A Chip Off the Old Block: The Brain Slice as a Model for Metabolic Studies of Brain Compartmentation and Neuropharmacology

2014 ◽  
pp. 217-241 ◽  
Author(s):  
Caroline Rae ◽  
Vladimir J. Balcar
Keyword(s):  
Brain Slice ◽  
Metabolic Studies ◽  
The Brain

TMOD-31. AN ORGANOTYPIC TISSUE PLATFORM TO BRIDGE IN VITRO AND IN VIVO ASSAYS FOR BRAIN CANCER TREATMENT

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi222-vi222
Author(s):  
Breanna Mann ◽  
Noah Bell ◽  
Denise Dunn ◽  
Scott Floyd ◽  
Shawn Hingtgen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Brain Cancer ◽  
Brain Slice ◽  
Brain Slices ◽  
In Vitro Assays ◽  
Preclinical Model ◽  
Short Period ◽  
The Brain

Abstract Brain cancers remain one of the greatest medical challenges. The lack of experimentally tractable models that recapitulate brain structure/function represents a major impediment. Platforms that enable functional testing in high-fidelity models are urgently needed to accelerate the identification and translation of therapies to improve outcomes for patients suffering from brain cancer. In vitro assays are often too simple and artificial while in vivo studies can be time-intensive and complicated. Our live, organotypic brain slice platform can be used to seed and grow brain cancer cell lines, allowing us to bridge the existing gap in models. These tumors can rapidly establish within the brain slice microenvironment, and morphologic features of the tumor can be seen within a short period of time. The growth, migration, and treatment dynamics of tumors seen on the slices recapitulate what is observed in vivo yet is missed by in vitro models. Additionally, the brain slice platform allows for the dual seeding of different cell lines to simulate characteristics of heterogeneous tumors. Furthermore, live brain slices with embedded tumor can be generated from tumor-bearing mice. This method allows us to quantify tumor burden more effectively and allows for treatment and retreatment of the slices to understand treatment response and resistance that may occur in vivo. This brain slice platform lays the groundwork for a new clinically relevant preclinical model which provides physiologically relevant answers in a short amount of time leading to an acceleration of therapeutic translation.

Measurement of Unbound Drug Exposure in Brain: Modeling of pH Partitioning Explains Diverging Results between the Brain Slice and Brain Homogenate Methods

2010 ◽  
Vol 39 (3) ◽  
pp. 353-362 ◽  
Author(s):  
Markus Fridén ◽  
Fredrik Bergström ◽  
Hong Wan ◽  
Mikael Rehngren ◽  
Gustav Ahlin ◽  
...  
Keyword(s):  
Brain Slice ◽  
Drug Exposure ◽  
Brain Homogenate ◽  
Brain Modeling ◽  
The Brain

scholarly journals Image-based stroke rat brain atrophy volume and infarct volume computation

2020 ◽  
Vol 76 (12) ◽  
pp. 10090-10121
Author(s):  
Yung-Kuan Chan ◽  
Chun-Fu Hong ◽  
Meng-Hsiun Tsai ◽  
Ya-Lan Chang ◽  
Ping-Hsuan Sun
Keyword(s):  
Ischemic Stroke ◽  
Rat Brain ◽  
Brain Slice ◽  
Infarct Volume ◽  
Brain Slices ◽  
Artery Occlusion ◽  
Tetrazolium Chloride ◽  
Rat Brain Slice ◽  
Cerebral Artery Occlusion ◽  
The Brain

Abstract Stroke is one of the leading causes of death as well as results in a massive economic burden for society. Stroke is a cerebrovascular disease mainly divided into two types: ischemic stroke and hemorrhagic stroke, which, respectively, refer to the partial blockage and bleeding inside brain blood vessels. Both stroke types lead to nutrient and oxygen deprivation in the brain, which ultimately cause brain damage or death. This study focuses on ischemic stroke in rats with middle cerebral artery occlusion (MCAO) as experimental subjects, and the volumes of infarct and atrophy are calculated based on the brain slice images of rat brains stained with 2,3,5-triphenyl tetrazolium chloride. In this study, a stroke rat brain infarct and atrophy volumes computation system (SRBIAVC system) is developed to segment the infarcts and atrophies from the rat brain slice images. Based on the segmentation results, the infarct and atrophy volumes of a rat brain can be computed. In this study, 168 images of brain slices cut from 28 rat brains with MCAO are used as the test samples. The experimental results show that the segmentation results obtained by the SRBIAVC system are close to those obtained by experts.

