scholarly journals Viscoelastic mapping of mouse brain tissue: relation to structure and age

Author(s):  
Nelda Antonovaite ◽  
Lianne A. Hulshof ◽  
Elly M. Hol ◽  
Wytse J. Wadman ◽  
Davide Iannuzzi

AbstractThere is growing evidence that mechanical factors affect brain functioning. However, brain components responsible for regulating the physiological mechanical environment and causing mechanical alterations during maturation are not completely understood. To determine the relationship between structure and stiffness of the brain tissue, we performed high resolution viscoelastic mapping by dynamic indentation of hippocampus and cerebellum of juvenile brain, and quantified relative area covered by immunohistochemical staining of NeuN (neurons), GFAP (astrocytes), Hoechst (nuclei), MBP (myelin), NN18 (axons) of juvenile and adult mouse brain slices. When compared the mechanical properties of juvenile mouse brain slices with previously obtained data on adult slices, the latter was ~ 20-150% stiffer, which correlates with an increase in the relative area covered by astrocytes. Heterogeneity within the slice, in terms of storage modulus, correlates negatively with the relative area of nuclei and neurons, as well as myelin and axons, while the relative area of astrocytes correlates positively. Several linear regression models are suggested to predict the mechanical properties of the brain tissue based on immunohistochemical stainings.

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv16-iv16
Author(s):  
Alastair Kirby ◽  
Jose Pedro Lavrador ◽  
Christian Brogna ◽  
Francesco Vergani ◽  
Bassel Zebian ◽  
...  

Abstract Gliomas often present clinically with seizures. Tumour-associated seizures can be difficult to control with medication. A deeper understanding of the cellular mechanisms underlying tumour-associated seizures would provide a basis for developing new treatments. Here, we investigate epileptic discharges in peritumoral cortex using living human brain tissue donated by people having a craniotomy for glioma resection (REC approval, 18/SW/002). The brain tissue was cut into thin slices, which preserved the architecture of the glioma and the adjacent healthy brain. The brain slices were incubated in 5-aminolevulinic acid to make the glioma cells fluorescent. This enabled us to make electrophysiological recordings of brain activity across the boundary between glioma and brain. We recorded from brain slices of 5 participants with glioblastoma and 4 participants with oligodendroglioma (WHO grade II – III). Spontaneous “seizure-like” discharges were recorded in brain slices from 5/8 participants (3 GBM, 2 oligodendroglioma) who reported seizures and from one participant (GBM) who had not had any clinical seizures. Further analysis of the seizure-like discharges revealed that they could be subdivided into two distinct types based on the major frequencies in the discharge. We concluded that human brain slices from people with either a low-grade or a high-grade glioma can generate spontaneous seizure-like discharges. The living human brain tissue preparation gives us a platform to study the mechanisms of tumour-associated seizures and how abnormal neural activity affects glioma growth.


The Analyst ◽  
2015 ◽  
Vol 140 (19) ◽  
pp. 6563-6570 ◽  
Author(s):  
G. Ojeda-Torres ◽  
L. Williams ◽  
D. E. Featherstone ◽  
S. A. Shippy

Low flow push–pull perfusion is used to measure extracellular glutamate levels from mouse brain tissue slices.


2021 ◽  
Vol 15 ◽  
Author(s):  
Siqi Chen ◽  
Zhixiang Liu ◽  
Anan Li ◽  
Hui Gong ◽  
Ben Long ◽  
...  

