WorldWideScience

Sample records for human brain slices

  1. Ultra-fast MRI of the human brain with simultaneous multi-slice imaging

    Science.gov (United States)

    Feinberg, David A.; Setsompop, Kawin

    2013-04-01

    The recent advancement of simultaneous multi-slice imaging using multiband excitation has dramatically reduced the scan time of the brain. The evolution of this parallel imaging technique began over a decade ago and through recent sequence improvements has reduced the acquisition time of multi-slice EPI by over ten fold. This technique has recently become extremely useful for (i) functional MRI studies improving the statistical definition of neuronal networks, and (ii) diffusion based fiber tractography to visualize structural connections in the human brain. Several applications and evaluations are underway which show promise for this family of fast imaging sequences.

  2. Human brain slices for epilepsy research: Pitfalls, solutions and future challenges.

    Science.gov (United States)

    Jones, Roland S G; da Silva, Anderson Brito; Whittaker, Roger G; Woodhall, Gavin L; Cunningham, Mark O

    2016-02-15

    Increasingly, neuroscientists are taking the opportunity to use live human tissue obtained from elective neurosurgical procedures for electrophysiological studies in vitro. Access to this valuable resource permits unique studies into the network dynamics that contribute to the generation of pathological electrical activity in the human epileptic brain. Whilst this approach has provided insights into the mechanistic features of electrophysiological patterns associated with human epilepsy, it is not without technical and methodological challenges. This review outlines the main difficulties associated with working with epileptic human brain slices from the point of collection, through the stages of preparation, storage and recording. Moreover, it outlines the limitations, in terms of the nature of epileptic activity that can be observed in such tissue, in particular, the rarity of spontaneous ictal discharges, we discuss manipulations that can be utilised to induce such activity. In addition to discussing conventional electrophysiological techniques that are routinely employed in epileptic human brain slices, we review how imaging and multielectrode array recordings could provide novel insights into the network dynamics of human epileptogenesis. Acute studies in human brain slices are ultimately limited by the lifetime of the tissue so overcoming this issue provides increased opportunity for information gain. We review the literature with respect to organotypic culture techniques that may hold the key to prolonging the viability of this material. A combination of long-term culture techniques, viral transduction approaches and electrophysiology in human brain slices promotes the possibility of large scale monitoring and manipulation of neuronal activity in epileptic microcircuits. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...... differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......-culture, large numbers of tyrosine hydroxylase (TH)-immunoreactive, catecholaminergic cells could be found underneath individual striatal slices. Cell counting revealed that up to 25.3% (average 16.1%) of the total number of cells in these areas were TH-positive, contrasting a few TH-positive cells (

  4. Image reconstruction for brain CT slices

    Institute of Scientific and Technical Information of China (English)

    吴建明; 施鹏飞

    2004-01-01

    Different modalities in biomedical images, like CT, MRI and PET scanners, provide detailed cross-sectional views of human anatomy. This paper introduces three-dimensional brain reconstruction based on CT slices. It contains filtering, fuzzy segmentation, matching method of contours, cell array structure and image animation. Experimental results have shown its validity. The innovation is matching method of contours and fuzzy segmentation algorithm of CT slices.

  5. Intersection-based registration of slice stacks to form 3D images of the human fetal brain

    DEFF Research Database (Denmark)

    Kim, Kio; Hansen, Mads Fogtmann; Habas, Piotr;

    2008-01-01

    Clinical fetal MR imaging of the brain commonly makes use of fast 2D acquisitions of multiple sets of approximately orthogonal 2D slices. We and others have previously proposed an iterative slice-to-volume registration process to recover a geometrically consistent 3D image. However, these approac...

  6. Organotypic slice culture of embryonic brain tissue.

    Science.gov (United States)

    Daza, Ray A M; Englund, Chris; Hevner, Robert F

    2007-12-01

    INTRODUCTIONThis protocol describes how to dissect, assemble, and cultivate mouse embryonic (E) brain tissue from age E11.5 to E18.5 (days) for organotypic slice culture. These preparations can be used for a variety of assays and studies including coculture of different brain regions, cell migration assays, axon guidance assays, and DNA electroporation experiments. During electroporation, an electric current is applied to the surface of a specific target area of the brain slice in order to open holes in the plasma membrane and introduce a plasmid of coding DNA. The floating slice-on-membrane construct helps to preserve the structural integrity of the brain slices, while maintaining easy experimental access and optimal viability. Experiments can be monitored in living slices (e.g., with confocal imaging), and further studies can be completed using slices that have been fixed and cryosectioned at the end of the experiment. Any region of embryonic brain or spinal tissue can be used in this protocol.

  7. Investigation of inter-slice magnetization transfer effects as a new method for MTR imaging of the human brain.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Barker

    Full Text Available We present a new method for magnetization transfer (MT ratio imaging in the brain that requires no separate saturation pulse. Interslice MT effects that are inherent to multi-slice balanced steady-state free precession (bSSFP imaging were controlled via an interslice delay time to generate MT-weighted (0 s delay and reference images (5-8 s delay for MT ratio (MTR imaging of the brain. The effects of varying flip angle and phase encoding (PE order were investigated experimentally in normal, healthy subjects. Values of up to ∼50% and ∼40% were observed for white and gray matter MTR. Centric PE showed larger MTR, higher SNR, and better contrast between white and gray matter than linear PE. Simulations of a two-pool model of MT agreed well with in vivo MTR values. Simulations were also used to investigate the effects of varying acquisition parameters, and the effects of varying flip angle, PE steps, and interslice delay are discussed. Lastly, we demonstrated reduced banding with a non-balanced SSFP-FID sequence and showed preliminary results of interslice MTR imaging of meningioma.

  8. Long-term brain slice culturing in a microfluidic platform

    DEFF Research Database (Denmark)

    Vedarethinam, Indumathi; Avaliani, N.; Tønnesen, J.;

    2011-01-01

    In this work, we present the development of a transparent poly(methyl methacrylate) (PMMA) based microfluidic culture system for handling long-term brain slice cultures independent of an incubator. The different stages of system development have been validated by culturing GFP producing brain...... brain slice culturing for 16 days....

  9. Preliminary Study of Realistic Blast Impact on Cultured Brain Slices

    Science.gov (United States)

    2015-04-01

    hippocampal slice samples to better understand blast-induced brain damage. 15. SUBJECT TERMS RDX spheres , organotypic cultures of hippocampus, small...Preliminary Study of Realistic Blast Impact on Cultured Brain Slices by Thuvan Piehler, Rohan Banton, Lars Piehler, Richard Benjamin, Ray...Aberdeen Proving Ground, MD 21005-5066 ARL-TR-7197 April 2015 Preliminary Study of Realistic Blast Impact on Cultured Brain Slices Thuvan

  10. Novel culturing platform for brain slices and neuronal cells

    DEFF Research Database (Denmark)

    Svendsen, Winnie Edith; Al Atraktchi, Fatima Al-Zahraa; Bakmand, Tanya

    2015-01-01

    In this paper we demonstrate a novel culturing system for brain slices and neuronal cells, which can control the concentration of nutrients and the waste removal from the culture by adjusting the fluid flow within the device. The entire system can be placed in an incubator. The system has been te...... tested successfully with brain slices and PC12 cells. The culture substrate can be modified using metal electrodes and/or nanostructures for conducting electrical measurements while culturing and for better mimicking the in vivo conditions.......In this paper we demonstrate a novel culturing system for brain slices and neuronal cells, which can control the concentration of nutrients and the waste removal from the culture by adjusting the fluid flow within the device. The entire system can be placed in an incubator. The system has been...

  11. Whole brain CT perfusion on a 320-slice CT scanner

    Directory of Open Access Journals (Sweden)

    Jai Jai Shiva Shankar

    2011-01-01

    Full Text Available Computed tomography perfusion (CTP has been criticized for limited brain coverage. This may result in inadequate coverage of the lesion, inadequate arterial input function, or omission of the lesion within the target perfusion volume. The availability of 320-slice CT scanners offers whole brain coverage. This minimizes the chances of misregistration of lesions regardless of location, and makes the selection of the arterial input function easy. We present different clinical scenarios in which whole brain CTP is especially useful.

  12. Slices

    KAUST Repository

    McCrae, James

    2011-01-01

    Minimalist object representations or shape-proxies that spark and inspire human perception of shape remain an incompletely understood, yet powerful aspect of visual communication. We explore the use of planar sections, i.e., the contours of intersection of planes with a 3D object, for creating shape abstractions, motivated by their popularity in art and engineering. We first perform a user study to show that humans do define consistent and similar planar section proxies for common objects. Interestingly, we observe a strong correlation between user-defined planes and geometric features of objects. Further we show that the problem of finding the minimum set of planes that capture a set of 3D geometric shape features is both NP-hard and not always the proxy a user would pick. Guided by the principles inferred from our user study, we present an algorithm that progressively selects planes to maximize feature coverage, which in turn influence the selection of subsequent planes. The algorithmic framework easily incorporates various shape features, while their relative importance values are computed and validated from the user study data. We use our algorithm to compute planar slices for various objects, validate their utility towards object abstraction using a second user study, and conclude showing the potential applications of the extracted planar slice shape proxies. © 2011 ACM.

  13. A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system.

    Science.gov (United States)

    Gulyás, Balázs; Makkai, Boglárka; Kása, Péter; Gulya, Károly; Bakota, Lidia; Várszegi, Szilvia; Beliczai, Zsuzsa; Andersson, Jan; Csiba, László; Thiele, Andrea; Dyrks, Thomas; Suhara, Tetsua; Suzuki, Kazutoshi; Higuchi, Makato; Halldin, Christer

    2009-01-01

    The binding of two radiolabelled analogues (N-(5-[125I]Iodo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide ([125I]desfluoro-DAA1106) and N-(5-[125I]Fluoro-2-phenoxyphenyl)-N-(2-[125I]Iodo-5-methoxybenzyl)acetamide ([125I]desmethoxy-DAA1106) of the peripheral benzodiazepine receptor (PBR) (or TSPO, 18kDa translocator protein) ligand DAA1106 was examined by in vitro autoradiography on human post mortem whole hemisphere brain slices obtained from Alzheimer's disease (AD) patients and age-matched controls. Both [(125)I]desfluoro-IDAA1106 and [(125)I]desmethoxy-IDAA1106 were effectively binding to various brain structures. The binding could be blocked by the unlabelled ligand as well as by other PBR specific ligands. With both radiolabelled compounds, the binding showed regional inhomogeneity and the specific binding values proved to be the highest in the hippocampus, temporal and parietal cortex, the basal ganglia and thalamus in the AD brains. Compared with age-matched control brains, specific binding in several brain structures (temporal and parietal lobes, thalamus and white matter) in Alzheimer brains was significantly higher, indicating that the radioligands can effectively label-activated microglia and the up-regulated PBR/TSPO system in AD. Complementary immunohistochemical studies demonstrated reactive microglia activation in the AD brain tissue and indicated that increased ligand binding coincides with increased regional microglia activation due to neuroinflammation. These investigations yield further support to the PBR/TSPO binding capacity of DAA1106 in human brain tissue, demonstrate the effective usefulness of its radio-iodinated analogues as imaging biomarkers in post mortem human studies, and indicate that its radiolabelled analogues, labelled with short half-time bioisotopes, can serve as prospective in vivo imaging biomarkers of activated microglia and the up-regulated PBR/TSPO system in the human brain.

  14. Visible Human Slice Web Server: a first assessment

    Science.gov (United States)

    Hersch, Roger D.; Gennart, Benoit A.; Figueiredo, Oscar; Mazzariol, Marc; Tarraga, Joaquin; Vetsch, S.; Messerli, Vincent; Welz, R.; Bidaut, Luc M.

    1999-12-01

    The Visible Human Slice Server started offering its slicing services at the end of June 1998. From that date until the end of May, more than 280,000 slices were extracted from the Visible Man, by layman interested in anatomy, by students and by specialists. The Slice Server is based one Bi-Pentium PC and 16 disks. It is a scaled down version of a powerful parallel server comprising 5 Bi-Pentium Pro PCs and 60 disks. The parallel server program was created thanks to a computer-aided parallelization framework, which takes over the task of creating a multi-threaded pipelined parallel program from a high-level parallel program description. On the full blown architecture, the parallel program enables the extraction and resampling of up to 5 color slices per second. Extracting 5 slice/s requires to access the disks and extract subvolumes of the Visible Human at an aggregate throughput of 105 MB/s. The publicly accessible server enables to extract slices having any orientation. The slice position and orientation can either be specified for each slice separately or as a position and orientation offered by a Java applet and possible future improvements. In the very near future, the Web Slice Server will offer additional services, such as the possibility to extract ruled surfaces and to extract animations incorporating slices perpendicular to a user defined trajectory.

  15. Differential Conditioning of Associative Synaptic Enhancement in Hippocampal Brain Slices

    Science.gov (United States)

    Kelso, Stephen R.; Brown, Thomas H.

    1986-04-01

    An electrophysiological stimulation paradigm similar to one that produces Pavlovian conditioning was applied to synaptic inputs to pyramidal neurons of hippocampal brain slices. Persistent synaptic enhancement was induced in one of two weak synaptic inputs by pairing high-frequency electrical stimulation of the weak input with stimulation of a third, stronger input to the same region. Forward (temporally overlapping) but not backward (temporally separate) pairings caused this enhancement. Thus hippocampal synapses in vitro can undergo the conditional and selective type of associative modification that could provide the substrate for some of the mnemonic functions in which the hippocampus is thought to participate.

  16. Fluidic system for long-term in vitro culturing and monitoring of organotypic brain slices

    DEFF Research Database (Denmark)

    Bakmand, Tanya; Troels-Smith, Ane R.; Dimaki, Maria

    2015-01-01

    Brain slice preparations cultured in vitro have long been used as a simplified model for studying brain development, electrophysiology, neurodegeneration and neuroprotection. In this paper an open fluidic system developed for improved long term culturing of organotypic brain slices is presented. ...

  17. A novel carbon fiber bundle microelectrode and modified brain slice chamber for recording long-term multiunit activity from brain slices.

    Science.gov (United States)

    Tcheng, T K; Gillette, M U

    1996-11-01

    The fabrication and characteristics of a novel multiunit recording electrode and modified brain slice chamber suitable for long-term recording from brain slices are described. The electrode consisted of an electrolyte-filled glass micropipette with a 20-50 microns thick wax-coated bundle of 5-micron diameter carbon fibers extending 2.5 cm from the tapered end and an AgCl-coated silver wire inserted into the open end and connected to a preamplifier. Both ends of the electrode were sealed with wax to prevent evaporation of the electrolyte. The brain slice was maintained over this extended period in an interface-type brain slice chamber modified to completely surround the slice with medium. Using this electrode, regular 24-h oscillations of spontaneous multiunit activity were recorded for 3 days from a single location in a 500 microns thick rat suprachiasmatic nucleus brain slice. Preliminary data suggest that this novel carbon fiber bundle electrode will be a favorable alternative to traditional metal electrodes for long-term recording of multiunit activity from brain slices.

  18. Profile analysis of hepatic porcine and murine brain tissue slices obtained with a vibratome.

    Science.gov (United States)

    Mattei, G; Cristiani, I; Magliaro, C; Ahluwalia, A

    2015-01-01

    This study is aimed at characterizing soft tissue slices using a vibratome. In particular, the effect of two sectioning parameters (i.e., step size and sectioning speed) on resultant slice thickness was investigated for fresh porcine liver as well as for paraformaldehyde-fixed (PFA-fixed) and fresh murine brain. A simple framework for embedding, sectioning and imaging the slices was established to derive their thickness, which was evaluated through a purposely developed graphical user interface. Sectioning speed and step size had little effect on the thickness of fresh liver slices. Conversely, the thickness of PFA-fixed murine brain slices was found to be dependent on the step size, but not on the sectioning speed. In view of these results, fresh brain tissue was sliced varying the step size only, which was found to have a significant effect on resultant slice thickness. Although precision-cut slices (i.e., with regular thickness) were obtained for all the tissues, slice accuracy (defined as the match between the nominal step size chosen and the actual slice thickness obtained) was found to increase with tissue stiffness from fresh liver to PFA-fixed brain. This quantitative investigation can be very helpful for establishing the most suitable slicing setup for a given tissue.

  19. Fast whole-brain optical tomography capable of automated slice-collection (Conference Presentation)

    Science.gov (United States)

    Yuan, Jing; Jiang, Tao; Deng, Lei; Long, Beng; Peng, Jie; Luo, Qingming; Gong, Hui

    2016-03-01

    Acquiring brain-wide composite information of neuroanatomical and molecular phenotyping is crucial to understand brain functions. However, current whole-brain imaging methods based on mechnical sectioning haven't achieved brain-wide acquisition of both neuroanatomical and molecular phenotyping due to the lack of appropriate whole-brain immunostaining of embedded samples. Here, we present a novel strategy of acquiring brain-wide structural and molecular maps in the same brain, combining whole-brain imaging and subsequent immunostaining of automated-collected slices. We developed a whole-brain imaging system capable of automatically imaging and then collecting imaged tissue slices in order. The system contains three parts: structured illumination microscopy for high-throughput optical sectioning, vibratome for high-precision sectioning and slice-collection device for automated collecting of tissue slices. Through our system, we could acquire a whole-brain dataset of agarose-embedded mouse brain at lateral resolution of 0.33 µm with z-interval sampling of 100 µm in 9 h, and automatically collect the imaged slices in sequence. Subsequently, we performed immunohistochemistry of the collected slices in the routine way. We acquired mouse whole-brain imaging datasets of multiple specific types of neurons, proteins and gene expression profiles. We believe our method could accelerate systematic analysis of brain anatomical structure with specific proteins or genes expression information and understanding how the brain processes information and generates behavior.

  20. Label-free dopamine imaging in live rat brain slices.

    Science.gov (United States)

    Sarkar, Bidyut; Banerjee, Arkarup; Das, Anand Kant; Nag, Suman; Kaushalya, Sanjeev Kumar; Tripathy, Umakanta; Shameem, Mohammad; Shukla, Shubha; Maiti, Sudipta

    2014-05-21

    Dopaminergic neurotransmission has been investigated extensively, yet direct optical probing of dopamine has not been possible in live cells. Here we image intracellular dopamine with sub-micrometer three-dimensional resolution by harnessing its intrinsic mid-ultraviolet (UV) autofluorescence. Two-photon excitation with visible light (540 nm) in conjunction with a non-epifluorescent detection scheme is used to circumvent the UV toxicity and the UV transmission problems. The method is established by imaging dopamine in a dopaminergic cell line and in control cells (glia), and is validated by mass spectrometry. We further show that individual dopamine vesicles/vesicular clusters can be imaged in cultured rat brain slices, thereby providing a direct visualization of the intracellular events preceding dopamine release induced by depolarization or amphetamine exposure. Our technique opens up a previously inaccessible mid-ultraviolet spectral regime (excitation ~270 nm, emission free imaging of native molecules in live tissue.

  1. Biocompatibility of silicon-based arrays of electrodes coupled to organotypic hippocampal brain slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, J; Thiébaud, P

    2001-01-01

    In this study we examined the passive biocompatibility of a three-dimensional microelectrode array (MEA), designed to be coupled to organotypic brain slice cultures for multisite recording of electrophysiological signals. Hippocampal (and corticostriatal) brain slices from 1-week-old (and newborn...

  2. Influence of Thin Slice Reconstruction on CT Brain Perfusion Analysis

    NARCIS (Netherlands)

    Bennink, Edwin; Oosterbroek, Jaap; Horsch, Alexander D.; Dankbaar, Jan Willem; Velthuis, BK; Viergever, Max A.; de Jong, Hugo W. A. M.

    2015-01-01

    Objectives Although CT scanners generally allow dynamic acquisition of thin slices (1 mm), thick slice (>= 5 mm) reconstruction is commonly used for stroke imaging to reduce data, processing time, and noise level. Thin slice CT perfusion (CTP) reconstruction may suffer less from partial volume effec

  3. Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices.

    Science.gov (United States)

    Bosch, Daniel; Asede, Douglas; Ehrlich, Ingrid

    2016-04-05

    Optogenetic approaches are now widely used to study the function of neural populations and circuits by combining targeted expression of light-activated proteins and subsequent manipulation of neural activity by light. Channelrhodopsins (ChRs) are light-gated cation-channels and when fused to a fluorescent protein their expression allows for visualization and concurrent activation of specific cell types and their axonal projections in defined areas of the brain. Via stereotactic injection of viral vectors, ChR fusion proteins can be constitutively or conditionally expressed in specific cells of a defined brain region, and their axonal projections can subsequently be studied anatomically and functionally via ex vivo optogenetic activation in brain slices. This is of particular importance when aiming to understand synaptic properties of connections that could not be addressed with conventional electrical stimulation approaches, or in identifying novel afferent and efferent connectivity that was previously poorly understood. Here, a few examples illustrate how this technique can be applied to investigate these questions to elucidating fear-related circuits in the amygdala. The amygdala is a key region for acquisition and expression of fear, and storage of fear and emotional memories. Many lines of evidence suggest that the medial prefrontal cortex (mPFC) participates in different aspects of fear acquisition and extinction, but its precise connectivity with the amygdala is just starting to be understood. First, it is shown how ex vivo optogenetic activation can be used to study aspects of synaptic communication between mPFC afferents and target cells in the basolateral amygdala (BLA). Furthermore, it is illustrated how this ex vivo optogenetic approach can be applied to assess novel connectivity patterns using a group of GABAergic neurons in the amygdala, the paracapsular intercalated cell cluster (mpITC), as an example.

  4. Influence of Thin Slice Reconstruction on CT Brain Perfusion Analysis.

    Directory of Open Access Journals (Sweden)

    Edwin Bennink

    Full Text Available Although CT scanners generally allow dynamic acquisition of thin slices (1 mm, thick slice (≥5 mm reconstruction is commonly used for stroke imaging to reduce data, processing time, and noise level. Thin slice CT perfusion (CTP reconstruction may suffer less from partial volume effects, and thus yield more accurate quantitative results with increased resolution. Before thin slice protocols are to be introduced clinically, it needs to be ensured that this does not affect overall CTP constancy. We studied the influence of thin slice reconstruction on average perfusion values by comparing it with standard thick slice reconstruction.From 50 patient studies, absolute and relative hemisphere averaged estimates of cerebral blood volume (CBV, cerebral blood flow (CBF, mean transit time (MTT, and permeability-surface area product (PS were analyzed using 0.8, 2.4, 4.8, and 9.6 mm slice reconstructions. Specifically, the influence of Gaussian and bilateral filtering, the arterial input function (AIF, and motion correction on the perfusion values was investigated.Bilateral filtering gave noise levels comparable to isotropic Gaussian filtering, with less partial volume effects. Absolute CBF, CBV and PS were 22%, 14% and 46% lower with 0.8 mm than with 4.8 mm slices. If the AIF and motion correction were based on thin slices prior to reconstruction of thicker slices, these differences reduced to 3%, 4% and 3%. The effect of slice thickness on relative values was very small.This study shows that thin slice reconstruction for CTP with unaltered acquisition protocol gives relative perfusion values without clinically relevant bias. It does however affect absolute perfusion values, of which CBF and CBV are most sensitive. Partial volume effects in large arteries and veins lead to overestimation of these values. The effects of reconstruction slice thickness should be taken into account when absolute perfusion values are used for clinical decision making.

  5. Optimized Protocol of Methanol Treatment for Immunofluorescent Staining in Fixed Brain Slices

    Science.gov (United States)

    Yuan, Feng; Cohen, Noam A.; Cohen, Akiva S.

    2017-01-01

    We optimized methanol treatment in paraformaldehyde-fixed slices for immunofluorescent staining of ependymal basal bodies in brain ventricles. As 100% methanol induced severe deformations to the slices (including rolling and folding over), we tried to decrease methanol concentration. We found that 33.3% to 75% methanol could result in ideal immunostaining of basal bodies without inducing obvious deformations. Instead of treating slices at −20°C (without proper cryoprotection measurements) as suggested in previous studies, we carried out methanol treatment at room temperature. Our modified protocol can not only raise immunostaining efficiency in tissue slices, it may also prevent potential freezing damages to the samples. PMID:26509907

  6. Repair pathways evident in human liver organ slices

    NARCIS (Netherlands)

    Vickers, Alison E. M.; Fisher, Robyn; Olinga, Peter; Dial, Sharon

    2011-01-01

    The extension of human liver slice culture viability for several days broadens the potential of this ex vivo model for characterizing pathways of organ injury and repair, and allows for the multiple dosing of compounds. Extended viability is demonstrated by continued synthesis of GSH and ATP, and ma

  7. Coculture system with an organotypic brain slice and 3D spheroid of carcinoma cells.

    Science.gov (United States)

    Chuang, Han-Ning; Lohaus, Raphaela; Hanisch, Uwe-Karsten; Binder, Claudia; Dehghani, Faramarz; Pukrop, Tobias

    2013-10-09

    Patients with cerebral metastasis of carcinomas have a poor prognosis. However, the process at the metastatic site has barely been investigated, in particular the role of the resident (stromal) cells. Studies in primary carcinomas demonstrate the influence of the microenvironment on metastasis, even on prognosis(1,2). Especially the tumor associated macrophages (TAM) support migration, invasion and proliferation(3). Interestingly, the major target sites of metastasis possess tissue-specific macrophages, such as Kupffer cells in the liver or microglia in the CNS. Moreover, the metastatic sites also possess other tissue-specific cells, like astrocytes. Recently, astrocytes were demonstrated to foster proliferation and persistence of cancer cells(4,5). Therefore, functions of these tissue-specific cell types seem to be very important in the process of brain metastasis(6,7). Despite these observations, however, up to now there is no suitable in vivo/in vitro model available to directly visualize glial reactions during cerebral metastasis formation, in particular by bright field microscopy. Recent in vivo live imaging of carcinoma cells demonstrated their cerebral colonization behavior(8). However, this method is very laborious, costly and technically complex. In addition, these kinds of animal experiments are restricted to small series and come with a substantial stress for the animals (by implantation of the glass plate, injection of tumor cells, repetitive anaesthesia and long-term fixation). Furthermore, in vivo imaging is thus far limited to the visualization of the carcinoma cells, whereas interactions with resident cells have not yet been illustrated. Finally, investigations of human carcinoma cells within immunocompetent animals are impossible(8). For these reasons, we established a coculture system consisting of an organotypic mouse brain slice and epithelial cells embedded in matrigel (3D cell sphere). The 3D carcinoma cell spheres were placed directly next to

  8. Altered regulation of brain-derived neurotrophic factor protein in hippocampus following slice preparation.

    Science.gov (United States)

    Danzer, S C; Pan, E; Nef, S; Parada, L F; McNamara, J O

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) and its cognate receptor tyrosine kinase B (TrkB) play important roles in regulating survival, structure, and function of CNS neurons. One method of studying the functions of these molecules has utilized in vitro hippocampal slice preparations. An important caveat to using slices, however, is that slice preparation itself might alter the expression of BDNF, thereby confounding experimental results. To address this concern, BDNF immunoreactivity was examined in rodent slices using two different methods of slice preparation. Rapid and anatomically selective regulation of BDNF content followed slice preparation using both methodologies; however, different patterns of altered BDNF immunoreactivity were observed. First, in cultured slices, BDNF content decreased in the dentate molecular layer and increased in the CA3 pyramidal cell layer and the mossy fiber pathway of the hippocampus after 30 min. Furthermore, an initially "punctate" pattern of BDNF labeling observed in the mossy fiber pathway of control sections changed to homogenous labeling of the pathway in vitro. In contrast to these findings, slices prepared as for acute slice physiology exhibited no change in BDNF content in the molecular layer and mossy fiber pathway 30 min after slicing, but exhibited significant increases in the dentate granule and CA3 pyramidal cell layers. These findings demonstrate that BDNF protein content is altered following slice preparation, that different methods of slice preparation produce different patterns of BDNF regulation, and raise the possibility that BDNF release and TrkB activation may also be regulated. These consequences of hippocampal slice preparation may confound analyses of exogenous or endogenous BDNF on hippocampal neuronal structure or function.

  9. Using laser confocal scanning microscope to study ischemia-hypoxia injury in rat brain slice

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The level of lipid peroxidation and cellular necrosis in rat living brain slices during brain ischemia-hypoxia injury have been observed using a laser confocal scanning microscope (LCSM) with double labeling of fluorescent probes D-399 (2,7-dichlorofluorescin diacetate) and propidium iodide (PI).The hypoxia and/or reoxygenation injury in rat brain slices is markedly decreased by pretreatment with L-NG-nitro-arginine (L-NNA) and N-acetylcysteine (NAC),showing that the nitric oxide (NO) and other free radicals play an important role in brain ischemia-hypoxia injury.

