Luana Gilio's research while affiliated with IRCCS Istituto Neurologico Mediterraneo Neuromed and other places

Publications (26)

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(1) Background: The clinical course of multiple sclerosis (MS) is critically influenced by the expression of different pro-inflammatory and anti-inflammatory cytokines. Interleukin 6 (IL-6) represents a major inflammatory molecule previously associated with exacerbated disease activity in relapsing remitting MS (RR-MS); however, the role of single-...
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The clinical course of multiple sclerosis (MS) is critically influenced by the interplay between inflammatory and neurodegenerative processes. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265), one of the most studied single-nucleotide polymorphisms (SNPs), influences brain functioning and neurodegenerative processes in he...
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Long lasting symptoms have been reported in a considerable proportion of patients after a severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. This condition, defined as either “post-acute coronavirus disease (COVID),” “long COVID,” or “long-haul COVID,” has also been described in outpatients and in individuals who are asymptomat...
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Background: Astrocytes and microglia play an important role in the inflammatory process of multiple sclerosis (MS). We investigated the associations between the cerebrospinal fluid (CSF) levels of glial fibrillary acid protein (GFAP) and soluble triggering receptors expressed on myeloid cells-2 (sTREM-2), inflammatory molecules, and clinical charac...
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Age at onset is the main risk factor for disease progression in patients with relapsing-remitting multiple sclerosis (RR-MS). In this cross-sectional study, we explored whether older age is associated with specific disease features involved in the progression independent of relapse activity (PIRA). In 266 patients with RR-MS, the associations betwe...
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Aim We recently proposed miR-142-3p as a molecular player in inflammatory synaptopathy, a new pathogenic hallmark of multiple sclerosis (MS) and of its mouse model experimental autoimmune encephalomyelitis (EAE), that leads to neuronal loss independently of demyelination. MiR-142-3p seems to be unique among potential biomarker candidates in MS, sin...
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Excessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS). The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear. In 179 MS patients (relapsing remitting, RR, n =...
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Exercise is increasingly recommended as a supportive therapy for people with Multiple Sclerosis (pwMS). While clinical research has still not disclosed the real benefits of exercise on MS disease, animal studies suggest a substantial beneficial effect on motor disability and pathological hallmarks such as central and peripheral dysregulated immune...
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The identification of microRNAs in biological fluids for diagnosis and prognosis is receiving great attention in the field of multiple sclerosis (MS) research but it is still in its infancy. In the present study, we observed in a large sample of MS patients that let-7b-5p levels in the cerebrospinal fluid (CSF) were highly correlated with a number...
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Background and Aims Interferon beta (IFNb) is a safe first-line drug commonly used for relapsing-remitting (RR)-MS. Nevertheless, a considerable proportion of patients do not respond to IFNb treatment. Therefore, until now, a number of studies have investigated various markers that could predict the patients who would respond to IFNb therapy. The o...
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In multiple sclerosis (MS), activated T and B lymphocytes and microglial cells release various proinflammatory cytokines, promoting neuroinflammation and negatively affecting the course of the disease. The immune response homeostasis is crucially regulated by the activity of the enzyme adenosine deaminase (ADA), as evidenced in patients with geneti...
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In multiple sclerosis (MS), inflammation alters synaptic transmission and plasticity, negatively influencing the disease course. In the present study, we aimed to explore the influence of the proinflammatory cytokine IL-1β on peculiar features of associative Hebbian synaptic plasticity, such as input specificity, using the paired associative stimul...
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Transcranial magnetic stimulation (TMS) has been employed in multiple sclerosis (MS) to assess the integrity of the corticospinal tract and the corpus callosum and to explore some physiological properties of the motor cortex. Specific alterations of TMS measures have been strongly associated to different pathophysiological mechanisms, particularly...
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Specific proinflammatory and anti-inflammatory molecules could represent useful cerebrospinal fluid (CSF) biomarkers to predict the clinical course of multiple sclerosis (MS). The proinflammatory molecule interleukin (IL)-6 has been investigated in the pathophysiology of MS and has been associated in previous smaller studies to increased disability...
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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelinating white matter lesions and neurodegeneration, with a variable clinical course. Brain network architecture provides efficient information processing and resilience to damage. The peculiar organization characterized by a low numb...
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Studies of brain network connectivity improved understanding on brain changes and adaptation in response to different pathologies. Synaptic plasticity, the ability of neurons to modify their connections, is involved in brain network remodeling following different types of brain damage (e.g., vascular, neurodegenerative, inflammatory). Although syna...
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Objectives: Skill acquisition after motor training involves synaptic long-term potentiation (LTP) in primary motor cortex (M1). In multiple sclerosis (MS), LTP failure ensuing from neuroinflammation could contribute to worsen clinical recovery. We therefore addressed whether practice-dependent plasticity is altered in MS. Methods: Eighteen relap...
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Background: Synaptic plasticity helps in reducing the clinical expression of brain damage and represents a useful mechanism to compensate the negative impact of new brain lesions in multiple sclerosis (MS). Inflammation, altering synaptic plasticity, could negatively influence the disease course in relapsing-remitting MS (RR-MS). Objective: In the...
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Background: Previous studies evidenced a link between metabolic dysregulation, inflammation, and neurodegeneration in multiple sclerosis (MS). Objectives: To explore whether increased adipocyte mass expressed as body mass index (BMI) and increased serum lipids influence cerebrospinal fluid (CSF) inflammation and disease severity. Methods: In t...
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Introduction: Disease course of multiple sclerosis (MS) is negatively influenced by proinflammatory molecules released by activated T and B lymphocytes and local immune cells. The endovanilloid system plays different physiological functions, and preclinical data suggest that transient receptor potential vanilloid type 1 (TRPV1) could modulate neuro...
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Background: Clinical deterioration of relapsing-remitting MS (RR-MS) patients reflects not only the number and severity of overt inflammatory and demyelinating episodes, but also subtle central damage caused by persistent exposure to inflammatory molecules. Objective: To explore the correlation between levels of CSF inflammatory molecules at the...
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The endocannabinoid system (ECS) has been recently recognized as a prominent promoter of the emotional homeostasis, mediating the effects of different environmental signals including rewarding and stressing stimuli. The ECS modulates the rewarding effects of environmental stimuli, influencing synaptic transmission in the dopaminergic projections to...
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Background: In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expressio...
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Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a cl...
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Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic...

