A5055174431- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Immune Response and Inflammation
- S100 Proteins and Annexins
- Retinal Imaging and Analysis
- Tryptophan and brain disorders
- Glaucoma and retinal disorders
- Circadian rhythm and melatonin
- Acute Ischemic Stroke Management
- Retinal Development and Disorders
- Neurological Disorders and Treatments
- Gut microbiota and health
- Axon Guidance and Neuronal Signaling
- Biochemical effects in animals
- Diet and metabolism studies
- Immune Cell Function and Interaction
- Stress Responses and Cortisol
- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- Dietary Effects on Health
- Memory and Neural Mechanisms
Universidad Complutense de Madrid
2014-2025
Research Institute Hospital 12 de Octubre
2014-2024
Spanish National Centre for Cardiovascular Research
2021-2024
Universidad Autónoma de Madrid
2019-2022
Centro de Biología Molecular Severo Ochoa
2019-2022
Universidad de Extremadura
2014
Biomedical Research Networking Center on Neurodegenerative Diseases
2013
Instituto Ramón y Cajal de Investigación Sanitaria
2011-2013
Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
2013
Hospital Universitario Ramón y Cajal
2013
Immune and inflammatory responses require leukocytes to migrate within through the vasculature, a process that is facilitated by their capacity switch polarized morphology with an asymmetric distribution of receptors. We report neutrophil polarization activated venules served organize protruding domain engaged platelets present in bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting redistribution receptors drive migration. Consequently,...
Background and Purpose— Neutrophils have been traditionally recognized as major mediators of a deleterious inflammatory response in acute ischemic stroke, but their potential therapeutic target remains unexplored. Recent evidence indicates that neutrophils may acquire different phenotypes contribute to resolution inflammation through the release anti-inflammatory mediators. Thus, similar M2 macrophages, proposed shift toward an N2 phenotype, polarization is peroxisome proliferator-activated...
Sirtuin 1 (SIRT1) is a member of NAD+-dependent protein deacetylases implicated in wide range cellular functions and has beneficial properties pathologies including ischemia/reperfusion processes neurodegeneration. However, no direct evidence been reported on the implication SIRT1 ischemic stroke. The aim this study was to establish role stroke using an experimental model mice.Wild-type Sirt1-/- mice were subjected permanent focal ischemia by ligature. In another set experiments, wild-type...
Background and Purpose— After stroke, the population of infiltrated neutrophils in brain is heterogeneous, including a alternative (N2) that express M2 phenotype markers. We explored role TLR4 (toll-like receptor 4) on neutrophil infiltration polarization this setting. Methods— Focal cerebral ischemia was induced by occlusion middle artery TLR4-KO WT (wild type) mice. Infarct size measured Nissl staining magnetic resonance imaging. Leukocyte quantified 48 hours after immunofluorescence flow...
Background— Aryl hydrocarbon receptor (AhR) is a transcription factor that belongs to the basic helix-loop-helix PAS (Per-Arnt-Sim homology domain) family known mediate toxic and carcinogenic effects of xenobiotics. Interestingly, AhR widely expressed in central nervous system, but its physiological pathological roles are still unclear. Methods Results— To define role stroke, we used middle cerebral artery occlusion mice oxygen-glucose deprivation rat cortical neurons. The results presented...
Poststroke cognitive impairment is considered one of the main complications during chronic phase ischemic stroke. In adult brain, hippocampus regulates both encoding and retrieval new information through neurogenesis. Nevertheless, lack predictive models studies based on forgetting processes hinders understanding memory alterations after Our aim was to explore whether poststroke neurogenesis participates in development long-term impairment. Here, we show a hippocampal burst that persisted 1...
Abstract NMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. The core mechanism for this thought be entirely neuronal. However, we now demonstrate astrocytic activity drives LTD at CA3-CA1 synapses. We have found induction enhances astrocyte-to-neuron communication mediated by glutamate, and Ca 2+ signaling SNARE-dependent vesicular release from astrocyte are required...
Stroke is a leading cause of adult disability characterized by physical, cognitive, and emotional disturbances. Unfortunately, pharmacological options are scarce. The cannabinoid type-2 receptor (CB2R) neuroprotective in acute experimental stroke anti-inflammatory mechanisms. However, its role chronic still unknown.Stroke was induced permanent middle cerebral artery occlusion mice; CB2R modulation assessed administering the agonist JWH133...
Since Toll-like receptor 4 (TLR4) mediates brain damage after stroke, development of TLR4 antagonists is a promising therapeutic strategy for this disease. Our aim was to generate TLR4-blocking DNA aptamers be used stroke treatment. From random oligonucleotide pool, we identified two (ApTLR#1R, ApTLR#4F) with high affinity human by systematic evolution ligands exponential enrichment (SELEX). Optimized truncated forms (ApTLR#1RT, ApTLR#4FT) were obtained. data demonstrate specific binding...
