A5033032639- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Traumatic Brain Injury and Neurovascular Disturbances
- S100 Proteins and Annexins
- Stress Responses and Cortisol
- Anesthesia and Neurotoxicity Research
- Neurotransmitter Receptor Influence on Behavior
- Immune cells in cancer
- Complement system in diseases
- Receptor Mechanisms and Signaling
- Cardiac Arrest and Resuscitation
- Tryptophan and brain disorders
- Immune Response and Inflammation
- Barrier Structure and Function Studies
- Mesoporous Materials and Catalysis
- Zeolite Catalysis and Synthesis
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Atherosclerosis and Cardiovascular Diseases
- Neonatal and fetal brain pathology
- Biomarkers in Disease Mechanisms
- Cardiac Health and Mental Health
- Catalysis and Hydrodesulfurization Studies
- Neurological Disease Mechanisms and Treatments
- Chemical Synthesis and Reactions
- Vitamin K Research Studies
Mario Negri Institute for Pharmacological Research
2015-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2013-2023
Institution of Engineering and Technology
2023
American Heart Association
2023
Chevron (United States)
2010
Czech Academy of Sciences, J. Heyrovský Institute of Physical Chemistry
2010
Instituto de Tecnología Química
2010
Eni (Italy)
1997-2008
University of Milan
1993-2003
Abstract Limbic status epilepticus was induced in rats by unilateral 60‐min electrical stimulation of the CA3 region ventral hippocampus. As assessed RT‐PCR followed Southern blot analysis, transcripts interleukin‐1β, interleukin‐6, interleukin‐1 receptor antagonist and inducible nitric oxide synthase were significantly increased 2 h after stimulated Induction maximal at 6 for interleukin‐1β (445%), interleukin‐6 (405%) tumour necrosis factor‐α (264%) 24 (494%) (432%). In with spontaneous...
Abstract Background Emerging evidence indicates that, similarly to what happens for peripheral macrophages, microglia can express different phenotypes depending on microenvironmental signals. In spite of the large literature inflammation after ischemia, information M/M phenotype marker expression, their colocalization and temporal evolution in injured brain is lacking. The present study investigates presence microglia/macrophage markers, whether they are concomitantly expressed by same...
Numerous treatments have been reported to provide a beneficial outcome in experimental animal stroke models; however, these (with the exception of tissue plasminogen activator) failed clinical trials. To improve translation treatment efficacy from bench bedside, we performed preclinical randomized controlled multicenter trial (pRCT) test potential therapy under circumstances closer design and rigor control trial. Anti-CD49d antibodies, which inhibit migration leukocytes into brain, were...
Summary: Purpose: We investigated the changes in expression of proinflammatory cytokines and related molecules rodent hippocampus after induction limbic seizures. then studied effects pharmacologic intervention on interleukin (IL)‐1 system seizures susceptibility to transgenic mice overexpressing naturally occurring antagonist IL‐1 (IL‐1Ra) astrocytes. Methods: Limbic were induced rodents by intrahippocampal injection kainic acid or bicuculline methiodide electrical stimulation causing...
Abstract Brain inflammatory reactions have been described in various neurological disorders, including epilepsy. Although there is clear evidence that cytokines affect neuroglial functions and blood–brain barrier permeability, scarce information available on the functional consequences of brain inflammation seizures. We studied role tumor necrosis factor‐α (TNF)‐α its p55 p75 receptors seizure modulation. found intrahippocampal injection murine recombinant TNF‐α potently inhibits mice while...
The chemokine CX3CL1 and its receptor CX3CR1 are constitutively expressed in the nervous system. In this study, we used vivo murine models of permanent middle cerebral artery occlusion (pMCAO) to investigate protective potential CX3CL1. We report that exogenous reduced ischemia-induced infarct size, neurological deficits, caspase-3 activation. CX3CL1-induced neuroprotective effects were long lasting, being observed up 50 d after pMCAO rats. action different brain injuries is mediated by...
Summary: Purpose: We investigated the activation of microglia and astrocytes, induction cytokines, hippocampal neuronal damage, 4 24 h after kainic acid–induced status epilepticus (SE) in postnatal day (PN) 9, 15, 21 rats. Methods: Limbic seizures were induced by systemic injection acid. Glia cell loss studied using immunocytochemistry Western blot. Cytokine expression was analyzed reverse transcriptase–polymerase chain reaction (RT‐PCR) followed Southern blot quantification. Results: After...
