Modeling invasion patterns in the glioblastoma battlefield

Glioblastoma is the most aggressive tumor of the central nervous system, due to its great infiltration capacity. Understanding the mechanisms that regulate the Glioblastoma invasion front is a major challenge with preeminent potential clinical relevances. In the infiltration front, the key features of tumor dynamics relate to biochemical and biomechanical aspects, which result in the extension of cellular protrusions known as tumor microtubes. The coordination of metalloproteases expression, extracellular matrix degradation, and integrin activity emerges as a leading mechanism that facilitates Glioblastoma expansion and infiltration in uncontaminated brain regions. We propose a novel multidisciplinary approach, based on in vivo experiments in Drosophila and mathematical models, that describes the dynamics of active and inactive integrins in relation to matrix metalloprotease concentration and tumor density at the Glioblastoma invasion front. The mathematical model is based on a non-linear system of evolution equations in which the mechanisms leading chemotaxis, haptotaxis, and front dynamics compete with the movement induced by the saturated flux in porous media. This approach is able to capture the relative influences of the involved agents and reproduce the formation of patterns, which drive tumor front evolution. These patterns have the value of providing biomarker information that is related to the direction of the dynamical evolution of the front and based on static measures of proteins in several tumor samples. Furthermore, we consider in our model biomechanical elements, like the tissue porosity, as indicators of the healthy tissue resistance to tumor progression.

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Targeting the central nervous system: In vivo experiments with peptide-derivatized nanoparticles loaded with Loperamide and Rhodamine-123

Journal of Controlled Release ◽

10.1016/j.jconrel.2007.05.022 ◽

2007 ◽

Vol 122 (1) ◽

pp. 1-9 ◽

Cited By ~ 153

Author(s):

G. Tosi ◽

L. Costantino ◽

F. Rivasi ◽

B. Ruozi ◽

E. Leo ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Rhodamine 123 ◽

In Vivo Experiments ◽

The Central Nervous System

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Differential addressing of 5-HT1A and 5-HT1B receptors in epithelial cells and neurons

Journal of Cell Science ◽

10.1242/jcs.112.6.967 ◽

1999 ◽

Vol 112 (6) ◽

pp. 967-976

Author(s):

A. Ghavami ◽

K.L. Stark ◽

M. Jareb ◽

S. Ramboz ◽

L. Segu ◽

...

Keyword(s):

Epithelial Cells ◽

Neuronal Cultures ◽

Striatal Neurons ◽

Primary Neuronal Cultures ◽

Axon Terminals ◽

In Vivo Experiments ◽

In Vitro Systems ◽

The Central Nervous System

The 5-HT1A and 5-HT1B serotonin receptors are expressed in a variety of neurons in the central nervous system. While the 5-HT1A receptor is found on somas and dendrites, the 5-HT1B receptor has been suggested to be localized predominantly on axon terminals. To study the intracellular addressing of these receptors, we have used in vitro systems including Madin-Darby canine kidney (MDCK II) epithelial cells and primary neuronal cultures. Furthermore, we have extended these studies to examine addressing in vivo in transgenic mice. In epithelial cells, 5-HT1A receptors are found on both apical and basolateral membranes while 5-HT1B receptors are found exclusively in intracellular vesicles. In hippocampal neuronal cultures, 5-HT1A receptors are expressed on somatodendritic membranes but are absent from axons. In contrast, 5-HT1B receptors are found on both dendritic and axonal membranes, including growth cones where they accumulate. Using 5-HT1A and 5-HT1B knockout mice and the binary tTA/tetO system, we generated mice expressing these receptors in striatal neurons. These in vivo experiments demonstrate that, in striatal medium spiny neurons, the 5-HT1A receptor is restricted to the somatodendritic level, while 5-HT1B receptors are shipped exclusively toward axon terminals. Therefore, in all systems we have examined, there is a differential sorting of the 5-HT1A and 5-HT1B receptors. Furthermore, we conclude that our in vivo transgenic system is the only model that reconstitutes proper sorting of these receptors.