Author Correction: Neural and sociocultural mediators of ethnic differences in pain (Nature Human Behaviour, (2020), 10.1038/s41562-020-0819-8)

2020 ◽  
Author(s):  
EAR Losin ◽  
CW Woo ◽  
NA Medina ◽  
JR Andrews-Hanna ◽  
Hedwig Eisenbarth ◽  
...  
Keyword(s):  
Ethnic Differences ◽  
Brain Slice ◽  
Brain Slices ◽  
Human Behaviour ◽  
The Brain

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. In the version of this article initially published, in Figs. 3a and 5a the labels on the brain slices labelled NAc should read ‘y = 5’ instead of ‘y = –12’, and in Fig. 3a the label ‘x = 45’ on the top brain slice labeled mFG was missing. The errors have been corrected in the HTML and PDF versions of the article.

Author Correction: Neural and sociocultural mediators of ethnic differences in pain (Nature Human Behaviour, (2020), 10.1038/s41562-020-0819-8)

2020 ◽  
Author(s):  
EAR Losin ◽  
CW Woo ◽  
NA Medina ◽  
JR Andrews-Hanna ◽  
Hedwig Eisenbarth ◽  
...  
Keyword(s):  
Ethnic Differences ◽  
Brain Slice ◽  
Brain Slices ◽  
Human Behaviour ◽  
The Brain

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. In the version of this article initially published, in Figs. 3a and 5a the labels on the brain slices labelled NAc should read ‘y = 5’ instead of ‘y = –12’, and in Fig. 3a the label ‘x = 45’ on the top brain slice labeled mFG was missing. The errors have been corrected in the HTML and PDF versions of the article.

Biochemistry

1936 ◽  
Vol 82 (339) ◽  
pp. 431-433
Author(s):  
J. H. Quastel
Keyword(s):  
Nervous System ◽  
Brain Tissue ◽  
Brain Slice ◽  
Brain Slices ◽  
Ringer Solution ◽  
Living Animal ◽  
Dominant Form ◽  
Straight Line ◽  
The Brain

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.

Localized and Automated Chemical and Oxygen Delivery System for Microfluidic Brain Slice Devices

2010 ◽  
Vol 4 (1) ◽  
Author(s):  
G. Yu ◽  
A.J. Blake ◽  
D.T. Eddington
Keyword(s):  
Programming Language ◽  
Delivery System ◽  
Oxygen Delivery ◽  
Brain Slice ◽  
Fluorescein Isothiocyanate ◽  
In Vitro Models ◽  
Localized Delivery ◽  
The Brain ◽  
Oxygen Concentrations

To better study in vitro models of the brain, a localized delivery system is necessary due to the region specific functionality of the brain. The proposed system allows drugs and oxygen of controllable concentrations to be delivered. The delivery system is integrated into a polydimethylsiloxane microfluidic brain slice device and uses valves controlled by the LabVIEW programming language. Delivery is controlled by adjusting the opening/closing frequencies of the valves. Fluorescein isothiocyanate, a fluorescent dye, was used to characterize the delivery with and without brain tissue (~300 μm). A linear relationship was found correlating the valve frequencies and the intensity showing how easily controlled concentrations can be delivered. A delivery system to automatically mix and deliver oxygen concentrations between 0% and 21% was developed. Accurate and precise outputs were obtained. Combined, these two delivery systems will allow controllable drug and oxygen concentrations to be tested at defined regions of the brain.