Abstract PPARγ-achieved neuroprotection in experimental stroke has been explained by the inhibition of inflammatory genes, an action which 5-LO, Alox5, is involved. In addition, PPARγ known to promote expression CD36, a scavenger receptor that binds lipoproteins and mediates bacterial recognition also phagocytosis. As phagocytic clearance neutrophils requisite for resolution response, PPARγ-induced CD36 might help limit tissue injury stroke, effect 5-LO be Homogenates, sections, cellular...
Toll-like receptor 4 (TLR4) mediates brain damage after stroke. Now our objective is to determine TLR4 involvement in stroke-induced neurogenesis. Stroke was induced by permanent middle cerebral artery occlusion wild-type and TLR4-deficient mice. Stereological densitometric analysis of immunofluorescence-labeled sections FACS cell suspensions were performed. Our results show that subventricular zone (SVZ) proliferation stroke depends on infarct size. Second, when comparing brains with...
CDP-choline has shown neuroprotective effects in cerebral ischemia. In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) that global recovery is similar and placebo groups, was to be more beneficial some patients, such as those with moderate stroke severity not treated t-PA. Several mechanisms have been proposed explain the actions of CDP-choline. We now studied participation Sirtuin1 (SIRT1) Fischer rats Sirt1⁻/⁻ mice were subjected permanent focal (0.2...
Abstract Background Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra (SN). Transforming growth factor-β1 (TGF-β1) levels increase patients with PD, although effects of this increment remain unclear. We have examined mesostriatal system adult mice deficient Smad3, a molecule involved intracellular TGF-β1 signalling cascade. Results Striatal monoamine oxidase (MAO)-mediated dopamine (DA) catabolism to 3,4-dihydroxyphenylacetic acid (DOPAC)...
Abstract Stroke is a devastating disease with an increasing prevalence. Part of the current development in stroke therapy focused chronic phase, where neurorepair mechanisms such as neurogenesis, are involved. In adult brain, one regions neurogenesis takes place subventricular zone (SVZ) lateral ventricles. Given possibility to develop pharmacological therapies stimulate this process, we have performed longitudinal analysis model cortical ischemia mice. Our results show initial decrease SVZ...
The aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor, largely known for its role in xenobiotic metabolism and detoxification as well crucial regulator of inflammation. Here, we have compared cohort wild‐type AhR‐null mice along aging to study the relationship between this age‐associated inflammation, termed “inflammaging,” both at systemic CNS level. Our results show that AhR deficiency associated with premature aged phenotype, characterized by early inflammaging,...
Increasing evidence from animal and epidemiological studies indicates that perinatal exposure to pesticides cause developmental neurotoxicity may increase the risk for psychiatric disorders such as autism intellectual disability. However, underlying pathogenic mechanisms remain largely elusive. This work was aimed at testing hypothesis different classes of hijacks intracellular neuronal signaling contributing synaptic behavioral alterations associated with neurodevelopmental (NDD). Low...
Aims/Purpose: Transgenic mouse models of Alzheimer's disease (AD) have shown a correlation between retinal abnormalities and brain pathology. The APP NL‐F/NL‐F murine humanized AD model accurately replicates many pathological features seen in patients. This study aims to analyze, using manual segmentation by optical coherence tomography (OCT), the changes occurring several layers at 6, 9, 12, 15, 17, 20 months age, comparison C57BL/6J mice (WT). Methods: A diachronic was conducted OCT for...
Aims/Purpose: Transgenic mouse models of Alzheimer's disease (AD) have shown a correlation between retinal abnormalities and brain pathology. The APP NL‐F/NL‐F murine humanized AD model accurately replicates many pathological features seen in patients. This study aims to analyze, using manual segmentation by optical coherence tomography (OCT), the changes occurring several layers at 6, 9, 12, 15, 17, 20 months age, comparison C57BL/6J mice (WT). Methods: A diachronic was conducted OCT for...
BACKGROUND: Acute ischemic stroke treatment typically involves tissue-type plasminogen activator (tPA) or tenecteplase, but about 50% of patients do not achieve successful reperfusion. The causes tPA resistance, influenced by thrombus composition and timing, are fully clear. Neutrophil extracellular traps (NETs), associated with poor outcomes reperfusion contribute to thrombosis. DNase-I, which degrades neutrophil traps, could improve thrombolytic efficacy. However, more studies needed...
Astrocytes are known to modulate neuronal activity by gliotransmission and through metabolic regulation. However, the connection between these two processes is still poorly defined. In this work we show that p110α isoform of phosphatidylinositol 3-kinase (PI3K) in astrocytes required for long-term potentiation (LTP) has an impact on learning memory. Using a specific deletion from hippocampal adult mice, found LTP depends astrocytic sustain D-serine levels activation NMDA receptors during...