scholarly journals Scatterometry Measurements With Scattered Light Imaging Enable New Insights Into the Nerve Fiber Architecture of the Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Miriam Menzel ◽  
Marouan Ritzkowski ◽  
Jan A. Reuter ◽  
David Gräßel ◽  
Katrin Amunts ◽  
...  
Keyword(s):  
Human Brain ◽  
Nerve Fiber ◽  
Brain Tissue ◽  
Scattered Light ◽  
Polar Angle ◽  
Nerve Fibers ◽  
Fiber Architecture ◽  
Whole Brain ◽  
Tissue Samples ◽  
The Brain

The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: the individual fiber orientations are determined by illuminating unstained histological brain sections from different directions, measuring the transmitted scattered light under normal incidence, and studying the light intensity profiles of each pixel in the resulting image series. So far, SLI measurements were performed with a fixed polar angle of illumination and a small number of illumination directions, providing only an estimate of the nerve fiber directions and limited information about the underlying tissue structure. Here, we use a display with individually controllable light-emitting diodes to measure the full distribution of scattered light behind the sample (scattering pattern) for each image pixel at once, enabling scatterometry measurements of whole brain tissue samples. We compare our results to coherent Fourier scatterometry (raster-scanning the sample with a non-focused laser beam) and previous SLI measurements with fixed polar angle of illumination, using sections from a vervet monkey brain and human optic tracts. Finally, we present SLI scatterometry measurements of a human brain section with 3 μm in-plane resolution, demonstrating that the technique is a powerful approach to gain new insights into the nerve fiber architecture of the human brain.

scholarly journals Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

2020 ◽  
Vol 11 (1) ◽  
pp. 241-250
Author(s):  
Zhenyu Li ◽  
Guangqian Ding ◽  
Yudi Wang ◽  
Zelong Zheng ◽  
Jianping Lv
Keyword(s):  
Gene Therapy ◽  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
Brain Tissue ◽  
Inflammatory Responses ◽  
Tissue Samples ◽  
Protein Levels ◽  
Virus Serotype ◽  
Transcription Factor Eb ◽  
The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

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 Vascular Genomics of the Human Brain

2002 ◽  
Vol 22 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Eric V. Shusta ◽  
Ruben J. Boado ◽  
Gary W. Mathern ◽  
William M. Pardridge
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Differential Gene Expression ◽  
Molecular Transport ◽  
Brain Diseases ◽  
Microvascular Endothelium ◽  
Whole Brain ◽  
Differential Gene ◽  
Brain Microvasculature ◽  
The Brain

The microvasculature of the human brain plays an important role in the development and maintenance of the central nervous system and in the pathogenesis of brain diseases, and is the site of differential gene expression within the brain. However, human brain microvascular-specific genes may not be detected in whole-brain gene microarray because the volume of the brain microvascular endothelium is relatively small (0.1%) compared with the whole brain. Therefore, the differential gene expression within the human brain microvasculature was evaluated using suppression subtractive hybridization with RNA isolated from human brain microvessels. Gene identification was restricted to the first 71 clones that were differentially expressed at the brain microvasculature. Twenty of these were genes encoding proteins with known function that were involved in angiogenesis, neurogenesis, molecular transport, and maintenance of endothelial tight junctions or the cytoskeleton. Eighteen genes coding for proteins of an unknown function were identified, including five genes containing satellite DNA sequences. The results provide the initial outline of the genomics of the human brain microvasculature, and have implications for the identification of both targets for brain-specific drug transport and changes in microvascular gene expression in brain diseases.

scholarly journals High-Throughput Strategy for Profiling Sequential Section With Multiplex Staining of Mouse Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Siqi Chen ◽  
Zhixiang Liu ◽  
Anan Li ◽  
Hui Gong ◽  
Ben Long ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Acute Stress ◽  
Brain Slices ◽  
Serial Sections ◽  
Whole Brain ◽  
Tissue Samples ◽  
Brain Functions ◽  
Multiple Samples ◽  
The Brain ◽  
Serial Brain

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.