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EEG-based brain imaging techniques in psychiatry

Acta Neuropsychiatrica ◽

10.1017/s0924270800032786 ◽

2009 ◽

Vol 21 (S2) ◽

pp. 65-66

Author(s):

Umberto Volpe

Keyword(s):

Brain Imaging ◽

Imaging Techniques ◽

High Sensitivity ◽

Brain Regions ◽

Psychiatric Illnesses ◽

Complex Processes ◽

Imaging Tool ◽

Complex Interactions ◽

The Central Nervous System

Abstract:Electroencephalography has probably represented the first modern and scientifically sound attempt to functionally explore the in vivo activity of the human brain and it has, since ever, attracted attention of psychiatrists, from both the clinical and the research viewpoint.Probably due to the limitations implied by their traditional low spatial resolution, the use of psychophysiological techniques in psychiatry has been not continuous over the last century; however, the availability of newer EEG-based brain imaging techniques has recently renovated some interest (1)). Furthermore, recent theories proposed that psychopathology may result from the failure to integrate the activity of different areas involved in cognitive processes, rather than from the impairment of one or more brain areas (2)); within this view, a reliable brain imaging tool should be able to explore the dynamics of complex interactions among brain regions, with high sensitivity to the subtle deviation in complex processes that last fractions of seconds; psychophysiological techniques, indeed, offer the possibility to explore the functional correlates of major psychiatric illnesses, as well as to understand of the effects of psychotropic drugs on the central nervous system, with incomparable time resolution. Finally, the recent technical possibility to combine different brain imaging approaches has further fostered a renovated enthusiasm to ward the use of EEG-based techniques in psychiatry.This contribution will provide an historical overview of the EEG-based brain imaging techniques and an update on some recent advances concerning the use of such techniques within the psychiatric field. Finally, some examples of psychophysiological and ''multimodal'' imaging investigations in subjects with different psychiatric conditions will be provided.

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Salsolinol—neurotoxic or Neuroprotective?

Neurotoxicity Research ◽

10.1007/s12640-019-00118-7 ◽

2019 ◽

Vol 37 (2) ◽

pp. 286-297 ◽

Cited By ~ 1

Author(s):

Magdalena Kurnik-Łucka ◽

Gniewomir Latacz ◽

Adrian Martyniak ◽

Andrzej Bugajski ◽

Katarzyna Kieć-Kononowicz ◽

...

Keyword(s):

Dopaminergic Neurons ◽

Neuroprotective Effect ◽

Serum Levels ◽

In Vivo Experiments ◽

Pathophysiological Role ◽

The Central Nervous System ◽

Significant Release ◽

6 Hydroxydopamine

AbstractSalsolinol (6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline), widely available in many edibles, is considered to alter the function of dopaminergic neurons in the central nervous system and thus, multiple hypotheses on its either physiological and/or pathophysiological role have emerged. The aim of our work was to revisit its potentially neurotoxic and/or neuroprotective role through a series of both in vitro and in vivo experiments. Salsolinol in the concentration range 10–250 μM did not show any significant release of lactate dehydrogenase from necrotic SH-SY5Y cells and was able in the concentration of 50 and 100 μM to rescue SH-SY5Y cells from death induced by H2O2. Its neuroprotective effect against neurotoxin 6-hydroxydopamine was also determined. Salsolinol was found to decrease significantly the reactive oxygen species level in SH-SY5Y cells treated by 500 μM H2O2 and the caspase activity induced by 300 μM of H2O2 or 100 μM of 6-hydroxydopamine. Serum levels of TNFα and CRP of salsolinol-treated rats were not significantly different from control animals. Both TNFα and CRP served as indirect markers of neurotoxicity and/or neuroprotection. Although the neurotoxic properties of salsolinol have numerously been emphasized, its neuroprotective properties should not be neglected and need greater consideration.

