Trazodone-gabapentin association increases sedation scores with mild hemodynamic and echocardiographic impact in healthy cats.

Despite the increasing use of drugs to facilitate feline management in veterinary care, there is still a lack of information on the anxiolytic and sedative effects and their specific physiological impacts. We aimed to compare the sedative, hematological, biochemical and cardiovascular effects of oral single-dose trazodone and gabapentin, alone or in combination, in 8 healthy adult mixed-breed domestic cats on a prospective, randomized, cross-over, and placebo-controlled study. Cats were assigned to receive an oral single dose of trazodone (50 mg) (TG), gabapentin (100 mg) (GG), trazodone (50 mg) and gabapentin (100 mg) (GTG), or placebo (PG).

Semaphorin-7A on Exosomes: A Promigratory Signal in the Glioma Microenvironment.

Exosomes are one of the most important mediators of the cross talk occurring between glioma stem cells (GSCs) and the surrounding microenvironment. We have previously shown that exosomes released by patient-derived glioma-associated stem cells (GASC) are able to increase, in vitro, the aggressiveness of both GSC and glioblastoma cell lines. To understand which molecules are responsible for this tumour-supporting function, we performed a descriptive proteomic analysis of GASC-exosomes and identified, among the others, Semaphorin7A (SEMA7A).

Expression and modulation of S100A4 protein by human mast cells.

S100A4 protein is expressed in fibroblasts during tissue remodelling and in cancer stem cells and it induces the metastatic spread of tumor cells. In mast cells (MCs) S100A4 have been found in some pathological conditions, but its function in normal MCs remains to be described. The purpose of this study was to characterize the cellular localization of the S100A4 protein in MCs of human tissues with inflammatory or tumor disorders and, to determine the consequence of reducing its expression in MC response.

Bone regeneration with adipose derived stem cells in a rabbit model.

It has been shown that stem cells are able to calcify both in vitro and in vivo once implanted under the skin, if conveniently differentiated. Nowadays, however, a study on their efficiency in osseous regeneration does not exist in scientific literature and this very task is the real aim of the present experimentation. Five different defects of 6 mm in diameter and 2 mm in depth were created in the calvaria of 8 white New Zealand rabbits.

An NF-κB signature predicts low-grade glioma prognosis: a precision medicine approach based on patient-derived stem cells.

Background: While recent genome-wide association studies have suggested novel low-grade glioma (LGG) stratification models based on a molecular classification, we explored the potential clinical utility of patient-derived cells. Specifically, we assayed glioma-associated stem cells (GASC) that are patient-derived and representative of the glioma microenvironment.

Methods: By next-generation sequencing, we analyzed the transcriptional profile of GASC derived from patients who underwent anaplastic transformation either within 48 months (GASC-BAD) or ≥7 years (GASC-GOOD) after surgery.

In vivo evaluation of chitosan-glycerol gel scaffolds seeded with stem cells for full-thickness mandibular bone regeneration.

The aim of this study was to evaluate in vivo bone regeneration, mediated by adipose-derived stem cells (ADSCs), induced to differentiate into osteoblasts and carried by a scaffold gel. In the test group, bone regeneration was mediated by ADSCs, induced to differentiate into osteoblasts, and carried by a scaffold gel. In the control group a scaffold without cells was used.

TRIM28 and β-actin identified via nanobody-based reverse proteomics approach as possible human glioblastoma biomarkers.

Malignant gliomas are among the rarest brain tumours, and they have the worst prognosis. Grade IV astrocytoma, known as glioblastoma multiforme (GBM), is a highly lethal disease where the standard therapies of surgery, followed by radiation and chemotherapy, cannot significantly prolong the life expectancy of the patients. Tumour recurrence shows more aggressive form compared to the primary tumour, and results in patient survival from 12 to 15 months only.

Glioma-associated stem cells: a novel class of tumor-supporting cells able to predict prognosis of human low-grade gliomas.

Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm.

Acceleration of neuronal precursors differentiation induced by substrate nanotopography.

Embryonic stem (ES) cell differentiation in specific cell lineages is a major issue in cell biology particularly in regenerative medicine. Differentiation is usually achieved by using biochemical factors and it is not clear whether mechanical properties of the substrate over which cells are grown can affect proliferation and differentiation. Therefore, we produced patterns in polydimethylsiloxane (PDMS) consisting of groove and pillar arrays of sub-micrometric lateral resolution as substrates for cell cultures.

Fragmentation as a mechanism for growth cone pruning and degeneration.

