scholarly journals Identification of the ZEB2 gene as a potential target for epilepsy therapy and the association between rs10496964 and ZEB2 expression

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052098052
Author(s):  
Shitao Wang ◽  
Dan Wang ◽  
Xuemei Cai ◽  
Qian Wu ◽  
Yanbing Han
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Interaction Analysis ◽  
Enrichment Analysis ◽  
Human Brain Tissue ◽  
Protein Protein Interaction ◽  
Epilepsy Therapy ◽  
The Brain ◽  
Zeb2 Expression

Objective An association between the rs10496964 polymorphism and the ZEB2 gene has not yet been reported, and the role of ZEB2 in epilepsy therapy is also unclear. The aims of this research were to evaluate the role of ZEB2 in the therapy of epilepsy and to explore the association between rs10496964 and ZEB2 expression. Methods We used the expression quantitative trait loci (eQTL) dataset resource from the Brain eQTL Almanac to evaluate the association between rs10496964 and ZEB2 expression in human brain tissue. Pathway and process enrichment analysis, protein–protein interaction analysis, and PhosphoSitePlus® analysis were then performed to further evaluate the role of ZEB2 in the therapy of epilepsy. Results The rs10496964 polymorphism was found to regulate the expression of ZEB2 in human brain tissue. The ZEB2 protein interacts with the targets of approved antiepileptic drugs, and a post-translational acetylation modification of ZEB2 was associated with an epilepsy drug therapy. Conclusion Our findings suggest that ZEB2 may be involved in the therapy of epilepsy, and rs10496964 regulates ZEB2 expression in human brain tissue.

scholarly journals Spontaneous glioma-induced seizures recorded in a living human brain tissue preparation

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv16-iv16
Author(s):  
Alastair Kirby ◽  
Jose Pedro Lavrador ◽  
Christian Brogna ◽  
Francesco Vergani ◽  
Bassel Zebian ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Aminolevulinic Acid ◽  
Brain Slices ◽  
Low Grade ◽  
Tissue Preparation ◽  
Spontaneous Seizure ◽  
Human Brain Tissue ◽  
Who Grade ◽  
The Brain

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.

scholarly journals P11.49 An electrophysiological signature of glioma infiltration in the ex vivo human brain

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii54-iii54
Author(s):  
A J Kirby ◽  
J P Lavrador ◽  
C Brogna ◽  
F Vergani ◽  
C Chandler ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Brain Slices ◽  
Glioma Cells ◽  
Low Grade ◽  
Tissue Preparation ◽  
High Grade ◽  
Spontaneous Seizure ◽  
Human Brain Tissue ◽  
The Brain

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.

scholarly journals Genome Sequences of Novel Torque Teno Viruses Identified in Human Brain Tissue

2020 ◽  
Vol 9 (37) ◽  
Author(s):  
Simona Kraberger ◽  
Diego Mastroeni ◽  
Elaine Delvaux ◽  
Arvind Varsani
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Complete Genome ◽  
Open Reading Frame ◽  
Human Brain Tissue ◽  
Genome Sequences ◽  
Reading Frame ◽  
The Brain ◽  
Open Reading Frame 1

ABSTRACT Complete genome sequences of two novel torque teno viruses (TTVs) were identified in human brain tissue. These sequences are 3,245 nucleotides (nt) and 2,900 nt long and share 68% and 72% open reading frame 1 (ORF1) identity, respectively, with other human TTVs. This report extends the identification of TTV sequences in the brain.

The right way, the wrong way, and the army way: A dendritic parable

1997 ◽  
Vol 20 (4) ◽  
pp. 575-575
Author(s):  
Arnold B. Scheibel
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Structural Studies ◽  
Human Brain Tissue ◽  
Tissue Mass ◽  
The Right ◽  
The Brain

We suggest that neither selectionism nor constructivism alone are responsible for learning-based changes in the brain. On the basis of quantitative structural studies of human brain tissue it has been possible to find evidence of both increase and decrease in tissue mass at synaptic and dendritic levels. It would appear that both processes are involved in the course of learning-dependent changes.