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Toxicological Aspects and Determination of the Main Components of Ayahuasca: A Critical Review

Medicines ◽

10.3390/medicines6040106 ◽

2019 ◽

Vol 6 (4) ◽

pp. 106 ◽

Cited By ~ 6

Author(s):

Simão ◽

Gonçalves ◽

Duarte ◽

Barroso ◽

Cristóvão ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Personal Growth ◽

Critical Review ◽

Metabolic Effects ◽

Special Focus ◽

In Vivo Experiments ◽

The Central Nervous System ◽

Main Components

Ayahuasca is a psychoactive beverage prepared traditionally from a mixture of the leaves and stems of Psychotria viridis and Banisteriopsis caapi, respectively, being originally consumed by indigenous Amazonian tribes for ritual and medicinal purposes. Over the years, its use has spread to other populations as a means to personal growth and spiritual connection. Also, the recreational use of its isolated compounds has become prominent. The main compounds of this tea-like preparation are N,N-dimethyltryptamine (DMT), β-Carbolines, and harmala alkaloids, such as harmine, tetrahydroharmine, and harmaline. The latter are monoamine-oxidase inhibitors and are responsible for DMT psychoactive and hallucinogenic effects on the central nervous system. Although consumers defend its use, its metabolic effects and those on the central nervous system are not fully understood yet. The majority of studies regarding the effects of this beverage and of its individual compounds are based on in vivo experiments, clinical trials, and even surveys. This paper will not only address the toxicological aspects of the ayahuasca compounds but also perform a comprehensive and critical review on the analytical methods available for their determination in biological and non-biological specimens, with special focus on instrumental developments and sample preparation approaches.

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Paullinia cupana Mart. var. Sorbilis protects human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity

Human & Experimental Toxicology ◽

10.1177/0960327110389837 ◽

2010 ◽

Vol 30 (9) ◽

pp. 1382-1391 ◽

Cited By ~ 27

Author(s):

Diêgo Madureira de Oliveira ◽

George Barreto ◽

Pablo Galeano ◽

Juan Ignacio Romero ◽

Mariana Inés Holubiec ◽

...

Keyword(s):

Cell Line ◽

Chromatin Condensation ◽

Antioxidant Properties ◽

Relevant Information ◽

Dependent Manner ◽

Active Constituent ◽

Paullinia Cupana ◽

In Vivo Experiments ◽

The Central Nervous System

Paullinia cupana Mart. var. Sorbilis, commonly known as Guaraná, is a Brazilian plant frequently cited for its antioxidant properties and different pharmacological activities on the central nervous system. The potential beneficial uses of Guaraná in neurodegenerative disorders, such as in Parkinson's disease (PD), the pathogenesis of which is associated with mitochondrial dysfunction and oxidative stress, has not yet been assessed. Therefore, the main aim of the present study was to evaluate if an extract of commercial powdered seeds of Guaraná could protect human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity. Two concentration of Guaraná dimethylsulfoxide extract (0.312 and 0.625 mg/mL) were added to SH-SY5Y cells treated with 300 nM rotenone for 48 h, and the cytoprotective effects were assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, measuring lactate dehydrogenase (LDH) levels, and analyzing nuclear integrity with Hoechst33258 stain. Results showed that the addition of Guaraná extract significantly increased the cell viability of SH-SY5Y cells treated with rotenone, in a dose-dependent manner. On the other hand, LDH levels were significantly reduced by addition of 0.312 mg/mL of Guaraná, but unexpectedly, no changes were observed with the higher concentration. Moreover, chromatin condensation and nuclear fragmentation were significantly reduced by addition of any of both concentrations of the extract. The results obtained in this work could provide relevant information about the mechanisms underlying the degeneration of dopaminergic neurons in PD and precede in vivo experiments. Further studies are needed to investigate which active constituent is responsible for the cytoprotective effect produced by Paullinia cupana.

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The Role of fMRI in the Assessment of Neuroplasticity in MS: A Systematic Review

Neural Plasticity ◽

10.1155/2018/3419871 ◽

2018 ◽

Vol 2018 ◽

pp. 1-27 ◽

Cited By ~ 4

Author(s):

De Giglio Laura ◽

Tommasin Silvia ◽

Petsas Nikolaos ◽

Pantano Patrizia

Keyword(s):