  10. Precise spatial and temporal control of oxygen within in vitro brain slices via microfluidic gas channels.

    Directory of Open Access Journals (Sweden)

    Gerardo Mauleon

    Full Text Available The acute brain slice preparation is an excellent model for studying the details of how neurons and neuronal tissue respond to a variety of different physiological conditions. But open slice chambers ideal for electrophysiological and imaging access have not allowed the precise spatiotemporal control of oxygen in a way that might realistically model stroke conditions. To address this problem, we have developed a microfluidic add-on to a commercially available perfusion chamber that diffuses oxygen throughout a thin membrane and directly to the brain slice. A microchannel enables rapid and efficient control of oxygen and can be modified to allow different regions of the slice to experience different oxygen conditions. Using this novel device, we show that we can obtain a stable and homogeneous oxygen environment throughout the brain slice and rapidly alter the oxygen tension in a hippocampal slice. We also show that we can impose different oxygen tensions on different regions of the slice preparation and measure two independent responses, which is not easily obtainable with current techniques.

  11. Three-dimensional electrode array for brain slice culture

    DEFF Research Database (Denmark)

    Vazquez Rodriguez, Patricia

    Multielektroder arrays (MEA) er rækker af elektroder mest i mikrometer størrelse, som er blevet brugt i stor omfang til at stimulere og måle elektrisk aktivitet fra neuronale netværker. Brug af disse for at analysere hjerne slices (hjerneskiver) kan give indsigt i interaktioner mellem neuroner...

  12. Monitoring axonal and somatodendritic dopamine release using fast-scan cyclic voltammetry in brain slices.

    Science.gov (United States)

    Patel, Jyoti C; Rice, Margaret E

    2013-01-01

    Brain dopamine pathways serve wide-ranging functions including the control of movement, reward, cognition, learning, and mood. Consequently, dysfunction of dopamine transmission has been implicated in clinical conditions such as Parkinson's disease, schizophrenia, addiction, and depression. Establishing factors that regulate dopamine release can provide novel insights into dopaminergic communication under normal conditions, as well as in animal models of disease in the brain. Here we describe methods for the study of somatodendritic and axonal dopamine release in brain slice preparations. Topics covered include preparation and calibration of carbon-fiber microelectrodes for use with fast-scan cyclic voltammetry, preparation of midbrain and forebrain slices, and procedures of eliciting and recording electrically evoked dopamine release from in vitro brain slices.

  13. Coupling of organotypic brain slice cultures to silicon-based arrays of electrodes

    DEFF Research Database (Denmark)

    Jahnsen, Henrik; Kristensen, Bjarne Winther; Thiébaud, P

    1999-01-01

    Fetal or early postnatal brain tissue can be cultured in viable and healthy condition for several weeks with development and preservation of the basic cellular and connective organization as so-called organotypic brain slice cultures. Here we demonstrate and describe how it is possible to establi...

  14. Binding of mescaline with subcellular fractions upon incubation of brain cortex slices with [14C] mescaline.

    Science.gov (United States)

    Datta, R K; Antopol, W; Ghosh, J J

    1977-01-01

    Incubation of brain cortex slices in the presence of glucose resulted in the permeation of about 65% of [14C] mescaline into slices. Of this, about one-third radioactivity was bound with nuclei, mitochondria, microsomes, and ribosomes. Dialysis of subcellular fractions did not markedly reduce the amounts of radioactivity bound to the fractions. The permeation into slices and the binding of mescaline to subcellular fractions were fairly time-dependent, but were inhibited by the presence of potassium cyanide, or by the absence of glucose and by heating to 80 degrees C for 1 min.

  15. An aerator for brain slice experiments in individual cell culture plate wells.

    Science.gov (United States)

    Dorris, David M; Hauser, Caitlin A; Minnehan, Caitlin E; Meitzen, John

    2014-12-30

    Ex vivo acute living brain slices are a broadly employed and powerful experimental preparation. Most new technology regarding this tissue has involved the chamber used when performing electrophysiological experiments. Alternatively we instead focus on the creation of a simple, versatile aerator designed to allow maintenance and manipulation of acute brain slices and potentially other tissue in a multi-well cell culture plate. Here we present an easily manufactured aerator designed to fit into a 24-well cell culture plate. It features a nylon mesh and a single microhole to enable gas delivery without compromising tissue stability. The aerator is designed to be individually controlled, allowing both high throughput and single well experiments. The aerator was validated by testing material leach, dissolved oxygen delivery, brain slice viability and neuronal electrophysiology. Example experiments are also presented, including a test of whether β1-adrenergic receptor activation regulates gene expression in ex vivo dorsal striatum using qPCR. Key differences include enhanced control over gas delivery to individual wells containing brain slices, decreased necessary volume, a sample restraint to reduce movement artifacts, the potential to be sterilized, the avoidance of materials that absorb water and small biological molecules, minimal production costs, and increased experimental throughput. This new aerator is of high utility and will be useful for experiments involving brain slices and other potentially tissue samples in 24-well cell culture plates. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Effects of ketamine, midazolam, thiopental, and propofol on brain ischemia injury in rat cerebral cortical slices

    Institute of Scientific and Technical Information of China (English)

    Qing-shengXUE; Bu-weiYU; Ze-jianWANG; Hong-zhuanCHEN

    2004-01-01

    AIM: To compare the effects of ketamine, midazolam, thiopental, and propofol on brain ischemia by the model of oxygen-glucose deprivation (OGD) in rat cerebral cortical slices. METHODS: Cerebral cortical slices were incu-bated in 2 % 2,3,5-triphenyltetrazolium chloride (TTC) solution after OGD, the damages and effects of ketamine,midazolam, thiopental, and propofol were quantitativlye evaluated by ELISA reader of absorbance (A) at 490 nm,which indicated the red formazan extracted from slices, lactic dehydrogenase (LDH) releases in the incubated supernate were also measured. RESULTS: Progressive prolongation of OGD resulted in decreases of TTC staining.The percentage of tissue injury had a positive correlation with LDH releases, r=0.9609, P<0.01. Two hours of reincubation aggravated the decrease of TTC staining compared with those slices stained immediately after OGD(P<0.01). These four anesthetics had no effects on the TTC staining of slices. Ketamine completely inhibited thedecrease of A value induced by 10 min of OGD injury. High concentrations of midazolam (10 μmol/L) and thiopental (400μmol/L) partly attenuated this decrease. Propofol at high concentration (100 μmol/L) enhanced the decrease of A value induced by 10 min of OGD injury (P<0.01). CONCLUSION; Ketamine, high concentration of midazolam and thiopental have neuroprotective effects against OGD injury in rat cerebral cortical slices, while high concentration of propofol augments OGD injury in rat cerebral cortical slices.

  17. Brain slices as models for neurodegenerative disease and screening platforms to identify novel therapeutics.

    Science.gov (United States)

    Cho, Seongeun; Wood, Andrew; Bowlby, Mark R

    2007-03-01

    Recent improvements in brain slice technology have made this biological preparation increasingly useful for examining pathophysiology of brain diseases in a tissue context. Brain slices maintain many aspects of in vivo biology, including functional local synaptic circuitry with preserved brain architecture, while allowing good experimental access and precise control of the extracellular environment, making them ideal platforms for dissection of molecular pathways underlying neuronal dysfunction. Importantly, these ex vivo systems permit direct treatment with pharmacological agents modulating these responses and thus provide surrogate therapeutic screening systems without recourse to whole animal studies. Virus or particle mediated transgenic expression can also be accomplished relatively easily to study the function of novel genes in a normal or injured brain tissue context.In this review we will discuss acute brain injury models in organotypic hippocampal and co-culture systems and the effects of pharmacological modulation on neurodegeneration. The review will also cover the evidence of developmental plasticity in these ex vivo models, demonstrating emergence of injury-stimulated neuronal progenitor cells, and neurite sprouting and axonal regeneration following pathway lesioning. Neuro-and axo-genesis are emerging as significant factors contributing to brain repair following many acute and chronic neurodegenerative disorders. Therefore brain slice models may provide a critical contextual experimental system to explore regenerative mechanisms in vitro.

  18. SYNCHROTRON RADIATION XRF MICROPROBE STUDY OF HUMAN BONE TUMOR SLICE

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The experimental apparatus of X-ray fluorescence (XRF) microprobe analysis at Beijing Synchrotron Radiation Facility (BSRF) is described Using the bovine liver as the standard reference.the minimum detection limit(MDL) of trace element was measured to determine the capability of biological sample analysis by synchrotron radiation XRF microprobe.The relative change of the content of the major or trace element in the normal and tumor part of human bone tissue slice was investigated The experimental result relation to the clinical medicine was also discussed.

  19. Dose-response testing of peptides by hippocampal brain slice recording.

    Science.gov (United States)

    Phillips, M I; Palovcik, R A

    1989-01-01

    The brain slice chamber described offers a method of studying, with intracellular electrodes, the relationship of response to dose of peptides. By raising the level of the slices 1 mm above the level of flowing perfusion medium, we can test substances in known concentrations, free from artifacts, during long duration, stable intracellular recordings. Manipulation of Ca2+/Mg2+ ratios in the medium can help to define synaptic and second messenger mediation of the responses. The addition of substances to the perfusion medium in this system could be combined with iontophoresis and/or micropressure techniques. Pathways in the slices may also be stimulated electrically and analyzed for the involvement of various synaptic transmitters. The results with the method so far show distinct differences among the peptides studied. Thus, there are several advantages to this method in establishing the physiological role of peptides in the brain.

  20. [Human brain resource--experience at the Brain Research Institute,University of Niigata].

    Science.gov (United States)

    Kakita, Akiyoshi; Takahashi, Hitoshi

    2010-10-01

    Through 40 years of neuropathological practice,the Brain Research Institute, University of Niigata (BRI-Niigata), Japan has accumulated extensive human brain resource,including fresh-frozen brain slices,for scientific research. Over 30,000 slices obtained from consecutive autopsies have been systematically stored in 25 deep freezers. Establishment of effective networks between brain banks and institutional collections in Japan is essential for promoting scientific activities that require human brain resource. We at the BRI-Niigata are eager to contribute to the establishment of such networks.

  1. Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

    Science.gov (United States)

    Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

    2016-03-01

    Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models.

  2. Mini-ruby is rapidly taken up by neurons and astrocytes in organotypic brain slices.

    Science.gov (United States)

    Ullrich, Celine; Humpel, Christian

    2011-10-01

    Cholinergic neurons are intensively studied, because they degenerate in Alzheimer's disease. Although neurotracer techniques are widely used to study axonal transport, guidance, regeneration or sprouting it is not clear if cholinergic neurons can be stained by tracer techniques and studied in brain slices. The aim of the present study was to evaluate the characteristics of the neurotracer Mini-ruby in organotypic brain slices of the basal nucleus of Meynert (nBM), focusing on cholinergic neurons. Mini-ruby is a biotinylated dextran amine and is taken up very fast by a variety of cells. When 2-week old nerve growth factor-incubated brain slices of the nBM were treated with Mini-ruby crystals for 1 h, only a few (2-3%) cholinergic neurons were clearly labeled as shown by co-localization with choline acetyltransferase. The staining was found in neuN-positive neurons and microtubule associated protein-2 (MAP-2)-positive nerve fibers. A very rapid dynamic change was observed in these labeled varicosities within seconds. However, Mini-ruby was taken up also by many glutamine synthethase-positive astrocytes. At the site of Mini-ruby application an intense CD11b-positive microglial staining was evident. In conclusion, neurons and astrocytes in organotypic brain slices can be labeled very fast with the fluorescent dye Mini-ruby which undergoes dynamic processes.

  3. 3D Data Mapping and Real-Time Experiment Control and Visualization in Brain Slices.

    Science.gov (United States)

    Navarro, Marco A; Hibbard, Jaime V K; Miller, Michael E; Nivin, Tyler W; Milescu, Lorin S

    2015-10-20

    Here, we propose two basic concepts that can streamline electrophysiology and imaging experiments in brain slices and enhance data collection and analysis. The first idea is to interface the experiment with a software environment that provides a 3D scene viewer in which the experimental rig, the brain slice, and the recorded data are represented to scale. Within the 3D scene viewer, the user can visualize a live image of the sample and 3D renderings of the recording electrodes with real-time position feedback. Furthermore, the user can control the instruments and visualize their status in real time. The second idea is to integrate multiple types of experimental data into a spatial and temporal map of the brain slice. These data may include low-magnification maps of the entire brain slice, for spatial context, or any other type of high-resolution structural and functional image, together with time-resolved electrical and optical signals. The entire data collection can be visualized within the 3D scene viewer. These concepts can be applied to any other type of experiment in which high-resolution data are recorded within a larger sample at different spatial and temporal coordinates.

  4. Cavitation Induced Structural and Neural Damage in Live Brain Tissue Slices: Relevance to TBI

    Science.gov (United States)

    2014-09-29

    the value of this experimental platform to investigate the single bubble cavitation- induced damage in a biological tissue is illustrated with an...Lei Wu, Malisa Sarntinoranont, Huikai Xie1. Refractive index measurement of acute rat brain tissue slices using optical coherence tomography, Optics...b-TBI, i.e. what is “broken”, in the brain during exposure to shock loading is currently unknown. While blast waves are well known to have negative

  5. Electrical coupling between hippocampal astrocytes in rat brain slices.

    Science.gov (United States)

    Meme, William; Vandecasteele, Marie; Giaume, Christian; Venance, Laurent

    2009-04-01

    Gap junctions in astrocytes play a crucial role in intercellular communication by supporting both biochemical and electrical coupling between adjacent cells. Despite the critical role of electrical coupling in the network organization of these glial cells, the electrophysiological properties of gap junctions have been characterized in cultures while no direct evidence has been sought in situ. In the present study, gap-junctional currents were investigated using simultaneous dual whole-cell patch-clamp recordings between astrocytes from rat hippocampal slices. Bidirectional electrotonic coupling was observed in 82% of the cell pairs with an average coupling coefficient of 5.1%. Double patch-clamp analysis indicated that junctional currents were independent of the transjunctional voltage over a range from -100 to +110 mV. Interestingly, astrocytic electrical coupling displayed weak low-pass filtering properties compared to neuronal electrical synapses. Finally, during uncoupling processes triggered by either the gap-junction inhibitor carbenoxolone or endothelin-1, an increase in the input resistance in the injected cell paralleled the decrease in the coupling coefficient. Altogether, these results demonstrate that hippocampal astrocytes are electrically coupled through gap-junction channels characterized by properties that are distinct from those of electrical synapses between neurons. In addition, gap-junctional communication is efficiently regulated by endogenous compounds. This is taken to represent a mode of communication that may have important implications for the functional role of astrocyte networks in situ.

  6. Functional imaging of single synapses in brain slices.

    Science.gov (United States)

    Oertner, Thomas G

    2002-11-01

    The strength of synaptic connections in the brain is not fixed, but can be modulated by numerous mechanisms. Traditionally, electrophysiology has been used to characterize connections between neurons. Electrophysiology typically reports the activity of populations of synapses, while most mechanisms of plasticity are thought to operate at the level of single synapses. Recently, two-photon laser scanning microscopy has enabled us to perform optical quantal analysis of individual synapses in intact brain tissue. Here we introduce the basic principle of the two-photon microscope and discuss its main differences compared to the confocal microscope. Using calcium imaging in dendritic spines as an example, we explain the advantages of simultaneous dual-dye imaging for quantitative calcium measurements and address two common problems, dye saturation and background fluorescence subtraction.

  7. The energy demand of fast neuronal network oscillations: insights from brain slice preparations

    Directory of Open Access Journals (Sweden)

    Oliver eKann

    2012-01-01

    Full Text Available Fast neuronal network oscillations in the gamma range (30-100 Hz in the cerebral cortex have been implicated in higher cognitive functions such as sensual perception, working memory, and, perhaps, consciousness. However, little is known about the energy demand of gamma oscillations. This is mainly caused by technical limitations that are associated with simultaneous recordings of neuronal activity and energy metabolism in small neuronal networks and at the level of mitochondria in vivo. Thus recent studies have focused on brain slice preparations to address the energy demand of gamma oscillations in vitro. Here, reports will be summarized and discussed that combined electrophysiological recordings, oxygen sensor microelectrodes and live-cell fluorescence imaging in acutely prepared slices and organotypic slice cultures of the hippocampus from both, mouse and rat. These reports consistently show that gamma oscillations can be reliably induced in hippocampal slice preparations by different pharmacological tools. They suggest that gamma oscillations are associated with high energy demand, requiring both rapid adaptation of oxidative energy metabolism and sufficient supply with oxygen and nutrients. These findings might help to explain the exceptional vulnerability of higher cognitive functions during pathological processes of the brain, such as circulatory disturbances, genetic mitochondrial diseases, and neurodegeneration.

  8. GnRH neuron firing and response to GABA in vitro depend on acute brain slice thickness and orientation.

    Science.gov (United States)

    Constantin, Stephanie; Piet, Richard; Iremonger, Karl; Hwa Yeo, Shel; Clarkson, Jenny; Porteous, Robert; Herbison, Allan E

    2012-08-01

    The GnRH neurons exhibit long dendrites and project to the median eminence. The aim of the present study was to generate an acute brain slice preparation that enabled recordings to be undertaken from GnRH neurons maintaining the full extent of their dendrites or axons. A thick, horizontal brain slice was developed, in which it was possible to record from the horizontally oriented GnRH neurons located in the anterior hypothalamic area (AHA). In vivo studies showed that the majority of AHA GnRH neurons projected outside the blood-brain barrier and expressed c-Fos at the time of the GnRH surge. On-cell recordings compared AHA GnRH neurons in the horizontal slice (AHAh) with AHA and preoptic area (POA) GnRH neurons in coronal slices [POA coronal (POAc) and AHA coronal (AHAc), respectively]. AHAh GnRH neurons exhibited tighter burst firing compared with other slice orientations. Although α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) excited GnRH neurons in all preparations, γ-aminobutyric acid (GABA) was excitatory in AHAc and POAc but inhibitory in AHAh slices. GABA(A) receptor postsynaptic currents were the same in AHAh and AHAc slices. Intriguingly, direct activation of GABA(A) or GABA(B) receptors respectively stimulated and inhibited GnRH neurons regardless of slice orientation. Subsequent experiments indicated that net GABA effects were determined by differences in the ratio of GABA(A) and GABA(B) receptor-mediated effects in "long" and "short" dendrites of GnRH neurons in the different slice orientations. These studies document a new brain slice preparation for recording from GnRH neurons with their extensive dendrites/axons and highlight the importance of GnRH neuron orientation relative to the angle of brain slicing in studying these neurons in vitro.

  9. Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

    Directory of Open Access Journals (Sweden)

    Alison E. M. Vickers

    2017-03-01

    Full Text Available Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM, diclofenac (DCF, 1 mM and etomoxir (ETM, 100 μM. Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM and cyclosporin A (CSA, 10 μM, while GSH was affected more than ATP by methimazole (MMI, 500 μM, terbinafine (TBF, 100 μM, and carbamazepine (CBZ 100 μM. Oxidative stress genes were affected by TBF (18%, CBZ, APAP, and ETM (12%–11%, and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%–6%. Apoptosis genes were affected by DCF (14%, while apoptosis plus necrosis were altered by APAP and ETM (15%. Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%, ETM (66%, DCF, TBF, MMI (61%–60%, APAP, CBZ (57%–56%, and DTL (48%. Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%, CBZ and ETM (44%–43%, APAP and DCF (40%–38%, MMI, TBF and CSA (37%–35%. This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

  10. Liver Effects of Clinical Drugs Differentiated in Human Liver Slices.

    Science.gov (United States)

    Vickers, Alison E M; Ulyanov, Anatoly V; Fisher, Robyn L

    2017-03-07

    Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM), diclofenac (DCF, 1 mM) and etomoxir (ETM, 100 μM). Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM) and cyclosporin A (CSA, 10 μM), while GSH was affected more than ATP by methimazole (MMI, 500 μM), terbinafine (TBF, 100 μM), and carbamazepine (CBZ 100 μM). Oxidative stress genes were affected by TBF (18%), CBZ, APAP, and ETM (12%-11%), and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%-6%). Apoptosis genes were affected by DCF (14%), while apoptosis plus necrosis were altered by APAP and ETM (15%). Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%), ETM (66%), DCF, TBF, MMI (61%-60%), APAP, CBZ (57%-56%), and DTL (48%). Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%), CBZ and ETM (44%-43%), APAP and DCF (40%-38%), MMI, TBF and CSA (37%-35%). This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

  11. Organotypic brain slice cultures of adult transgenic P301S mice--a model for tauopathy studies.

    Directory of Open Access Journals (Sweden)

    Agneta Mewes

    Full Text Available BACKGROUND: Organotypic brain slice cultures represent an excellent compromise between single cell cultures and complete animal studies, in this way replacing and reducing the number of animal experiments. Organotypic brain slices are widely applied to model neuronal development and regeneration as well as neuronal pathology concerning stroke, epilepsy and Alzheimer's disease (AD. AD is characterized by two protein alterations, namely tau hyperphosphorylation and excessive amyloid β deposition, both causing microglia and astrocyte activation. Deposits of hyperphosphorylated tau, called neurofibrillary tangles (NFTs, surrounded by activated glia are modeled in transgenic mice, e.g. the tauopathy model P301S. METHODOLOGY/PRINCIPAL FINDINGS: In this study we explore the benefits and limitations of organotypic brain slice cultures made of mature adult transgenic mice as a potential model system for the multifactorial phenotype of AD. First, neonatal (P1 and adult organotypic brain slice cultures from 7- to 10-month-old transgenic P301S mice have been compared with regard to vitality, which was monitored with the lactate dehydrogenase (LDH- and the MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays over 15 days. Neonatal slices displayed a constant high vitality level, while the vitality of adult slice cultures decreased significantly upon cultivation. Various preparation and cultivation conditions were tested to augment the vitality of adult slices and improvements were achieved with a reduced slice thickness, a mild hypothermic cultivation temperature and a cultivation CO(2 concentration of 5%. Furthermore, we present a substantial immunohistochemical characterization analyzing the morphology of neurons, astrocytes and microglia in comparison to neonatal tissue. CONCLUSION/SIGNIFICANCE: Until now only adolescent animals with a maximum age of two months have been used to prepare organotypic brain slices. The current study

  12. Fluorescence imaging of changes in intracellular chloride in living brain slices.

    Science.gov (United States)

    Inglefield, J R; Schwartz-Bloom, R D

    1999-06-01

    In brain slice preparations, chloride movements across the cell membrane of living cells are measured traditionally with 36Cl- tracer methods, Cl--selective microelectrodes, or whole-cell recording using patch clamp analysis. We have developed an alternative, noninvasive technique that uses the fluorescent Cl- ion indicator, 6-methoxy-N-ethylquinolinium iodide (MEQ), to study changes in intracellular Cl- by epifluorescence or UV laser scanning confocal microscopy. In brain slices taken from rodents younger than 22 days of age, excellent cellular loading is achieved with the membrane-permeable form of the dye, dihydro-MEQ. Subsequent intracellular oxidation of dihydro-MEQ to the Cl--sensitive MEQ traps the polar form of the dye inside the neurons. Because MEQ is a single-excitation and single-emission dye, changes in intracellular Cl- concentrations can be calibrated from the Stern-Volmer relationship, determined in separate experiments. Using MEQ as the fluorescent indicator for Cl-, Cl- flux through the gamma-aminobutyric acid (GABA)-gated Cl- channel (GABAA receptor) can be studied by dynamic video imaging and either nonconfocal (epifluorescence) or confocal microscopy in the acute brain slice preparation. Increases in intracellular Cl- quench MEQ fluorescence, thereby reflecting GABAA receptor activation. GABAA receptor functional activity can be measured in discrete cells located in neuroanatomically defined populations within areas such as the neocortex and hippocampus. Changes in intracellular Cl- can also be studied under various conditions such as oxygen/glucose deprivation ("in vitro ischemia") and excitotoxicity. In such cases, changes in cell volume may also occur due to the dependence of cell volume regulation on Na+, K+, and Cl- flux. Because changes in cell volume can affect optical fluorescence measurements, we assess cell volume changes in the brain slice using the fluorescent indicator calcein-AM. Determination of changes in MEQ fluorescence versus

  13. Automatic brain cropping and atlas slice matching using a PCNN and a generalized invariant Hough transform

    Science.gov (United States)

    Swathanthira Kumar, M. M.; Sullivan, John M., Jr.

    2007-03-01

    Medical research is dominated by animal models, especially rats and mice. Within a species most laboratory subjects exhibit little variation in brain anatomy. This uniformity of features is used to crop regions of interest based upon a known, cropped brain atlas. For any study involving N subjects, image registration or alignment to an atlas is required to construct a composite result. A highly resolved stack of T2 weighted MRI anatomy images of a Sprague-Dawley rat was registered and cropped to a known segmented atlas. This registered MRI volume was used as the reference atlas. A Pulse Coupled Neural Network (PCNN) was used to separate brain tissue from surrounding structures, such as cranium and muscle. Each iteration of the PCNN produces binary images of increasing area as the intensity spectrum is increased. A rapid filtering algorithm is applied that breaks narrow passages connecting larger segmented areas. A Generalized Invariant Hough Transform is applied subsequently to each PCNN segmented area to identify which segmented reference slice it matches. This process is repeated for multiple slices within each subject. Since we have apriori knowledge of the image ordering and fields of view this information provides initial estimates for subsequent registration codes. This process of subject slice extraction to PCNN mask creations and GIHT matching with known atlas locations is fully automatic.

  14. Effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

    We have studied the action of deltamethrin on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice. Deltamethrin depolarized the hypoglossal motoneurons, increased the background synaptic noise and reduced the frequency and amplitude of current elicited action...

  15. A Unified Approach to Diffusion Direction Sensitive Slice Registration and 3-D DTI Reconstruction From Moving Fetal Brain Anatomy

    DEFF Research Database (Denmark)

    Hansen, Mads Fogtmann; Seshamani, Sharmishtaa; Kroenke, Christopher

    2014-01-01

    This paper presents an approach to 3-D diffusion tensor image (DTI) reconstruction from multi-slice diffusion weighted (DW) magnetic resonance imaging acquisitions of the moving fetal brain. Motion scatters the slice measurements in the spatial and spherical diffusion domain with respect...... to the underlying anatomy. Previous image registration techniques have been described to estimate the between slice fetal head motion, allowing the reconstruction of 3D a diffusion estimate on a regular grid using interpolation. We propose Approach to Unified Diffusion Sensitive Slice Alignment and Reconstruction...... (AUDiSSAR) that explicitly formulates a process for diffusion direction sensitive DW-slice-to-DTI-volume alignment. This also incorporates image resolution modeling to iteratively deconvolve the effects of the imaging point spread function using the multiple views provided by thick slices acquired...

  16. Parkia biglobosa Improves Mitochondrial Functioning and Protects against Neurotoxic Agents in Rat Brain Hippocampal Slices

    Directory of Open Access Journals (Sweden)

    Kayode Komolafe

    2014-01-01

    Full Text Available Objective. Methanolic leaf extracts of Parkia biglobosa, PBE, and one of its major polyphenolic constituents, catechin, were investigated for their protective effects against neurotoxicity induced by different agents on rat brain hippocampal slices and isolated mitochondria. Methods. Hippocampal slices were preincubated with PBE (25, 50, 100, or 200 µg/mL or catechin (1, 5, or 10 µg/mL for 30 min followed by further incubation with 300 µM H2O2, 300 µM SNP, or 200 µM PbCl2 for 1 h. Effects of PBE and catechin on SNP- or CaCl2-induced brain mitochondrial ROS formation and mitochondrial membrane potential (ΔΨm were also determined. Results. PBE and catechin decreased basal ROS generation in slices and blunted the prooxidant effects of neurotoxicants on membrane lipid peroxidation and nonprotein thiol contents. PBE rescued hippocampal cellular viability from SNP damage and caused a significant boost in hippocampus Na+, K+-ATPase activity but with no effect on the acetylcholinesterase activity. Both PBE and catechin also mitigated SNP- or CaCl2-dependent mitochondrial ROS generation. Measurement by safranine fluorescence however showed that the mild depolarization of the ΔΨm by PBE was independent of catechin. Conclusion. The results suggest that the neuroprotective effect of PBE is dependent on its constituent antioxidants and mild mitochondrial depolarization propensity.

  17. Preparation and culture of precision-cut organ slices from human and animal.

    Science.gov (United States)

    Fisher, Robyn L; Vickers, Alison E M

    2013-01-01

    1.Human and animal precision-cut organ slices are being widely used to obtain drug metabolism and toxicity profiles in vitro. These data are then used to predict what might be seen in human patients. The accuracy of this prediction and extrapolation of the findings based on human or animal in vitro systems to the findings that occur in vivo is dependent on both the quality of the tissue itself and the quality of the in vitro system. 2.The quality of human organs used in research is dependent on procurement methods, warm ischaemia time, preservation solutions, cold ischaemia time, and donor-specific factors. It is important to confirm that the organs being used are highly viable and fully functional before using them in scientific studies. 3.The optimal preparation and incubation of organ slices is also essential in maintaining slice viability and function. It is important to prepare the slices in a cold preservation solution, to prepare the slices at a correct thickness, and to incubate the slices in a system where the slice rotates in out of the oxygen atmosphere and medium. 4.Meeting the criteria outlined here will lead to successful organ slice cultures for investigating drug-induced mechanisms and organ-specific toxicity.

