Bridging pro-inflammatory signals, synaptic transmission and protection in spinal explants in vitro

Multiple sclerosis is characterized by tissue atrophy involving the brain and the spinal cord, where reactive inflammation contributes to the neurodegenerative processes. Recently, the presence of synapse alterations induced by the inflammatory responses was suggested by experimental and clinical observations, in experimental autoimmune encephalomyelitis mouse model and in patients, respectively. Further knowledge on the interplay between pro-inflammatory agents, neuroglia and synaptic dysfunction is crucial to the design of unconventional protective molecules. Here we report the effects, on spinal cord circuits, of a cytokine cocktail that partly mimics the signature of T lymphocytes sub population Th1. In embryonic mouse spinal organ-cultures, containing neuronal cells and neuroglia, cytokines induced inflammatory responses accompanied by a significant increase in spontaneous synaptic activity. We suggest that cytokines specifically altered signal integration in spinal networks by speeding the decay of GABAA responses. This hypothesis is supported by the finding that synapse protection by a non-peptidic NGF mimetic molecule prevented both the changes in the time course of GABA events and in network activity that were left unchanged by the cytokine production from astrocytes and microglia present in the cultured tissue. In conclusion, we developed an important tool for the study of synaptic alterations induced by inflammation, that takes into account the role of neuronal and not neuronal resident cells

Tuning the reduction of graphene oxide nanoflakes differently affects neuronal networks in the zebrafish

The increasing engineering of biomedical devices and the design of drug-delivery platforms enriched by graphene-based components demand careful investigations of the impact of graphene-related materials (GRMs) on the nervous system. In addition, the enhanced diffusion of GRM-based products and technologies that might favor the dispersion in the environment of GRMs nanoparticles urgently requires the potential neurotoxicity of these compounds to be addressed. One of the challenges in providing definite evidence supporting the harmful or safe use of GRMs is addressing the variety of this family of materials, with GRMs differing for size and chemistry. Such a diversity impairs reaching a unique and predictive picture of the effects of GRMs on the nervous system. Here, by exploiting the thermal reduction of graphene oxide nanoflakes (GO) to generate materials with different oxygen/carbon ratios, we used a high-throughput analysis of early-stage zebrafish locomotor behavior to investigate if modifications of a specific GRM chemical property influenced how these nanomaterials affect vertebrate sensory-motor neurophysiology—exposing zebrafish to GO downregulated their swimming performance. Conversely, reduced GO (rGO) treatments boosted locomotor activity. We concluded that the tuning of single GRM chemical properties is sufficient to produce differential effects on nervous system physiology, likely interfering with different signaling pathways

Ictal apnea: A prospective monocentric study in patients with epilepsy

Background and purpose: Ictal respiratory disturbances have increasingly been reported, in both generalized and focal seizures, especially involving the temporal lobe. Recognition of ictal breathing impairment has gained importance for the risk of sudden unexpected death in epilepsy (SUDEP). The aim of this study was to evaluate the incidence of ictal apnea (IA) and related hypoxemia during seizures. Methods: We collected and analyzed electroclinical data from consecutive patients undergoing long-term video-electroencephalographic (video-EEG) monitoring with cardiorespiratory polygraphy. Patients were recruited at the epilepsy monitoring unit of the Civil Hospital of Baggiovara, Modena Academic Hospital, from April 2020 to February 2022. Results: A total of 552 seizures were recorded in 63 patients. IA was observed in 57 of 552 (10.3%) seizures in 16 of 63 (25.4%) patients. Thirteen (81.2%) patients had focal seizures, and 11 of 16 patients showing IA had a diagnosis of temporal lobe epilepsy; two had a diagnosis of frontal lobe epilepsy and three of epileptic encephalopathy. Apnea agnosia was reported in all seizure types. Hypoxemia was observed in 25 of 57 (43.9%) seizures with IA, and the severity of hypoxemia was related to apnea duration. Apnea duration was significantly associated with epilepsy of unknown etiology (magnetic resonance imaging negative) and with older age at epilepsy onset (p < 0.001). Conclusions: Ictal respiratory changes are a frequent clinical phenomenon, more likely to occur in focal epilepsies, although detected even in patients with epileptic encephalopathy. Our findings emphasize the need for respiratory polygraphy during long-term video-EEG monitoring for diagnostic and prognostic purposes, as well as in relation to the potential link of ictal apnea with the SUDEP risk