The studies on fractalkine and its unique receptor CX3CR1 in neurological disorders yielded contrasting results. We have explored the consequences of deletion ischemic (30′ MCAo) mice on: (1) brain infarct size; (2) microglia dynamism morphology; (3) expression markers microglia/macrophages (M/M) activation polarization. observed smaller infarcts cx3cr1 −/− (26.42 ± 7.41 mm 3 , mean sd) compared to wild type (36.29 11.57) −/+ (34.49 8.91) mice. longitudinally analyzed by vivo two‐photon...
The study of microglia and macrophage (M/M) morphology represents a key tool to understand the functional activation state pattern distribution these cells in acute brain injury. identification reliable quantitative morphological parameters is urgently needed cell roles injury explore strategies aimed at therapeutically manipulating inflammatory response.We used three different clinically relevant murine models focal injury, namely, controlled cortical impact (traumatic (TBI)) transient...
This study was designed to test the hypothesis that improved mitochondrial biogenesis could help reducing ischemic cerebral injury. We found levels of proliferator-activated receptor γ coactivator 1α and nuclear respiratory factor-1, DNA content other markers function were reduced in primary mouse cortical neurons under oxygen-glucose deprivation (OGD). The glycogen synthase kinase-3 (GSK-3) inhibitor SB216763 activated an efficient program control counteracted OGD-mediated impairment....
We investigated the effect of long-term, peripheral treatment with enoxaparin, a low molecular weight heparin, in transgenic mice overexpressing human amyloid precursor protein 751 . Enoxaparin (6 IU per mouse intraperitoneally, three times week for 6 months) significantly lowered number and area occupied by cortical β-amyloid deposits total (1-40) concentration. Immunocytochemical analysis glial fibrillary acid protein-positive cells showed that enoxaparin markedly reduced activated...
We investigated the occurrence of endotoxin (lipopolysaccharide, LPS) preconditioning in traumatic brain injury (TBI), evaluating time window LPS-induced protection, its persistence, and associated molecular mechanisms. Mice received 0.1 mg/kg LPS or saline intraperitoneally subsequently TBI (by controlled cortical impact injury) at various intervals. receiving 3, 5, 7 days before showed attenuated motor deficits 1 week after compared with mice saline. Those 5 had also a reduced contusion...
An impaired ability to regulate microglia activation by fractalkine (CX3CL1) leads chronic sub-activation. How this condition affects outcome after acute brain injury is still debated, with studies showing contrasting results depending on the timing and pathology. Here, we investigated early delayed consequences of receptor (CX3CR1) deletion neurological phenotypical features myeloid cells present in lesions mice traumatic (TBI). Wild type (WT) CX3CR1(-/-) C57Bl/6 were subjected sham or...
The aim of the study was to evaluate effects C1-inhibitor (C1-INH), an endogenous inhibitor complement and kinin systems, on neurobehavioral histological outcome following controlled cortical impact brain injury.Experimental prospective randomized in mice.Experimental laboratory.Male C57Bl/6 mice (n = 81).Mice were subjected injury followed by intravenous bolus either C1-INH (15 U at 10 minutes or 1 hour postinjury) saline (equal volume, 150 microl postinjury). Sham-operated received...
The role of tumor necrosis factor (TNF) and its receptors after traumatic brain injury (TBI) remains unclear. We evaluated the effects genetic deletion either p55 or p75 TNF receptor on neurobehavioral outcome, histopathology, DNA damage apoptosis-related cell death/survival gene expression (bcl-2/bax), microglia/macrophage (M/M) activation in wild-type (WT) knockout mice TBI. Injured (-/-) showed a significant attenuation while worsening sensorimotor deficits compared with WT over 4 weeks...
Background: Basic science studies have reported remote ischemic conditioning (RIC) as neuroprotective in acute stroke, while clinical evidence remains conflicting. The TRICS BASIC study investigated the efficacy and safety of RIC experimental stroke using a rigorous trial methodology. Methods: Multi-center, multi-species, parallel group, randomized, controlled, preclinical transient femoral artery clipping to induce female male rats mice subjected endovascular occlusion middle cerebral...
Prophylactic administration of simvastatin has been shown to protect against brain damage and its long-lasting behavioral consequences in neonatal rats. To establish the drug treatment window, we evaluated effectiveness administered at different intervals before after stroke. Furthermore, determined whether affected endothelial nitric oxide synthase (eNOS) or inflammatory cytokines tissue cholesterol levels serum.On postnatal day 7, male rats were subjected hypoxia-ischemia (HI). The...