  18. Minimum conditions for the induction of cortical spreading depression in brain slices

    Science.gov (United States)

    Tang, Yujie T.; Mendez, Jorge M.; Theriot, Jeremy J.; Sawant, Punam M.; López-Valdés, Héctor E.; Ju, Y. Sungtaek

    2014-01-01

    Cortical spreading depression (CSD) occurs during various forms of brain injury such as stroke, subarachnoid hemorrhage, and brain trauma, but it is also thought to be the mechanism of the migraine aura. It is therefore expected to occur over a range of conditions including the awake behaving state. Yet it is unclear how such a massive depolarization could occur under relatively benign conditions. Using a microfluidic device with focal stimulation capability in a mouse brain slice model, we varied extracellular potassium concentration as well as the area exposed to increased extracellular potassium to determine the minimum conditions necessary to elicit CSD. Importantly, we focused on potassium levels that are physiologically plausible (≤145 mM; the intracellular potassium concentration). We found a strong correlation between the threshold concentration and the slice area exposed to increased extracellular potassium: minimum area of exposure was needed with the highest potassium concentration, while larger areas were needed at lower concentrations. We also found that moderate elevations of extracellular potassium were able to elicit CSD in relatively small estimated tissue volumes that might be activated under noninjury conditions. Our results thus show that CSD may be inducible under the conditions that expected in migraine aura as well as those related to brain trauma. PMID:25122714

  19. Organotypic hippocampal slice cultures for studies of brain damage, neuroprotection and neurorepair

    DEFF Research Database (Denmark)

    Noraberg, Jens; Poulsen, Frantz Rom; Blaabjerg, Morten

    2005-01-01

    ), Alzheimer's disease (AD) and epilepsia. Studies of non-excitotoxic neurotoxic compounds and the experimental use of slice cultures in studies of HIV neurotoxicity, traumatic brain injury (TBI) and neurogenesis are included. For cerebral ischemia, experimental models with oxygen-glucose deprivation (OGD......) and exposure to glutamate receptor agonists (excitotoxins) are reviewed. For epilepsia, focus is on induction of seizures with effects on neuronal loss, axonal sprouting and neurogenesis. For Alzheimer's disease, the review centers on the use of beta-amyloid (Abeta) in different models, while the section...... on repair is focused on neurogenesis and cell migration. The culturing techniques, set-up of models, and analytical tools, including markers for neurodegeneration, like the fluorescent dye propidium iodide (PI), are reviewed and discussed. Comparisons are made between hippocampal slice cultures and other...

  20. Rapid imaging of mammalian brain slices with a compact light sheet fluorescent microscope

    Science.gov (United States)

    Yang, Zhengyi; Haslehurst, Peter; Scott, Suzanne; Emptage, Nigel; Dholakia, Kishan

    2017-02-01

    Light sheet fluorescent microscopy is able to provide high acquisition speed and high contrast images, as well as the low photo-bleaching and photo-damage brought to the sample. Here we describe a compact setup design optimized for applications in neuroscience, in particular fast imaging of sub-neuronal structures in mammalian brain slices. We report this prototype instrument is capable of rapid imaging wide area of the dendritic or axonal arbor of a dye-filled neuron in hippocampal slice. We also show several applications of this compact light sheet fluorescent microscope, to demonstrate that our approach offers a powerful functionality to the neuroscience community that is not achievable with traditional imaging methods.

  1. Histamine H3 receptor-mediated inhibition of noradrenaline release in the human brain.

    Science.gov (United States)

    Schlicker, E; Werthwein, S; Zentner, J

    1999-01-01

    Stimulation-evoked 3H-noradrenaline release in human cerebrocortical slices was inhibited by histamine (in a manner sensitive to clobenpropit) and by imetit, suggesting H3 receptor-mediated inhibition of noradrenaline release in human brain.

  2. Distribution of melatonin receptor in human fetal brain

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

    2001-01-01

    Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

  3. Unstable periodic orbits in human epileptic hippocampal slices.

    Science.gov (United States)

    Pen-Ning Yu; Min-Chi Hsiao; Dong Song; Liu, Charles Y; Heck, Christi N; Millett, David; Berger, Theodore W

    2014-01-01

    Inter-ictal activity is studied in hippocampal slices resected from patients with epilepsy using local field potential recording. Inter-ictal activity in the dentate gyrus (DG) is induced by high-potassium (8 mM), low-magnesium (0.25 mM) aCSF with additional 100 μM 4-aminopyridine(4-AP). The dynamics of the inter-ictal activity is investigated by developing the first return map with inter-pulse intervals. Unstable periodic orbits (UPOs) are detected in the hippocampal slice at the DG area according to both the topological recurrence method and the periodic orbit transform method. Surrogate analysis suggests the presence of UPOs in hippocampal slices from patients with epilepsy. This finding also suggests that inter-ictal activity is a chaotic system and will allow us to apply chaos control techniques to manipulate inter-ictal activity.

  4. Ex-vivo evaluation of gene therapy vectors in human pancreatic (cancer) tissue slices

    Institute of Scientific and Technical Information of China (English)

    Michael A van Geer; Koert FD Kuhlmann; Conny T Bakker; Fibo JW ten Kate; Ronald PJ Oude Elferink; Piter J Bosma

    2009-01-01

    AIM: To culture human pancreatic tissue obtained from small resection specimens as a pre-clinical model for examining virus-host interactions.METHODS: Human pancreatic tissue samples (malignant and normal) were obtained from surgical specimens and processed immediately to tissue slices.Tissue slices were cultured ex vivo for 1-6 d in an incubator using 95% O2. Slices were subsequently analyzed for viability and morphology. In addition the slices were incubated with different viral vectors expressing the repor ter genes GFP or DsRed.Expression of these reporter genes was measured at 72 h after infection.RESULTS: With the Krumdieck tissue slicer, uniform slices could be generated from pancreatic tissue but only upon embedding the tissue in 3% low melting agarose. Immunohistological examination showed the presence of all pancreatic cell types. Pancreatic normal and cancer tissue slices could be cultured for up to 6 d, while retaining viability and a moderate to good morphology. Reporter gene expression indicated that the slices could be infected and transduced efficiently by adenoviral vectors and by adeno associated viral vectors, whereas transduction with lentiviral vectors was limited. For the adenoviral vector, the transduction seemed limited to the peripheral layers of the explants.CONCLUSION: The presented sys tem al lows reproducible processing of minimal amounts of pancreatic tissue into slices uniform in size, suitable for pre-clinical evaluation of gene therapy vectors.

  5. Oligodendrocyte transcription factor 1 mRNA and protein expression in organotypic rat brain slices

    Institute of Scientific and Technical Information of China (English)

    Hong Cui; Lijun Yang; Dezhuang Huang; Wandong Zhang; Weijuan Han; Yanqing Yao; Wenxing Jiang

    2010-01-01

    Numerous studies have confirmed that oligodendrocyte transcription factor 1 (Olig-1) is vital for myelin repair. However, the effects of hypoxia and ischemia on Olig-1 expression remain unknown.In this study, Olig-1 mRNA and protein expressions were analyzed by in situ hybridization and immunohistochemistry, to determine the expression profile of Olig-1 in rat brain slices exposed to hypoxia and ischemia. Brains were obtained from 2-day-old Sprague-Dawley rats, and sections were randomly assigned to control and hypoxia/ischemia groups. Hematoxylin-eosin staining revealed karyorrhexis and karyopyknosis in cells from the hypoxia/ischemia group. Under electron microscopy, mitochondria swelling and neuropil edema were observed in the hypoxia/ischemia group. Olig-1 mRNA and protein expressions were increased at 1 day after hypoxia and ischemia treatment. These results suggest that in situ hybridization and immunohistochemistry could be used simultaneously to detect mRNA and protein expression in brain slices.

  6. Inhibitory effects of matrine on electrical signals and amino acid neurotransmitters in hippocampal brain slices

    Institute of Scientific and Technical Information of China (English)

    Xuping Wang; Jiping Chen; Guizhi Zhao; Dan Shou; Xuezhi Hong; Jianmin Zhang

    2009-01-01

    BACKGROUND: Studies on electrical signals of hippocampal brain slices in vivo have shown that matrine inhibits benzylpenicillin sodium-induced activation of neuronal signal transduction.OBJECTIVE: To verify the inhibition effect of matrine on activation of electrical signals in rat brain slices and the role matrine plays in hippocampal amino acid transmitter release.DESIGN, TIME AND SETTING: The in vitro, neurophysiological, controlled experiment was performed in the Zhejiang Province Key Laboratory of Cardio-cerebrovascular Disease and Nerve System Drugs Appraisement and Chinese Traditional Medicine Screening and Research between July 2003 and May 2004. The in vivo, neuronal, biochemical experiment was performed in the Zhejiang Province Key Laboratory of Chinese Traditional Medicine Quality Standardization from July 2005 to December 2006.MATERIALS: Forty healthy, Sprague Dawley rats, 7-8 weeks old, and 120 healthy, ICR mice, 5-6weeks old, were included in this study, irrespective of gender. Matrine powder was provided by the National Institute for the Control of Pharmaceutical and Biological Products, China. Matrine injection was purchased from Zhuhai Biochemical Pharmaceutical Factory, China. Penicillin was bought from Shijiazhuang Pharmaceutical Group Co., Ltd., China.METHODS: (1) Rats were randomly assigned to four groups: control, penicillin model, and matrine high-dose and low-dose, with 10 rats in each group. The control group was perfused with artificial cerebrospinal fluid, in the remaining three groups, hippocampal brain slices were perfused with normal artificial cerebrospinal fluid containing 1x106 U/L penicillin for the first 10 minutes. The penicillin model group received artificial cerebrospinal fluid for an additional 30 minutes, while the matrine high-dose and low-dose groups received 0.1 g/L and 0.05 g/L matdne, respectively, for an additional 30 minutes. (2) Mice were randomly assigned to four groups (n=30). The matrine high-,medium-, and low

  7. Examining the complex regulation and drug-induced plasticity of dopamine release and uptake using voltammetry in brain slices.

    Science.gov (United States)

    Ferris, Mark J; Calipari, Erin S; Yorgason, Jordan T; Jones, Sara R

    2013-05-15

    Fast scan cyclic voltammetry in brain slices (slice voltammetry) has been used over the last several decades to increase substantially our understanding of the complex local regulation of dopamine release and uptake in the striatum. This technique is routinely used for the study of changes that occur in the dopamine system associated with various disease states and pharmacological treatments, and to study mechanisms of local circuitry regulation of dopamine terminal function. In the context of this Review, we compare the relative advantages of voltammetry using striatal slice preparations versus in vivo preparations, and highlight recent advances in our understanding of dopamine release and uptake in the striatum specifically from studies that use slice voltammetry in drug-naïve animals and animals with a history of psychostimulant self-administration.

  8. Epileptiform synchronization and high-frequency oscillations in brain slices comprising piriform and entorhinal cortices.

    Science.gov (United States)

    Hamidi, S; Lévesque, M; Avoli, M

    2014-12-05

    We employed field potential recordings in extended in vitro brain slices form Sprague-Dawley rats containing the piriform and entorhinal cortices (PC and EC, respectively) to identify the characteristics of epileptiform discharges and concomitant high-frequency oscillations (HFOs, ripples: 80-200Hz, fast ripples: 250-500Hz) during bath application of 4-aminopyridine (4AP, 50μM). Ictal-like discharges occurred in PC and EC either synchronously or independently of each other; synchronous ictal discharges always emerged from a synchronous "fast" interictal background whereas asynchronous ictal discharges were preceded by a "slow" interictal event. In addition, asynchronous ictal discharges had longer duration and interval of occurrence than synchronous ictal discharges, and contained a higher proportion of ripples and fast ripples. Cutting the connections between PC and EC made synchronicity disappear and increased ictal discharges duration in the EC but failed in changing HFO occurrence in both areas. Finally, antagonizing ionotropic glutamatergic receptors abolished ictal activity in all experiments, increased the duration and rate of occurrence of interictal discharges occurring in PC-EC interconnected slices while it did not influence the slow asynchronous interictal discharges in both areas. Our results identify some novel in vitro interactions between olfactory (PC) and limbic (EC) structures that presumably contribute to in vivo ictogenesis as well.

  9. Dibucaine mitigates spreading depolarization in human neocortical slices and prevents acute dendritic injury in the ischemic rodent neocortex.

    Directory of Open Access Journals (Sweden)

    W Christopher Risher

    Full Text Available Spreading depolarizations that occur in patients with malignant stroke, subarachnoid/intracranial hemorrhage, and traumatic brain injury are known to facilitate neuronal damage in metabolically compromised brain tissue. The dramatic failure of brain ion homeostasis caused by propagating spreading depolarizations results in neuronal and astroglial swelling. In essence, swelling is the initial response and a sign of the acute neuronal injury that follows if energy deprivation is maintained. Choosing spreading depolarizations as a target for therapeutic intervention, we have used human brain slices and in vivo real-time two-photon laser scanning microscopy in the mouse neocortex to study potentially useful therapeutics against spreading depolarization-induced injury.We have shown that anoxic or terminal depolarization, a spreading depolarization wave ignited in the ischemic core where neurons cannot repolarize, can be evoked in human slices from pediatric brains during simulated ischemia induced by oxygen/glucose deprivation or by exposure to ouabain. Changes in light transmittance (LT tracked terminal depolarization in time and space. Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. Remarkably, the occurrence of ouabain-induced terminal depolarization was delayed at a concentration of 1 µM that preserves synaptic function. Moreover, in vivo two-photon imaging in the penumbra revealed that, though spreading depolarizations did still occur, spreading depolarization-induced dendritic injury was inhibited by dibucaine administered intravenously at 2.5 mg/kg in a mouse stroke model.Dibucaine mitigated the effects of spreading depolarization at a concentration that could be well-tolerated therapeutically. Hence, dibucaine is a promising candidate to protect the brain from ischemic injury with an approach that does not rely on

  10. Histamine H1 and endothelin ETB receptors mediate phospholipase D stimulation in rat brain hippocampal slices.

    Science.gov (United States)

    Sarri, E; Picatoste, F; Claro, E

    1995-08-01

    Different neurotransmitter receptor agonists [carbachol, serotonin, noradrenaline, histamine, endothelin-1, and trans-(1S,3R)-aminocyclopentyl-1,3-dicarboxylic acid (trans-ACPD)], known as stimuli of phospholipase C in brain tissue, were tested for phospholipase D stimulation in [32P]Pi-prelabeled rat brain cortical and hippocampal slices. The accumulation of [32P]phosphatidylethanol was measured as an index of phospholipase D-catalyzed transphosphatidylation in the presence of ethanol. Among the six neurotransmitter receptor agonists tested, only noradrenaline, histamine, endothelin-1, and trans-ACPD stimulated phospholipase D in hippocampus and cortex, an effect that was strictly dependent of the presence of millimolar extracellular calcium concentrations. The effect of histamine (EC50 18 microM) was inhibited by the H1 receptor antagonist mepyramine with a Ki constant of 0.7 nM and was resistant to H2 and H3 receptor antagonists (ranitidine and tioperamide, respectively). Endothelin-1-stimulated phospholipase D (EC50 44 nM) was not blocked by BQ-123, a specific antagonist of the ETA receptor. Endothelin-3 and the specific ETB receptor agonist safarotoxin 6c were also able to stimulate phospholipase D with efficacies similar to that of endothelin-1, and EC50 values of 16 and 3 nM, respectively. These results show that histamine and endothelin-1 stimulate phospholipase D in rat brain through H1 and ETB receptors, respectively.

  11. Ex-vivo evaluation of gene therapy vectors in human pancreatic (cancer) tissue slices

    NARCIS (Netherlands)

    van Geer, M.A.; Kuhlmann, K.F.D.; Bakker, C.T.; ten Kate, F.J.W.; Oude Elferink, R.P.J.; Bosma, P.J.

    2009-01-01

    AIM: To culture human pancreatic tissue obtained from small resection specimens as a pre-clinical model for examining virus-host interactions. METHODS: Human pancreatic tissue samples (malignant and normal) were obtained from surgical specimens and processed immediately to tissue slices. Tissue slic

  12. Ex-vivo evaluation of gene therapy vectors in human pancreatic (cancer) tissue slices

    NARCIS (Netherlands)

    van Geer, M.A.; Kuhlmann, K.F.D.; Bakker, C.T.; ten Kate, F.J.W.; Oude Elferink, R.P.J.; Bosma, P.J.

    2009-01-01

    AIM: To culture human pancreatic tissue obtained from small resection specimens as a pre-clinical model for examining virus-host interactions. METHODS: Human pancreatic tissue samples (malignant and normal) were obtained from surgical specimens and processed immediately to tissue slices. Tissue slic

  13. Adult human brain cell culture for neuroscience research.

    Science.gov (United States)

    Gibbons, Hannah M; Dragunow, Mike

    2010-06-01

    Studies of the brain have progressed enormously through the use of in vivo and in vitro non-human models. However, it is unlikely such studies alone will unravel the complexities of the human brain and so far no neuroprotective treatment developed in animals has worked in humans. In this review we discuss the use of adult human brain cell culture methods in brain research to unravel the biology of the normal and diseased human brain. The advantages of using adult human brain cells as tools to study human brain function from both historical and future perspectives are discussed. In particular, studies using dissociated cultures of adult human microglia, astrocytes, oligodendrocytes and neurons are described and the applications of these types of study are evaluated. Alternative sources of human brain cells such as adult neural stem cells, induced pluripotent stem cells and slice cultures of adult human brain tissue are also reviewed. These adult human brain cell culture methods could benefit basic research and more importantly, facilitate the translation of basic neuroscience research to the clinic for the treatment of brain disorders. Copyright 2009 Elsevier Ltd. All rights reserved.

  14. A testbed to explore the optimal electrical stimulation parameters for suppressing inter-ictal spikes in human hippocampal slices.

    Science.gov (United States)

    Min-Chi Hsiao; Pen-Ning Yu; Dong Song; Liu, Charles Y; Heck, Christi N; Millett, David; Berger, Theodore W

    2014-01-01

    New interventions using neuromodulatory devices such as vagus nerve stimulation, deep brain stimulation and responsive neurostimulation are available or under study for the treatment of refractory epilepsy. Since the actual mechanisms of the onset and termination of the seizure are still unclear, most researchers or clinicians determine the optimal stimulation parameters through trial-and-error procedures. It is necessary to further explore what types of electrical stimulation parameters (these may include stimulation frequency, amplitude, duration, interval pattern, and location) constitute a set of optimal stimulation paradigms to suppress seizures. In a previous study, we developed an in vitro epilepsy model using hippocampal slices from patients suffering from mesial temporal lobe epilepsy. Using a planar multi-electrode array system, inter-ictal activity from human hippocampal slices was consistently recorded. In this study, we have further transferred this in vitro seizure model to a testbed for exploring the possible neurostimulation paradigms to inhibit inter-ictal spikes. The methodology used to collect the electrophysiological data, the approach to apply different electrical stimulation parameters to the slices are provided in this paper. The results show that this experimental testbed will provide a platform for testing the optimal stimulation parameters of seizure cessation. We expect this testbed will expedite the process for identifying the most effective parameters, and may ultimately be used to guide programming of new stimulating paradigms for neuromodulatory devices.

  15. Mechanistic studies of antibody mediated clearance of tau aggregates using an ex vivo brain slice model

    Directory of Open Access Journals (Sweden)

    Pavan eKrishnamurthy

    2011-10-01

    Full Text Available Recent studies have shown that immunotherapy clears amyloid beta (A plaques and reduces A levels in mouse models of Alzheimer’s disease (AD, as well as in AD patients. Tangle pathology is also relevant for the neurodegeneration in AD, and our studies have shown that active immunization with an AD related phospho-tau peptide reduces aggregated tau within the brain and slows the progression of tauopathy-induced behavioural impairments. Thus, clearance of neurofibrillary tangles and/or their precursors may reduce synaptic and neuronal loss associated with AD and other tauopathies. So far the mechanisms involved in antibody-mediated clearance of tau pathology are yet to be elucidated. In this study we have used a mouse brain slice model to examine the uptake and localization of FITC labeled anti-tau antibodies. Confocal microscopy analysis showed that the FITC labelled anti-tau antibody co-stained with phosphorylated tau, had a perinuclear appearance and co-localised with markers of the endosomal/lysosomal pathway. Additionally, tau and FITC IgG were found together in an enriched lysosome fraction. In summary, antibody-mediated clearance of intracellular tau aggregates appears to occur via the lysosomal pathway.

  16. Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model

    Institute of Scientific and Technical Information of China (English)

    Sylvie; Lagaye; Sonia; Brun; Jesintha; Gaston; Hong; Shen; Ruzena; Stranska; Claire; Camus; Clarisse; Dubray; Géraldine; Rousseau; Pierre-Philippe; Massault; Jer?me; Courcambeck; Firas; Bassisi; Philippe; Halfon; Stanislas; Pol

    2016-01-01

    AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices(2.7 × 106 cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant(multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription- polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dosedependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect(compared to hydroxychloroquine EC50 = 1.17 μmol/L).CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dosedependent manner without cytotoxic effect.

  17. Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis

    NARCIS (Netherlands)

    Stribos, Elisabeth G D; Luangmonkong, Theerut; Leliveld, Anna M.; de Jong, Igle J; van Son, Willem J; Hillebrands, Jan-Luuk; Seelen, Marc A.; van Goor, Harry; Olinga, Peter; Mutsaers, Henricus A M

    Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue

  18. Organotypic slice cultures from rat brain tissue: a new approach for Naegleria fowleri CNS infection in vitro.

    Science.gov (United States)

    Gianinazzi, C; Schild, M; Müller, N; Leib, S L; Simon, F; Nuñez, S; Joss, P; Gottstein, B

    2005-12-01

    The free-living amoeba Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis (PAM), a disease leading to death in the vast majority of cases. In patients suffering from PAM, and in corresponding animal models, the brain undergoes a massive inflammatory response, followed by haemorrhage and severe tissue necrosis. Both, in vivo and in vitro models are currently being used to study PAM infection. However, animal models may pose ethical issues, are dependent upon availability of specific infrastructural facilities, and are time-consuming and costly. Conversely, cell cultures lack the complex organ-specific morphology found in vivo, and thus, findings obtained in vitro do not necessarily reflect the situation in vivo. The present study reports infection of organotypic slice cultures from rat brain with N. fowleri and compares the findings in this culture system with in vivo infection in a rat model of PAM, that proved complementary to that of mice. We found that brain morphology, as present in vivo, is well retained in organotypic slice cultures, and that infection time-course including tissue damage parallels the observations in vivo in the rat. Therefore, organotypic slice cultures from rat brain offer a new in vitro approach to study N. fowleri infection in the context of PAM.

  19. Inhibitory effect of morphine on excitatory synaptic transmission via presynaptic mechanism in rat SON neurons in brain slices

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-bin; HU San-jue; JU Gong

    2001-01-01

    To observe the effects of morphine on the excitatory postsynaptic currents (EPSCs) and miniature EPSCs (mEPSCs) in rat supraoptic nucleus (SON) neurons and to explore its synaptic mechanism. Methods: Using whole-cell voltage-clamp recording technique in the brain slices, the EPSCS and mEPSCs of rat SON neurons were recorded, respectively. Results: Morphine (20 μmol/L) decreased the frequency of EPSCs and mEPSCs (by 65% for EPSCS and by 45% for mEPSCs), and reduced the amplitude of EPSCs by 44% in all SON neurons, but the amplitude distribution ofmEPSCs was not affected. Conclusion: Morphine inhibits the excitatory transmissions via presynaptic mechanisms in SON neurons from rat brain slices.

  20. Effects of the blood components on the AMPA and NMDA synaptic responses in brain slices in the onset of hemorrhagic stroke.

    Science.gov (United States)

    Mokrushin, Anatoly A; Pavlinova, Larisa I

    2013-12-01

    Blood-borne events play a major role in post bleeding disturbances of the neuronal network. However, very little is known about the early effects of blood plasma, leucocytes, and the red blood cells on the AMPA and NMDA-mediated synaptic responses in the onset of experimental intracranial hemorrhage (ICH). In this study, we used the technique of on-line monitoring of electrophysiological parameters referred to synaptic activity in piriform cortex of SHR rat slice. We exposed the olfactory cortex slices to diluted autologous blood or its components and compared with effects of ferric chloride. Whole blood exerted a total inhibition of synaptic activity in piriform cortex within first 5 min. Dilution of blood induced prolonged epileptic synaptic activation of NMDA receptors. Blood plasma and fraction of leucocytes induced hyperactivation of neurons transforming to epileptiform discharges. Fraction of red blood cells acted biphasic, an initial sharp activity of AMPA- and NMDA-mediated receptors replaced by a following total depression. Our slice-based models of experimental stroke revealed the mechanism of the earliest pathophysiologic events occur in brain tissue during bleeding that may be relevant to the human ICH.

  1. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine, CA 92612 (United States); Fisher, Robyn L. [Vitron Inc., Tucson, AZ (United States); Vickers, Alison E.M., E-mail: vickers_alison@allergan.com [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine, CA 92612 (United States)

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  2. Biocompatibility of silicon-based arrays of electrodes coupled to organotypic hippocampal brain slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, J; Thiébaud, P

    2001-01-01

    ) rats were grown for 4-8 weeks on the perforated silicon chips with silicon nitride surfaces and 40 microm sized holes and compared with corresponding tissue slices grown on conventional semiporous membranes. In terms of preservation of the basic cellular and connective organization, as visualized...... around the upper recording part of the 47-microm-high platinum-tip electrodes. Slice cultures grown on a separate set of chips with platinum instead of silicon nitride surfaces also displayed normal MAP2 and GFAP immunostaining. The width of the GFAP-rich zone (glia limitans) at the bottom surface...... of the slice cultures was the same ( approximately 20 microm) in cultures grown on chips with silicon nitride and platinum surfaces and on conventional insert membranes. The slice cultures grown on chips maintained a normal, subfield differentiated susceptibility to the glutamate receptor agonist N...

  3. Brain perfusion CT for acute stroke using a 256-slice CT: improvement of diagnostic information by large volume coverage

    Energy Technology Data Exchange (ETDEWEB)

    Dorn, F. [Technical University, Department of Radiology, Klinikum rechts der Isar, Munich (Germany); Institut fuer Radiologie, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Muenchen (Germany); Muenzel, D.; Meier, R.; Rummeny, E.J.; Huber, A. [Technical University, Department of Radiology, Klinikum rechts der Isar, Munich (Germany); Poppert, H. [Technical University, Department of Neurology, Klinikum rechts der Isar, Munich (Germany)

    2011-09-15

    To compare a 256-slice CT with a simulated standard CT for brain CT perfusion (CTP). CTP was obtained in 51 patients using a 256-slice CT (128 detector rows, flying z-focus, 8-cm detector width, 80 kV, 120mAs, 20 measurements, 1 CT image/2.5 s). Signal-to-noise ratios (SNR) were compared in grey and white matter. Perfusion maps were evaluated for cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) in hypoperfused areas and corresponding contralateral regions. Two reconstructed 10-mm slices for simulation of a standard CT (SDCT) were compared with the complete data sets (large-volume CT, LVCT). Adequate image quality was achieved in 50/51 cases. SNR were significantly different in grey and white matter. A perfusion deficit was present in 27 data sets. Differences between the hypoperfusions and the control regions were significant for MTT and CBF, but not for CBV. Three lesions were missed by SDCT but detected by LVCT; 24 lesions were covered incompletely by SDCT, and 6 by LVCT. 21 lesions were detected completely by LVCT, but none by SDCT. CTP imaging of the brain using an increased detector width can detect additional ischaemic lesions and cover most ischaemic lesions completely. (orig.)

  4. Internalization of 125I-human choriogonadotropin in bovine luteal slices. A biochemical study.

    Science.gov (United States)

    Chegini, N; Rao, C V; Carman, F R

    1984-04-01

    Various intracellular organelles as well as outer cell membranes of bovine corpora lutea intrinsically contain gonadotropin receptors (Rao et al., J biol chem 256 (1981) 2628 [5]). In order to investigate whether exogenously added human choriogonadotropin (hCG) can internalize and bind to the intracellular sites, bovine luteal slices that had been carefully checked with respect to structural and functional integrity were incubated with 0.1 nM 125I-hCG. Following incubation, specific radioactivity was found to be associated with various intracellular organelles, but not with cytosol. The order of radioactivity uptake by subcellular organelles following a 2-h incubation was: Golgi medium greater than Golgi heavy greater than Golgi light greater than plasma membranes = rough endoplasmic reticulum greater than mitochondria-lysosomes- greater than nuclei. The 5'-nucleotidase activity and electron microscopic examination of the fractions revealed that the presence of radioactivity in the intracellular organelles cannot be attributed solely to plasma membrane contamination. The internalization and intracellular binding of 125I-hCG was time and temperature-dependent. Only excess unlabeled hCG and hLH (but not hCG subunits, FSH and PRL) competed with 125I-hCG for internalization in luteal slices. Very little or no 125I-hCG added was internalized in liver or kidney slices; luteal, liver and kidney slices accumulated neither 125I-BSA nor 125I. The radioactivity eluted from various luteal subcellular organelles was able to rebind to fresh corresponding organelles and came off Sepharose 6B columns in a position corresponding to native 125I-hCG. The gel filtration profile of detergent-solubilized radioactivity revealed that 125I-hCG was macromolecular bound. The degraded and altered 125I-hCG was found in the incubation media.

