scholarly journals Acute but not inherited demyelination in mouse models leads to brain tissue stiffness changes

2018 ◽  
Author(s):  
Dominic Eberle ◽  
Georgia Fodelianaki ◽  
Thomas Kurth ◽  
Anna Jagielska ◽  
Stephanie Möllmert ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Brain Tissue ◽  
Ex Vivo ◽  
Brain Regions ◽  
Demyelinating Diseases ◽  
Tissue Stiffness ◽  
Mechanical Heterogeneity ◽  
Healthy State ◽  
Demyelinating Lesions

AbstractThe alteration or decrease of axonal myelination is an important hallmark of aging and disease. Demyelinated axons are impaired in their function and degenerate over time. Oligodendrocytes, the cells responsible for myelination of axons, are sensitive to mechanical properties of their environment. Growing evidence indicates that mechanical properties of demyelinating lesions are different from the healthy state and thus have the potential to affect myelinating potential of oligodendrocytes. We performed a high-resolution spatial mapping of the mechanical heterogeneity of demyelinating lesions using Atomic Force Microscope enabled indentation. Our results indicate that the stiffness of specific regions of mouse brain tissue is influenced by age and degree of myelination. Here we specifically demonstrate that acute but not inherited demyelination leads to decreased tissue stiffness, which could lower remyelination potential of oligodendrocytes. We also demonstrate that specific brain regions have unique ranges of stiffness in white and grey matter. Our ex vivo findings may help the design of future in vitro models to mimic mechanical environment of the brain in healthy and disease state. Reported here, mechanical properties of demyelinating lesions may facilitate novel approaches in treating demyelinating diseases such as multiple sclerosis.

Monocytes as Carriers of Magnetic Nanoparticles for Tracking Inflammation in the Epileptic Rat Brain

2019 ◽  
Vol 16 (7) ◽  
pp. 637-644 ◽  
Author(s):  
Hadas Han ◽  
Sara Eyal ◽  
Emma Portnoy ◽  
Aniv Mann ◽  
Miriam Shmuel ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Ex Vivo ◽  
In Vivo Studies ◽  
Nanoparticle Distribution ◽  
Spontaneous Seizures ◽  
Systemic Distribution ◽  
Hippocampal Ca1 ◽  
Pilocarpine Model

Background: Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite- laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain. Objective: In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded monocytes. Methods: The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated using immunohistochemistry. Results: 89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and 380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater nanoparticle accumulation within the liver and the spleen (p<0.05). Conclusion: Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds. The effect of seizures on monocyte biodistribution should be further explored to better understand the systemic effects of epilepsy.

scholarly journals Preferential Infection of Mature Dendritic Cells by Mouse Hepatitis Virus Strain JHM

2006 ◽  
Vol 80 (5) ◽  
pp. 2506-2514 ◽  
Author(s):  
Haixia Zhou ◽  
Stanley Perlman
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Virus Strain ◽  
Hepatitis Virus ◽  
Ex Vivo ◽  
Mouse Hepatitis Virus ◽  
Demyelinating Diseases ◽  
Immature Cells

ABSTRACT Mouse hepatitis virus strain JHM (MHV-JHM) causes acute encephalitis and acute and chronic demyelinating diseases in mice. Dendritic cells (DCs) are key cells in the initiation of innate and adaptive immune responses, and infection of these cells could potentially contribute to a dysregulated immune response; consistent with this, recent results suggest that DCs are readily infected by another strain of mouse hepatitis virus, the A59 strain (MHV-A59). Herein, we show that the JHM strain also productively infected DCs. Moreover, mature DCs were at least 10 times more susceptible than immature DCs to infection with MHV-JHM. DC function was impaired after MHV-JHM infection, resulting in decreased stimulation of CD8 T cells in vitro. Preferential infection of mature DCs was not due to differential expression of the MHV-JHM receptor CEACAM-1a on mature or immature cells or to differences in apoptosis. Although we could not detect infected DCs in vivo, both CD8+ and CD11b+ splenic DCs were susceptible to infection with MHV-JHM directly ex vivo. This preferential infection of mature DCs may inhibit the development of an efficient immune response to the virus.

scholarly journals Multiple Irradiation Affects Cellular and Extracellular Components of the Mouse Brain Tissue and Adhesion and Proliferation of Glioblastoma Cells in Experimental System In Vivo

2021 ◽  
Vol 22 (24) ◽  
pp. 13350
Author(s):  
Maxim O. Politko ◽  
Alexandra Y. Tsidulko ◽  
Oxana A. Pashkovskaya ◽  
Konstantin E. Kuper ◽  
Anastasia V. Suhovskih ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Mouse Brain ◽  
Glial Cells ◽  
Ex Vivo ◽  
Experimental System ◽  
Normal Brain ◽  
Biosynthetic Activity ◽  
Normal Brain Tissue