Citations

... In addition to these complications. we urge the scientific community to deeply investigate mood disorders that might develop on a psychological substrate in response to stressors established during the pandemic period [46,52,60,61]. Various mechanisms may underlie the neurological implications of SARS-CoV-2 [35,62]. ...
... MCP-1/CCL2, IL-8 and MIP-1a/CCL3 have been demonstrated to be important proinflammatory mediators involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and MS. IL-8 levels in the cerebrospinal fluid of MS patients were elevated compared to controls and correlated with the course of MS (78). Interestingly, activated microglia and macrophages in active MS lesions are a major source of oxidative stress. ...
... Thus, different patterns of miRNA, as well as changes in miRNA expression related to its immunomodulatory effects, could modify the therapeutic response to this drug. There are several articles describing the miRNA changes associated with other disease modifying treatments such as IFN (36)(37)(38)(39)(40), natalizumab (41)(42)(43)(44), dimethyl fumarate (45,46) or fingolimod (47-51), but less information is available regarding GA (52,53). In one article that analyzed the miRNAs changes in a mouse-EAE model treated with GA, the authors found miR-155.5p, ...
... For instance, Choi et al. identified one of the main proposed mechanisms whereby exercise affects cognitive function by increasing the brain-derived neurotrophic factor (BDNF) [7]. Furthermore, aerobic exercise can also upregulate the expression of synaptic plasticityassociated proteins [8]. These findings imply that exercise may be an effective treatment for diabetes-related cognitive impairment. ...
... accessed on 1 July 2021), the vast majority of these miRNAs have validated synaptic targets, as listed in Supplementary Table S2. To narrow their number, the miRNAs were further selected using the following criteria: enrichment in microglia/peripheral immune cells and EVs thereof [33][34][35][36][37][38][39][40][41][42][43], release under inflammatory or neurodegenerative stimuli [23], previous identification as candidate biomarkers for MS pathology [44][45][46][47][48][49][50][51][52][53][54][55] and dysregulation in neurodegenerative diseases [31,[56][57][58]. The miRNAs that passed the selection criteria were the following: miR-146a-5p, miR-223-3p, miR-16-5p, miR-23a-3p, miR-20a, miR-21-5p, miR-125a-5p, miR-146b-5p, miR-150-5p, miR-24-3p, miR-15a-5p, let-7b-5p, miR-451a and miR-126-5p (Table 2). ...
... A study of 561 Caucasian RRMS patients treated with cladribine showed that the allele C for the SNP rs244072 (T>C) was associated to higher expanded disability status scale (EDSS) (TT patients median = 1.5, Interquartile range (IQR) = 1-2.5; CT/CC median = 2; IQR = 1-3; p = 0.011) [99]. ...
... Increased MIP-1α/CCL3 expression has been reported in T lymphocytes of patients with MS and astrocytes and macrophages within the plaque (Balashov et al., 1999). Notably, in patients with RR-MS treated with IFN-β, MIP1α/CCL3 CSF undetectability predicted the absence of clinical/radiological relapses and disability progression 1 year after diagnosis (Stampanoni Bassi et al., 2020). In this study, a strong association between MCP-1/CCL2 and age was evidenced. ...
... A substantial body of research supports the fact that inflammatory cytokines and other immune mediators are capable of affecting synaptic transmission and plasticity (25,27,30,(44)(45)(46). Indeed, bacteremia and sepsis trigger complex responses in the central nervous system including microglia activation and alterations in synaptic plasticity (47,48). ...
... iSP onset) (Giovannelli et al., 2009;Kuo et al., 2017;Rossini et al., 2015). TMS has several uses in MS to enhance understanding of the pathophysiological processes of both the inflammatory and progressive stages of the disease (Ayache et al., 2014;Ayache et al., 2015;Brum et al., 2015;Chalah et al., 2021;Mori et al., 2016;Nicoletti et al., 2019;Stampanoni Bassi et al., 2020;Zipser et al., 2018) and to evaluate novel disease-modifying and rehabilitative therapies (Ayache et al., 2014;Ayache and Chalah, 2017;Chaves et al., 2020a;Chaves et al., 2020b;Stampanoni Bassi et al., 2017). ...
... For these reasons, it is extremely difficult to elucidate the role of each specific cytokine even though some molecules have been consistently associated with increased inflammation and a worse clinical course in MS. More specifically, interleukin (IL)-6 represents one of the most important pro-inflammatory cytokines in the pathophysiology of MS [2,6,7]. Preclinical studies in animal models of MS (i.e., experimental autoimmune encephalomyelitis, EAE), have shown that IL-6 deficient mice were fully resistant to the disease induction [8]. ...