  5. Excitatory amino acid neurotoxicity and modulation of glutamate receptor expression in organotypic brain slice cultures

    DEFF Research Database (Denmark)

    Zimmer, J; Kristensen, Bjarne Winther; Jakobsen, B

    2000-01-01

    Using organotypic slice cultures of hippocampus and cortex-striatum from newborn to 7 day old rats, we are currently studying the excitotoxic effects of kainic acid (KA), AMPA and NMDA and the neuroprotective effects of glutamate receptor blockers, like NBQX. For detection and quantitation of the...

  6. Educating the Human Brain. Human Brain Development Series

    Science.gov (United States)

    Posner, Michael I.; Rothbart, Mary K.

    2006-01-01

    "Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

  7. Educating the Human Brain. Human Brain Development Series

    Science.gov (United States)

    Posner, Michael I.; Rothbart, Mary K.

    2006-01-01

    "Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

  8. Protective effect of bone marrow-derived mesenchymal stem cells on dopaminergic neurons against 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in rat brain slices

    Institute of Scientific and Technical Information of China (English)

    Lirong Jin; Zhen Hong; Chunjiu Zhong; Yang Wang

    2009-01-01

    BACKGROUND: To date, the use of bone marrow-derived mesenchymal stem cells (MSCs) for the treatment of Parkinson's disease have solely focused on in vivo animal models. Because of the number of influencing factors, it has been difficult to determine a consistent outcome. OBJECTIVE: To establish an injury model in brain slices of substantia nigra and striatum using 1-methyl-4-phenylpytidinium ion (MPP+), and to investigate the effect of MSCs on dopaminergic neurons following MPP+ induced damage.DESIGN, TIME AND SETTING: An in vitro, randomized, controlled, animal experiment using immunohistochemistry was performed at the Laboratory of the Department of Anatomy, Fudan University between January 2004 and December 2006.MATERIALS: Primary MSC cultures were obtained from femurs and tibias of adult Sprague Dawley rats. Organotypic brain slices were isolated from substantia nigra and striatum of 1-day-old Sprague Dawley rat pups. Monoclonal antibodies for tyrosine hydroxylase (TH, 1:5 000) were from Santa Cruz (USA); goat anti-rabbit IgG antibodies labeled with FITC were from Boster Company (China).METHODS: Organotypic brain slices were cultured for 5 days in whole culture medium supplemented with 50% DMEM, 25% equine serum, and 25% Tyrode's balanced salt solution. The medium was supplemented with 5 μg/mL Ara-C, and the culture was continued for an additional 5 days. The undergrowth of brain slices was discarded at day 10. Eugonic brain slices were cultured with basal media for an additional 7 days. The brain slices were divided into three groups: control, MPP+ exposure, and co-culture. For the MPP+ group, MPP+ (30 μmol/L) was added to the media at day 17 and brain slices were cultured for 4 days, followed by control media. For the co-culture group, the MPP+ injured brain slices were placed over MSCs in the well and were further cultured for 7 days.MAIN OUTCOME MEASURES: After 28 days in culture, neurite outgrowth was examined in the brain slices under phase

  9. Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

    Science.gov (United States)

    Hansen, Suzanne L; Sterjev, Zoran; Werngreen, Marie; Simonsen, Bodil J; Knudsen, Katrine E; Nielsen, Ane H; Pedersen, Mikael E; Badolo, Lassiana; Kristiansen, Uffe; Vestergaard, Henrik T

    2012-05-05

    The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been reported to lack effect in this model. The neuroplastic changes induced in acute and chronic animal models of epilepsy are known to affect the pharmacological profile of AEDs in vivo. Hence, we investigated whether brain slices from pentylenetetrazole (PTZ)-kindled animals could provide a more predictive screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline-injected and PTZ-kindled mice. Our data suggest that the use of slices from PTZ-kindled mice in the cortical wedge does not increase the predictive validity of the model as an in vitro screening model for AEDs. Traditionally, the incidence of certain seizure types is widely used as a measure to characterize drug action in animal models of epilepsy. In our study, the anticonvulsant effect of the AEDs was investigated in vivo using several observational parameters (i.e., incidence and duration of convulsions, latency to clonic convulsions, and severity of convulsions). We found that including the observational parameter "severity" offered important additional information about the drug profile that would otherwise be lost if only a single parameter as "incidence" was used.

  10. Normobaric hyperoxia stimulates superoxide and nitric oxide production in the caudal solitary complex of rat brain slices.

    Science.gov (United States)

    Ciarlone, Geoffrey E; Dean, Jay B

    2016-12-01

    Central CO2-chemosensitive neurons in the caudal solitary complex (cSC) are stimulated not only by hypercapnic acidosis, but by hyperoxia as well. While a cellular mechanism for the CO2 response has yet to be isolated, previous data show that a redox-sensitive mechanism underlies neuronal excitability to hyperoxia. However, it remains unknown how changes in Po2 affect the production of reactive oxygen and nitrogen species (RONS) in the cSC that can lead to increased cellular excitability and, with larger doses, to cellular dysfunction and death. To this end, we used fluorescence microscopy in real time to determine how normobaric hyperoxia increases the production of key RONS in the cSC. Because neurons in the region are CO2 sensitive, we also examined the potential effects of CO2 narcosis, used during euthanasia before brain slice harvesting, on RONS production. Our findings show that normobaric hyperoxia (0.4 → 0.95 atmospheres absolute O2) increases the fluorescence rates of fluorogenic dyes specific to both superoxide and nitric oxide. Interestingly, different results were seen for superoxide fluorescence when CO2 narcosis was used during euthanasia, suggesting long-lasting changes in superoxide production and/or antioxidant activity subsequent to CO2 narcosis before brain slicing. Further research needs to distinguish whether the increased levels of RONS reported here are merely increases in oxidative and nitrosative signaling or, alternatively, evidence of redox and nitrosative stress.

  11. A combined long-term recording system for single-unit activity and neurotransmitter efflux of a brain slice

    Science.gov (United States)

    Sheu, Y. H.; Young, M. S.

    1998-04-01

    A combined long-term measurement and recording system for neurotransmission research of brain slices is presented in this study. This system, based on the IBM PC or compatible computer, is capable of simultaneously measuring and recording both single-unit neural electropotential signals and the electrochemical signals of neurotransmitter efflux from the same neuron in a brain slice for long periods of time (time limited largely by hard disk capacity, 100 h or more not being unreasonable with contemporary hardware) using a single carbon microelectrode for both measurements. The combined long-term recording system uses a simple switching circuit to switch periodically the single microelectrode between two data acquisition subsystems, one for electrochemical data and one for electrophysiological data. The simple switching circuit separates the electrophysiological signals and electrochemical signals, overcoming the traditional interference problem caused by the two different measuring techniques. Software designed for the proposed system allows easy reconstruction of the full time course of the compressed measured data and easy, simultaneous display of both types of signals on the same time scale. On-line and recorded displays are available. Test results of a practical implementation of the proposed system verify that the combined long-term recording system meets actual requirements for electrophysiological and neurochemical research.

  12. Conductor compounds of phenylpentane in Mycoleptodonoides aitchisonii mycelium enhance the release of dopamine from rat brain striatum slices.

    Science.gov (United States)

    Okuyama, Satoshi; Sawasaki, Emi; Yokogoshi, Hidehiko

    2004-04-01

    Monoterpene compound is a major component of essential oils in various aromatic species. Previous reports about the monoterpene compound linalool and its effect on the brain neurotransmitters glutamic acid, GABA and acetylcholine, but not catecholamines, have been reported. In this study, we investigated the effect of linalool or conductor compounds of phenylpentane, including 1-phenyl-3-pentanol and 1-phenyl-3-pentanone, on dopamine release using rat striatal slices. The edible mushroom Mycoleptodonoides aitchisonii belongs to the Climacodontaceae family, and its cultivate medium or mycelium contains derivatives of the fragrant conductor compound, phenylpentane. Compared to basal levels, 2.5 microg linalool increased dopamine from striatal slices 3-fold. A 4-fold increase in dopamine release resulted from 2.5 microg 1-phenyl-3-pentanol administration, while a half dose of this compound induced a 2.5-fold increase. A greater than 2-fold increase resulted with 2.5 microg 1-phenyl-3-pentanone. These data indicate that striatum has sensitivity for these fragrant compounds and different releasing effects result with differ structures. These actions may affect other neurotransmitters and influence brain function.

  13. Human Brain and Its Size

    Institute of Scientific and Technical Information of China (English)

    邹国如

    2006-01-01

    @@ Two studies suggest that the human brain continues to change through the process of evolution.The findings conflict with a common belief that the brain has evolved about as much as it ever will.Scientists say modern humans developed about two hundred thousand years ago.Bruce Lahn of the Howard Hughes Medical Institute and the University of Chicago led the studies.The findings appeared in Science magazine.

  14. Hyperexcitability in combined entorhinal/hippocampal slices of adult rat after exposure to brain-derived neurotrophic factor.

    Science.gov (United States)

    Scharfman, H E

    1997-08-01

    Effects of brain-derived neurotrophic factor (BDNF) in area CA3, the dentate gyrus, and medial entorhinal cortex were examined electrophysiologically by bath application of BDNF in slices containing the hippocampus and entorhinal cortex. Bath application of 25-100 ng/ml BDNF for 30-90 min increased responses to single afferent stimuli in selective pathways in the majority of slices. In area CA3, responses to mossy fiber stimulation increased in 73% of slices and entorhinal cortex responses to white matter stimulation increased in 64% of slices. After exposure to BDNF, these areas also demonstrated evidence of hyperexcitability, because responses to repetitive stimulation (1-Hz paired pulses for several s) produced multiple population spikes in response to mossy fiber stimulation in CA3 or multiple field potentials in response to white matter stimulation in the entorhinal cortex. Repetitive field potentials persisted after repetitive stimulation ended and usually were followed by spreading depression. Enhancement of responses to single stimuli and hyperexcitability were never evoked in untreated slices or after bath application of boiled BDNF or cytochrome C. The tyrosine kinase antagonist K252a (2 microM) blocked the effects of BDNF. In area CA3, both the potentiation of responses to single stimuli and hyperexcitability showed afferent specificity, because responses to mossy fiber stimulation were affected but responses to fimbria or Schaffer collateral stimulation were not. In addition, regional specificity was demonstrated in that the dentate gyrus was much less affected. The effects of BDNF in area CA3 were similar to those produced by bath application of low doses of kainic acid, which is thought to modulate glutamate release from mossy fiber terminals by a presynaptic action. These results suggest that BDNF has acute effects on excitability in different areas of the hippocampal-entorhinal circuit. These effects appear to be greatest in areas that are highly

  15. Comparison of bNOS and chat immunohistochemistry in the laterodorsal tegmentum (LDT) and the pedunculopontine tegmentum (PPT) of the mouse from brain slices prepared for electrophysiology

    DEFF Research Database (Denmark)

    Veleanu, Maxime; Axen, Tina E; Kristensen, Morten P

    2016-01-01

    maintains that antibody staining for enzymes involved in synthesis or transport, of acetylcholine would be a more definitive marker and hence, preferable. NEW METHOD: Colocalization of bNOS and CHAT in the LDT/PPT, and presence of parvalbumin (PV), was examined in non-ideally prepared mouse brain slices......BACKGROUND: Identification of cell phenotype from brain slices upon which in vitro electrophysiological recordings have been performed often relies on conducting post hoc immunohistochemistry on tissue that necessarily has not been ideally prepared for immunohistochemical procedures...

  16. Human precision-cut liver slices as a model to test antifibrotic drugs in the early onset of liver fibrosis

    NARCIS (Netherlands)

    Westra, Inge M.; Mutsaers, Henricus A. M.; Luangmonkong, Theerut; Hadi, Mackenzie; Oosterhuis, Dorenda; de Jong, Koert P.; Groothuis, Geny M. M.; Olinga, Peter

    2016-01-01

    Liver fibrosis is the progressive accumulation of connective tissue ultimately resulting in loss of organ function. Currently, no effective antifibrotics are available due to a lack of reliable human models. Here we investigated the fibrotic process in human precision-cut liver slices (PCLS) and stu

  17. S100b Counteracts Neurodegeneration of Rat Cholinergic Neurons in Brain Slices after Oxygen-Glucose Deprivation

    Directory of Open Access Journals (Sweden)

    Daniela Serbinek

    2010-01-01

    Full Text Available Alzheimer's disease is a severe chronic neurodegenerative disorder characterized by beta-amyloid plaques, tau pathology, cerebrovascular damage, inflammation, reactive gliosis, and cell death of cholinergic neurons. The aim of the present study is to test whether the glia-derived molecule S100b can counteract neurodegeneration of cholinergic neurons after oxygen-glucose deprivation (OGD in organotypic brain slices of basal nucleus of Meynert. Our data showed that 3 days of OGD induced a marked decrease of cholinergic neurons (60% of control, which could be counteracted by 50 μg/mL recombinant S100b. The effect was dose and time dependent. Application of nerve growth factor or fibroblast growth factor-2 was less protective. C-fos-like immunoreactivity was enhanced 3 hours after OGD indicating metabolic stress. We conclude that S100b is a potent neuroprotective factor for cholinergic neurons during ischemic events.

  18. Neuroprotection afforded by diazepam against oxygen/glucose deprivation-induced injury in rat cortical brain slices.

    Science.gov (United States)

    Ricci, Lorenzo; Valoti, Massimo; Sgaragli, Giampietro; Frosini, Maria

    2007-04-30

    The aim of the present investigation was to assess neuroprotection exerted by diazepam (0.1-25 microM) in rat cortical brain slices subjected to oxygen-glucose deprivation and reoxygenation. Neuronal injury and neuroprotection were assessed by measuring the release of glutamate and lactate dehydrogenase and tissue water content. Results demonstrate that diazepam exerted neuroprotective effects according to a "U-shaped", hormetic-like, concentration-response curve, with an efficacy window of 0.5-5 microM concentration. Flumazenil (20 microM) fully antagonised neuroprotection afforded by 5 microM diazepam. In conclusion, the hormetic response of diazepam should be taken into consideration when designing experiments aimed at assessing diazepam neuroprotection against ischemia/reoxygenation injury.

  19. Depolarizing and calcium-mobilizing stimuli fail to enhance synthesis and release of endocannabinoids from rat brain cerebral cortex slices.

    Science.gov (United States)

    Sarmad, Sarir; Alexander, Stephen P H; Barrett, David A; Marsden, Charles A; Kendall, David A

    2011-05-01

    The concentrations of the endocannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonylethanolamine (anandamide) were examined in rat brain cerebral cortex slices and surrounding medium. Basal concentrations of endocannabinoids were similar to those identified previously in rat brain, with anandamide content being much lower (19 pmol/g) than that of 2-AG (7300 pmol/g). In contrast, basal concentrations in the surrounding medium were proportionally much lower for 2-arachidonoylglycerol (16 pmol/mL) compared to anandamide (0.6 pmol/mL). Incubation of slices with glutamate receptor agonists, depolarizing concentrations of KCl, or ionomycin failed to alter tissue concentrations of endocannabinoids, while endocannabinoids in the medium were unaltered by elevated KCl. Cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester, an inhibitor of fatty acid amide hydrolase, significantly enhanced tissue concentrations of anandamide (and related N-acylethanolamines), without altering 2-AG, while evoking proportional elevations of anandamide in the medium. Removal of extracellular calcium ions failed to alter tissue concentrations of anandamide, but significantly reduced 2-AG in the tissue by 90% and levels in the medium to below the detection limit. Supplementation of the medium with 50 μM N-oleoylethanolamine only raised tissue concentrations of N-oleoylethanolamine in the presence of cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester and failed to alter either tissue or medium anandamide or 2-AG concentrations. These results highlight the ongoing turnover of endocannabinoids, and the importance of calcium ions in maintaining 2-AG concentrations in this tissue.

  20. A LED-based method for monitoring NAD(P)H and FAD fluorescence in cell cultures and brain slices.

    Science.gov (United States)

    Rösner, Jörg; Liotta, Agustin; Schmitz, Dietmar; Heinemann, Uwe; Kovács, Richard

    2013-01-30

    Nicotinamide- and flavine-adenine-dinucleotides (NAD(P)H and FADH₂) are electron carriers involved in cellular energy metabolism and in a multitude of enzymatic processes. As reduced NAD(P)H and oxidised FAD molecules are fluorescent, changes in tissue auto-fluorescence provide valuable information on the cellular redox state and energy metabolism. Since fluorescence excitation, by mercury arc lamps (HBO) is inherently coupled to photo-bleaching and photo-toxicity, microfluorimetric monitoring of energy metabolism might benefit from the replacement of HBO lamps by light emitting diodes (LEDs). Here we describe a LED-based custom-built setup for monitoring NAD(P)H and FAD fluorescence at the level of single cells (HEK293) and of brain slices. We compared NAD(P)H bleaching characteristics with two light sources (HBO lamp and LED) as well as sensitivity and signal to noise ratio of three different detector types (multi-pixel photon counter (MPPC), photomultiplier tube (PMT) and photodiode). LED excitation resulted in reduced photo-bleaching at the same fluorescence output in comparison to excitation with the HBO lamp. Transiently increasing LED power resulted in reversible bleaching of NAD(P)H fluorescence. Recovery kinetics were dependent on metabolic substrates indicating coupling of NAD(P)H fluorescence to metabolism. Electrical stimulation of brain slices induced biphasic redox changes, as indicated by NAD(P)H/FAD fluorescence transients. Increasing the gain of PMT and decreasing the LED power resulted in similar sensitivity as obtained with the MPPC and the photodiode, without worsening the signal to noise ratio. In conclusion, replacement of HBO lamp with LED might improve conventional PMT based microfluorimetry of tissue auto-fluorescence.

  1. Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen and glucose deprivation in acute brain slices.

    Science.gov (United States)

    Chazalviel, Laurent; Blatteau, Jean-Eric; Vallée, Nicolas; Risso, Jean-Jacques; Besnard, Stéphane; Abraini, Jacques H

    2016-01-01

    Normobaric oxygen (NBO) and hyperbaric oxygen (HBO) are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO2) = 1 atmospheres absolute (ATA) = 0.1 MPa) and HBO (pO2 = 2.5 ATA = 0.25 MPa) through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support) of the brain parenchyma requires oxygen partial pressure higher than 1 ATA.

  2. Optimizing full-brain coverage in human brain MRI through population distributions of brain size.

    Science.gov (United States)

    Mennes, Maarten; Jenkinson, Mark; Valabregue, Romain; Buitelaar, Jan K; Beckmann, Christian; Smith, Stephen

    2014-09-01

    When defining an MRI protocol, brain researchers need to set multiple interdependent parameters that define repetition time (TR), voxel size, field-of-view (FOV), etc. Typically, researchers aim to image the full brain, making the expected FOV an important parameter to consider. Especially in 2D-EPI sequences, non-wasteful FOV settings are important to achieve the best temporal and spatial resolution. In practice, however, imperfect FOV size estimation often results in partial brain coverage for a significant number of participants per study, or, alternatively, an unnecessarily large voxel-size or number of slices to guarantee full brain coverage. To provide normative FOV guidelines we estimated population distributions of brain size in the x-, y-, and z-direction using data from 14,781 individuals. Our results indicated that 11mm in the z-direction differentiate between obtaining full brain coverage for 90% vs. 99.9% of participants. Importantly, we observed that rotating the FOV to optimally cover the brain, and thus minimize the number of slices needed, effectively reduces the required inferior-superior FOV size by ~5%. For a typical adult imaging study, 99.9% of the population can be imaged with full brain coverage when using an inferior-superior FOV of 142mm, assuming optimal slice orientation and minimal within-scan head motion. By providing population distributions for brain size in the x-, y-, and z-direction we improve the potential for obtaining full brain coverage, especially in 2D-EPI sequences used in most functional and diffusion MRI studies. We further enable optimization of related imaging parameters including the number of slices, TR and total acquisition time.

  3. Cytoprotective effect of hydroxytyrosyl alkyl ether derivatives after oral administration to rats in a model of glucose-oxygen deprivation in brain slices.

    Science.gov (United States)

    Muñoz-Marín, Javier; De La Cruz, José Pedro; Guerrero, Ana; López-Leiva, Inmaculada; López-Villodres, Juan Antonio; Reyes, José Julio; Espartero, José Luis; Madrona, Andrés; Labajos, María Teresa; González-Correa, José Antonio

    2012-08-08

    This study was designed to determine whether the oral administration of hydroxytyrosol (HT) alkyl ether derivatives has a neuroprotective effect in rats. The animals were treated for 7 days with HT or ethyl, butyl, hexyl, octyl, and dodecyl HT ether. A method of in vitro hypoxia-reoxygenation in brain slices was used. Hexyl, octyl, and dodecyl HT derivatives reduced brain cell death (LDH efflux). Lipid peroxidation and nitrite concentrations were inhibited most by hexyl, octyl, and dodecyl derivatives. Concentrations of 3-nitrotyrosine were reduced by HT butyl, hexyl, octyl, and dodecyl ether derivatives. Interleukin-1β was significantly reduced in brain slices from rats treated with all HT ether derivatives. LDH efflux showed a linear correlation with brain concentrations of lipid peroxides, nitrites plus nitrates, and interleukin 1β. The reduction in oxidative and nitrosative stress and decreased production of pro-inflammatory interleukins may be the basis for the observed neuroprotective effects.

  4. Genetic basis of human brain evolution

    OpenAIRE

    Vallender, Eric J.; Mekel-Bobrov, Nitzan; Lahn, Bruce T

    2008-01-01

    Human evolution is characterized by a rapid increase in brain size and complexity. Decades of research have made important strides in identifying anatomical and physiological substrates underlying the unique features of the human brain. By contrast, it has become possible only very recently to examine the genetic basis of human brain evolution. Through comparative genomics, tantalizing insights regarding human brain evolution have emerged. The genetic changes that potentially underlie human b...

  5. GABA, taurine and learning: release of amino acids from slices of chick brain following filial imprinting.

    Science.gov (United States)

    McCabe, B J; Horn, G; Kendrick, K M

    2001-01-01

    The intermediate and medial hyperstriatum ventrale (IMHV) is a forebrain region in the domestic chick that is a site of information storage for the learning process of imprinting. We enquired whether imprinting is associated with learning-related increases in calcium-dependent, potassium-stimulated release of neurotransmitter amino acids from the IMHV. Chicks were hatched and reared in darkness until 15-30 h after hatching. They then either remained in darkness or were trained for 2 h by exposure to an imprinting stimulus. One hour later, the chicks were given a preference test and a preference score was calculated from the results of this test, as a measure of imprinting. Chicks were killed 2 h after training. Slices from the left and right IMHV of trained and untrained chicks were superfused with Krebs' solution either with or without calcium and the superfusate assayed for arginine, aspartate, citrulline, GABA, glutamate, glycine and taurine using high-performance liquid chromatography. For calcium-containing superfusates from the left IMHV, preference score was significantly correlated with potassium-stimulated release of (i) GABA (r=0.51, 23 d.f., P=0.008) and (ii) taurine (r=0.77, 23 d.f., Pimprinting is associated with increases in releasable pools of GABA and taurine and/or membrane excitability in the left IMHV.

  6. Effect of cold and warm ischaemia on drug metabolism in isolated hepatocytes and slices from human and monkey liver

    NARCIS (Netherlands)

    Olinga, Peter; Hof, I.H; de Jager, M.H; de Jong, Kurt; Slooff, M.JH; Meijer, D.K F; Groothuis, Geny; Merema, M.T.

    1998-01-01

    1. The influence of short-term cold storage in University of Wisconsin organ preservation solution (UW) on the ability to metabolize lidocaine, testosterone and 7-ethoxycoumarin in isolated human and cynomolgus monkey (Macaca fascicularis) hepatocytes and liver slices has been investigated. 2. The h

  7. Cytosolic NADH-NAD+ Redox Visualized in Brain Slices by Two-Photon Fluorescence Lifetime Biosensor Imaging

    Science.gov (United States)

    Mongeon, Rebecca; Venkatachalam, Veena

    2016-01-01

    Abstract Aim: Cytosolic NADH-NAD+ redox state is central to cellular metabolism and a valuable indicator of glucose and lactate metabolism in living cells. Here we sought to quantitatively determine NADH-NAD+ redox in live cells and brain tissue using a fluorescence lifetime imaging of the genetically-encoded single-fluorophore biosensor Peredox. Results: We show that Peredox exhibits a substantial change in its fluorescence lifetime over its sensing range of NADH-NAD+ ratio. This allows changes in cytosolic NADH redox to be visualized in living cells using a two-photon scanning microscope with fluorescence lifetime imaging capabilities (2p-FLIM), using time-correlated single photon counting. Innovation: Because the lifetime readout is absolutely calibrated (in nanoseconds) and is independent of sensor concentration, we demonstrate that quantitative assessment of NADH redox is possible using a single fluorophore biosensor. Conclusion: Imaging of the sensor in mouse hippocampal brain slices reveals that astrocytes are typically much more reduced (with higher NADH:NAD+ ratio) than neurons under basal conditions, consistent with the hypothesis that astrocytes are more glycolytic than neurons. Antioxid. Redox Signal. 25, 553–563. PMID:26857245

  8. Direct Visualization of Neurotransmitters in Rat Brain Slices by Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI - MS)

    Science.gov (United States)

    Fernandes, Anna Maria A. P.; Vendramini, Pedro H.; Galaverna, Renan; Schwab, Nicolas V.; Alberici, Luciane C.; Augusti, Rodinei; Castilho, Roger F.; Eberlin, Marcos N.

    2016-12-01

    Mass spectrometry imaging (MSI) of neurotransmitters has so far been mainly performed by matrix-assisted laser desorption/ionization (MALDI) where derivatization reagents, deuterated matrix and/or high resolution, or tandem MS have been applied to circumvent problems with interfering ion peaks from matrix and from isobaric species. We herein describe the application of desorption electrospray ionization mass spectrometry imaging (DESI)-MSI in rat brain coronal and sagittal slices for direct spatial monitoring of neurotransmitters and choline with no need of derivatization reagents and/or deuterated materials. The amino acids γ-aminobutyric (GABA), glutamate, aspartate, serine, as well as acetylcholine, dopamine, and choline were successfully imaged using a commercial DESI source coupled to a hybrid quadrupole-Orbitrap mass spectrometer. The spatial distribution of the analyzed compounds in different brain regions was determined. We conclude that the ambient matrix-free DESI-MSI is suitable for neurotransmitter imaging and could be applied in studies that involve evaluation of imbalances in neurotransmitters levels.

  9. Direct Visualization of Neurotransmitters in Rat Brain Slices by Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI - MS)

    Science.gov (United States)

    Fernandes, Anna Maria A. P.; Vendramini, Pedro H.; Galaverna, Renan; Schwab, Nicolas V.; Alberici, Luciane C.; Augusti, Rodinei; Castilho, Roger F.; Eberlin, Marcos N.

    2016-10-01

    Mass spectrometry imaging (MSI) of neurotransmitters has so far been mainly performed by matrix-assisted laser desorption/ionization (MALDI) where derivatization reagents, deuterated matrix and/or high resolution, or tandem MS have been applied to circumvent problems with interfering ion peaks from matrix and from isobaric species. We herein describe the application of desorption electrospray ionization mass spectrometry imaging (DESI)-MSI in rat brain coronal and sagittal slices for direct spatial monitoring of neurotransmitters and choline with no need of derivatization reagents and/or deuterated materials. The amino acids γ-aminobutyric (GABA), glutamate, aspartate, serine, as well as acetylcholine, dopamine, and choline were successfully imaged using a commercial DESI source coupled to a hybrid quadrupole-Orbitrap mass spectrometer. The spatial distribution of the analyzed compounds in different brain regions was determined. We conclude that the ambient matrix-free DESI-MSI is suitable for neurotransmitter imaging and could be applied in studies that involve evaluation of imbalances in neurotransmitters levels.

