scholarly journals Position sensitive measurement of trace lithium in the brain with NIK (neutron-induced coincidence method) in suicide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
J. Schoepfer ◽  
R. Gernhäuser ◽  
S. Lichtinger ◽  
A. Stöver ◽  
M. Bendel ◽  
...  
Keyword(s):  
Human Brain ◽  
Psychiatric Treatment ◽  
Three Dimensional ◽  
Monovalent Cation ◽  
Mood Stabilizers ◽  
Metabolic Effects ◽  
Lithium Content ◽  
Coincidence Method ◽  
Human Brain Tissue ◽  
Position Sensitive

AbstractMood disorder is the leading intrinsic risk factor for suicidal ideation. Questioning any potency of mood-stabilizers, the monovalent cation lithium still holds the throne in medical psychiatric treatment. Furthermore, lithium`s anti-aggressive and suicide-preventive capacity in clinical practice is well established. But little is still known about trace lithium distribution and any associated metabolic effects in the human body. We applied a new technique (neutron-induced coincidence method “NIK”) utilizing the 6Li(n,α)3H reaction for the position sensitive, 3D spatially resolved detection of lithium traces in post-mortem human brain tissue in suicide versus control. NIK allowed, for the first time in lithium research, to collect a three dimensional high resolution map of the regional trace lithium content in the non lithium-medicated human brain. The results show an anisotropic distribution of lithium, thus indicating a homeostatic regulation under physiological conditions as a remarkable link to essentiality. In contrast to suicide we could empirically prove significantly higher endogenous lithium concentrations in white compared to gray matter as a general trend in non-suicidal individuals and lower lithium concentrations in emotion-modulating regions in suicide.

scholarly journals Three-dimensional visualizations from a dataset of immunohistochemical stained serial sections of human brain tissue containing tuberculosis related granulomas

Data in Brief ◽  
2020 ◽  
Vol 33 ◽  
pp. 106532
Author(s):  
Stefan-Dan Zaharie ◽  
Daniel J. Franken ◽  
Martijn van der Kuip ◽  
Sabine van Elsland ◽  
Bernadette S. de Bakker ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Three Dimensional ◽  
Serial Sections ◽  
Human Brain Tissue

scholarly journals Optimizing tissue clearing and imaging methods for human brain tissue

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052110017
Author(s):  
Min Sun Kim ◽  
Jang Ho Ahn ◽  
Ji Eun Mo ◽  
Ha Young Song ◽  
Deokhyeon Cheon ◽  
...  
Keyword(s):  
Human Brain ◽  
Three Dimensional ◽  
Cell Nuclei ◽  
Human Brain Tissue ◽  
Dapi Staining ◽  
Brain Images ◽  
Microscopy Imaging ◽  
Antibody Staining ◽  
Staining Methods ◽  
Human Brains

Objectives To identify optimum sample conditions for human brains, we compared the clearing efficiency, antibody staining efficiency, and artifacts between fresh and cadaver samples. Methods Fresh and cadaver samples were cleared using X-CLARITY™. Clearing efficiency and artifact levels were calculated using ImageJ, and antibody staining efficiency was evaluated after confocal microscopy imaging. Three staining methods were compared: 4-day staining (4DS), 11-day staining (11DS), and 4-day staining with a commercial kit (4DS-C). The optimum staining method was then selected by evaluating staining time, depth, method complexity, contamination, and cost. Results Fresh samples outperformed cadaver samples in terms of the time and quality of clearing, artifacts, and 4′,6-diamidino-2-phenylindole (DAPI) staining efficiency, but had a glial fibrillary acidic protein (GFAP) staining efficiency that was similar to that of cadaver samples. The penetration depth and DAPI staining improved in fresh samples as the incubation period lengthened. 4DS-C was the best method, with the deepest penetration. Human brain images containing blood vessels, cell nuclei, and astrocytes were visualized three-dimensionally. The chemical dye staining depth reached 800 µm and immunostaining depth exceeded 200 µm in 4 days. Conclusions We present optimized sample preparation and staining protocols for the visualization of three-dimensional macrostructure in the human brain.

scholarly journals Three-dimensional cellular and subcellular structures of human brain tissue determined by microtomography

2009 ◽  
Vol 186 ◽  
pp. 012108
Author(s):  
Ryuta Mizutani ◽  
Akihisa Takeuchi ◽  
Susumu Takekoshi ◽  
R Yoshiyuki Osamura ◽  
Kentaro Uesugi ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Three Dimensional ◽  
Human Brain Tissue

scholarly journals Human pluripotent stem cell-derived brain organoids as in vitro models for studying neural disorders and cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan Luo ◽  
Peng Li
Keyword(s):  
Human Brain ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Resource Limitation ◽  
In Vitro Models ◽  
Human Brain Tissue ◽  
Self Organized ◽  
Future Direction ◽  
Neural Disorders