scholarly journals Manufacturing process for hydrogel vessel phantoms

2019 ◽  
Vol 5 (1) ◽  
pp. 537-540
Author(s):  
Marco Kalmar ◽  
Thomas Hoffmann ◽  
Jörg Sauerhering ◽  
Fabian Klink
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Manufacturing Process ◽  
Uv Light ◽  
Tissue Perfusion ◽  
Human Brain Tissue ◽  
Physiological Processes ◽  
Building Models ◽  
3D Printed ◽  
The Brain

AbstractPhantoms mimicking special physiological processes of the human body are essential for evaluating prototypes of medical devices. Especially for thermometric MRI measurements, the temperature distribution in the brain needs to be simulated. Since this parameter is dependent on the tissue perfusion, a new hydrogel by MAGDASSIS et al. was evaluated in this work for building models with hollow artery structures. This hydrogel can be polymerized through UV-light due to the nanoparticles contained in it. Additionally, thermal parameters were measured and compared to human brain tissue. The indirect manufacturing of hydrogel phantoms showed good qualitative results for vessels with a diameter > 3 mm. In this process a 3D printed wax core was inserted in the hydrogel and the structure was then UV cured after molding. After curing the core was dissolved in an isopropanol bath. The thermal properties, obtained by the transient planesource- method, showed similar values compared to that of human brain tissue mentioned in literature. Further limitations in the manufacturing process needs to be overcome to use the indirect manufacture approach for smaller vessels of the brain.

scholarly journals Preclinical evaluation of (S)-[18F]GE387, a novel 18-kDa translocator protein (TSPO) PET radioligand with low binding sensitivity to human polymorphism rs6971

2021 ◽  
Author(s):  
Nisha K. Ramakrishnan ◽  
Matthew Hird ◽  
Stephen Thompson ◽  
David J. Williamson ◽  
Luxi Qiao ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Rhesus Macaques ◽  
Biological Evaluation ◽  
Translocator Protein ◽  
Normal Brain ◽  
Human Brain Tissue ◽  
Peripheral Tissues ◽  
Low Sensitivity ◽  
The Brain

Abstract Purpose Positron emission tomography (PET) studies with radioligands for 18-kDa translocator protein (TSPO) have been instrumental in increasing our understanding of the complex role neuroinflammation plays in disorders affecting the brain. However, (R)-[11C]PK11195, the first and most widely used TSPO radioligand has limitations, while the next-generation TSPO radioligands have suffered from high interindividual variability in binding due to a genetic polymorphism in the TSPO gene (rs6971). Herein, we present the biological evaluation of the two enantiomers of [18F]GE387, which we have previously shown to have low sensitivity to this polymorphism. Methods Dynamic PET scans were conducted in male Wistar rats and female rhesus macaques to investigate the in vivo behaviour of (S)-[18F]GE387 and (R)-[18F]GE387. The specific binding of (S)-[18F]GE387 to TSPO was investigated by pre-treatment with (R)-PK11195. (S)-[18F]GE387 was further evaluated in a rat model of lipopolysaccharide (LPS)-induced neuroinflammation. Sensitivity to polymorphism of (S)-GE387 was evaluated in genotyped human brain tissue. Results (S)-[18F]GE387 and (R)-[18F]GE387 entered the brain in both rats and rhesus macaques. (R)-PK11195 blocked the uptake of (S)-[18F]GE387 in healthy olfactory bulb and peripheral tissues constitutively expressing TSPO. A 2.7-fold higher uptake of (S)-[18F]GE387 was found in the inflamed striatum of LPS-treated rodents. In genotyped human brain tissue, (S)-GE387 was shown to bind similarly in low affinity binders (LABs) and high affinity binders (HABs) with a LAB to HAB ratio of 1.8. Conclusion We established that (S)-[18F]GE387 has favourable kinetics in healthy rats and non-human primates and that it can distinguish inflamed from normal brain regions in the LPS model of neuroinflammation. Crucially, we have reconfirmed its low sensitivity to the TSPO polymorphism on genotyped human brain tissue. Based on these factors, we conclude that (S)-[18F]GE387 warrants further evaluation with studies on human subjects to assess its suitability as a TSPO PET radioligand for assessing neuroinflammation.

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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