  10. A visual thalamocortical slice.

    Science.gov (United States)

    MacLean, Jason N; Fenstermaker, Vivian; Watson, Brendon O; Yuste, Rafael

    2006-02-01

    We describe a thalamocortical slice preparation in which connectivity between the mouse lateral geniculate nucleus (LGN) and primary visual cortex (V1) is preserved. Through DiI injections in fixed brains we traced and created a three-dimensional model of the mouse visual pathways. From this computer model we designed a slice preparation that contains a projection from LGN to V1. We prepared brain slices with these predicted coordinates and demonstrated anatomical LGN-V1 connectivity in these slices after LGN tracer injections. We also revealed functional LGN-V1 connectivity by stimulating LGN electrically and detecting responses in layer 4 of V1 using calcium imaging, field potential recordings and whole-cell recordings. We also identified layer-4 neurons that receive direct thalamocortical input. Finally, we compared cortical activity after LGN stimulation with spontaneous cortical activity and found significant overlap of the spatiotemporal dynamics generated by both types of events.

  11. Expression of hypoxia-inducible factor 1 alpha and oligodendrocyte lineage gene-1 in cultured brain slices after oxygen-glucose deprivation

    Institute of Scientific and Technical Information of China (English)

    Hong Cui; Weijuan Han; Lijun Yang; Yanzhong Chang

    2013-01-01

    Oligodendrocyte lineage gene-1 expressed in oligodendrocytes may trigger the repair of neuronal myelin impairment, and play a crucial role in myelin repair. Hypoxia-inducible factor 1α, a transcription factor, is of great significance in premature infants with hypoxic-ischemic brain damage. There is little evidence of direct regulatory effects of hypoxia-inducible factor 1α on oligodendrocyte lineage gene-1. In this study, brain slices of Sprague-Dawley rats were cultured and subjected to oxygen-glucose deprivation. Then, slices were transfected with hypoxia-inducible factor 1α or oligodendrocyte lineage gene-1. The expression levels of hypoxia-inducible factor 1α and oligodendrocyte lineage gene-1 were significantly up-regulated in rat brains prior to transfection, as detected by immunohistochemical staining. Eight hours after transfection of slices with hypoxia-inducible factor 1α, oligodendrocyte lineage gene-1 expression was upregulated, and reached a peak 24 hours after transfection. Oligodendrocyte lineage gene-1 transfection induced no significant differences in hypoxia-inducible factor 1α levels in rat brain tissues with oxygen-glucose deprivation. These experimental findings indicate that hypoxia-inducible factor 1α can regulate oligodendrocyte lineage gene-1 expression in hypoxic brain tissue, thus repairing the neural impairment.

  12. Presynaptically mediated effects of cholecystokinin-8 on the excitability of area postrema neurons in rat brain slices.

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    Sugeta, Shingo; Hirai, Yoshiyuki; Maezawa, Hitoshi; Inoue, Nobuo; Yamazaki, Yutaka; Funahashi, Makoto

    2015-08-27

    Cholecystokinin (CCK) is a well-known gut hormone that shows anorexigenic effects via action at peripheral and central receptors. CCK is also widely distributed throughout the mammalian brain and appears to function as a neurotransmitter and neuromodulator. The area postrema is one of the circumventricular organs, located on the dorsal surface of the medulla oblongata at the caudal end of the fourth ventricle. Blood vessels in the area postrema lack a blood brain barrier, offering specific central neural elements unique access to circulating substances. Immunohistochemical studies show CCK-A receptors in the area postrema, and we reported CCK-sensitive area postrema neurons. However, the receptive mechanism of CCK in area postrema neurons still remains unexplained. We investigated the responses of area postrema neurons to agonists and antagonists of CCK receptors using whole cell and perforated patch-clamp recordings in rat brain slices. The application of CCK-8 elicited excitatory responses, such as increases in the frequency of mEPSCs (miniature excitatory postsynaptic currents), a shift toward larger amplitude mEPSCs, and increases in the frequency of action potentials. These changes were found mostly in cells not displaying the hyperpolarization-activated cation current (Ih), except for small excitatory changes in a minority of Ih-positive neurons. Tonic inward currents or an inhibitory response to CCK-8 were never seen. Analysis of the amplitude of mEPSCs before and after the administration of CCK-8 indicated the responses mediated via the presynaptic receptors. The effect of CCK-8 was abolished in the presence of CNQX (AMPA type glutamate receptor antagonist). In the presence of lorglumide (a selective CCK-A receptor antagonist), CCK-8-induced excitatory responses were inhibited. No cells responded to the administration of non-sulfated CCK-8 (CCK-8NS, a selective CCK-B receptor agonist). We conclude that CCK-8 exerts its action via presynaptic CCK-A receptors

  13. Microglial Kv1.3 Channels and P2Y12 Receptors Differentially Regulate Cytokine and Chemokine Release from Brain Slices of Young Adult and Aged Mice.

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    Nicoletta Charolidi

    Full Text Available Brain tissue damage following stroke or traumatic brain injury is accompanied by neuroinflammatory processes, while microglia play a central role in causing and regulating neuroinflammation via production of proinflammatory substances, including cytokines and chemokines. Here, we used brain slices, an established in situ brain injury model, from young adult and aged mice to investigate cytokine and chemokine production with particular focus on the role of microglia. Twenty four hours after slice preparation, higher concentrations of proinflammatory cytokines, i.e. TNF-α and IL-6, and chemokines, i.e. CCL2 and CXCL1, were released from brain slices of aged mice than from slices of young adult mice. However, maximal microglial stimulation with LPS for 24 h did not reveal age-dependent differences in the amounts of released cytokines and chemokines. Mechanisms underlying microglial cytokine and chemokine production appear to be similar in young adult and aged mice. Inhibition of microglial Kv1.3 channels with margatoxin reduced release of IL-6, but not release of CCL2 and CXCL1. In contrast, blockade of microglial P2Y12 receptors with PSB0739 inhibited release of CCL2 and CXCL1, whereas release of IL-6 remained unaffected. Cytokine and chemokine production was not reduced by inhibitors of Kir2.1 K+ channels or adenosine receptors. In summary, our data suggest that brain tissue damage-induced production of cytokines and chemokines is age-dependent, and differentially regulated by microglial Kv1.3 channels and P2Y12 receptors.

  14. A brain slice culture model for studies of endogenous and exogenous precursor cell migration in the rostral migratory stream

    DEFF Research Database (Denmark)

    Tanvig, Mette; Blaabjerg, Morten; Andersen, Rikke K

    2009-01-01

    The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone (SVZ) cells reach the olfactory bulb (OB) in rodents. This migration has been well studied in vivo, but an organotypic in vitro model would facilitate more experimental investigations. Here we introduce...... a slice culture preparation of the rat forebrain including en suite the rostral part of the lateral ventricle, the RMS and the OB. The preparation was validated with regard to endogenous cell proliferation and migration by tracking bromodeoxyuridine (BrdU)-labelled cells in newly established and 3 and 6...... week old cultures. For testing the migratory abilities of exogenous precursor cells, rat SVZ neurospheres and human neural (HNS1 cells) and mesenchymal (hMSC-TERT) stem cell lines were micrografted to the rostral SVZ of 1 and 7 day old cultures. Two weeks later graft derivatives were identified...

  15. Muscarinic acetylcholine receptor-mediated effects in slices from human epileptogenic cortex.

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    Gigout, S; Wierschke, S; Lehmann, T-N; Horn, P; Dehnicke, C; Deisz, R A

    2012-10-25

    Acetylcholine has been implicated in higher cortical functions such as learning, memory and cognition, yet the cellular effects of muscarinic acetylcholine receptor (mAChR) activation are poorly understood in the human cortex. Here we investigated the effect of the mAChR agonist carbachol (CCh) and various mAChR antagonists in human cortical slices (from tissue removed during neurosurgical treatment of epilepsy) by intracellular and extracellular recordings. CCh increased neuronal firing, which was antagonised by atropine (non-selective mAChR antagonist) and pirenzepine (M(1)/M(4) mAChRs antagonist) when applied before or after CCh application. AF-DX 116 (M(2)/M(4) mAChRs antagonist) had no effect on CCh-induced increase of firing. CCh also reduced evoked excitatory postsynaptic potentials (EPSP), and the CCh-induced depression of EPSP was fully reversed by atropine. Pirenzepine reversed the depression of CCh on EPSP, but failed to prevent the depression when applied before CCh. AF-DX 116 prevented the CCh-induced depression of evoked EPSP when applied before CCh. CCh also depressed GABAergic transmission and this effect was antagonised by AF-DX 116. Xanomeline (M(1)/M(4) mAChR agonist) increased neuronal firing and decreased EPSP, but had no effect on GABAergic transmission. Reduction (with linopirdine) and enhancement (with retigabine) of the M-current (mediated by K(V)7 channels), increased and decreased neuronal firing, respectively, but had marginal effects on the evoked EPSP. Our results indicate that three pharmacologically distinct mAChRs modulate neuronal firing, glutamatergic and GABAergic transmissions in the human epileptogenic neocortex. The data are discussed towards possible implications of altered mAChR signalling in hyperexcitability and cognitive functions in the human neocortex. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Thin slice three dimentional (3D reconstruction versus CT 3D reconstruction of human breast cancer

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    Yi Zhang

    2013-01-01

    Full Text Available Background & objectives: With improvement in the early diagnosis of breast cancer, breast conserving therapy (BCT is being increasingly used. Precise preoperative evaluation of the incision margin is, therefore, very important. Utilizing three dimentional (3D images in a preoperative evaluation for breast conserving surgery has considerable significance, but the currently 3D CT scan reconstruction commonly used has problems in accurately displaying breast cancer. Thin slice 3D reconstruction is also widely used now to delineate organs and tissues of breast cancers. This study was aimed to compare 3D CT with thin slice 3D reconstruction in breast cancer patients to find a better technique for accurate evaluation of breast cancer. Methods: A total of 16-slice spiral CT scans and 3D reconstructions were performed on 15 breast cancer patients. All patients had been treated with modified radical mastectomy; 2D and 3D images of breast and tumours were obtained. The specimens were fixed and sliced at 2 mm thickness to obtain serial thin slice images, and reconstructed using 3D DOCTOR software to gain 3D images. Results: Compared with 2D CT images, thin slice images showed more clearly the morphological characteristics of tumour, breast tissues and the margins of different tissues in each slice. After 3D reconstruction, the tumour shapes obtained by the two reconstruction methods were basically the same, but the thin slice 3D reconstruction showed the tumour margins more clearly. Interpretation & conclusions: Compared with 3D CT reconstruction, thin slice 3D reconstruction of breast tumour gave clearer images, which could provide guidance for the observation and application of CT 3D reconstructed images and contribute to the accurate evaluation of tumours using CT imaging technology.

  17. Ethyl-eicosapentaenoate modulates changes in neurochemistry and brain lipids induced by parkinsonian neurotoxin 1-methyl-4-phenylpyridinium in mouse brain slices.

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    Meng, QingJia; Luchtman, Dirk W; El Bahh, Bouchaib; Zidichouski, Jeffrey A; Yang, Jun; Song, Cai

    2010-12-15

    Evidence suggests a link between Parkinson's disease and the dietary intake of omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs). Presently, we investigated whether an acute dose of parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) affects brain n-3 and n-6 PUFA content and expression of fatty acid metabolic enzymes cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2) in brain slices from C57Bl/6 mice. Furthermore, we investigated whether feeding a diet of n-3 PUFA ethyl-eicosapentaenoate (E-EPA) to these mice can attenuate the MPP(+) induced changes in brain PUFA content and expression of cPLA2 and COX-2, and attenuate MPP(+) induced changes in neurotransmitters and metabolites and apoptotic markers, bax, bcl-2 and caspase-3. MPP(+) increased brain content of n-6 PUFAs linoleic acid and arachidonic acid, and increased the mRNA expression of cPLA2. MPP(+) also depleted striatal dopamine levels and increased dopamine turnover, and depleted noradrenaline levels in the frontal cortex. The neurotoxin induced increases in bax, bcl-2 and caspase-3 mRNA expression that approached significance. E-EPA by itself increased brain n-3 content, including EPA and docosapentaenoic acid (C22:5, n-3), and increased cortical dopamine. More importantly, E-EPA attenuated the MPP(+) induced increase in n-6 fatty acids content, partially attenuated the striatal dopaminergic turnover, and prevented the increases of pro-apoptotic bax and caspase-3 mRNAs. In conclusion, increases in n-6 PUFAs in the acute stage of exposure to parkinsonian neurotoxins may promote pro-inflammatory conditions. EPA may provide modest beneficial effects in Parkinson's disease, but further investigation is warranted.

  18. Dual activities of the anti-cancer drug candidate PBI-05204 provide neuroprotection in brain slice models for neurodegenerative diseases and stroke.

    Science.gov (United States)

    Van Kanegan, Michael J; Dunn, Denise E; Kaltenbach, Linda S; Shah, Bijal; He, Dong Ning; McCoy, Daniel D; Yang, Peiying; Peng, Jiangnan; Shen, Li; Du, Lin; Cichewicz, Robert H; Newman, Robert A; Lo, Donald C

    2016-05-12

    We previously reported neuroprotective activity of the botanical anti-cancer drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, in brain slice and in vivo models of ischemic stroke. We showed that one component of this neuroprotective activity is mediated through its principal cardiac glycoside constituent, oleandrin, via induction of the potent neurotrophic factor brain-derived neurotrophic factor (BDNF). However, we also noted that the concentration-relation for PBI-05204 in the brain slice oxygen-glucose deprivation (OGD) model is considerably broader than that for oleandrin as a single agent. We thus surmised that PBI-05204 contains an additional neuroprotective component(s), distinct from oleandrin. We report here that neuroprotective activity is also provided by the triterpenoid constituents of PBI-05204, notably oleanolic acid. We demonstrate that a sub-fraction of PBI-05204 (Fraction 0-4) containing oleanolic and other triterpenoids, but without cardiac glycosides, induces the expression of cellular antioxidant gene transcription programs regulated through antioxidant transcriptional response elements (AREs). Finally, we show that Fraction 0-4 provides broad neuroprotection in organotypic brain slice models for neurodegeneration driven by amyloid precursor protein (APP) and tau implicated in Alzheimer's disease and frontotemporal dementias, respectively, in addition to ischemic injury modeled by OGD.

  19. Antioxidant effects of 1,4-dihydropyridine and nitroso aryl derivatives on the Fe+3/ascorbate-stimulated lipid peroxidation in rat brain slices.

    Science.gov (United States)

    Díaz-Araya, G; Godoy, L; Naranjo, L; Squella, J A; Letelier, M E; Núñez-Vergara, L J

    1998-09-01

    1. Lipid peroxidation in rat brain slices was induced by Fe+3/ascorbate. 2. Brain lipid peroxidation, as measured by malondialdehyde formation, was inhibited by all the tested nitro aryl 1,4-dihydropyridine derivatives over a wide range of concentrations. The time-course antioxidant effects of the most representative agents were assessed. On the basis of both time-course and IC50 experiments the tentative order of antioxidant activity on rat brain slices could be: nicardipine>nisoldipine> (R,S/S,R)-furnidipine > (R,R/S,S)-furnidipine>nitrendipine>nimodipine> nifedipine. 3. 1,4-Dihydropyridine derivatives that lack of a nitro group in the molecule (isradipine, amlodipine) also inhibited lipid peroxidation in rat brain slices but at higher concentrations than that of nitro-substituted derivatives. 4. All the tested nitroso aryl derivatives [2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridinedicar. boxylic acid dimethyl ester (NTP), nitrosotoluene, nitrosobenzene] were more potent inhibitors of lipid peroxidation than were the parent nitro compounds. In conclusion, on the basis of the IC50 values determined, the rank order of antioxidant potency for these derivatives can be established as: ortho-nitrosotoluene>NTP>nitrosobenzene.

  20. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

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    Tamar ePashut

    2014-06-01

    Full Text Available Although transcranial magnetic stimulation (TMS is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

  1. Mathematical Identification of a Neuronal Network Consisting of GABA and DA in Striatal Slices of the Rat Brain

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    L. Ramrath

    2009-01-01

    Full Text Available High frequency stimulation (HFS has been used to treat various neurological and psychiatric diseases. Although further disorders are under investigation to extend the clinical application of HFS, the complex effect of HFS within a neuronal network is still unknown. Thus, it would be desirable to find a theoretical model that allows an estimation of the expected effect of applied HFS. Based on the neurochemical analysis of effects of the γ-aminobutyric acid (GABAA receptor antagonist bicuculline, the D2-like receptor antagonist sulpiride and the D1-like receptor antagonist SCH-23390 on HFS evoked GABA and dopamine (DA release from striatal slices of the rat brain, a mathematical network model is proposed including the neurotransmitters GABA, DA and glutamate (GLU. The model reflects inhibitory and excitatory interactions of the neurotransmitters outflow in the presence of HFS. Under the assumption of linear interactions and static measurements, the model is expressed analytically. Numerical identification of inhibition and excitation is performed on a basis of real outflow levels of GABA and DA in the rat striatum. Results validate the nature of the proposed model. Therefore, this leads to an analytical model of the interactions within distinct neural network components of the rat striatum.

  2. Specific accumulation of {sup 18}F-deoxyglucose in three-dimensional long-term cultures of human and rodent brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Hocke, C.; Prante, O.; Kuwert, T. [Clinic of Nuclear Medicine, Univ. of Erlangen-Nuernberg (Germany); Bluemcke, I.; Jeske, I. [Dept. of Neuropathology, Univ. of Erlangen-Nuernberg (Germany); Romstoeck, J. [Dept. of Neurosurgery, Univ. of Erlangen-Nuernberg (Germany); Stefan, H. [Dept. of Neurology, Univ. of Erlangen-Nuernberg (Germany)

    2007-07-01

    Aim: Organotypic slice cultures (OSC) of human brain specimens represent an intriguing experimental model for translational studies addressing, e.g., stem cell transplantation in neurodegenerative diseases or targeting invasion by malignant glioma ex vivo. However, long-term viability and phenomena of structural reorganization of human OSC remain to be further characterized. Here, we report the use of {sup 18}F-deoxyglucose (FDG) for evaluating the viability of brain slice preparations obtained either from postnatal rats or human hippocampal specimens. Methods: Anatomically well preserved human hippocampi obtained from epilepsy surgery and rat hippocampus slice cultures obtained from six day old Wistar rats were dissected into horizontal slices. The slices were incubated with FDG in phosphate buffered saline up to 1 h, either with or without supplementation of glucose at a concentration of 2.5 mg/ml. Radioactivity within the medium or slice cultures was measured using a gamma-counter. In addition, distribution of radioactivity was autoradiographically visualized and quantified as counts per mm{sup 2}. Results: In rat hippocampal slices, FDG accumulated with 1 300 000 {+-} 68 000 counts/mm{sup 2}, whereas the incorporation of the radioactive label in human slices was in the order of 1 500 000 {+-} 370 000 counts/mm{sup 2}. The elevation of glucose concentration within the medium led to a significant three-fold decrease of FDG accumulation in rat slices and to a 2.4-fold decrease in human specimens. Conclusions: FDG accumulated in organotypic brain cultures of human or rodent origin. FDG is thus suited to investigate the viability of OSC. Furthermore, these preparations open new ways to study the factors governing cerebral FDG uptake in brain tissue ex vivo. (orig.)

  3. Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis.

    Science.gov (United States)

    Stribos, Elisabeth G D; Luangmonkong, Theerut; Leliveld, Anna M; de Jong, Igle J; van Son, Willem J; Hillebrands, Jan-Luuk; Seelen, Marc A; van Goor, Harry; Olinga, Peter; Mutsaers, Henricus A M

    2016-04-01

    Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue obtained from tumor nephrectomies and cultured up to 96 hours. Morphology, cell viability, and metabolic functionality (ie, uridine 5'-diphospho-glucuronosyltransferase and transporter activity) were determined to assess the integrity of PCKSs. Furthermore, inflammatory and fibrosis-related gene expressions were characterized. Finally, to validate the model, renal fibrogenesis was induced using transforming growth factor β1 (TGF-β1). Preparation of PCKSs induced an inflammatory tissue response, whereas long-term incubation (96 hours) induced fibrogenesis as shown by an increased expression of collagen type 1A1 (COL1A1) and fibronectin 1 (FN1). Importantly, PCKSs remained functional for more than 48 hours as evidenced by active glucuronidation and phenolsulfonphthalein uptake. In addition, cellular diversity appeared to be maintained, yet we observed a clear loss of nephrin messenger RNA levels suggesting that our model might not be suitable to study the role of podocytes in renal pathology. Moreover, TGF-β1 exposure augmented fibrosis, as illustrated by an increased expression of multiple fibrosis markers including COL1A1, FN1, and α-smooth muscle actin. In conclusion, PCKSs maintain their renal phenotype during culture and appear to be a promising model to investigate renal diseases, for example, renal fibrosis. Moreover, the human origin of PCKSs makes this model very suitable for translational research.

  4. Effect of. cap alpha. -,. beta. -adrenergic receptor agonists and antagonists of the efflux of /sup 22/Na and uptake of /sup 42/K by rat brain cortical slices

    Energy Technology Data Exchange (ETDEWEB)

    Phillis, J.W.; Wu, P.H.; Thierry, D.L.

    1982-03-18

    The effects of norepinephrine on ion fluxes in rat brain cortical slices have now been ascertained. /sup 22/Na efflux and /sup 42/K influx are enhanced by norepinephrine. The increase in ion fluxes can be blocked by ouabain, phentolamine and propranolol, suggesting that the catecholamine activates a membrane sodium pump by a receptor-mediated step. The facilitation of /sup 22/Na efflux is stereospecific as demonstrated by the very weak action of D-norepinephrine at 10/sup -5/ M concentration. Various ..cap alpha..-adrenergic and ..beta..-adrenergic receptor agonists, including oxymetazoline, naphazoline, clonidine, tramazoline, methoxamine, phenylephrine, L-isoproterenol and methoxyphenamine are potent stimulants of the sodium pump as demonstrated by their enhancement of ion fluxes in rat brain cortical slices. The results are consistent with the hypothesis that norepinephrine hyperpolarizes central neurons by activating an ouabain-sensitive, receptor-mediated sodium pump.

  5. Sexual differences of human brain

    Directory of Open Access Journals (Sweden)

    Masoud Pezeshki Rad

    2014-04-01

    Full Text Available During the last decades there has been an increasing interest in studying the differences between males and females. These differences extend from behavioral to cognitive to micro- and macro- neuro-anatomical aspects of human biology. There have been many methods to evaluate these differences and explain their determinants. The most studied cause of this dimorphism is the prenatal sex hormones and their organizational effect on brain and behavior. However, there have been new and recent attentions to hormone's activational influences in puberty and also the effects of genomic imprinting. In this paper, we reviewed the sex differences of brain, the evidences for possible determinants of these differences and also the methods that have been used to discover them. We reviewed the most conspicuous findings with specific attention to macro-anatomical differences based on Magnetic Resonance Imaging (MRI data. We finally reviewed the findings and the many opportunities for future studies.

  6. Brain-derived neurotrophic factor, but not neurotrophin-3, prevents ischaemia-induced neuronal cell death in organotypic rat hippocampal slice cultures.

    Science.gov (United States)

    Pringle, A K; Sundstrom, L E; Wilde, G J; Williams, L R; Iannotti, F

    1996-06-28

    We have investigated the neuroprotective actions of neurotrophins in a model of ischaemia using slice cultures. Ischaemia was induced in organotypic hippocampal cultures by simultaneous oxygen and glucose deprivation. Cell death was assessed 24 h later by propidium iodide fluorescence. Pre- but not post-ischaemic addition of brain-derived neurotrophic factor (BDNF) produced a concentration-dependent reduction in neuronal damage. Neurotrophin-3 was not neuroprotective. These data suggest that BDNF may form part of an endogenous neuroprotective mechanism.

  7. Whole-brain CT perfusion and CT angiography assessment of Moyamoya disease before and after surgical revascularization: preliminary study with 256-slice CT.

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    Jun Zhang

    Full Text Available BACKGROUND/AIMS: The 256-slice CT enables the entire brain to be scanned in a single examination. We evaluated the application of 256-slice whole-brain CT perfusion (CTP in determining graft patency as well as investigating cerebral hemodynamic changes in Moyamoya disease before and after surgical revascularization. METHODS: Thirty-nine cases of Moyamoya disease were evaluated before and after surgical revascularization with 256-slice CT. Whole-brain perfusion images and dynamic 3D CT angiographic images generated from perfusion source data were obtained in all patients. Cerebral blood flow (CBF, cerebral blood volume (CBV, time to peak (TTP and mean transit time (MTT of one hemisphere in the region of middle cerebral artery (MCA distribution and contralateral mirroring areas were measured. Relative CTP values (rCBF, rCBV, rTTP, rMTT were also obtained. Differences in pre- and post- operation perfusion CT values were assessed with paired t test or matched-pairs signed-ranks test. RESULTS: Preoperative CBF, MTT and TTP of potential surgical side were significantly different from those of contralateral side (P<0.01 for all. All graft patencies were displayed using the 3D-CTA images. Postoperative CBF, rCBF and rCBV values of surgical side in the region of MCA were significantly higher than those before operation (P<0.01 for all. Postoperative MTT, TTP, rMTT and rTTP values of the surgical side in the region of MCA were significantly lower than those before operation (P<0.05 for all. CONCLUSION: The 256-slice whole-brain CTP can be used to evaluate cerebral hemodynamic changes in Moyamoya disease before and after surgery and the 3D-CTA is useful for assessing the abnormalities of intracranial arteries and graft patencies.

  8. Injury Response of Resected Human Brain Tissue In Vitro.

    Science.gov (United States)

    Verwer, Ronald W H; Sluiter, Arja A; Balesar, Rawien A; Baaijen, Johannes C; de Witt Hamer, Philip C; Speijer, Dave; Li, Yichen; Swaab, Dick F

    2015-07-01

    Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by resection (interruption of the circulation) and aggravated by the preparation of slices (severed neuronal and glial processes and blood vessels) reflect the reaction of human brain tissue to severe injury. We investigated this process using immunocytochemical markers, reverse transcriptase quantitative polymerase chain reaction and Western blot analysis. Essential features were rapid shrinkage of neurons, loss of neuronal marker expression and proliferation of reactive cells that expressed Nestin and Vimentin. Also, microglia generally responded strongly, whereas the response of glial fibrillary acidic protein-positive astrocytes appeared to be more variable. Importantly, some reactive cells also expressed both microglia and astrocytic markers, thus confounding their origin. Comparison with post-mortem human brain tissue obtained at rapid autopsies suggested that the reactive process is not a consequence of epilepsy. © 2014 International Society of Neuropathology.

  9. Analysis of acute brain slices by electron microscopy: a correlative light-electron microscopy workflow based on Tokuyasu cryo-sectioning.

    Science.gov (United States)

    Loussert Fonta, Celine; Leis, Andrew; Mathisen, Cliff; Bouvier, David S; Blanchard, Willy; Volterra, Andrea; Lich, Ben; Humbel, Bruno M

    2015-01-01

    Acute brain slices are slices of brain tissue that are kept vital in vitro for further recordings and analyses. This tool is of major importance in neurobiology and allows the study of brain cells such as microglia, astrocytes, neurons and their inter/intracellular communications via ion channels or transporters. In combination with light/fluorescence microscopies, acute brain slices enable the ex vivo analysis of specific cells or groups of cells inside the slice, e.g. astrocytes. To bridge ex vivo knowledge of a cell with its ultrastructure, we developed a correlative microscopy approach for acute brain slices. The workflow begins with sampling of the tissue and precise trimming of a region of interest, which contains GFP-tagged astrocytes that can be visualised by fluorescence microscopy of ultrathin sections. The astrocytes and their surroundings are then analysed by high resolution scanning transmission electron microscopy (STEM). An important aspect of this workflow is the modification of a commercial cryo-ultramicrotome to observe the fluorescent GFP signal during the trimming process. It ensured that sections contained at least one GFP astrocyte. After cryo-sectioning, a map of the GFP-expressing astrocytes is established and transferred to correlation software installed on a focused ion beam scanning electron microscope equipped with a STEM detector. Next, the areas displaying fluorescence are selected for high resolution STEM imaging. An overview area (e.g. a whole mesh of the grid) is imaged with an automated tiling and stitching process. In the final stitched image, the local organisation of the brain tissue can be surveyed or areas of interest can be magnified to observe fine details, e.g. vesicles or gold labels on specific proteins. The robustness of this workflow is contingent on the quality of sample preparation, based on Tokuyasu's protocol. This method results in a reasonable compromise between preservation of morphology and maintenance of

  10. β-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices

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    Cilio Corrado

    2010-12-01

    Full Text Available Abstract Background Inflammation acting in synergy with brain ischemia aggravates perinatal ischemic brain damage. The sensitizing effect of pro-inflammatory exposure prior to hypoxia is dependent on signaling by TNF-α through TNF receptor (TNFR 1. Adrenoceptor (AR activation is known to modulate the immune response and synaptic transmission. The possible protective effect of α˜ and β˜AR activation against neuronal damage caused by tissue ischemia and inflammation, acting in concert, was evaluated in murine hippocampal organotypic slices treated with lipopolysaccharide (LPS and subsequently subjected to oxygen-glucose deprivation (OGD. Method Hippocampal slices from mice were obtained at P6, and were grown in vitro for 9 days on nitrocellulose membranes. Slices were treated with β1(dobutamine-, β2(terbutaline-, α1(phenylephrine- and α2(clonidine-AR agonists (5 and 50 μM, respectively during LPS (1 μg/mL, 24 h -exposure followed by exposure to OGD (15 min in a hypoxic chamber. Cell death in the slice CA1 region was assessed by propidium iodide staining of dead cells. Results Exposure to LPS + OGD caused extensive cell death from 4 up to 48 h after reoxygenation. Co-incubation with β1-agonist (50 μM during LPS exposure before OGD conferred complete protection from cell death (P -/- and TNFR2-/- slices exposed to LPS followed by OGD. Conclusions Our data demonstrate that activation of both β1- and β2-receptors is neuroprotective and may offer mechanistic insights valuable for development of neuro-protective strategies in neonates.

