A5054377627- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- Neurological Disease Mechanisms and Treatments
- S100 Proteins and Annexins
- Neurological Disorders and Treatments
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Peroxisome Proliferator-Activated Receptors
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune cells in cancer
- Acute Ischemic Stroke Management
- Biochemical effects in animals
- Adipose Tissue and Metabolism
- Anesthesia and Neurotoxicity Research
- Gut microbiota and health
- Neonatal and fetal brain pathology
- Traumatic Brain Injury and Neurovascular Disturbances
- Cardiac Ischemia and Reperfusion
- Sinusitis and nasal conditions
- Stress Responses and Cortisol
- Cholesterol and Lipid Metabolism
- Otitis Media and Relapsing Polychondritis
- Adipokines, Inflammation, and Metabolic Diseases
- Inflammatory mediators and NSAID effects
- Diet and metabolism studies
Research Institute Hospital 12 de Octubre
2013-2025
Universidad Complutense de Madrid
2014-2024
University of Manchester
2012-2016
University of Ottawa
2013
Hospital Clínico San Carlos
2013
Ottawa Hospital Research Institute
2013
Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
2013
Background— Stroke is the second to third leading cause of death. Toll-like receptor 4 (TLR4) a signaling in innate immunity that specific immunologic response systemic bacterial infection and cerebral injury. The role TLR4 brain ischemia has not been examined yet. We have therefore investigated whether inflammation produced by permanent occlusion middle artery differ mice lack functional pathway. Methods Results— Permanent was performed on 2 strains TLR4-deficient (C3H/HeJ C57BL/10ScNJ)...
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— Psychological stress causes an inflammatory response in the brain is able to exacerbate damage caused by experimental stroke. We previously reported that subacute immobilization mice worsens stroke outcome through mechanisms involve mechanisms, such as accumulation of oxidative/nitrosative mediators expression inducible nitric oxide synthase cyclooxygenase-2 brain. Some these could be regulated innate immunity, activation which takes place produces mediated toll-like...
Many neuroprotective agents have been effective in experimental stroke, yet few translated into clinical application. One reason for this may be failure to consider comorbidities/risk factors models. We shown that a naturally occurring interleukin-1 receptor antagonist (IL-1Ra) is protective against ischemic brain damage healthy animals. However, effects of IL-1Ra not determined comorbid Thus, we tested whether protects injury induced by ischemia aged JCR-LA (corpulent) rats, which...
Background and Purpose— Recanalization of the occluded artery is a primary goal in stroke treatment. Unfortunately, endovascular treatment not always available, tPA (tissue-type plasminogen activator) therapy limited by its narrow therapeutic window; importantly, rate early arterial recanalization after administration low, especially for platelet-rich thrombi. The mechanisms this resistance are well known. Since neutrophil extracellular traps (NETs) have been implicated setting, our aim was...
It has been demonstrated that a short ischemic event (ischemic preconditioning, IPC) results in subsequent resistance to severe ischemia tolerance, IT). We have recently the role of innate immunity and particular toll-like receptor (TLR) 4 brain ischemia. Several evidences suggest TLR4 might also be involved IT. Therefore, we now used an vivo model IPC investigate whether is A 6-min temporary bilateral common carotid arteries occlusion was for focal it performed on TLR4-deficient mice...
Peroxisome proliferator-activated receptors gamma (PPARγ) are nuclear with essential roles as transcriptional regulators of glucose and lipid homeostasis. PPARγ also potent anti-inflammatory receptors, a property that contributes to the neuroprotective effects agonists in experimental stroke. The mechanism these beneficial actions, however, is not fully elucidated. Therefore, we have explored further actions agonist rosiglitazone stroke induced by permanent middle cerebral artery occlusion...
Neuroprotective strategies for ischemic stroke have failed to translate from bench bedside, possibly due the lack of consideration key clinical co-morbidities. Stroke and co-morbidities are associated with raised levels pro-inflammatory cytokine interleukin-1 (IL-1). Inhibition IL-1 by administration receptor antagonist (IL-1Ra) has shown be neuroprotective after experimental cerebral ischemia. can also trigger a robust neuroreparative response following injury, yet many these new born...
Aging is not just a risk factor of stroke, but it has also been associated with poor recovery. It known that stroke-induced neurogenesis reduced maintained in the aged brain. However, there no consensus on how affected after stroke animals. Our objective to determine role aging process stroke.We have studied by analyzing proliferation, migration, and formation new neurons, as well inflammatory parameters, model cerebral ischemia induced permanent occlusion middle artery young- (2 3 months)...
Stroke represents a global challenge and is leading cause of permanent disability worldwide. Despite much effort, translation research findings to clinical benefit has not yet been successful. Failure neuroprotection trials considered, in part, due the low quality preclinical studies, level reproducibility across different laboratories that stroke co-morbidities have fully considered experimental models. More rigorous testing new drug candidates models initiation cross-laboratory studies...
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...
Objective Bacterial infection contributes to diverse noninfectious diseases and worsens outcome after stroke. Streptococcus pneumoniae , the most common in patients at risk of stroke, is a major cause prolonged hospitalization death stroke patients, but how impacts clinical not known. Methods We induced sustained pulmonary by human S . isolate naive comorbid rodents investigate effect on vascular inflammatory responses prior cerebral ischemia. Results S. triggered atherogenesis, led systemic...
A short ischemic event (ischemic preconditioning (IPC)) can result in subsequent resistance to severe injury tolerance (IT)). The expression and neuroprotective role of tumor necrosis factor (TNF- α) have been described models IPC we showed the participation its processing enzyme, TNF- α convertase enzyme (TACE) this process. We now decided explore localization TNF receptors (TNFR) as well other signalling mechanisms involved IT. period 10 mins temporary middle cerebral artery occlusion...
Abstract 3,4‐Methylenedioxymethamphetamine (MDMA) administration to rats produces acute hyperthermia and 5‐HT release. Interleukin‐1β (IL‐1β) is a pro‐inflammatory pyrogen produced by activated microglia in the brain. We examined effect of neurotoxic dose MDMA on IL‐1β concentration glial activation their relationship with depletion. MDMA, given housed at 22°C, increased levels hypothalamus cortex from 1 6 h [ 3 H]‐(1‐(2‐chlorophenyl)‐ N ‐methyl‐ ‐(1‐methylpropyl)3‐isoquinolinecarboxamide)...
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 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...
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...