CSF/serum matrix metallopeptidase-9 ratio discriminates neuro Behcet from multiple sclerosis

In neuro Behcet disease with multiple sclerosis-like features, diagnosis could be challenging. Here, we studied the cerebrospinal fluid and serum inflammatory profile of 11 neuro Behcet and 21 relapsing-remitting multiple sclerosis patients. Between the soluble factors analyzed (MMP9, TNF, IL6, CXCL13, CXCL10, CXCL8, IFN, IL10, IL17, IL23, and others) we found MMP9 increased in neuro Behcet serum compared to multiple sclerosis and decreased in cerebrospinal fluid. Furthermore, neuro Behcet analysis of circulating natural killer CD56(DIM) subset suggests their potential involvement in increased MMP9 production. We believe that these findings may have a translational utility in clinical practice

A narrow band neutrino beam with high precision flux measurements

The ENUBET facility is a proposed narrow band neutrino beam where lepton production is monitored at single particle level in the instrumented decay tunnel. This facility addresses simultaneously the two most important challenges for the next generation of cross section experiments: a superior control of the flux and flavor composition at source and a high level of tunability and precision in the selection of the energy of the outcoming neutrinos. We report here the latest results in the development and test of the instrumentation for the decay tunnel. Special emphasis is given to irradiation tests of the photo-sensors performed at INFN-LNL and CERN in 2017 and to the first application of polysiloxane-based scintillators in high energy physics.Comment: Poster presented at NuPhys2017 (London, 20-22 December 2017). 5 pages, 2 figure

LEMMA approach for the production of low-emittance muon beams

This work introduces an experimental test of the new proposal for a low–emittance muon accelerator (LEMMA). A low–emittance muon beam is obtained from the e+e− → μ+μ− annihilation process at the threshold energy of 45 GeV eliminating the need for a dedicated muon cooling system. A series of two testbeam campaigns were carried out at CERN to validate this concept. The experimental setup is presented together with first preliminary results from the obtained data

Dynamical modeling of collective behavior from pigeon flight data: flock cohesion and dispersion

Several models of flocking have been promoted based on simulations with qualitatively naturalistic behavior. In this paper we provide the first direct application of computational modeling methods to infer flocking behavior from experimental field data. We show that this approach is able to infer general rules for interaction, or lack of interaction, among members of a flock or, more generally, any community. Using experimental field measurements of homing pigeons in flight we demonstrate the existence of a basic distance dependent attraction/repulsion relationship and show that this rule is sufficient to explain collective behavior observed in nature. Positional data of individuals over time are used as input data to a computational algorithm capable of building complex nonlinear functions that can represent the system behavior. Topological nearest neighbor interactions are considered to characterize the components within this model. The efficacy of this method is demonstrated with simulated noisy data generated from the classical (two dimensional) Vicsek model. When applied to experimental data from homing pigeon flights we show that the more complex three dimensional models are capable of predicting and simulating trajectories, as well as exhibiting realistic collective dynamics. The simulations of the reconstructed models are used to extract properties of the collective behavior in pigeons, and how it is affected by changing the initial conditions of the system. Our results demonstrate that this approach may be applied to construct models capable of simulating trajectories and collective dynamics using experimental field measurements of herd movement. From these models, the behavior of the individual agents (animals) may be inferred

Super-hydrodynamic limit in interacting particle systems

This paper is a follow-up of the work initiated in [3], where it has been investigated the hydrodynamic limit of symmetric independent random walkers with birth at the origin and death at the rightmost occupied site. Here we obtain two further results: first we characterize the stationary states on the hydrodynamic time scale and show that they are given by a family of linear macroscopic profiles whose parameters are determined by the current reservoirs and the system mass. Then we prove the existence of a super-hyrdrodynamic time scale, beyond the hydrodynamic one. On this larger time scale the system mass fluctuates and correspondingly the macroscopic profile of the system randomly moves within the family of linear profiles, with the randomness of a Brownian motion.Comment: 22 page

Fas gene polymorphisms are not associated with systemic lupus erythematosus, multiple sclerosis and HIV infection

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