  11. The Appetite-Inducing Peptide, Ghrelin, Induces Intracellular Store-Mediated Rises in Calcium in Addiction and Arousal-Related Laterodorsal Tegmental Neurons in Mouse Brain Slices

    DEFF Research Database (Denmark)

    Hauberg, Katrine; Kohlmeier, Kristi Anne

    2015-01-01

    Ghrelin, a gut and brain peptide, has recently been shown to be involved in motivated behavior and regulation of the sleep and wakefulness cycle. The laterodorsal tegmental nucleus (LDT) is involved in appetitive behavior and control of the arousal state of an organism, and accordingly, behavioral...... this peptide has been shown in other cell types to lead to rises in calcium via release of calcium from intracellular stores. To determine whether ghrelin induced intracellular calcium rises in mouse LDT neurons, we conducted calcium imaging studies in LDT brain slices loaded with the calcium binding dye, Fura...

  12. Properties of gamma-frequency oscillations initiated by propagating population bursts in retrohippocampal regions of rat brain slices.

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    Funahashi, M; Stewart, M

    1998-07-01

    1. In the hippocampal formation in vivo, brief periods of gamma-frequency activity follow population bursts called sharp waves. The approximately 200 Hz activity of the sharp wave itself may serve to enhance synaptic connections and the approximately 40 Hz gamma activity has been offered as a mechanism for solving the 'binding' problem. We describe epochs of gamma-frequency activity which follow population spikes evoked by low frequency repetitive extracellular stimuli in retrohippocampal neurons of horizontal rat brain slices. 2. gamma-Frequency activity recorded intracellularly from deep layer neurons of entorhinal cortex, presubiculum and parasubiculum consisted of one action potential correlated with each of the three to five gamma cycles recorded with a proximate field potential electrode. A minority of cells exhibited only sub-threshold gamma-frequency membrane potential oscillations (ranging from 5 to 10 mV). No cells fired more than one spike per gamma cycle under any conditions. 3. The range of synchrony varied from individual cells which showed gamma-frequency firing without corresponding oscillations in close field recordings to field potential recordings of oscillations which were well correlated across regions. The lead or lag between any two retrohippocampal regions was in the direction of the conduction delay for the primary population spike, but typically was less, and approached zero milliseconds for some cycles in most cells. The level of synchrony was stable for particular stimulating conditions (intensity, stimulation rate, stimulus location). 4. The duration of the period of gamma activity had the duration of a slow depolarizing potential which was mediated by NMDA receptor activation. NMDA receptor antagonists or low concentrations of AMPA receptor antagonists reduced the duration of, or completely abolished the slow potential, thereby eliminating the gamma portion of the evoked response. 5. gamma-Frequency firing was eliminated by the GABAA

  13. Preserving GABAergic interneurons in acute brain slices of mice using the N-methyl-D-glucamine-based artificial cerebrospinal fluid method.

    Science.gov (United States)

    Pan, Geng; Li, Yue; Geng, Hong-Yan; Yang, Jian-Ming; Li, Ke-Xin; Li, Xiao-Ming

    2015-04-01

    Defects in the function and development of GABAergic interneurons have been linked to psychiatric disorders, so preservation of these interneurons in brain slices is important for successful electrophysiological recording in various ex vivo methods. However, it is difficult to maintain the activity and morphology of neurons in slices from mice of >30 days old. Here we evaluated the N-methyl-D-glucamine (NMDG)-based artificial cerebrospinal fluid (aCSF) method for the preservation of interneurons in slices from mice of up to ∼6 months old and discussed the steps that may affect their quality during slicing. We found that the NMDG-aCSF method rescued more cells than sucrose-aCSF and successfully preserved different types of interneurons including parvalbumin- and somatostatin-positive interneurons. In addition, both the chemical and electrical synaptic signaling of interneurons were maintained. These results demonstrate that the NMDG-aCSF method is suitable for the preservation of interneurons, especially in studies of gap junctions.

  14. Comparison of bNOS and chat immunohistochemistry in the laterodorsal tegmentum (LDT) and the pedunculopontine tegmentum (PPT) of the mouse from brain slices prepared for electrophysiology.

    Science.gov (United States)

    Veleanu, Maxime; Axen, Tina E; Kristensen, Morten P; Kohlmeier, Kristi A

    2016-04-01

    Identification of cell phenotype from brain slices upon which in vitro electrophysiological recordings have been performed often relies on conducting post hoc immunohistochemistry on tissue that necessarily has not been ideally prepared for immunohistochemical procedures. In such studies, antibody labeling against neuronal nitric oxide synthase (bNOS) has been used to identify cholinergic neurons of the laterodorsal tegmental nucleus (LDT) and the pedunculopontine tegmental nuclei (PPT), two brainstem nuclei importantly involved in arousal. However, a widespread perception maintains that antibody staining for enzymes involved in synthesis or transport, of acetylcholine would be a more definitive marker and hence, preferable. Colocalization of bNOS and CHAT in the LDT/PPT, and presence of parvalbumin (PV), was examined in non-ideally prepared mouse brain slices using currently available antibodies. Using fluorescent-based immunohistochemistry in LDT/PPT slices prepared for in vitro recordings, a near 100% colocalization of bNOS and CHAT was observed. We confirm in the mouse, findings of near 100% colocalization of bNOS and CHAT in the LDT/PPT, and we expand upon data from rat studies using optimally prepared tissue, that for dendritic visualization, bNOS staining exceeded the quality of CHAT staining for visualization of a higher degree of detail of fine processes. PV is not highly present in the mouse LDT/PPT. CHAT and bNOS are equally useful target proteins for immunofluorescent identification of cholinergic LDT/PPT cells in mouse brain slices prepared for in vitro recordings, however, antibody targeting of bNOS allows for a superior appreciation of structural detail. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Comparison of iterative model, hybrid iterative, and filtered back projection reconstruction techniques in low-dose brain CT: impact of thin-slice imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nakaura, Takeshi; Iyama, Yuji; Kidoh, Masafumi; Yokoyama, Koichi [Amakusa Medical Center, Diagnostic Radiology, Amakusa, Kumamoto (Japan); Kumamoto University, Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto (Japan); Oda, Seitaro; Yamashita, Yasuyuki [Kumamoto University, Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto (Japan); Tokuyasu, Shinichi [Philips Electronics, Kumamoto (Japan); Harada, Kazunori [Amakusa Medical Center, Department of Surgery, Kumamoto (Japan)

    2016-03-15

    The purpose of this study was to evaluate the utility of iterative model reconstruction (IMR) in brain CT especially with thin-slice images. This prospective study received institutional review board approval, and prior informed consent to participate was obtained from all patients. We enrolled 34 patients who underwent brain CT and reconstructed axial images with filtered back projection (FBP), hybrid iterative reconstruction (HIR) and IMR with 1 and 5 mm slice thicknesses. The CT number, image noise, contrast, and contrast noise ratio (CNR) between the thalamus and internal capsule, and the rate of increase of image noise in 1 and 5 mm thickness images between the reconstruction methods, were assessed. Two independent radiologists assessed image contrast, image noise, image sharpness, and overall image quality on a 4-point scale. The CNRs in 1 and 5 mm slice thickness were significantly higher with IMR (1.2 ± 0.6 and 2.2 ± 0.8, respectively) than with FBP (0.4 ± 0.3 and 1.0 ± 0.4, respectively) and HIR (0.5 ± 0.3 and 1.2 ± 0.4, respectively) (p < 0.01). The mean rate of increasing noise from 5 to 1 mm thickness images was significantly lower with IMR (1.7 ± 0.3) than with FBP (2.3 ± 0.3) and HIR (2.3 ± 0.4) (p < 0.01). There were no significant differences in qualitative analysis of unfamiliar image texture between the reconstruction techniques. IMR offers significant noise reduction and higher contrast and CNR in brain CT, especially for thin-slice images, when compared to FBP and HIR. (orig.)

  16. Brain mechanisms underlying human communication.

    Science.gov (United States)

    Noordzij, Matthijs L; Newman-Norlund, Sarah E; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C; Toni, Ivan

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the "mirror neurons system"). However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender) and recognizing the communicative intention of the same actions (by a receiver) relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus). The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

  17. Brain mechanisms underlying human communication

    Directory of Open Access Journals (Sweden)

    Matthijs L Noordzij

    2009-07-01

    Full Text Available Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”. However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender and recognizing the communicative intention of the same actions (by a receiver relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus. The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

  18. Genetic basis of human brain evolution.

    Science.gov (United States)

    Vallender, Eric J; Mekel-Bobrov, Nitzan; Lahn, Bruce T

    2008-12-01

    Human evolution is characterized by a rapid increase in brain size and complexity. Decades of research have made important strides in identifying anatomical and physiological substrates underlying the unique features of the human brain. By contrast, it has become possible only very recently to examine the genetic basis of human brain evolution. Through comparative genomics, tantalizing insights regarding human brain evolution have emerged. The genetic changes that potentially underlie human brain evolution span a wide range from single-nucleotide substitutions to large-scale structural alterations of the genome. Similarly, the functional consequences of these genetic changes vary greatly, including protein-sequence alterations, cis-regulatory changes and even the emergence of new genes and the extinction of existing ones. Here, we provide a general review of recent findings into the genetic basis of human brain evolution, highlight the most notable trends that have emerged and caution against over-interpretation of current data.

  19. Establishment of an in vitro model of the human placental barrier by placenta slice culture and ussing chamber.

    Science.gov (United States)

    Song, Dianrong; Guo, Jie; Han, Fang; Zhang, Wei; Wang, Yanan; Wang, Yuhua

    2013-01-01

    Our purpose was to establish an in vitro model of the human placental barrier based on placenta slice culture and Ussing chamber. The villous morphology, beta-human chorionic gonadotropin (β-hCG), mRNA and efflux function of P-glycoprotein (P-gp), and the permeability of the fluorescent marker were confirmed. The results showed that syncytiotrophoblast cells with abundant endoplasmic reticulum and mitochondria were covered with a dense microvillus in the placenta slice. The β-hCG secretion levels in the Ussing chamber were 274.13 ± 13.52 mIU/mL at 5 h, significantly higher than that in the incubator 95.2 ± 13.14 mIU/mL, and β-hCG continued to secrete for 48 h. P-gp mRNA was expressed in the placenta slice. The Rho123 apparent permeability coefficient (Papp) value from maternal side to the fetal side was 26.34 ± 1.87 nm/s, but it was significantly increased, to 289.55 ± 6.02 nm/s after adding verapamil. The Rho123 efflux value was >2. The fluorescein Papp value was (3.42 ± 0.24) × 10(-3) nm/s. In contrast, the fluorescein isothiocyanate-dextran (FD70) Papp value was (3.93 ± 0.08) × 10(-5) nm/s. This indicates that the placenta slice in the Ussing chamber had the activity of a placenta, and can act as a valuable in vitro model of placental barrier.

  20. Human Brain Reacts to Transcranial Extraocular Light.

    Science.gov (United States)

    Sun, Lihua; Peräkylä, Jari; Kovalainen, Anselmi; Ogawa, Keith H; Karhunen, Pekka J; Hartikainen, Kaisa M

    2016-01-01

    Transcranial extraocular light affects the brains of birds and modulates their seasonal changes in physiology and behavior. However, whether the human brain is sensitive to extraocular light is unknown. To test whether extraocular light has any effect on human brain functioning, we measured brain electrophysiology of 18 young healthy subjects using event-related potentials while they performed a visual attention task embedded with emotional distractors. Extraocular light delivered via ear canals abolished normal emotional modulation of attention related brain responses. With no extraocular light delivered, emotional distractors reduced centro-parietal P300 amplitude compared to neutral distractors. This phenomenon disappeared with extraocular light delivery. Extraocular light delivered through the ear canals was shown to penetrate at the base of the scull of a cadaver. Thus, we have shown that extraocular light impacts human brain functioning calling for further research on the mechanisms of action of light on the human brain.

  1. Raman microspectroscopy of fixed rabbit and human lenses and lens slices: New potentialities

    NARCIS (Netherlands)

    Bot, Annet C.C.; Huizinga, Alex; Mul, de Frits F.M.; Vrensen, Gijs F.J.M.; Greve, Jan

    1989-01-01

    Raman spectroscopy is a non-invasive, non-destructive technique for the study of the macromolecular composition of tissues. Raman spectra were obtained from intact fresh and paraformaldehyde fixed rabbit lenses and from thin slices prepared from these lenses. In addition the Raman spectrum of an int

  2. Brain evolution and human neuropsychology: the inferential brain hypothesis.

    Science.gov (United States)

    Koscik, Timothy R; Tranel, Daniel

    2012-05-01

    Collaboration between human neuropsychology and comparative neuroscience has generated invaluable contributions to our understanding of human brain evolution and function. Further cross-talk between these disciplines has the potential to continue to revolutionize these fields. Modern neuroimaging methods could be applied in a comparative context, yielding exciting new data with the potential of providing insight into brain evolution. Conversely, incorporating an evolutionary base into the theoretical perspectives from which we approach human neuropsychology could lead to novel hypotheses and testable predictions. In the spirit of these objectives, we present here a new theoretical proposal, the Inferential Brain Hypothesis, whereby the human brain is thought to be characterized by a shift from perceptual processing to inferential computation, particularly within the social realm. This shift is believed to be a driving force for the evolution of the large human cortex. (JINS, 2012, 18, 394-401).

  3. Architectural slicing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2013-01-01

    a system and a slicing criterion, architectural slicing produces an architectural prototype that contain the elements in the architecture that are dependent on the ele- ments in the slicing criterion. Furthermore, we present an initial design and implementation of an architectural slicer for Java.......Architectural prototyping is a widely used practice, con- cerned with taking architectural decisions through experiments with light- weight implementations. However, many architectural decisions are only taken when systems are already (partially) implemented. This is prob- lematic in the context...... of architectural prototyping since experiments with full systems are complex and expensive and thus architectural learn- ing is hindered. In this paper, we propose a novel technique for harvest- ing architectural prototypes from existing systems, \\architectural slic- ing", based on dynamic program slicing. Given...

  4. Slice Sampling

    CERN Document Server

    Neal, R M

    2000-01-01

    Markov chain sampling methods that automatically adapt to characteristics of the distribution being sampled can be constructed by exploiting the principle that one can sample from a distribution by sampling uniformly from the region under the plot of its density function. A Markov chain that converges to this uniform distribution can be constructed by alternating uniform sampling in the vertical direction with uniform sampling from the horizontal `slice' defined by the current vertical position, or more generally, with some update that leaves the uniform distribution over this slice invariant. Variations on such `slice sampling' methods are easily implemented for univariate distributions, and can be used to sample from a multivariate distribution by updating each variable in turn. This approach is often easier to implement than Gibbs sampling, and more efficient than simple Metropolis updates, due to the ability of slice sampling to adaptively choose the magnitude of changes made. It is therefore attractive f...

  5. Architectural Slicing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2013-01-01

    a system and a slicing criterion, architectural slicing produces an architectural prototype that contain the elements in the architecture that are dependent on the ele- ments in the slicing criterion. Furthermore, we present an initial design and implementation of an architectural slicer for Java.......Architectural prototyping is a widely used practice, con- cerned with taking architectural decisions through experiments with light- weight implementations. However, many architectural decisions are only taken when systems are already (partially) implemented. This is prob- lematic in the context...... of architectural prototyping since experiments with full systems are complex and expensive and thus architectural learn- ing is hindered. In this paper, we propose a novel technique for harvest- ing architectural prototypes from existing systems, \\architectural slic- ing", based on dynamic program slicing. Given...

  6. L-mimosine increases the production of vascular endothelial growth factor in human tooth slice organ culture model.

    Science.gov (United States)

    Trimmel, K; Cvikl, B; Müller, H-D; Nürnberger, S; Gruber, R; Moritz, A; Agis, H

    2015-03-01

    To assess the pro-angiogenic and pro-inflammatory capacity of the dentine-pulp complex in response to the prolyl hydroxylase inhibitor L-mimosine in a tooth slice organ culture model. Human teeth were sectioned transversely into 600-μm-thick slices and cultured in medium supplemented with serum and antibiotics. Then, pulps were stimulated for 48 h with L-mimosine. Pulps were subjected to viability measurements based on formazan formation in MTT assays. In addition, histological evaluation of pulps was performed based on haematoxylin and eosin staining. Culture supernatants were subjected to immunoassays for vascular endothelial growth factor (VEGF) to determine the pro-angiogenic capacity and to immunoassays for interleukin (IL)-6 and IL-8 to assess the pro-inflammatory response. Interleukin-1 served as pro-inflammatory control. Echinomycin was used to inhibit hypoxia-inducible factor-1 (HIF-1) alpha activity. Data were analysed using Student's t-test and Mann-Whitney U test. Pulps within tooth slices remained vital upon L-mimosine stimulation as indicated by formazan formation and histological evaluation. L-mimosine increased VEGF production when normalized to formazan formation in the pulp tissue of the tooth slices (P  0.05), whilst treatment with IL-1, which served as positive control, increased IL-6 (P model whilst inducing no prominent increase in IL-6 and IL-8. Pre-clinical studies will reveal if these in vitro effects translate into dental pulp regeneration. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  7. Brain Evolution and Human Neuropsychology: The Inferential Brain Hypothesis

    OpenAIRE

    Koscik, Timothy R.; Tranel, Daniel

    2012-01-01

    Collaboration between human neuropsychology and comparative neuroscience has generated invaluable contributions to our understanding of human brain evolution and function. Further cross-talk between these disciplines has the potential to continue to revolutionize these fields. Modern neuroimaging methods could be applied in a comparative context, yielding exciting new data with the potential of providing insight into brain evolution. Conversely, incorporating an evolutionary base into the the...

  8. Actions of brain-derived neurotrophic factor in slices from rats with spontaneous seizures and mossy fiber sprouting in the dentate gyrus.

    Science.gov (United States)

    Scharfman, H E; Goodman, J H; Sollas, A L

    1999-07-01

    This study examined the acute actions of brain-derived neurotrophic factor (BDNF) in the rat dentate gyrus after seizures, because previous studies have shown that BDNF has acute effects on dentate granule cell synaptic transmission, and other studies have demonstrated that BDNF expression increases in granule cells after seizures. Pilocarpine-treated rats were studied because they not only have seizures and increased BDNF expression in granule cells, but they also have reorganization of granule cell "mossy fiber" axons. This reorganization, referred to as "sprouting," involves collaterals that grow into novel areas, i.e., the inner molecular layer, where granule cell and interneuron dendrites are located. Thus, this animal model allowed us to address the effects of BDNF in the dentate gyrus after seizures, as well as the actions of BDNF on mossy fiber transmission after reorganization. In slices with sprouting, BDNF bath application enhanced responses recorded in the inner molecular layer to mossy fiber stimulation. Spontaneous bursts of granule cells occurred, and these were apparently generated at the site of the sprouted axon plexus. These effects were not accompanied by major changes in perforant path-evoked responses or paired-pulse inhibition, occurred only after prolonged (30-60 min) exposure to BDNF, and were blocked by K252a. The results suggest a preferential action of BDNF at mossy fiber synapses, even after substantial changes in the dentate gyrus network. Moreover, the results suggest that activation of trkB receptors could contribute to the hyperexcitability observed in animals with sprouting. Because human granule cells also express increased BDNF mRNA after seizures, and sprouting can occur in temporal lobe epileptics, the results may have implications for understanding temporal lobe epilepsy.

  9. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  10. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  11. Fast scan cyclic voltammetry as a novel method for detection of real-time gonadotropin-releasing hormone release in mouse brain slices.

    Science.gov (United States)

    Glanowska, Katarzyna M; Venton, B Jill; Moenter, Suzanne M

    2012-10-17

    Pulsatile gonadotropin-releasing hormone (GnRH) release is critical for the central regulation of fertility. There is no method allowing real-time GnRH detection in brain slices. We developed fast-scan cyclic voltammetry (FSCV) using carbon-fiber microelectrodes (CFME) to detect GnRH release and validated it using a biologically relevant system. FSCV parameters (holding potential, switching potential, and scan rate) were determined for stable GnRH detection in vitro, then optimized for GnRH detection in mouse brain slices. Placement of CFMEs in the median eminence (ME) near GnRH terminals allowed detection of both KCl-evoked and spontaneous GnRH release. GnRH release was also detected from GnRH fibers passing near GnRH soma and near fiber-fiber appositions in the preoptic area. No GnRH signal was detected from CFMEs in the ME of hpg mice, which lack GnRH, or in regions not containing GnRH neurons in wild-type mice; application of exogenous GnRH produced a signal similar to that observed for spontaneous/evoked endogenous GnRH release. Using an established mouse model that produces diurnal variations in GnRH neuron activity, we demonstrated corresponding changes in spontaneous GnRH release in the median eminence. These results validate FSCV to detect GnRH in brain slices and provide new information on the sites and amounts of GnRH release, providing insight into its neuromodulatory functions.

  12. GTP effects in rat brain slices support the non-interconvertability of M/sub 1/ and M/sub 2/ muscarinic acetylcholine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, D.G. Jr.; Horvath, E.; Traber, J.; Van Rooijen, L.A.A.

    1988-01-01

    GTP (guanosine-5'-triphosphate) markedly reduced high-affinity /sup 3/H-oxotremorine-M binding to M/sub 2/ receptors on brain slices in autoradiographic experiments while /sup 3/H-pirenzepine binding to M/sub 1/ receptors was largely unaffected. The distribution of M/sub 1/ receptors so labelled was also not altered by GTP to include former M/sub 2/-rich regions, thus indicating that GTP could not, by itself, interconvert high agonist-affinity M/sub 2/ receptors to M/sub 1/ receptors. 18 references, 1 figure.

  13. In vitro metabolism of beclomethasone dipropionate, budesonide, ciclesonide, and fluticasone propionate in human lung precision-cut tissue slices

    Directory of Open Access Journals (Sweden)

    Fisher Robyn

    2007-09-01

    Full Text Available Abstract Background The therapeutic effect of inhaled corticosteroids (ICS may be affected by the metabolism of the drug in the target organ. We investigated the in vitro metabolism of beclomethasone dipropionate (BDP, budesonide (BUD, ciclesonide (CIC, and fluticasone propionate (FP in human lung precision-cut tissue slices. CIC, a new generation ICS, is hydrolyzed by esterases in the upper and lower airways to its pharmacologically active metabolite desisobutyryl-ciclesonide (des-CIC. Methods Lung tissue slices were incubated with BDP, BUD, CIC, and FP (initial target concentration of 25 μM for 2, 6, and 24 h. Cellular viability was assessed using adenosine 5'-triphosphate content and protein synthesis in lung slices. Metabolites and remaining parent compounds in the tissue samples were analyzed by HPLC with UV detection. Results BDP was hydrolyzed to the pharmacologically active metabolite beclomethasone-17-monopropionate (BMP and, predominantly, to inactive beclomethasone (BOH. CIC was hydrolyzed initially to des-CIC with a slower rate compared to BDP. A distinctly smaller amount (approximately 10-fold less of fatty acid esters were formed by BMP (and/or BOH than by BUD or des-CIC. The highest relative amounts of fatty acid esters were detected for BUD. For FP, no metabolites were detected at any time point. The amount of drug-related material in lung tissue (based on initial concentrations at 24 h was highest for CIC, followed by BUD and FP; the smallest amount was detected for BDP. Conclusion The in vitro metabolic pathways of the tested ICS in human lung tissue were differing. While FP was metabolically stable, the majority of BDP was converted to inactive polar metabolites. The formation of fatty acid conjugates was confirmed for BMP (and/or BOH, BUD, and des-CIC.

  14. Microcutting of living brain slices by a pulsed ultrafine water jet which allows simultaneous electrophysiological recordings (micromingotome).

    Science.gov (United States)

    Speckmann, E J; Köhling, R; Lücke, A; Straub, H; Wittkowski, W; Elger, C E; Wiemann, M; Bingmann, D

    1998-07-01

    Up to now microsurgical dissections in living nervous tissue (e.g. in slices or cell cultures) are performed either by micro-scalpels or by laser beams. As an alternative technique, a device for cutting with an ultrafine pulsed water jet was developed to allow precise, visually controled dissections in neuronal circuits even during electrophysiological recordings. Water is ejected by pressure (20-30 bar) from patch pipettes with tip diameters of 10-12 microm. By means of a piezo-element the pipette and the water jet are forced to oscillate vertically with a frequency of 200-400 Hz with an adjustable amplitude. These oscillations facilitate the transsection of neuronal connections even in thick slice preparations. Best results were obtained when the tip of the pipette was about 500 microm above the surface of the submerged slice tissue. This micromingotome offers the following advantages: (i) histological studies show that the water jet cleans the cutting surface, thus avoiding debris and its uncontrolable effects on cells underneath; (ii) the arrangement enables ongoing electrophysiological recordings from hippocampal slices during the cutting procedure and thus facilitates studies of the functions of neuronal connections; (iii) the device allows even disconnection in cultured nervous tissue overgrowing polyamid grids with 50 microm wide meshes.

  15. Significance of MDR1 and multiple drug resistance in refractory human epileptic brain

    Directory of Open Access Journals (Sweden)

    Dini Gabriele

    2004-10-01

    Full Text Available Abstract Background The multiple drug resistance protein (MDR1/P-glycoprotein is overexpressed in glia and blood-brain barrier (BBB endothelium in drug refractory human epileptic tissue. Since various antiepileptic drugs (AEDs can act as substrates for MDR1, the enhanced expression/function of this protein may increase their active extrusion from the brain, resulting in decreased responsiveness to AEDs. Methods Human drug resistant epileptic brain tissues were collected after surgical resection. Astrocyte cell cultures were established from these tissues, and commercially available normal human astrocytes were used as controls. Uptake of fluorescent doxorubicin and radioactive-labeled Phenytoin was measured in the two cell populations, and the effect of MDR1 blockers was evaluated. Frozen human epileptic brain tissue slices were double immunostained to locate MDR1 in neurons and glia. Other slices were exposed to toxic concentrations of Phenytoin to study cell viability in the presence or absence of a specific MDR1 blocker. Results MDR1 was overexpressed in blood vessels, astrocytes and neurons in human epileptic drug-resistant brain. In addition, MDR1-mediated cellular drug extrusion was increased in human 'epileptic' astrocytes compared to 'normal' ones. Concomitantly, cell viability in the presence of cytotoxic compounds was increased. Conclusions Overexpression of MDR1 in different cell types in drug-resistant epileptic human brain leads to functional alterations, not all of which are linked to drug pharmacokinetics. In particular, the modulation of glioneuronal MDR1 function in epileptic brain in the presence of toxic concentrations of xenobiotics may constitute a novel cytoprotective mechanism.

  16. Anti-inflammatory efficacy of dexamethasone and Nrf2 activators in the CNS using brain slices as a model of acute injury.

    Science.gov (United States)

    Graber, David J; Hickey, William F; Stommel, Elijah W; Harris, Brent T

    2012-03-01

    Limiting excessive production of inflammatory mediators is an effective therapeutic strategy for many diseases. It's also a promising remedy for neurodegenerative diseases and central nervous system (CNS) injuries. Glucocorticoids are valuable anti-inflammatory agents, but their use is constrained by adverse side-effects. Activators of NF-E2-related factor-2 (Nrf2) signaling represent an attractive anti-inflammatory alternative. In this study, dexamethasone, a synthetic glucocorticoid, and several molecular activators of Nrf2 were evaluated for efficacy in slices of cerebral cortex derived from adult SJL/J mice. Cortical explants increased expression of IL-1β and TNF-α mRNAs in culture within 5 h of sectioning. This expression was inhibited with dexamethasone in the explant medium or injected systemically in mice before sectioning. Semi-synthetic triterpenoid (SST) derivatives, potent activators of the Nrf2 pathway, demonstrated fast-acting anti-inflammatory activity in microglia cultures, but not in the cortical slice system. Quercetin, luteolin, and dimethyl fumarate were also evaluated as molecular activators of Nrf2. While expression of inflammatory mediators in microglia cultures was inhibited, these compounds did not demonstrate anti-inflammatory efficacy in cortical slices. In conclusion, brain slices were amenable to pharmacological modification as demonstrated by anti-inflammatory activity with dexamethasone. The utilization of Nrf2 activators to limit inflammatory mediators within the CNS requires further investigation. Inactivity in CNS tissue, however, suggests their safe use without neurological side-effects in treating non-CNS disorders. Short-term CNS explants may provide a more accurate model of in vivo conditions than microglia cultures since the complex tissue microenvironment is maintained.