Multiple Sclerosis ◽

Environmental Changes ◽

Brain Regions ◽

Pharmacological Therapy ◽

Adaptive Plasticity ◽

Disease Evolution ◽

Functional Changes ◽

Maladaptive Plasticity ◽

The Central Nervous System

Neuroplasticity, which is the ability of the brain to adapt to internal and external environmental changes, physiologically occurs during growth and in response to damage. The brain’s response to damage is of particular interest in multiple sclerosis, a chronic disease characterized by inflammatory and neurodegenerative damage to the central nervous system. Functional MRI (fMRI) is a tool that allows functional changes related to the disease and to its evolution to be studied in vivo. Several studies have shown that abnormal brain recruitment during the execution of a task starts in the early phases of multiple sclerosis. The increased functional activation during a specific task observed has been interpreted mainly as a mechanism of adaptive plasticity designed to contrast the increase in tissue damage. More recent fMRI studies, which have focused on the activity of brain regions at rest, have yielded nonunivocal results, suggesting that changes in functional brain connections represent mechanisms of either adaptive or maladaptive plasticity. The few longitudinal studies available to date on disease evolution have also yielded discrepant results that are likely to depend on the clinical features considered and the length of the follow-up. Lastly, fMRI has been used in interventional studies to investigate plastic changes induced by pharmacological therapy or rehabilitation, though whether such changes represent a surrogate of neuroplasticity remains unclear. The aim of this paper is to systematically review the existing literature in order to provide an overall description of both the neuroplastic process itself and the evolution in the use of fMRI techniques as a means of assessing neuroplasticity. The quantitative and qualitative approach adopted here ensures an objective analysis of published, peer-reviewed research and yields an overview of up-to-date knowledge.

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SU-8 Based Waveguide for Optrodes

Proceedings ◽

10.3390/proceedings2130814 ◽

2018 ◽

Vol 2 (13) ◽

pp. 814

Author(s):

Sara Pimenta ◽

João F. Ribeiro ◽

Sandra B. Goncalves ◽

Marino J. Maciel ◽

Rosana A. Dias ◽

...

Keyword(s):

Optical Fiber ◽

Optical Power ◽

Brain Regions ◽

Neural Probes ◽

Tissue Penetration ◽

In Vivo Experiments ◽

Small Probe ◽

Promising Solution ◽

Neural Probe

Neural probes can be equipped with light for optogenetics applications. Different approaches are used for delivering light to the tissue: an optical fiber coupled to the probe, a µLED or a waveguide integrated on the probe. Small probe dimensions, adequate optical power for photostimulation and good tissue penetration for in-vivo experiments are critical requirements. Thus, integrating a waveguide is a promising solution. This work shows the design and simulation of a SU-8 based waveguide for integration in a neural probe. The waveguide contains 3 apertures, spaced by 0.5 mm, which will allow the photostimulation of different brain regions simultaneously.

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Neonatal cortical astrocytes possess intrinsic potential in neuronal conversion in defined media

Acta Pharmacologica Sinica ◽

10.1038/s41401-020-00586-0 ◽

2021 ◽

Author(s):

Peng Zeng ◽

Qiu-hong Hua ◽

Jun-yuan Gong ◽

Chang-jie Shi ◽

Xiao-ping Pi ◽

...

Keyword(s):

Detailed Comparison ◽

Brain Regions ◽

Culture Conditions ◽

Neuronal Markers ◽

Electrophysiological Properties ◽

Neuronal Progenitor ◽

Cortical Astrocytes ◽

The Central Nervous System ◽

And Function

AbstractAstrocytes are multifunctional brain cells responsible for maintaining the health and function of the central nervous system. Accumulating evidence suggests that astrocytes might be complementary source across different brain regions to supply new neurons during adult neurogenesis. In this study, we found that neonatal mouse cortical astrocytes can be directly converted into neurons when exposed to neurogenic differentiation culture conditions, with insulin being the most critical component. Detailed comparison studies between mouse cortical astrocytes and neuronal progenitor cells (NPCs) demonstrated the converted neuronal cells originate indeed from the astrocytes rather than NPCs. The neurons derived from mouse cortical astrocytes display typical neuronal morphologies, express neuronal markers and possess typical neuronal electrophysiological properties. More importantly, these neurons can survive and mature in the mouse brain in vivo. Finally, by comparing astrocytes from different brain regions, we found that only cortical astrocytes but not astrocytes from other brain regions such as hippocampus and cerebellum can be converted into neurons under the current condition. Altogether, our findings suggest that neonatal astrocytes from certain brain regions possess intrinsic potential to differentiate/transdifferentiate into neurons which may have clinical relevance in the future.

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