During early development of the central nervous system, there is an excessive outgrowth of neuronal projections, which later need to be refined to achieve precise connectivity. Axon pruning and degeneration are strategies used to remove exuberant neurites and connections in the immature nervous system to ensure the proper formation of functional circuitry. To observe morphological changes and physical mechanisms underlying this process, early differentiating embryonic stem cell-derived neurons were used combining video imaging of live growth cones (GCs) with confocal laser scanning microscopy and atomic force microscopy, both on fixed and living neurons.

Sequential steps underlying neuronal plasticity induced by a transient exposure to gabazine.

Periods of intense electrical activity can initiate neuronal plasticity leading to long lasting changes of network properties. By combining multielectrode extracellular recordings with DNA microarrays, we have investigated in rat hippocampal cultures the temporal sequence of events of neuronal plasticity triggered by a transient exposure to the GABA(A) receptor antagonist gabazine (GabT). GabT induced a synchronous bursting pattern of activity.

Calcium control of gene regulation in rat hippocampal neuronal cultures.

Blockage of GABA-A receptors in hippocampal neuronal cultures triggers synchronous bursts of spikes initiating neuronal plasticity, partly mediated by changes of gene expression. By using specific pharmacological blockers, we have investigated which sources of Ca2+ entry primarily control changes of gene expression induced by 20 microM gabazine applied for 30 min (GabT). Intracellular Ca2+ transients were monitored with Ca2+ imaging while recording electrical activity with patch clamp microelectrodes.

Elevation of somatic Ca2+ upregulates genes Nr4a1 and Egr2, but not Bdnf and Arc.

Blockage of Ca2+ uptake with thapsigargin, a specific antagonist of sarco/endoplasmic reticulum Ca2+-ATPase pumps, causes an increase of somatic Ca2+, with negligible changes of Ca2+ levels in dendrites. Treatment with thapsigargin in the presence of blockers of NMDA (N-methyl-D-aspartic acid) receptors upregulates some activity-dependent genes (Egr2 and Nr4a1), leaving unaltered the expression level of other activity-dependent genes (Bdnf and Arc). These results show that the elevation of somatic Ca2+ can initiate transcription of specific genes, independently of activation of NMDA receptors, but that transcription of other genes is not initiated by a simple elevation of intracellular Ca2+.

Characterization of the time course of changes of the evoked electrical activity in a model of a chemically-induced neuronal plasticity.

Background: Neuronal plasticity is initiated by transient elevations of neuronal networks activity leading to changes of synaptic properties and providing the basis for memory and learning 1. An increase of electrical activity can be caused by electrical stimulation 2 or by pharmacological manipulations: elevation of extracellular K+ 3, blockage of inhibitory pathways 4 or by an increase of second messengers intracellular concentrations 5. Neuronal plasticity is mediated by several biochemical pathways leading to the modulation of synaptic strength, density of ionic channels and morphological changes of neuronal arborisation 6.

Integration of confocal and atomic force microscopy images.

Atomic force microscopy (AFM) provides the possibility to map the 3D structure of viewed objects with a nanometric resolution, which cannot be achieved with other imaging methods such as conventional video imaging and confocal fluorescent microscopy. Video imaging with CCD cameras can provide an analysis of biological events with a temporal and spatial resolution not possible with AFM, while confocal imaging allows the simultaneous acquisition of immunofluorescence images. In this communication we present a simple method to combine AFM and confocal images to study differentiating embryonic stem (ES) cells-derived and dorsal root ganglia (DRG) neurons in culture.

On the dynamics of the spontaneous activity in neuronal networks.

Most neuronal networks, even in the absence of external stimuli, produce spontaneous bursts of spikes separated by periods of reduced activity. The origin and functional role of these neuronal events are still unclear. The present work shows that the spontaneous activity of two very different networks, intact leech ganglia and dissociated cultures of rat hippocampal neurons, share several features.

Embryonic stem cell-derived neurons form functional networks in vitro.

Embryonic stem (ES) cells provide a flexible and unlimited source for a variety of neuronal types. Because mature neurons establish neuronal networks very easily, we tested whether ES-derived neurons are capable of generating functional networks and whether these networks, generated in vitro, are capable of processing information. Single-cell electrophysiology with pharmacological antagonists demonstrated the presence of both excitatory and inhibitory synaptic connections.

Statistical properties of information processing in neuronal networks.

Information processing and coding were analysed in dissociated hippocampal cultures, grown on multielectrode arrays. Multisite stimulation was used to activate different neurons and pathways of the network. The neural activity was binned into firing rates and the variability of the firing of individual neurons and of the whole population was analysed.

Toward the neurocomputer: image processing and pattern recognition with neuronal cultures.

Information processing in the nervous system is based on parallel computation, adaptation and learning. These features cannot be easily implemented on conventional silicon devices. In order to obtain a better insight of how neurons process information, we have explored the possibility of using biological neurons as parallel and adaptable computing elements for image processing and pattern recognition.