AbstractThe sheer complexities of brain and resource limitation of human brain tissue greatly hamper our understanding of the brain disorders and cancers. Recently developed three-dimensional (3D) brain organoids (BOs) are self-organized and spontaneously differentiated from human pluripotent stem cells (hPSCs) in vitro, which exhibit similar features with cell type diversity, structural organization, and functional connectivity as the developing human brain. Based on these characteristics, hPSC-derived BOs (hPDBOs) provide new opportunities to recapitulate the complicated processes during brain development, neurodegenerative disorders, and brain cancers in vitro. In this review, we will provide an overview of existing BO models and summarize the applications of this technology in modeling the neural disorders and cancers. Furthermore, we will discuss the challenges associated with their use as in vitro models for disease modeling and the potential future direction.

scholarly journals Characterization of the nuclear and cytosolic transcriptomes in human brain tissue reveals new insights into the subcellular distribution of RNA transcripts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ammar Zaghlool ◽  
Adnan Niazi ◽  
Åsa K. Björklund ◽  
Jakub Orzechowski Westholm ◽  
Adam Ameur ◽  
...  
Keyword(s):  
Human Brain ◽  
Expression Analysis ◽  
Differential Expression Analysis ◽  
Adult Brain ◽  
Sequencing Data ◽  
Human Brain Tissue ◽  
Protein Coding ◽  
Rna Transcripts ◽  
Nuclear Rna ◽  
The Impact

AbstractTranscriptome analysis has mainly relied on analyzing RNA sequencing data from whole cells, overlooking the impact of subcellular RNA localization and its influence on our understanding of gene function, and interpretation of gene expression signatures in cells. Here, we separated cytosolic and nuclear RNA from human fetal and adult brain samples and performed a comprehensive analysis of cytosolic and nuclear transcriptomes. There are significant differences in RNA expression for protein-coding and lncRNA genes between cytosol and nucleus. We show that transcripts encoding the nuclear-encoded mitochondrial proteins are significantly enriched in the cytosol compared to the rest of protein-coding genes. Differential expression analysis between fetal and adult frontal cortex show that results obtained from the cytosolic RNA differ from results using nuclear RNA both at the level of transcript types and the number of differentially expressed genes. Our data provide a resource for the subcellular localization of thousands of RNA transcripts in the human brain and highlight differences in using the cytosolic or the nuclear transcriptomes for expression analysis.

scholarly journals RBIO-06. IMPLEMENTATION OF HUMAN INDUCED PLURIPOTENT STEM CELL DERIVED CEREBRAL ORGANOIDS TO MODEL NORMAL TISSUE RADIORESPONSE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii193-ii193
Author(s):  
Lawrence Bronk ◽  
Sanjay Singh ◽  
Riya Thomas ◽  
Luke Parkitny ◽  
Mirjana Maletic-Savatic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Brain Tissue ◽  
Human Tissue ◽  
Model Systems ◽  
Human Brain Tissue ◽  
Post Irradiation ◽  
Mature Neurons ◽  
Induced Pluripotent ◽  
Effects Of Radiation

Abstract Treatment-related sequelae following cranial irradiation have life changing impacts for patients and their caregivers. Characterization of the basic response of human brain tissue to irradiation has been difficult due to a lack of preclinical models. The direct study of human brain tissue in vitro is becoming possible due to advances in stem cell biology, neuroscience, and tissue engineering with the development of organoids as novel model systems which enable experimentation with human tissue models. We sought to establish a cerebral organoid (CO) model to study the radioresponse of normal human brain tissue. COs were grown using human induced pluripotent stem cells and a modified Lancaster protocol. Compositional analysis during development of the COs showed expected populations of neurons and glia. We confirmed a population of microglia-like cells within the model positive for the makers Iba1 and CD68. After 2-months of maturation, COs were irradiated to 0, 10, and 20 Gy using a Shepard Mark-II Cs-137 irradiator and returned to culture. Subsets of COs were prepared for immunostaining at 30- and 70-days post-irradiation. To examine the effect of irradiation on the neural stem cell (NSC) population, sections were stained for SOX2 and Ki-67 expression denoting NSCs and proliferation respectively. Slides were imaged and scored using the CellProfiler software package. The percentage of proliferating NSCs 30-days post-irradiation was found to be significantly reduced for irradiated COs (5.7% (P=0.007) and 3.4% (P=0.001) for 10 and 20 Gy respectively) compared to control (12.7%). The reduction in the proliferating NSC population subsequently translated to a reduced population of NeuN-labeled mature neurons 70 days post-irradiation. The loss of proliferating NSCs and subsequent reduction in mature neurons demonstrates the long-term effects of radiation. Our initial results indicate COs will be a valuable model to study the effects of radiation therapy on normal and diseased human tissue.

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