Intensive adjuvant radiotherapy (RT) is a standard treatment for glioblastoma multiforme (GBM) patients; however, its effect on the normal brain tissue remains unclear. Here, we investigated the short-term effects of multiple irradiation on the cellular and extracellular glycosylated components of normal brain tissue and their functional significance. Triple irradiation (7 Gy*3 days) of C57Bl/6 mouse brain inhibited the viability, proliferation and biosynthetic activity of normal glial cells, resulting in a fast brain-zone-dependent deregulation of the expression of proteoglycans (PGs) (decorin, biglycan, versican, brevican and CD44). Complex time-point-specific (24–72 h) changes in decorin and brevican protein and chondroitin sulfate (CS) and heparan sulfate (HS) content suggested deterioration of the PGs glycosylation in irradiated brain tissue, while the transcriptional activity of HS-biosynthetic system remained unchanged. The primary glial cultures and organotypic slices from triple-irradiated brain tissue were more susceptible to GBM U87 cells’ adhesion and proliferation in co-culture systems in vitro and ex vivo. In summary, multiple irradiation affects glycosylated components of normal brain extracellular matrix (ECM) through inhibition of the functional activity of normal glial cells. The changed content and pattern of PGs and GAGs in irradiated brain tissues are accompanied by the increased adhesion and proliferation of GBM cells, suggesting a novel molecular mechanism of negative side-effects of anti-GBM radiotherapy.

FORMULATION AND EVALUATION OF FAST DISSOLVING BUCCAL FILMS OF DIMENHYDRINATE

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (09) ◽  
pp. 34-41
Author(s):  
M. R Andrea ◽  
◽  
P. M. Dandagi ◽  
A. P. Gadad
Keyword(s):  
Mechanical Properties ◽  
Ex Vivo ◽  
Poloxamer 407 ◽  
Solvent Casting ◽  
Stability Studies ◽  
Casting Method ◽  
Disintegration Time ◽  
In Vitro Drug Release ◽  
Buccal Films

The aim of the present study was to develop a fast dissolving buccal film of dimenhydrinate with good mechanical properties and fast disintegration, producing an acceptable taste when placed in the mouth. The formulations were developed by solvent casting method by using HPMC E5 and HPMC E15 as film formers in different concentrations, propylene glycol as plasticizer and Poloxamer 407 as solubiliser. The resultant films were evaluated for various parameters. the films were found to be satisfactory for all the parameters. All formulations released more than 85% of the drug within 15 minutes. Formulation F7 (1% HPMC E5: 1% HPMC E15) was selected as the optimized formulation based upon the least disintegration time (24.3sec), optimum mechanical properties, percentage drug content (94.96%) and in vitro drug release (95.20%). The ex vivo release was found to be acceptable. Stability studies revealed that the formulation was stable on storage for two months.

scholarly journals Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography

2018 ◽  
Vol 69 ◽  
pp. 10-18 ◽  
Author(s):  
Charlotte A. Guertler ◽  
Ruth J. Okamoto ◽  
John L. Schmidt ◽  
Andrew A. Badachhape ◽  
Curtis L. Johnson ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Brain Tissue ◽  
Ex Vivo ◽  
Mr Elastography ◽  
Porcine Brain ◽  
Porcine Brain Tissue

scholarly journals FORMULATION AND EVALUATION OF BILAYERED FELODIPINE TRANSDERMAL PATCHES: IN VITRO AND EX VIVO CHARACTERIZATION

2021 ◽  
pp. 106-111
Author(s):  
KEERTHANA M ◽  
SHIRISHA S ◽  
SAHOO SUNIT KUMAR ◽  
MADHUSUDAN RAO Y
Keyword(s):  
Mechanical Properties ◽  
Moisture Absorption ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Pharmacokinetic Parameters ◽  
Physicochemical Interaction ◽  
Eucalyptus Oil ◽  
Transdermal Patches ◽  
Lemongrass Oil

Objective: Felodipine (FD) is an effective Biopharmaceutics Classification System Class II calcium channel blocker mainly used in the management of hypertension and angina pectoris. It has poor solubility and low oral bioavailability (15%). To overcome these disadvantages and to maintain constant plasma concentration for maximum therapeutic activity, there is a need to design an alternative route, that is, transdermal route. The pharmacokinetic parameters make FD a suitable candidate for transdermal delivery. The present investigation consists of the study of in vitro and ex vivo skin flux of FD from bilayered transdermal patches. Methods: The patches were fabricated by solvent casting method using hydrophilic and hydrophobic polymer with different composition. Tween 80 incorporated as solubilizer, polyethylene glycol 600 as plasticizer, menthol, eucalyptus oil, and lemongrass oil used as permeation enhancers, respectively. The prepared transdermal drug delivery system was extensively evaluated for in vitro release, ex vivo permeation through pig ear skin, moisture content, moisture absorption, water vapor transmission, and mechanical properties. The physicochemical interaction between FD and polymers was investigated by Fourier-transform infrared (FTIR) spectroscopy. Results: All the formulations exhibited satisfactory physicochemical and mechanical characteristics. A flux of 35.2 μg/cm2 h, 27.9 μg/cm2 h, and 25.25 μg/cm2 h was achieved for optimized formulations containing lemongrass oil, eucalyptus oil, and menthol, respectively, permeation enhances. Values of tensile strength (0.0652±0.034 kg/mm²) and elongation at break (0.8749±0.0.0029% mm²) revealed that formulation F9 was strong but not brittle. Drug and excipients compatibility studies showed no evidence of interaction between the active ingredient and polymers. Conclusion: Bilayered FD transdermal patches could be prepared with required flux and suitable mechanical properties.