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 VIROLOGICAL AND SEROLOGICAL DIAGNOSIS OF RABIES IN BATS FROM AN URBAN AREA IN THE BRAZILIAN AMAZON

2015 ◽  
Vol 57 (6) ◽  
pp. 497-503 ◽  
Author(s):  
Rubens Souza de OLIVEIRA ◽  
Lanna Jamile Corrêa da COSTA ◽  
Fernanda Atanaena Gonçalves de ANDRADE ◽  
Wilson UIEDA ◽  
Luzia Fátima Alves MARTORELLI ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Urban Area ◽  
Amazon Basin ◽  
Common Species ◽  
Urban Context ◽  
Serum Samples ◽  
Tissue Samples ◽  
Dry Seasons ◽  
The Brain ◽  
Wet And Dry Seasons

The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and 2005, in the northeast of the Brazilian State of Para, eastern Amazon basin, made this a priority area for studies on this zoonosis. Given this, the present study provides data on this phenomenon in an urban context, in order to assess the possible circulation of the classic rabies virus (RABV) among bat species in Capanema, a town in the Amazon basin. Bats were collected, in 2011, with mist nets during the wet and dry seasons. Samples of brain tissue and blood were collected for virological and serological survey, respectively. None of the 153 brain tissue samples analyzed tested positive for RABV infection, but 50.34% (95% CI: 45.67-55.01%) of the serum samples analyzed were seropositive. Artibeus planirostris was the most common species, with a high percentage of seropositive individuals (52.46%, 95% CI: 52.31 52.60%). Statistically, equal proportions of seropositive results were obtained in the rainy and dry seasons (c2 = 0.057, d.f. = 1, p = 0.88). Significantly higher proportions of males (55.96%, 95% CI: 48.96-62.96%) and adults (52.37%, 95% CI: 47.35-57.39%) were seropositive. While none of the brain tissue samples tested positive for infection, the high proportion of seropositive specimens indicates that RABV may be widespread in this urban area.

Brain Nerve Fiber Tracking Algorithm Based on Improved Optical Flow in Combination of Bayesian Prior Constraints

2020 ◽  
Vol 10 (2) ◽  
pp. 452-457
Author(s):  
Shen Jian ◽  
Chen Huan ◽  
Zuo Jianjian ◽  
Pan Xuming
Keyword(s):  
Optical Flow ◽  
Nerve Fiber ◽  
Diffusion Tensor ◽  
Three Dimensional ◽  
Fiber Tracking ◽  
Nerve Fibers ◽  
Tracking Algorithm ◽  
Brain Diseases ◽  
Field Estimation ◽  
The Brain

Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) can track the brain nerve fiber and reconstruct non-invasively the three-dimensional image by tracing the local tensor orientation. The commonly used tracking method is usually based on the local diffusion information and insufficient to consider the geometrical structure and fractional anisotropy which is constrained by anatomical structure and physiological function of human. Therefore, a novel brain nerve fiber tracking algorithm based on Bayesian optical-flow constrained framework is proposed. The construction of energy function is the core step of global optical flow field estimation technology. In this paper, data fidelity constraint, prior constraint, penalty function and weight factor are introduced to construct Bayesian constraint function. The fiber trend model is displayed intuitively to obtain the structure and direction of the inner nerve fibers of the brain, which can better assist in the diagnosis and treatment of clinical brain diseases, and lay a foundation for subsequent brain tissue research.

Changes in myelin basic protein and demyelination in the rat brain within 3 months of single 2-, 10-, or 30-Gy whole-brain radiation treatments

2008 ◽  
Vol 109 (5) ◽  
pp. 881-888 ◽  
Author(s):  
Ye Tian ◽  
Zhige Shi ◽  
Shu Yang ◽  
Yingzhu Chen ◽  
Shiyao Bao
Keyword(s):  
Myelin Basic Protein ◽  
Brain Tissue ◽  
Basic Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Whole Brain ◽  
Whole Brain Radiation ◽  
Injured Brain ◽  
Brain Radiation ◽  
The Brain ◽  
Myelin Staining