  17. Male microchimerism in the human female brain.

    Directory of Open Access Journals (Sweden)

    William F N Chan

    Full Text Available In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus. Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n=26, or women who had Alzheimer's disease (n=33. We report that 63% of the females (37 of 59 tested harbored male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p=0.03 and concentration (p=0.06 of male microchimerism in the brains of women with Alzheimer's disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain.

  18. Lymphoreticular cells in human brain tumours and in normal brain.

    OpenAIRE

    1982-01-01

    The present investigation, using various rosetting assays of cell suspensions prepared by mechanical disaggregation or collagenase digestion, demonstrated lymphoreticular cells in human normal brain (cerebral cortex and cerebellum) and in malignant brain tumours. The study revealed T and B lymphocytes and their subsets (bearing receptors for Fc(IgG) and C3) in 5/14 glioma suspensions, comprising less than 15% of the cell population. Between 20-60% of cells in tumour suspensions morphologicall...

  19. Quantitation of dopamine, serotonin and adenosine content in a tissue punch from a brain slice using capillary electrophoresis with fast-scan cyclic voltammetry detection.

    Science.gov (United States)

    Fang, Huaifang; Pajski, Megan L; Ross, Ashley E; Venton, B Jill

    2013-01-01

    Methods to determine neurochemical concentrations in small samples of tissue are needed to map interactions among neurotransmitters. In particular, correlating physiological measurements of neurotransmitter release and the tissue content in a small region would be valuable. HPLC is the standard method for tissue content analysis but it requires microliter samples and the detector often varies by the class of compound being quantified; thus detecting molecules from different classes can be difficult. In this paper, we develop capillary electrophoresis with fast-scan cyclic voltammetry detection (CE-FSCV) for analysis of dopamine, serotonin, and adenosine content in tissue punches from rat brain slices. Using field-amplified sample stacking, the limit of detection was 5 nM for dopamine, 10 nM for serotonin, and 50 nM for adenosine. Neurotransmitters could be measured from a tissue punch as small as 7 µg (7 nL) of tissue, three orders of magnitude smaller than a typical HPLC sample. Tissue content analysis of punches in successive slices through the striatum revealed higher dopamine but lower adenosine content in the anterior striatum. Stimulated dopamine release was measured in a brain slice, then a tissue punch collected from the recording region. Dopamine content and release had a correlation coefficient of 0.71, which indicates much of the variance in stimulated release is due to variance in tissue content. CE-FSCV should facilitate measurements of tissue content in nanoliter samples, leading to a better understanding of how diseases or drugs affect dopamine, serotonin, and adenosine content.

  20. Transcranial magnetic stimulation and the human brain

    Science.gov (United States)

    Hallett, Mark

    2000-07-01

    Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.

  1. Acute and Long-Term Effects of Noise Exposure on the Neuronal Spontaneous Activity in Cochlear Nucleus and Inferior Colliculus Brain Slices

    Directory of Open Access Journals (Sweden)

    Moritz Gröschel

    2014-01-01

    Full Text Available Noise exposure leads to an immediate hearing loss and is followed by a long-lasting permanent threshold shift, accompanied by changes of cellular properties within the central auditory pathway. Electrophysiological recordings have demonstrated an upregulation of spontaneous neuronal activity. It is still discussed if the observed effects are related to changes of peripheral input or evoked within the central auditory system. The present study should describe the intrinsic temporal patterns of single-unit activity upon noise-induced hearing loss of the dorsal and ventral cochlear nucleus (DCN and VCN and the inferior colliculus (IC in adult mouse brain slices. Recordings showed a slight, but significant, elevation in spontaneous firing rates in DCN and VCN immediately after noise trauma, whereas no differences were found in IC. One week postexposure, neuronal responses remained unchanged compared to controls. At 14 days after noise trauma, intrinsic long-term hyperactivity in brain slices of the DCN and the IC was detected for the first time. Therefore, increase in spontaneous activity seems to develop within the period of two weeks, but not before day 7. The results give insight into the complex temporal neurophysiological alterations after noise trauma, leading to a better understanding of central mechanisms in noise-induced hearing loss.

  2. Acute and long-term effects of noise exposure on the neuronal spontaneous activity in cochlear nucleus and inferior colliculus brain slices.

    Science.gov (United States)

    Gröschel, Moritz; Ryll, Jana; Götze, Romy; Ernst, Arne; Basta, Dietmar

    2014-01-01

    Noise exposure leads to an immediate hearing loss and is followed by a long-lasting permanent threshold shift, accompanied by changes of cellular properties within the central auditory pathway. Electrophysiological recordings have demonstrated an upregulation of spontaneous neuronal activity. It is still discussed if the observed effects are related to changes of peripheral input or evoked within the central auditory system. The present study should describe the intrinsic temporal patterns of single-unit activity upon noise-induced hearing loss of the dorsal and ventral cochlear nucleus (DCN and VCN) and the inferior colliculus (IC) in adult mouse brain slices. Recordings showed a slight, but significant, elevation in spontaneous firing rates in DCN and VCN immediately after noise trauma, whereas no differences were found in IC. One week postexposure, neuronal responses remained unchanged compared to controls. At 14 days after noise trauma, intrinsic long-term hyperactivity in brain slices of the DCN and the IC was detected for the first time. Therefore, increase in spontaneous activity seems to develop within the period of two weeks, but not before day 7. The results give insight into the complex temporal neurophysiological alterations after noise trauma, leading to a better understanding of central mechanisms in noise-induced hearing loss.

  3. An introduction to human brain anatomy

    NARCIS (Netherlands)

    Forstmann, B.U.; Keuken, M.C.; Alkemade, A.; Forstmann, B.U.; Wagenmakers, E.-J.

    2015-01-01

    This tutorial chapter provides an overview of the human brain anatomy. Knowledge of brain anatomy is fundamental to our understanding of cognitive processes in health and disease; moreover, anatomical constraints are vital for neurocomputational models and can be important for psychological

  4. Long-term GnRH-induced gonadotropin secretion in a novel hypothalamo-pituitary slice culture from tilapia brain.

    Science.gov (United States)

    Bloch, Corinne L; Kedar, Noa; Golan, Matan; Gutnick, Michael J; Fleidervish, Ilya A; Levavi-Sivan, Berta

    2014-10-01

    Organotypic cultures, prepared from hypothalamo-pituitary slices of tilapia, were developed to enable long-term study of secretory cells in the pituitary of a teleost. Values of membrane potential at rest were similar to those recorded from acute slices, and cells presented similar spontaneous spikes and spikelets. Some cells also exhibited slow spontaneous oscillations in membrane potential, which may be network-driven. Long-term (6days) continuous exposure to GnRH induced increases in LH and FSH secretion. FSH levels reached the highest levels after 24h of exposure to GnRH, and the highest secretion of LH was observed in days 4 and 5 of the experiment. Since slices were viable for several weeks in culture, maintaining the original cytoarchitecture, electrical membrane properties and the ability to secrete hormones in response to exogenous GnRH, this technique is ideal for studying the mechanisms regulating cell-to-cell communication under conditions resembling the in vivo tissue organization.

  5. Interoperable atlases of the human brain.

    Science.gov (United States)

    Amunts, K; Hawrylycz, M J; Van Essen, D C; Van Horn, J D; Harel, N; Poline, J-B; De Martino, F; Bjaalie, J G; Dehaene-Lambertz, G; Dehaene, S; Valdes-Sosa, P; Thirion, B; Zilles, K; Hill, S L; Abrams, M B; Tass, P A; Vanduffel, W; Evans, A C; Eickhoff, S B

    2014-10-01

    The last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different aspects of the human brain including micro- and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topographically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and representation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Analysis of a human brain transcriptome map

    Directory of Open Access Journals (Sweden)

    Greene Jonathan R

    2002-04-01

    Full Text Available Abstract Background Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. Results Examination of ESTs derived from brain tissues (excluding brain tumor tissues suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. Conclusions This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment.

  7. Lactate fuels the human brain during exercise

    DEFF Research Database (Denmark)

    Quistorff, Bjørn; Secher, Niels H; Van Lieshout, Johannes J

    2008-01-01

    The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up...... suggests that lactate may partially replace glucose as a substrate for oxidation. Thus, the notion of the human brain as an obligatory glucose consumer is not without exceptions....... blockade but not with beta(1)-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a beta(2)-adrenergic receptor mechanism enhances glucose and perhaps lactate transport across the blood-brain barrier. The pattern of CMR decrease under various forms of brain activation...

  8. The human brain: rewired and running hot.

    Science.gov (United States)

    Preuss, Todd M

    2011-05-01

    The past two decades have witnessed tremendous advances in noninvasive and postmortem neuroscientific techniques, advances that have made it possible, for the first time, to compare in detail the organization of the human brain to that of other primates. Studies comparing humans to chimpanzees and other great apes reveal that human brain evolution was not merely a matter of enlargement, but involved changes at all levels of organization that have been examined. These include the cellular and laminar organization of cortical areas; the higher order organization of the cortex, as reflected in the expansion of association cortex (in absolute terms, as well as relative to primary areas); the distribution of long-distance cortical connections; and hemispheric asymmetry. Additionally, genetic differences between humans and other primates have proven to be more extensive than previously thought, raising the possibility that human brain evolution involved significant modifications of neurophysiology and cerebral energy metabolism.

  9. Human brain evolution: insights from microarrays.

    Science.gov (United States)

    Preuss, Todd M; Cáceres, Mario; Oldham, Michael C; Geschwind, Daniel H

    2004-11-01

    Several recent microarray studies have compared gene-expression patterns n humans, chimpanzees and other non-human primates to identify evolutionary changes that contribute to the distinctive cognitive and behavioural characteristics of humans. These studies support the surprising conclusion that the evolution of the human brain involved an upregulation of gene expression relative to non-human primates, a finding that could be relevant to understanding human cerebral physiology and function. These results show how genetic and genomic methods can shed light on the basis of human neural and cognitive specializations, and have important implications for neuroscience, anthropology and medicine.

  10. Effect of pre-ischaemic conditioning on hypoxic depolarization of dopamine efflux in the rat caudate brain slice measured in real-time with fast cyclic voltammetry.

    Science.gov (United States)

    Davidson, Colin; Coomber, Ben; Gibson, Claire L; Young, Andrew M J

    2011-10-01

    Fast cyclic voltammetry can be used to measure dopamine release after oxygen and glucose deprivation (OGD) induced anoxic depolarization in vitro. Here we measure dopamine efflux with 1s time resolution, which is appropriate to measure OGD-evoked dopamine efflux accurately. In the present study, we examined whether OGD-evoked dopamine efflux could be used to show pre-ischaemic conditioning in the rat caudate brain slice. Caudate slices were exposed to 0, 2, or 10 min OGD pre-ischaemic conditioning, then 60 min later exposed to a second OGD event of 15 min duration. We measured the OGD-evoked dopamine efflux using fast cyclic voltammetry and in some experiments caudate dopamine and DOPAC tissue levels were measured using HPLC and 20 μm cryostat sections were Nissl stained to indicate neuronal loss. We found that 10 but not 2 min OGD pre-ischaemic conditioning resulted in a longer time to onset of OGD-evoked dopamine efflux on the main OGD event (475 ± 31 and 287 ± 30 s for 10 Vs 0 min pre-ischaemic conditioning respectively). Further, 10 min OGD pre-ischaemic conditioning resulted in less dopamine efflux on the second OGD event (4.23 ± 1.12 and 8.14 ± 0.82 μM for 10 Vs 0 min pre-ischaemic conditioning respectively), despite these slices having similar tissue dopamine content and DOPAC/DA ratio, and the rate of dopamine release was slower in the main OGD event (21 ± 5 and 74 ± 8 nM/s for 10 Vs 0 min pre-ischaemic conditioning respectively). These data suggest that 10 min OGD pre-ischaemic conditioning can evoke tolerance to a second OGD event and that voltammetric recording of OGD-evoked dopamine efflux is a useful model of pre-ischaemic conditioning in neuronal tissue.

  11. The Molecular Basis of Human Brain Evolution.

    Science.gov (United States)

    Enard, Wolfgang

    2016-10-24

    Humans are a remarkable species, especially because of the remarkable properties of their brain. Since the split from the chimpanzee lineage, the human brain has increased three-fold in size and has acquired abilities for vocal learning, language and intense cooperation. To better understand the molecular basis of these changes is of great biological and biomedical interest. However, all the about 16 million fixed genetic changes that occurred during human evolution are fully correlated with all molecular, cellular, anatomical and behavioral changes that occurred during this time. Hence, as humans and chimpanzees cannot be crossed or genetically manipulated, no direct evidence for linking particular genetic and molecular changes to human brain evolution can be obtained. Here, I sketch a framework how indirect evidence can be obtained and review findings related to the molecular basis of human cognition, vocal learning and brain size. In particular, I discuss how a comprehensive comparative approach, leveraging cellular systems and genomic technologies, could inform the evolution of our brain in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Reproducibility of perfusion CT derived CBV and rCBV measurements with different slice thickness in patients with brain neoplasms%脑瘤灌注CT不同层厚CBV与rCBV测量的可重复性研究

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume(CBV)and relative cerebral blood volume(rCBV)with different slice thickness in patients with brain neoplasms.Methods: Three independent observers who were blinded to the histopathologic diagnosis performed perfusion derived CBV and rCBV measurements with 5 mm and 10 mm slice thickness in 52 patients with various cerebral neoplasms.The results of the measurements with different slice thickness were compared.Calculation of coefficient of variation(CV), and relative paired difference of the measurements were used to determine the levels of inter-and intraobserver reproducibility.Results: The differences of CBV and rCBV measurements between different slice thickness groups were statistically significant(P<0.05)respectively in observer 2, and were not significant in the other two observers(P>0.05).For the same slice thickness, both the difference of CBV and rCBV measurements among the three observers were not statistically significant.Interobserver CV and relative paired difference of the measurements with 10 mm slice thickness group were slightly lower than those of 5 mm slice thickness group.Interobserver CV and relative paired difference of CBV group were slightly lower than those of rCBV group.The intraobserver differences of CBV and rCBV in 10 mm slice thickness group were statistically significant for observer 2 respectively.No other intraobserver differences of measurements were statistically significant.CV and relative paired difference of intraobserver CBV and rCBV measurements for observer 2 were significantly higher than for the other two observers.Conclusion: High reproducibility of CBV and rCBV measurements was acquired with the two different slice thickness.Suitable training may be helpful to maintain a high level of consistency for measurements.

  13. Human brain mapping: Experimental and computational approaches

    Energy Technology Data Exchange (ETDEWEB)

    Wood, C.C.; George, J.S.; Schmidt, D.M.; Aine, C.J. [Los Alamos National Lab., NM (US); Sanders, J. [Albuquerque VA Medical Center, NM (US); Belliveau, J. [Massachusetts General Hospital, Boston, MA (US)

    1998-11-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This program developed project combined Los Alamos' and collaborators' strengths in noninvasive brain imaging and high performance computing to develop potential contributions to the multi-agency Human Brain Project led by the National Institute of Mental Health. The experimental component of the project emphasized the optimization of spatial and temporal resolution of functional brain imaging by combining: (a) structural MRI measurements of brain anatomy; (b) functional MRI measurements of blood flow and oxygenation; and (c) MEG measurements of time-resolved neuronal population currents. The computational component of the project emphasized development of a high-resolution 3-D volumetric model of the brain based on anatomical MRI, in which structural and functional information from multiple imaging modalities can be integrated into a single computational framework for modeling, visualization, and database representation.

  14. Human brain mapping: Experimental and computational approaches

    Energy Technology Data Exchange (ETDEWEB)

    Wood, C.C.; George, J.S.; Schmidt, D.M.; Aine, C.J. [Los Alamos National Lab., NM (US); Sanders, J. [Albuquerque VA Medical Center, NM (US); Belliveau, J. [Massachusetts General Hospital, Boston, MA (US)

    1998-11-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This program developed project combined Los Alamos' and collaborators' strengths in noninvasive brain imaging and high performance computing to develop potential contributions to the multi-agency Human Brain Project led by the National Institute of Mental Health. The experimental component of the project emphasized the optimization of spatial and temporal resolution of functional brain imaging by combining: (a) structural MRI measurements of brain anatomy; (b) functional MRI measurements of blood flow and oxygenation; and (c) MEG measurements of time-resolved neuronal population currents. The computational component of the project emphasized development of a high-resolution 3-D volumetric model of the brain based on anatomical MRI, in which structural and functional information from multiple imaging modalities can be integrated into a single computational framework for modeling, visualization, and database representation.

  15. Transcriptional landscape of the prenatal human brain.

    Science.gov (United States)

    Miller, Jeremy A; Ding, Song-Lin; Sunkin, Susan M; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L; Royall, Joshua J; Aiona, Kaylynn; Arnold, James M; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A; Dee, Nick; Dolbeare, Tim A; Facer, Benjamin A C; Feng, David; Fliss, Tim P; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W; Gu, Guangyu; Howard, Robert E; Jochim, Jayson M; Kuan, Chihchau L; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D; Parry, Sheana E; Stevens, Allison; Pletikos, Mihovil; Reding, Melissa; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V; Shen, Elaine H; Sjoquist, Nathan; Slaughterbeck, Clifford R; Smith, Michael; Sodt, Andy J; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark B; Geschwind, Daniel H; Glass, Ian A; Hawrylycz, Michael J; Hevner, Robert F; Huang, Hao; Jones, Allan R; Knowles, James A; Levitt, Pat; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G; Lein, Ed S

    2014-04-10

    The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

  16. Acute hypercapnic hyperoxia stimulates reactive species production in the caudal solitary complex of rat brain slices but does not induce oxidative stress.

    Science.gov (United States)

    Ciarlone, Geoffrey E; Dean, Jay B

    2016-12-01

    Central CO2 chemoreceptive neurons in the caudal solitary complex (cSC) are stimulated by hyperoxia via a free radical mechanism. Hyperoxia has been shown to increase superoxide and nitric oxide in the cSC, but it remains unknown how changes in Pco2 during hyperoxia affect the production of O2-dependent reactive oxygen and nitrogen species (RONS) downstream that can lead to increased levels of oxidative and nitrosative stress, cellular excitability, and, potentially, dysfunction. We used real-time fluorescence microscopy in rat brain slices to determine how hyperoxia and hypercapnic acidosis (HA) modulate one another in the production of key RONS, as well as colorimetric assays to measure levels of oxidized and nitrated lipids and proteins. We also examined the effects of CO2 narcosis and hypoxia before euthanasia and brain slice harvesting, as these neurons are CO2 sensitive and hypothesized to employ CO2/H(+) mechanisms that exacerbate RONS production and potentially oxidative stress. Our findings show that hyperoxia ± HA increases the production of peroxynitrite and its derivatives, whereas increases in Fenton chemistry are most prominent during hyperoxia + HA. Using CO2 narcosis before euthanasia modulates cellular sensitivity to HA postmortem and enhances the magnitude of the peroxynitrite pathway, but blunts the activity of Fenton chemistry. Overall, hyperoxia and HA do not result in increased production of markers of oxidative and nitrosative stress as expected. We postulate this is due to antioxidant and proteosomal removal of damaged lipids and proteins to maintain cell viability and avoid death during protracted hyperoxia.

  17. Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury

    NARCIS (Netherlands)

    van Swelm, Rachel P. L.; Hadi, Mackenzie; Laarakkers, Coby M. M.; Masereeuw, Rosalinde; Groothuis, Geny M. M.; Russel, Frans G. M.

    2014-01-01

    Drug-induced liver injury is one of the leading causes of drug withdrawal from the market. In this study, we investigated the applicability of protein profiling of the incubation medium of human, mouse and rat precision-cut liver slices (PCLS) exposed to liver injury-inducing drugs for biomarker ide

  18. Brain mechanisms underlying human communication

    NARCIS (Netherlands)

    Noordzij, M.L.; Newman-Norlund, S.E.; Ruiter, J.P.A. de; Hagoort, P.; Levinson, S.C.; Toni, I.

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the "mirror neurons system"). However, this view does not explain how these conventions could develop in the first place. Here we

  19. Brain mechanisms underlying human communication

    NARCIS (Netherlands)

    Noordzij, Matthijs Leendert; Newman-Norlund, Sarah E.; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C.; Toni, Ivan

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”). However, this view does not explain how these conventions could develop in the first place. Here we

  20. Human brain evolution writ large and small.

    Science.gov (United States)

    Sherwood, Chet C; Bauernfeind, Amy L; Bianchi, Serena; Raghanti, Mary Ann; Hof, Patrick R

    2012-01-01

    Human evolution was marked by an extraordinary increase in total brain size relative to body size. While it is certain that increased encephalization is an important factor contributing to the origin of our species-specific cognitive abilities, it is difficult to disentangle which aspects of human neural structure and function are correlated by-products of brain size expansion from those that are specifically related to particular psychological specializations, such as language and enhanced "mentalizing" abilities. In this chapter, we review evidence from allometric scaling studies demonstrating that much of human neocortical organization can be understood as a product of brain enlargement. Defining extra-allometric specializations in humans is often hampered by a severe lack of comparative data from the same neuroanatomical variables across a broad range of primates. When possible, we highlight evidence for features of human neocortical architecture and function that cannot be easily explained as correlates of brain size and, hence, might be more directly associated with the evolution of uniquely human cognitive capacities. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Marco Schlepütz

    Full Text Available The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS respond to electric field stimulation (EFS and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM caused bronchoconstriction in human (4 from 7 and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC. However, this effect was notably smaller in human responder (30 ± 7.1% than in guinea pig (79 ± 5.1% PCLS. The transient receptor potential (TRP channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

  2. Consumption of seaweeds and the human brain

    DEFF Research Database (Denmark)

    Cornish, M. Lynn; Critchley, Alan T.; Mouritsen, Ole G.

    2017-01-01

    Much of the content of the human head is brain matter. This functions as the epicenter of human physical existence, including a sense of well-being and the manifestation of human consciousness. The human brain is a precious and complex organ which increases from 350 to 400 g in infants to 1......, and the impacts of anti-oxidant activities in neuroprotection. These elements have the capacity to help in the defense of human cognitive disorders, such as dementia, Alzheimer’s disease, depression, bipolar diseases, and adverse conditions characterized by progressive neurodegeneration. Psychological benefits...... associated with the moderate consumption of a diet fortified with macroalgae are also discussed in terms of reduction of depressive symptoms and furthermore highlighting possible improvements in sexual function....

  3. The human brain. Prenatal development and structure

    Energy Technology Data Exchange (ETDEWEB)

    Marin-Padilla, Miguel

    2011-07-01

    This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

  4. Molecular insights into human brain evolution.

    Science.gov (United States)

    Hill, Robert Sean; Walsh, Christopher A

    2005-09-01

    Rapidly advancing knowledge of genome structure and sequence enables new means for the analysis of specific DNA changes associated with the differences between the human brain and that of other mammals. Recent studies implicate evolutionary changes in messenger RNA and protein expression levels, as well as DNA changes that alter amino acid sequences. We can anticipate having a systematic catalogue of DNA changes in the lineage leading to humans, but an ongoing challenge will be relating these changes to the anatomical and functional differences between our brain and that of our ancient and more recent ancestors.

  5. Human intelligence and brain networks.

    Science.gov (United States)

    Colom, Roberto; Karama, Sherif; Jung, Rex E; Haier, Richard J

    2010-01-01

    Intelligence can be defined as a general mental ability for reasoning, problem solving, and learning. Because of its general nature, intelligence integrates cognitive functions such as perception, attention, memory, language, or planning. On the basis of this definition, intelligence can be reliably measured by standardized tests with obtained scores predicting several broad social outcomes such as educational achievement, job performance, health, and longevity. A detailed understanding of the brain mechanisms underlying this general mental ability could provide significant individual and societal benefits. Structural and functional neuroimaging studies have generally supported a frontoparietal network relevant for intelligence. This same network has also been found to underlie cognitive functions related to perception, short-term memory storage, and language. The distributed nature of this network and its involvement in a wide range of cognitive functions fits well with the integrative nature of intelligence. A new key phase of research is beginning to investigate how functional networks relate to structural networks, with emphasis on how distributed brain areas communicate with each other.

  6. REVISITING GLYCOGEN CONTENT IN THE HUMAN BRAIN

    Science.gov (United States)

    Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Seaquist, Elizabeth R.

    2015-01-01

    Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3–4 µmol/g brain glycogen content using in vivo 13C magnetic resonance spectroscopy (MRS) in conjunction with [1-13C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3–5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state 13C labeling in glycogen, here we administered [1-13C]glucose to healthy volunteers for 80 hours. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-13C]glucose administration and 13C-glycogen levels in the occipital lobe were measured by 13C MRS approximately every 12 hours. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the 13C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain. PMID:26202425

  7. Essential fatty acids and human brain.

    Science.gov (United States)

    Chang, Chia-Yu; Ke, Der-Shin; Chen, Jen-Yin

    2009-12-01

    The human brain is nearly 60 percent fat. We've learned in recent years that fatty acids are among the most crucial molecules that determine your brain's integrity and ability to perform. Essential fatty acids (EFAs) are required for maintenance of optimal health but they can not synthesized by the body and must be obtained from dietary sources. Clinical observation studies has related imbalance dietary intake of fatty acids to impaired brain performance and diseases. Most of the brain growth is completed by 5-6 years of age. The EFAs, particularly the omega-3 fatty acids, are important for brain development during both the fetal and postnatal period. Dietary decosahexaenoic acid (DHA) is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Beyond their important role in building the brain structure, EFAs, as messengers, are involved in the synthesis and functions of brain neurotransmitters, and in the molecules of the immune system. Neuronal membranes contain phospholipid pools that are the reservoirs for the synthesis of specific lipid messengers on neuronal stimulation or injury. These messengers in turn participate in signaling cascades that can either promote neuronal injury or neuroprotection. The goal of this review is to give a new understanding of how EFAs determine our brain's integrity and performance, and to recall the neuropsychiatric disorders that may be influenced by them. As we further unlock the mystery of how fatty acids affect the brain and better understand the brain's critical dependence on specific EFAs, correct intake of the appropriate diet or supplements becomes one of the tasks we undertake in pursuit of optimal wellness.

  8. Dynamic Multi-Coil Shimming of the Human Brain at 7 Tesla

    Science.gov (United States)

    Juchem, Christoph; Nixon, Terence W.; McIntyre, Scott; Boer, Vincent O.; Rothman, Douglas L.; de Graaf, Robin A.

    2011-01-01

    High quality magnetic field homogenization of the human brain (i.e. shimming) for MR imaging and spectroscopy is a demanding task. The susceptibility differences between air and tissue are a longstanding problem as they induce complex field distortions in the prefrontal cortex and the temporal lobes. To date, the theoretical gains of high field MR have only been realized partially in the human brain due to limited magnetic field homogeneity. A novel shimming technique for the human brain is presented that is based on the combination of non-orthogonal basis fields from 48 individual, circular coils. Custom-built amplifier electronics enabled the dynamic application of the multi-coil shim fields in a slice-specific fashion. Dynamic multi-coil (DMC) shimming is shown to eliminate most of the magnetic field inhomogeneity apparent in the human brain at 7 Tesla and provided improved performance compared to state-of-the-art dynamic shim updating with zero through third order spherical harmonic functions. The novel technique paves the way for high field MR applications of the human brain for which excellent magnetic field homogeneity is a prerequisite. PMID:21824794

  9. Constrained reverse diffusion for thick slice interpolation of 3D volumetric MRI images.

    Science.gov (United States)

    Neubert, Aleš; Salvado, Olivier; Acosta, Oscar; Bourgeat, Pierrick; Fripp, Jurgen

    2012-03-01

    Due to physical limitations inherent in magnetic resonance imaging scanners, three dimensional volumetric scans are often acquired with anisotropic voxel resolution. We investigate several interpolation approaches to reduce the anisotropy and present a novel approach - constrained reverse diffusion for thick slice interpolation. This technique was compared to common methods: linear and cubic B-Spline interpolation and a technique based on non-rigid registration of neighboring slices. The methods were evaluated on artificial MR phantoms and real MR scans of human brain. The constrained reverse diffusion approach delivered promising results and provides an alternative for thick slice interpolation, especially for higher anisotropy factors.