scholarly journals Effect of in vitro storage duration on measured mechanical properties of brain tissue

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Wei Zhang ◽  
Li-fu Liu ◽  
Yue-jiao Xiong ◽  
Yi-fan Liu ◽  
Sheng-bo Yu ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Brain Tissue ◽  
Storage Duration ◽  
In Vitro Storage

scholarly journals Cochlear Dummy Electrodes for Insertion Training and Research Purposes: Fabrication, Mechanical Characterization, and Experimental Validation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jan-Philipp Kobler ◽  
Anandhan Dhanasingh ◽  
Raphael Kiran ◽  
Claude Jolly ◽  
Tobias Ortmaier
Keyword(s):  
Mechanical Properties ◽  
Force Measurement ◽  
Ex Vivo ◽  
Low Cost ◽  
Hearing Preservation ◽  
Insertion Force ◽  
A New Technique ◽  
Temporal Bones

To develop skills sufficient for hearing preservation cochlear implant surgery, surgeons need to perform several electrode insertion trials inex vivotemporal bones, thereby consuming relatively expensive electrode carriers. The objectives of this study were to evaluate the insertion characteristics of cochlear electrodes in a plastic scala tympani model and to fabricate radio opaque polymer filament dummy electrodes of equivalent mechanical properties. In addition, this study should aid the design and development of new cochlear electrodes. Automated insertion force measurement is a new technique to reproducibly analyze and evaluate the insertion dynamics and mechanical characteristics of an electrode. Mechanical properties of MED-EL’s FLEX28, FLEX24, and FLEX20electrodes were assessed with the help of an automated insertion tool. Statistical analysis of the overall mechanical behavior of the electrodes and factors influencing the insertion force are discussed. Radio opaque dummy electrodes of comparable characteristics were fabricated based on insertion force measurements. The platinum-iridium wires were replaced by polymer filament to provide sufficient stiffness to the electrodes and to eradicate the metallic artifacts in X-ray and computed tomography (CT) images. These low-cost dummy electrodes are cheap alternatives for surgical training and forin vitro, ex vivo, andin vivoresearch purposes.

scholarly journals Ex vivo Methods for Measuring Cardiac Muscle Mechanical Properties

2021 ◽  
Vol 11 ◽  
Author(s):  
Walter E. Knight ◽  
Hadi R. Ali ◽  
Stephanie J. Nakano ◽  
Cortney E. Wilson ◽  
Lori A. Walker ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Cardiac Function ◽  
Cardiac Muscle ◽  
Protein Interactions ◽  
Ex Vivo ◽  
The United States ◽  
Muscle Performance ◽  
Mechanical Function ◽  
Whole Heart

Cardiovascular disease continues to be the leading cause of morbidity and mortality in the United States and thousands of manuscripts each year are aimed at elucidating mechanisms underlying cardiac disease. The methods for quantifying cardiac performance are quite varied, with each technique assessing unique features of cardiac muscle mechanical properties. Accordingly, in this review, we discuss current ex vivo methods for quantifying cardiac muscle performance, highlighting what can be learned from each method, and how each technique can be used in conjunction to complement others for a more comprehensive understanding of cardiac function. Importantly, cardiac function can be assessed at several different levels, from the whole organ down to individual protein-protein interactions. Here, we take a reductionist view of methods that are commonly used to measure the distinct aspects of cardiac mechanical function, beginning with whole heart preparations and finishing with the in vitro motility assay. While each of the techniques are individually well-documented in the literature, there is a significant need for a comparison of the techniques, delineating the mechanical parameters that can are best measured with each technique, as well as the strengths and weaknesses inherent to each method. Additionally, we will consider complementary techniques and how these methods can be used in combination to improve our understanding of cardiac mechanical function. By presenting each of these methods, with their strengths and limitations, in a single manuscript, this review will assist cardiovascular biologists in understanding the existing literature on cardiac mechanical function, as well as designing future experiments.

scholarly journals How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
N.R. Chevalier ◽  
E. Gazquez ◽  
L. Bidault ◽  
T. Guilbert ◽  
C. Vias ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Cell Migration ◽  
Neural Crest ◽  
Ex Vivo ◽  
Second Harmonic ◽  
Neural Crest Cell ◽  
Congenital Defects ◽  
Migration Behavior ◽  
Collagen Gels

Abstract Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development.

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