Object The aim of this study was to determine the relation between changes in myelin basic protein (MBP) levels during the acute and subacute phases of central nervous system injury following whole-brain radiation and delayed demyelination in the radiation-injured brain tissue. Methods Adult Sprague–Dawley rats were treated with single fractions of 2, 10, or 30 Gy of whole-brain radiation. The authors measured MBP gene expression and protein levels in the brain tissue by using reverse transcription–polymerase chain reaction and enzyme-linked immunosorbent assay at 1 week and 1–3 months following irradiation to monitor myelin changes in the brain. Demyelination was determined with Luxol fast blue myelin staining and routine histopathological and electron microscopy examination of injured brain tissue. The changes in MBP levels in the different animal groups at specific time points were correlated with demyelination in corresponding dose groups. Results At 1 month after applying the 10 and 30 Gy of radiation, MBP mRNA expression showed a transient but significant decrease, followed by recovery to baseline levels at 3 months after treatment. The MBP levels were decreased by only 70–75% at 1 month after 10 and 30 Gy of radiation. At 2–3 months after applying the higher dose of 30 Gy, however, the MBP levels continued to decline, and typical demyelination changes were observed with myelin staining and ultrastructural examination. Conclusions The authors' results suggest that the early radiation-induced MBP changes between 1 and 3 months after single treatments of 10 and 30 Gy of radiation to the whole brain are indicative of permanent injury shown as demyelination of irradiated brain tissue.

Design and Evaluation of Advanced Smart Needles for Brain Biopsy

2017 ◽  
Author(s):  
Mohammad Sahlabadi ◽  
Seyedvahid Khodaei ◽  
Parsaoran Hutapea
Keyword(s):  
Brain Tissue ◽  
Needle Biopsy ◽  
Brain Biopsy ◽  
Lateral Movement ◽  
Open Biopsy ◽  
Tissue Samples ◽  
Tissue Cutting ◽  
Nitinol Wire ◽  
The Brain ◽  
Stereotactic Core

Biopsy involves removing a piece of tissues for further medical examination. Brain biopsy is generally performed using different techniques, such as open biopsy, stereotactic core biopsy, and needle biopsy. Open biopsy is the most common and the most invasive form of the brain biopsy. During the procedure, a piece of the skull is removed and the brain is exposed. Stereotactic core and needle biopsies are minimally invasive. In these procedures, a hole is usually drilled into the skull and a needle is inserted through the hole to extract the tissue. Brain biopsy has its risks and complications due to the vulnerability of the brain tissue. Although using needle or stereotactic biopsies reduce the risks, brain biopsy may cause swelling or bleeding in the brain, and in some cases, can result in infection, stroke, seizure or even coma. A needle biopsy with conventional needles involves pulling or pushing the cutting stylet inside the needle hollow body (cannula). The manual pulling and pushing procedure induces lateral movement of the needle, which increases the damage in brain tissue. The goal here is to completely remove the needle harmful lateral movement. In this work, design of smart biopsy needles is proposed and demonstrated by incorporating nitinol wires and springs to control the lateral movement of the cutting stylet. The first design comprises of two parts. The first part of the needle is a 360° tissue cutting stylet, and the second part is the cannula. The cutting stylet can slide inside the cannula and a nitinol wire is embedded at the end of the stylet and the end of the cannula. As the electric current is applied on the nitinol wire, it shrinks and pulls the cutting stylet. The second design is almost similar to the first design, but it has a 180° tissue cutting stylet with a similar actuating mechanism. The last design uses a nitinol torsion spring that is attached to the cutting stylet. It cuts tissue samples by activating the nitinol spring to rotate the cutting stylet.

Bio-Degradable Glass for Neural Probe Application

2013 ◽  
Vol 740 ◽  
pp. 555-559 ◽  
Author(s):  
Rui Qi Lim ◽  
Kwan Ling Tan ◽  
Wei Guo Chen ◽  
Mink Yu Je ◽  
Tack Boon Yee ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Brain Neuron ◽  
Tissue Movement ◽  
Neural Probe ◽  
The Brain

This work presents a bio-degradable glass probes and its biocompatibility assessment for neural applications. The probes can be implanted into different sites of the human brain for recording and stimulating purposes. Current existing neural probe address the probe stiffness requirement for the penetration of brain tissue. However, this requirement normally resulted in the rigidity of the probe which is non-compatible with the brain tissue movement for long term implantation. The brain neuron cells will be damaged by too rigid probe substrate. In order to address this issue, bio-degradable glass probes having sufficient stiffness for a smooth brain insertion as well as ability to degrade after implantation; leaving behind the flexible circuitry substrate was being explored. The biodegradability of the proposed probe was evaluated.

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