The brain modulates specific functions in its various regions. Understanding the organization of different cells in the whole brain is crucial for investigating brain functions. Previous studies have focused on several regions and have had difficulty analyzing serial tissue samples. In this study, we introduced a pipeline to acquire anatomical and histological information quickly and efficiently from serial sections. First, we developed a serial brain-slice-staining method to stain serial sections and obtained more than 98.5% of slices with high integrity. Subsequently, using the self-developed analysis software, we registered and quantified the signals of imaged sections to the Allen Mouse Brain Common Coordinate Framework, which is compatible with multimodal images and slant section planes. Finally, we validated the pipeline with immunostaining by analyzing the activity variance in the whole brain during acute stress in aging and young mice. By removing the problems resulting from repeated manual operations, this pipeline is widely applicable to serial brain slices from multiple samples in a rapid and convenient manner, which benefits to facilitate research in life sciences.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii54-iii54
Author(s):  
A J Kirby ◽  
J P Lavrador ◽  
C Brogna ◽  
F Vergani ◽  
C Chandler ◽  
...  

Abstract BACKGROUND Invading glioma cells affect the physiological function of the peritumoural cortex. This may manifest clinically as seizures. Here, we investigate the effect the invading glioma cells on the electrophysiological signalling of the peritumoral cortex using living human brain tissue donated by people having a craniotomy for glioma resection (REC approval, 18/SW/002). MATERIAL AND METHODS The brain tissue was cut into thin slices, which preserved the architecture of the glioma and the adjacent healthy brain. The brain slices were incubated in 5-aminolevulinic acid to make the glioma cells fluorescent. We observed 5-ALA induced fluorescence in both low-grade and high-grade gliomas. This enabled us to make electrophysiological recordings of brain activity across the boundary between glioma and brain. RESULTS We recorded from brain slices of 5 participants with glioblastoma and 4 participants with oligodendroglioma (WHO grade II - III). Spontaneous “seizure-like” discharges were recorded in brain slices from 5/8 participants (3 GBM, 2 oligodendroglioma) who reported seizures and from one participant (GBM) who had not had any clinical seizures. Further analysis of the electrical discharges revealed that they could be subdivided into two distinct types based on the major frequencies in the discharge. CONCLUSION We concluded that human brain slices from people with either a low-grade or a high-grade glioma can generate spontaneous seizure-like discharges. This electrophysiological signature will be compared to infiltration and grade of the glioma cells in the donated sample. The living human brain tissue preparation gives us a platform to study the mechanisms of tumour-associated seizures and how abnormal neural activity affects glioma growth.


2020 ◽  
Author(s):  
Tomas Fiala ◽  
Jihang Wang ◽  
Matthew Dunn ◽  
Peter Šebej ◽  
Se Joon Choi ◽  
...  

Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. These sensors, rendered highly lipophilic to anchor the conjugated pi-wire molecular framework in the membrane, offer several favorable functional parameters including fast response kinetics and high sensitivity to membrane potential changes. The impact of VSDs has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals. We address this key challenge by introducing a non-genetic molecular platform for cell- and molecule-specific targeting of synthetic voltage sensitive dyes in the brain. We employ a dextran polymer particle to overcome the inherent lipophilicity of voltage sensitive dyes by dynamic encapsulation, and high-affinity ligands to target the construct to specific neuronal cells utilizing only native components of the neurotransmission machinery at physiological expression levels. Dichloropane, a monoamine transporter ligand, enables targeting of dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential changes in a similar manner to the parent dyes, as shown by whole-cell patch recording. We demonstrate the feasibility of optical voltage recording with our probes in brain tissue with one-photon and two-photon fluorescence microscopy and define the signal limits of optical voltage imaging with synthetic sensors under a low photon budget determined by the native expression levels of the target proteins. We envision that modularity of our platform will enable its application to a variety of molecular targets and sensors, as well as lipophilic drugs and signaling modulators. This work demonstrates the feasibility of a chemical targeting approach and expands the possibilities of cell-specific imaging and pharmacology.