The postnatal development of geniculocortical axon arbors in owl monkeys

1994 ◽  
Vol 11 (1) ◽  
pp. 71-90 ◽  
Author(s):  
Marcie W. Pospichal ◽  
Sherre L. Florence ◽  
Jon H. Kaas
Keyword(s):  
Postnatal Development ◽  
Brain Slice ◽  
Morphological Changes ◽  
Area 17 ◽  
Serial Sections ◽  
Cortical Layers ◽  
Surface View ◽  
Owl Monkeys ◽  
Plastic Responses ◽  
The Brain

AbstractTo characterize the postnatal development of geniculocortical axon arbor morphology in owl monkeys at a series of ages from birth to adulthood, individual arbors were bulk-filled with HRP in brain slice preparations and were reconstructed from serial sections. At all ages, cortical layers and sublayers were obvious. Presumed M or magnocellular arbors were largely confined to layer IVα, but they also extended into layer IIIc (IVB of Brodmann, 1909); presumed P or parvocellular arbors were almost exclusively confined to layer IVβ. Other axons that may reflect feedback projections from MT terminated in layer IIIc. Overall, M axon arbors increased in size and complexity from birth to adulthood with mean surface-view arbor areas ranging from 0.08 ± 0.01 mm2 in newborns to 0.24 ± 0.02 mm2 in adults. The developing P arbor areas were, on average, as large or larger than adult (newborn = 0.07 ± 0.01 mm2, adult = 0.047 ± 0.01 mm2; n.s.) but the arbors were somewhat less complex. Since the brain and area 17 increase in size postnatally, the proportion of area 17 subserved by each P arbor would decrease in postnatal development. Terminal boutons with immature features were evident in both M and P populations at all developmental ages. The results indicate that, while both LGN axon types in monkeys undergo morphological changes postnatally, M arbors appear to mature by increasing arbor size and terminal branching complexity, whereas P arbors increase in complexity but not in size. These distinct programs of axon arbor development suggest that the periods of susceptibility of geniculocortical axon arbors to postnatal influences of the environment, and the types of plastic responses they potentially exhibit, are class-specific.

Neurohumoral Mechanisms in the Brain Slice

1971 ◽  
pp. 1-30 ◽  
Author(s):  
Richard I. Katz ◽  
Thomas N. Chase
Keyword(s):  
Brain Slice ◽  
The Brain

scholarly journals Soticlestat, a novel cholesterol 24-hydroxylase inhibitor shows a therapeutic potential for neural hyperexcitation in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Toshiya Nishi ◽  
Shinichi Kondo ◽  
Maki Miyamoto ◽  
Sayuri Watanabe ◽  
Shigeo Hasegawa ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Brain Slice ◽  
Therapeutic Potential ◽  
Dependent Manner ◽  
Wild Type ◽  
Short Life Span ◽  
Premature Deaths ◽  
Knockout Animals ◽  
Dose Dependent ◽  
The Brain

Abstract Cholesterol 24-hydroxylase (CH24H) is a brain-specific enzyme that converts cholesterol into 24S-hydroxycholesterol, the primary mechanism of cholesterol catabolism in the brain. The therapeutic potential of CH24H activation has been extensively investigated, whereas the effects of CH24H inhibition remain poorly characterized. In this study, the therapeutic potential of CH24H inhibition was investigated using a newly identified small molecule, soticlestat (TAK-935/OV935). The biodistribution and target engagement of soticlestat was assessed in mice. CH24H-knockout mice showed a substantially lower level of soticlestat distribution in the brain than wild-type controls. Furthermore, brain-slice autoradiography studies demonstrated the absence of [3H]soticlestat staining in CH24H-knockout mice compared with wild-type mice, indicating a specificity of soticlestat binding to CH24H. The pharmacodynamic effects of soticlestat were characterized in a transgenic mouse model carrying mutated human amyloid precursor protein and presenilin 1 (APP/PS1-Tg). These mice, with excitatory/inhibitory imbalance and short life-span, yielded a remarkable survival benefit when bred with CH24H-knockout animals. Soticlestat lowered brain 24S-hydroxycholesterol in a dose-dependent manner and substantially reduced premature deaths of APP/PS1-Tg mice at a dose lowering brain 24S-hydroxycholesterol by approximately 50%. Furthermore, microdialysis experiments showed that soticlestat can suppress potassium-evoked extracellular glutamate elevations in the hippocampus. Taken together, these data suggest that soticlestat-mediated inhibition of CH24H may have therapeutic potential for diseases associated with neural hyperexcitation.

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