs extending from pericytes to were morphologically diverse, exhibiting claw-like morphologies at edge...
Electron microscopy is the primary approach to study ultrastructural features of cerebrovasculature. However, 2D snapshots a vascular bed capture only small fraction its complexity. Recent efforts synaptically map neuronal circuitry using volume electron have also sampled brain microvasculature in 3D. Here, we perform meta-analysis 7 data sets spanning different species and regions, including two from MICrONS consortium that made segment vasculature addition all parenchymal cell types mouse...
Abstract Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, with an average life expectancy of 12–15 months. GBM highly infiltrated by microglial cells (MG) promoting tumor growth invasiveness. Moreover, microglia activation subsequent neuroinflammation seem to be involved in blood–brain barrier (BBB) dysfunction commonly observed several central nervous system diseases, including tumors. Nevertheless, how crosstalk between interferes BBB function far from...
From early in life, experiences like prenatal stress profoundly affect long-term health and behavior. Fetal exposure to increased levels of glucocorticoids (GC), via maternal or through antenatal corticosteroid therapy (commonly used women at risk preterm birth), can disrupt brain development raise the susceptibility psychiatric disorders. Previous studies on synthetic GCs, such as dexamethasone (DEX), revealed impairments neurogenesis dendritic spine development. However, impact stress,...
The high metabolic demand of brain tissue is supported by a constant supply blood flow through dense microvascular networks. Capillaries are the smallest class vessels in and their lumens vary diameter between ~2 5 μm. This range plays significant role optimizing resistance, cell distribution, oxygen extraction. control capillary has largely been ascribed to pericyte contractility, but it remains unclear if architecture endothelial wall also contributes diameter. Here, we use public,...
Brain development and function are highly reliant on adequate establishment maintenance of vascular networks. Early impairments in health can impact brain maturation energy metabolism, which may lead to neurodevelopmental anomalies. Our recent work not only provides novel insights into the cerebrovascular networks but also emphasizes importance their well-being for proper maturation. In particular, we have demonstrated that endothelial dysfunction autism spectrum disorders (ASD) mouse models...
Perivascular fibroblasts (PVFs) are a fibroblast-like cell type that reside on large-diameter blood vessels in the adult meninges and central nervous system (CNS). PVFs contribute to fibrosis following injury but their homeostatic functions not defined. were previously shown be absent from most brain regions at birth only detected postnatally within cerebral cortex. However, origin, timing cellular mechanisms of PVF development known. We used Col1a1-GFP Col1a2-CreERT2 transgenic mice track...
Perivascular fibroblasts (PVFs) are a fibroblast-like cell type that reside on large-diameter blood vessels in the adult meninges and central nervous system (CNS). PVFs drive fibrosis following injury but their homeostatic functions not well detailed. In mice, were previously shown to be absent from most brain regions at birth only detected postnatally within cerebral cortex. However, origin, timing, cellular mechanisms of PVF development known. We used Col1a1-GFP Col1a2-CreERT transgenic...
The high metabolic demand of brain tissue is supported by a constant supply blood through dense microvascular networks. Capillaries are the smallest class vessels and vary in diameter between ∼2 to 5 μm brain. This range plays significant role optimization flow resistance, cell distribution, oxygen extraction. control capillary has largely been ascribed pericyte contractility, but it remains unclear if endothelial wall architecture also contributes heterogeneity. Here, we use public,...