1936 ◽  
Vol 82 (339) ◽  
pp. 431-433
Author(s):  
J. H. Quastel

I want to speak of the work we have been doing in Cardiff on the metabolism of the nervous system. The work was carried out there because of the importance of the narcosis treatment. It seemed to us there a pity that a treatment such as that should be given up because of the considerable toxicity possible in relation to it. The research was undertaken to see if we could diminish the toxicity, at the same time seeking an idea as to how narcotics work. I ask that you will realize that the main substance burned by the brain is glucose. The dominant form of metabolism in the nervous system is connected with the breakdown of glucose and lactic acid, and this can be proved by experiment in the living animal and with brain-tissue in vitro. In doing experiments we are not able to carry out work with human brain, because we cannot get human tissue fresh enough, so we have to carry out experiments with animals. They are carried out in this way. We cut slices of the cortex of the brain as soon as the animal is dead, that is to say, within ten minutes of death the brain is out and slices have been cut. They are placed in a physiological medium in the presence of glucose, and we follow the metabolism of that tissue, which allows us to estimate the amount of oxygen being taken up by the brain. If luminal, chloretone, hyoscine or somnifaine be placed with the brain-tissue, then the respiration, instead of being at the usual level, starts lower down, and maintains a straight line. We wanted to see whether this action is reversible or irreversible. If the latter, then on removing the brain-slices from the narcotic it should no longer behave like a normal piece of tissue. Actually, when the brain-slice is removed and placed in Ringer solution, with no narcotic, the respiration goes up and becomes equal to that shown by the slice which had no narcotic. That is to say, the process is reversible.


Author(s):  
Dennis P. Heaton ◽  
Fred Travis ◽  
Ravi Subramaniam

Management education is seeking creative innovations that can have a real impact on integrity. In this chapter, the authors present our recent research on the relationship between integrity in the brain, as measured by the Brain Integration Scale, and measures of moral reasoning. Further, they summarize research indicating longitudinal growth in coherent brain functioning, intelligence, personality maturity, moral development, and psychological health through the Consciousness-Based approach to management education practiced at Maharishi University of Management. This research supports a potentially innovative approach to management education that does not just address education for integrity on the level of ethical theories or values, but demonstrably transforms the neurophysiology, leading to changes in moral reasoning and heightened effectiveness of performance.


1995 ◽  
Vol 73 (8) ◽  
pp. 1194-1197 ◽  
Author(s):  
H. Xiong ◽  
J.M. WoJtwics ◽  
A. Baskys

Adenosine is a potent inhibitory modulator in the brain. It suppresses glutarnatergic synaptic transmission and possibly acts as a brain endogenous neuroprotective agent. In this study we have examined the effects of a clinically used porcine brain tissue hydrolysate, Cerebrolysin™, on synaptic transmission in the CA1 area of rat hippocampal slices. A major effect of the drug at doses approximating those administered clinically to demented patients was a depression of synaptic transmission at the Schaffer collateral–commissural pathway in CA1. Detailed analysis showed that the inhibition is presynaptic and can be reduced by low doses of a specific blocker of adenosine A1 receptors, 8-cyclopentyltheophylline. Because Cerebrolysin™ does not contain a detectable amount of adenosine, the effect on adenosine A1 receptors must be indirect, perhaps by release of the endogenous agonist. This action of Cerebrolysin™ is consistent with a putative neuroprotective action underlying its clinical usage.Key words: adenosine, Cerebrolysin™, hippocampus, brain slices, synaptic transmission.


Author(s):  
Asghar Rezaei ◽  
Ghodrat Karami ◽  
Fardad Azarmi ◽  
Mehdi Salimi Jazi ◽  
Mariusz Ziejewski

This research is intended to examine the amount of changes that can happen in material characteristics after retesting. Stress relaxation test is conducted on the same samples of the swine brain tissue for several times in small and large deformations. The mechanical properties of the substance are calculated before and after retest and the constants of the tissue, as mechanical characteristics, are determined and compared. Short- and long-term moduli, relaxation times and relaxation functions are of those data that are calculated and compared to understand how much they decay after repeating the experiments. The results show that applying different tests on one sample slightly changes the mechanical properties of the tissue and, as a result, it is partly possible to perform more than one test on the same sample resulting in less sample preparation, time and effort.


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