  10. Simple models of human brain functional networks.

    Science.gov (United States)

    Vértes, Petra E; Alexander-Bloch, Aaron F; Gogtay, Nitin; Giedd, Jay N; Rapoport, Judith L; Bullmore, Edward T

    2012-04-10

    Human brain functional networks are embedded in anatomical space and have topological properties--small-worldness, modularity, fat-tailed degree distributions--that are comparable to many other complex networks. Although a sophisticated set of measures is available to describe the topology of brain networks, the selection pressures that drive their formation remain largely unknown. Here we consider generative models for the probability of a functional connection (an edge) between two cortical regions (nodes) separated by some Euclidean distance in anatomical space. In particular, we propose a model in which the embedded topology of brain networks emerges from two competing factors: a distance penalty based on the cost of maintaining long-range connections; and a topological term that favors links between regions sharing similar input. We show that, together, these two biologically plausible factors are sufficient to capture an impressive range of topological properties of functional brain networks. Model parameters estimated in one set of functional MRI (fMRI) data on normal volunteers provided a good fit to networks estimated in a second independent sample of fMRI data. Furthermore, slightly detuned model parameters also generated a reasonable simulation of the abnormal properties of brain functional networks in people with schizophrenia. We therefore anticipate that many aspects of brain network organization, in health and disease, may be parsimoniously explained by an economical clustering rule for the probability of functional connectivity between different brain areas.

  11. Effects of aspirin plus alpha-tocopherol on brain slices damage after hypoxia-reoxygenation in rats with type 1-like diabetes mellitus.

    Science.gov (United States)

    González-Correa, J A; Arrebola, M M; Cansino, A L; Muñoz-Marín, J; Guerrero, A; Sánchez de la Cuesta, F; De la Cruz, J P

    2006-06-12

    Diabetes mellitus is a risk factor for cerebrovascular ischemic disease. Aspirin (acetylsalicylic acid) is the most widely used drug for the secondary prevention of thrombotic phenomena. It has been also recently demonstrated that alpha-tocopherol influenced in vitro the antiplatelet effect of aspirin. The aim of the present study is to evaluate the effects aspirin plus alpha-tocopherol on cerebral oxidative stress, prostaglandin production and the nitric oxide pathway in a model of hypoxia-reoxygenation in rat brain slices. Our results show an imbalance in brain oxidative status (reflected mainly as the increase in lipid peroxides) as a result of diabetes itself rather than a failure of the glutathione-based antioxidant system. Moreover, our results also show a higher concentration of prostaglandins in the brain of diabetic animals and a higher nitric oxide concentration, mainly through a high iNOS activity. After 180 min of post-hypoxia reoxygenation, LDH activity was 40.6% higher in animals with diabetes, in comparison to non-diabetic animals. The increase of the LDH efflux observed in non-treated rats was reduced by 31.2% with aspirin, by 34.7% with alpha-tocopherol and by 69.8% with the association aspirin-alpha-tocopherol. The accumulation of prostaglandin E2 observed in diabetic non-treated rats was reduced statistically after the treatment with aspirin (34.2% inhibition), alpha-tocopherol (19.3% inhibition) or the association aspirin-alpha-tocopherol (54.4% inhibition). Nitric oxide production after 180 min reoxygenation was significantly reduced in aspirin (36.4%), alpha-tocopherol (22.7%) and aspirin-alpha-tocopherol (77.8%) treated rats with respect to diabetic non-treated animals; this was related mainly with a reduction in iNOS activity. The association between aspirin and alpha tocopherol could protects against brain ischemic-reperfusion damage with a better profile than aspirin alone.

  12. Time-lapse Confocal Imaging of Migrating Neurons in Organotypic Slice Culture of Embryonic Mouse Brain Using In Utero Electroporation.

    Science.gov (United States)

    Wiegreffe, Christoph; Feldmann, Svenja; Gaessler, Simeon; Britsch, Stefan

    2017-07-25

    In utero electroporation is a rapid and powerful approach to study the process of radial migration in the cerebral cortex of developing mouse embryos. It has helped to describe the different steps of radial migration and characterize the molecular mechanisms controlling this process. To directly and dynamically analyze migrating neurons they have to be traced over time. This protocol describes a workflow that combines in utero electroporation with organotypic slice culture and time-lapse confocal imaging, which allows for a direct examination and dynamic analysis of radially migrating cortical neurons. Furthermore, detailed characterization of migrating neurons, such as migration speed, speed profiles, as well as radial orientation changes, is possible. The method can easily be adapted to perform functional analyses of genes of interest in radially migrating cortical neurons by loss and gain of function as well as rescue experiments. Time-lapse imaging of migrating neurons is a state-of-the-art technique that once established is a potent tool to study the development of the cerebral cortex in mouse models of neuronal migration disorders.

  13. The impact of PPARalpha activation on whole genome gene expression in human precision cut liver slices

    NARCIS (Netherlands)

    Janssen, A.W.H.; Betzel, B; Stoopen, G.; Berends, F.J.; Janssen, I.M.C.; Peijnenburg, A.A.; Kersten, S.

    2015-01-01

    BACKGROUND: Studies in mice have shown that PPARalpha is an important regulator of lipid metabolism in liver and key transcription factor involved in the adaptive response to fasting. However, much less is known about the role of PPARalpha in human liver. METHODS: Here we set out to study the functi

  14. Effect of human liver source on the functionality of isolated hepatocytes and liver slices

    NARCIS (Netherlands)

    Olinga, Peter; Hof, I.H; de Jong, Kurt; Slooff, M.JH; Meijer, D.K F; Groothuis, Geny; Merema, M.T.

    1998-01-01

    In vitro experiments using human liver tissue to study drug metabolism and transport are usually performed and interpreted without real consideration of the differences in procurement of the tissue, if it is obtained from different sources. Therefore, in this study the functionality of isolated hepa

  15. Brain activation during human male ejaculation

    NARCIS (Netherlands)

    Holstege, Ger; Georgiadis, Janniko R.; Paans, Anne M.J.; Meiners, Linda C.; Graaf, Ferdinand H.C.E. van der; Reinders, A.A.T.Simone

    2003-01-01

    Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers.

  16. Culturing of PC12 Cells, Neuronal Cells, Astrocytes Cultures and Brain Slices in an Open Microfluidic System

    DEFF Research Database (Denmark)

    Al Atraktchi, Fatima Al-Zahraa; Bakmand, Tanya; Rømer Sørensen, Ane

    The brain is the center of the nervous system, where serious neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s are products of functional loss in the neural cells (1). Typical techniques used to investigate these diseases lack precise control of the cellular surroundings...

  17. The inflammatory molecules IL-1β and HMGB1 can rapidly enhance focal seizure generation in a brain slice model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Angela eChiavegato

    2014-06-01

    Full Text Available Epilepsy is a neurological disorder characterized by a hyperexcitable brain tissue and unpredictable seizures, i.e., aberrant firing discharges in large neuronal populations. It is well established that proinflammatory cytokines, in addition to their canonical involvement in the immune response, have a crucial role in the mechanism of seizure generation. The purpose of the present study was to investigate the role of interleukin-1β (IL-1β and high mobility group B1 (HMGB1 in the generation of seizure-like discharges using two models of focal epilepsy in a rat entorhinal cortex slice preparation. Seizure like-discharges were evoked by either slice perfusion with low Mg2+ and picrotoxin or with a double NMDA local stimulation in the presence of the proconvulsant 4-amino-pyridine. The effects of IL-1β or HMGB1 were evaluated by monitoring seizure discharge generation through laser scanning microscope imaging of Ca2+ signals from neurons and astrocytes. In the picrotoxin model, we revealed that both cytokines increased the mean frequency of spontaneous ictal-like discharges, whereas only IL-1β reduced the latency and prolonged the duration of the first ictal-like event. In the second model, a single NMDA pulse, per se ineffective, became successful when it was performed after IL-β or HMGB1 local applications. These findings demonstrate that both IL-1β and HMGB1 can rapidly lower focal ictal event threshold and strengthen the possibility that targeting these inflammatory pathways may represent an effective therapeutic strategy to prevent seizures.

  18. Adeno-Associated Viral Vectors Transduce Mature Human Adipocytes in Three-Dimensional Slice Cultures.

    Science.gov (United States)

    Kallendrusch, Sonja; Schopow, Nikolas; Stadler, Sonja C; Büning, Hildegard; Hacker, Ulrich T

    2016-10-01

    Adipose tissue plays a pivotal role, both in the regulation of energy homeostasis and as an endocrine organ. Consequently, adipose tissue dysfunction is closely related to insulin resistance, morbid obesity, and metabolic syndrome. To study molecular mechanisms and to develop novel therapeutic strategies, techniques are required to genetically modify mature adipocytes. Here, we report on adeno-associated viral (AAV) vectors as a versatile tool to transduce human mature adipocytes in organotypic three-dimensional tissue cultures.

  19. Evolution and genomics of the human brain.

    Science.gov (United States)

    Rosales-Reynoso, M A; Juárez-Vázquez, C I; Barros-Núñez, P

    2015-08-21

    Most living beings are able to perform actions that can be considered intelligent or, at the very least, the result of an appropriate reaction to changing circumstances in their environment. However, the intelligence or intellectual processes of humans are vastly superior to those achieved by all other species. The adult human brain is a highly complex organ weighing approximately 1500g, which accounts for only 2% of the total body weight but consumes an amount of energy equal to that required by all skeletal muscle at rest. Although the human brain displays a typical primate structure, it can be identified by its specific distinguishing features. The process of evolution and humanisation of the Homo sapiens brain resulted in a unique and distinct organ with the largest relative volume of any animal species. It also permitted structural reorganization of tissues and circuits in specific segments and regions. These steps explain the remarkable cognitive abilities of modern humans compared not only with other species in our genus, but also with older members of our own species. Brain evolution required the coexistence of two adaptation mechanisms. The first involves genetic changes that occur at the species level, and the second occurs at the individual level and involves changes in chromatin organisation or epigenetic changes. The genetic mechanisms include: a) genetic changes in coding regions that lead to changes in the sequence and activity of existing proteins; b) duplication and deletion of previously existing genes; c) changes in gene expression through changes in the regulatory sequences of different genes; and d) synthesis of non-coding RNAs. Lastly, this review describes some of the main documented chromosomal differences between humans and great apes. These differences have also contributed to the evolution and humanisation process of the H. sapiens brain. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights

  20. Magnetite pollution nanoparticles in the human brain

    Science.gov (United States)

    Maher, Barbara A.; Ahmed, Imad A. M.; Karloukovski, Vassil; MacLaren, Donald A.; Foulds, Penelope G.; Allsop, David; Mann, David M. A.; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

    2016-09-01

    Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.

  1. [Evolution of human brain and intelligence].

    Science.gov (United States)

    Lakatos, László; Janka, Zoltán

    2008-07-30

    The biological evolution, including human evolution is mainly driven by environmental changes. Accidental genetic modifications and their innovative results make the successful adaptation possible. As we know the human evolution started 7-8 million years ago in the African savannah, where upright position and bipedalism were significantly advantageous. The main drive of improving manual actions and tool making could be to obtain more food. Our ancestor got more meat due to more successful hunting, resulting in more caloric intake, more protein and essential fatty acid in the meal. The nervous system uses disproportionally high level of energy, so better quality of food was a basic condition for the evolution of huge human brain. The size of human brain was tripled during 3.5 million years, it increased from the average of 450 cm3 of Australopithecinae to the average of 1350 cm3 of Homo sapiens. A genetic change in the system controlling gene expression could happen about 200 000 years ago, which influenced the development of nervous system, the sensorimotor function and learning ability for motor processes. The appearance and stabilisation of FOXP2 gene structure as feature of modern man coincided with the first presence and quick spread of Homo sapiens on the whole Earth. This genetic modification made opportunity for human language, as the basis of abrupt evolution of human intelligence. The brain region being responsible for human language is the left planum temporale, which is much larger in left hemisphere. This shows the most typical human brain asymmetry. In this case the anatomical asymmetry means a clearly defined functional asymmetry as well, where the brain hemispheres act differently. The preference in using hands, the lateralised using of tools resulted in the brain asymmetry, which is the precondition of human language and intelligence. However, it cannot be held anymore, that only humans make tools, because our closest relatives, the chimpanzees are

  2. Zika virus impairs growth in human neurospheres and brain organoids.

    Science.gov (United States)

    Garcez, Patricia P; Loiola, Erick Correia; Madeiro da Costa, Rodrigo; Higa, Luiza M; Trindade, Pablo; Delvecchio, Rodrigo; Nascimento, Juliana Minardi; Brindeiro, Rodrigo; Tanuri, Amilcar; Rehen, Stevens K

    2016-05-13

    Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased considerably in Brazil; however, causality between the viral epidemic and malformations in fetal brains needs further confirmation. We examined the effects of ZIKV infection in human neural stem cells growing as neurospheres and brain organoids. Using immunocytochemistry and electron microscopy, we showed that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and brain organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development.

  3. Epilepsy: Extreme Events in the Human Brain

    Science.gov (United States)

    Lehnertz, Klaus

    The analysis of Xevents arising in dynamical systems with many degrees of freedom represents a challenge for many scientific fields. This is especially true for the open, dissipative, and adaptive system known as the human brain. Due to its complex structure, its immense functionality, and — as in the case of epilepsy — due to the coexistence of normal and abnormal functions, the brain can be regarded as one of the most complex and fascinating systems in nature. Data gathered so far show that the epileptic process exhibits a high spatial and temporal variability. Small, specific, regions of the brain are responsible for the generation of focal epileptic seizures, and the amount of time a patient spends actually having seizures is only a small fraction of his/her lifetime. In between these Xevents large parts of the brain exhibit normal functioning. Since the occurrence of seizures usually can not be explained by exogenous factors, and since the brain recovers its normal state after a seizure in the majority of cases, this might indicate that endogenous nonlinear (deterministic and/or stochastic) properties are involved in the control of these Xevents. In fact, converging evidence now indicates that (particularly) nonlinear approaches to the analysis of brain activity allow us to define precursors which, provided sufficient sensitivity and specificity can be obtained, might lead to the development of patient-specific seizure anticipation and seizure prevention strategies.

  4. The pedunculopontine tegmental nucleus: from basic neuroscience to neurosurgical applications: arousal from slices to humans: implications for DBS.

    Science.gov (United States)

    Garcia-Rill, Edgar; Simon, Christen; Smith, Kristen; Kezunovic, Nebosja; Hyde, James

    2011-10-01

    One element of the reticular activating system (RAS) is the pedunculopontine nucleus (PPN), which projects to the thalamus to trigger thalamocortical rhythms and the brainstem to modulate muscle tone and locomotion. The PPN is a posterior midbrain site known to induce locomotion in decerebrate animals when activated at 40-60 Hz, and has become a target for DBS in disorders involving gait deficits. We developed a research program using brainstem slices containing the PPN to study the cellular and molecular organization of this region. We showed that PPN neurons preferentially fire at gamma band frequency (30-60 Hz) when maximally activated, accounting for the effects of electrical stimulation. In addition, we developed the P13 midlatency auditory evoked potential, which is generated by PPN outputs, in freely moving rats. This allows the study of PPN cellular and molecular mechanisms in the whole animal. We also study the P50 midlatency auditory evoked potential, which is the human equivalent of the rodent P13 potential, allowing us to study PPN-related processes detected in vitro, confirmed in the whole animal, and tested in humans. Previous findings on the P50 potential in PD suggest that PPN output in this disorder is overactive. This translational research program led to the discovery of a novel mechanism of sleep-wake control based on electrical coupling, pointing the way to a number of new clinical applications in the development of novel stimulants (e.g., modafinil) and anesthetics. In addition, it provides methods for monitoring therapeutic efficacy of DBS in humans and animal models.

  5. An ex vivo model to induce early fibrosis-like changes in human precision-cut lung slices.

    Science.gov (United States)

    Alsafadi, Hani N; Staab-Weijnitz, Claudia A; Lehmann, Mareike; Lindner, Michael; Peschel, Britta; Königshoff, Melanie; Wagner, Darcy E

    2017-06-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating chronic interstitial lung disease (ILD) characterized by lung tissue scarring and high morbidity. Lung epithelial injury, myofibroblast activation, and deranged repair are believed to be key processes involved in disease onset and progression, but the exact molecular mechanisms behind IPF remain unclear. Several drugs have been shown to slow disease progression, but treatments that halt or reverse IPF progression have not been identified. Ex vivo models of human lung have been proposed for drug discovery, one of which is precision-cut lung slices (PCLS). Although PCLS production from IPF explants is possible, IPF explants are rare and typically represent end-stage disease. Here we present a novel model of early fibrosis-like changes in human PCLS derived from patients without ILD/IPF using a combination of profibrotic growth factors and signaling molecules (transforming growth factor-β, tumor necrosis factor-α, platelet-derived growth factor-AB, and lysophosphatidic acid). Fibrotic-like changes of PCLS were qualitatively analyzed by histology and immunofluorescence and quantitatively by water-soluble tetrazolium-1, RT-qPCR, Western blot analysis, and ELISA. PCLS remained viable after 5 days of treatment, and fibrotic gene expression (FN1, SERPINE1, COL1A1, CTGF, MMP7, and ACTA2) increased as early as 24 h of treatment, with increases in protein levels at 48 h and increased deposition of extracellular matrix. Alveolar epithelium reprogramming was evident by decreases in surfactant protein C and loss of HOPX In summary, using human-derived PCLS, we established a novel ex vivo model that displays characteristics of early fibrosis and could be used to evaluate novel therapies and study early-stage IPF pathomechanisms. Copyright © 2017 the American Physiological Society.

  6. Native Mutant Huntingtin in Human Brain

    Science.gov (United States)

    Sapp, Ellen; Valencia, Antonio; Li, Xueyi; Aronin, Neil; Kegel, Kimberly B.; Vonsattel, Jean-Paul; Young, Anne B.; Wexler, Nancy; DiFiglia, Marian

    2012-01-01

    Huntington disease (HD) is caused by polyglutamine expansion in the N terminus of huntingtin (htt). Analysis of human postmortem brain lysates by SDS-PAGE and Western blot reveals htt as full-length and fragmented. Here we used Blue Native PAGE (BNP) and Western blots to study native htt in human postmortem brain. Antisera against htt detected a single band broadly migrating at 575–850 kDa in control brain and at 650–885 kDa in heterozygous and Venezuelan homozygous HD brains. Anti-polyglutamine antisera detected full-length mutant htt in HD brain. There was little htt cleavage even if lysates were pretreated with trypsin, indicating a property of native htt to resist protease cleavage. A soluble mutant htt fragment of about 180 kDa was detected with anti-htt antibody Ab1 (htt-(1–17)) and increased when lysates were treated with denaturants (SDS, 8 m urea, DTT, or trypsin) before BNP. Wild-type htt was more resistant to denaturants. Based on migration of in vitro translated htt fragments, the 180-kDa segment terminated ≈htt 670–880 amino acids. If second dimension SDS-PAGE followed BNP, the 180-kDa mutant htt was absent, and 43–50 kDa htt fragments appeared. Brain lysates from two HD mouse models expressed native full-length htt; a mutant fragment formed if lysates were pretreated with 8 m urea + DTT. Native full-length mutant htt in embryonic HD140Q/140Q mouse primary neurons was intact during cell death and when cell lysates were exposed to denaturants before BNP. Thus, native mutant htt occurs in brain and primary neurons as a soluble full-length monomer. PMID:22375012

  7. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

    2004-01-01

    Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

  8. Quantitative evaluation of benign meningioma and hemangiopericytoma with peritumoral brain edema by 64-slice CT perfusion imaging

    Institute of Scientific and Technical Information of China (English)

    REN Guang; CHEN Shuang; WANG Yin; ZHU Rui-jiang; GENG Dao-ying; FENG Xiao-yuan

    2010-01-01

    Background Hemangiopericytomas (HPCs) have a relentless tendency for local recurrence and metastases,differentiating between benign meningiomas and HPCs before surgery is important for both treatment planning and the prognosis appraisal.The purpose of this study was to evaluate the correlations between CT perfusion parameters and microvessel density (MVD) in extra-axial tumors and the possible role of CT perfusion imaging in preoperatively differentiating benign meningiomas and HPCs.Methods Seventeen patients with benign meningiomas and peritumoral edema, 12 patients with HPCs and peritumoral edema underwent 64-slice CT perfusion imaging pre-operation.Perfusion was calculated using the Patlak method.The quantitative parameters, include cerebral blood volume (CBV), permeability surface (PS) of parenchyma, peritumoral edema among benign meningiomas and HPCs were compared respectively.CBV and PS in parenchyma, peritumoral edema of benign meningiomas and HPCs were also compared to that of the contrallateral normal white matter respectively.The correlations between CBV, PS of tumoral parenchyma and MVD were examined.Results The value of CBV and PS in parenchyma of HPCs were significantly higher than that of benign meningiomas (P<0.05), while the values of CBV and PS in peritumoral edema of benign meningiomas and HPCs were not significantly different (P >0.05).MVD in parenchyma of HPCs were significantly higher than that of benign meningiomas (P<0.05).There were positive correlations between CBV and MVD (r=0.648, P<0.05), PS and MVD (r=0.541, P<0.05) respectively.Furthermore, the value of CBV and PS in parenchyma of benign meningiomas and HPCs were significantly higher than that of contrallateral normal white matter (P<0.05), the value of CBV in peritumoral edema of benign meningiomas and HPCs were significantly lower than that of contrallateral normal white matter (P<0.05), while the value of PS in peritumoral edema of benign meningiomas and HPCs were not

  9. Evaluation of 2D multiband EPI imaging for high-resolution, whole-brain, task-based fMRI studies at 3T: Sensitivity and slice leakage artifacts.

    Science.gov (United States)

    Todd, Nick; Moeller, Steen; Auerbach, Edward J; Yacoub, Essa; Flandin, Guillaume; Weiskopf, Nikolaus

    2016-01-01

    Functional magnetic resonance imaging (fMRI) studies that require high-resolution whole-brain coverage have long scan times that are primarily driven by the large number of thin slices acquired. Two-dimensional multiband echo-planar imaging (EPI) sequences accelerate the data acquisition along the slice direction and therefore represent an attractive approach to such studies by improving the temporal resolution without sacrificing spatial resolution. In this work, a 2D multiband EPI sequence was optimized for 1.5mm isotropic whole-brain acquisitions at 3T with 10 healthy volunteers imaged while performing simultaneous visual and motor tasks. The performance of the sequence was evaluated in terms of BOLD sensitivity and false-positive activation at multiband (MB) factors of 1, 2, 4, and 6, combined with in-plane GRAPPA acceleration of 2× (GRAPPA 2), and the two reconstruction approaches of Slice-GRAPPA and Split Slice-GRAPPA. Sensitivity results demonstrate significant gains in temporal signal-to-noise ratio (tSNR) and t-score statistics for MB 2, 4, and 6 compared to MB 1. The MB factor for optimal sensitivity varied depending on anatomical location and reconstruction method. When using Slice-GRAPPA reconstruction, evidence of false-positive activation due to signal leakage between simultaneously excited slices was seen in one instance, 35 instances, and 70 instances over the ten volunteers for the respective accelerations of MB 2×GRAPPA 2, MB 4×GRAPPA 2, and MB 6×GRAPPA 2. The use of Split Slice-GRAPPA reconstruction suppressed the prevalence of false positives significantly, to 1 instance, 5 instances, and 5 instances for the same respective acceleration factors. Imaging protocols using an acceleration factor of MB 2×GRAPPA 2 can be confidently used for high-resolution whole-brain imaging to improve BOLD sensitivity with very low probability for false-positive activation due to slice leakage. Imaging protocols using higher acceleration factors (MB 3 or MB 4

  10. Differentiation of human bone marrow precursor cells into neuronal-like cells after transplantation into canine spinal cord organotypic slice cultures

    Institute of Scientific and Technical Information of China (English)

    FEI Zhi-qiang; XIONG Jian-yi; CHEN Lei; SHEN Hui-yong; Ngo Stephanie; Wang Jeffrey; WANG Da-ping

    2012-01-01

    Background Treatments to regenerate different tissue involving the transplantation of bone marrow derived mesenchymal precursor cells are anticipated.Using an alternative methods,in vitro organotypic slice culture method,would be useful to transplant cells and assessing the effects.This study was to determine the possibility of differentiating human bone marrow precursor cells into cells of the neuronal lineage by transplanting into canine spinal cord organotypic slice cultures.Methods Bone marrow aspirates were obtained from posterior superior iliac spine(PSIS)of patients that had undergone spinal fusion due to a degenerative spinal disorder.For cell imaging,mesenchymal precursor cells(MPCs)were pre-stained with PKH-26 just before transplantation to canine spinal cord slices.Canine spinal cord tissues were obtained from three adult beagle dogs.Spinal cords were cut into transverse slices of 1 mm using tissue chopper.Two slices were transferred into 6-well plate containing 3 ml DMEM with antibiotics.Prepared MPCs(1×104)were transplanted into spinal cord slices.On days 0,3,7,14,MPCs were observed for morphological changes and expression of neuronal markers through immunofluorescence and reverse transcription-polymerase chain reaction(RT-PCR).Results The morphological study showed:spherical cells in the control and experiment groups on day 0;and on day 3,cells in the control group had one or two thick,short processes and ones in the experiment group had three or four thin,long processes.On day 7,these variously-sized processes contacted each other in the experiment group,but showed typical spindle-shaped cells in the control group.Immunofluorescence showed that PKH-26(+)MPCs stained positive for NeuN(+)and GFAP(+)in experimental group only.Also RT-PCR showed weak expression of β-tubulinⅢ?and GFAP.Conclusions Human bone marrow mesenchymal precursor cells(hMPCs)have the potential to differentiate into the neuronal like cells in this canine spinal cord organotypic

  11. Infrasounds and biorhythms of the human brain

    Science.gov (United States)

    Panuszka, Ryszard; Damijan, Zbigniew; Kasprzak, Cezary; McGlothlin, James

    2002-05-01

    Low Frequency Noise (LFN) and infrasound has begun a new public health hazard. Evaluations of annoyance of (LFN) on human occupational health were based on standards where reactions of human auditory system and vibrations of parts of human body were small. Significant sensitivity has been observed on the central nervous system from infrasonic waves especially below 10 Hz. Observed follow-up effects in the brain gives incentive to study the relationship between parameters of waves and reactions obtained of biorhythms (EEG) and heart action (EKG). New results show the impact of LFN on the electrical potentials of the brain are dependent on the pressure waves on the human body. Electrical activity of circulatory system was also affected. Signals recorded in industrial workplaces were duplicated by loudspeakers and used to record data from a typical LFN spectra with 5 and 7 Hz in a laboratory chamber. External noise, electromagnetic fields, temperature, dust, and other elements were controlled. Results show not only a follow-up effect in the brain but also a result similar to arrhythmia in the heart. Relaxations effects were observed of people impacted by waves generated from natural sources such as streams and waterfalls.

  12. Broadband criticality of human brain network synchronization.

    Directory of Open Access Journals (Sweden)

    Manfred G Kitzbichler

    2009-03-01

    Full Text Available Self-organized criticality is an attractive model for human brain dynamics, but there has been little direct evidence for its existence in large-scale systems measured by neuroimaging. In general, critical systems are associated with fractal or power law scaling, long-range correlations in space and time, and rapid reconfiguration in response to external inputs. Here, we consider two measures of phase synchronization: the phase-lock interval, or duration of coupling between a pair of (neurophysiological processes, and the lability of global synchronization of a (brain functional network. Using computational simulations of two mechanistically distinct systems displaying complex dynamics, the Ising model and the Kuramoto model, we show that both synchronization metrics have power law probability distributions specifically when these systems are in a critical state. We then demonstrate power law scaling of both pairwise and global synchronization metrics in functional MRI and magnetoencephalographic data recorded from normal volunteers under resting conditions. These results strongly suggest that human brain functional systems exist in an endogenous state of dynamical criticality, characterized by a greater than random probability of both prolonged periods of phase-locking and occurrence of large rapid changes in the state of global synchronization, analogous to the neuronal "avalanches" previously described in cellular systems. Moreover, evidence for critical dynamics was identified consistently in neurophysiological systems operating at frequency intervals ranging from 0.05-0.11 to 62.5-125 Hz, confirming that criticality is a property of human brain functional network organization at all frequency intervals in the brain's physiological bandwidth.

  13. Human brain disease recreated in mice

    Energy Technology Data Exchange (ETDEWEB)

    Marx, J.

    1990-12-14

    In the early 1980s, neurologist Stanley Prusiner suggested that scrapie, an apparently infectious degenerative brain disease of sheep, could be transmitted by prions, infectious particles made just of protein - and containing no nucleic acids. But prion research has come a long way since then. In 1985, the cloning of the gene encoding the prion protein proved that it does in fact exist. And the gene turned out to be widely expressed in the brains of higher organisms, a result suggesting that the prion protein has a normal brain function that can somehow be subverted, leading to brain degeneration. Then studies done during the past 2 years suggested that specific mutations in the prion gene might cause two similar human brain diseases, Gerstmann-Straeussler-Scheinker syndrome (GSS) and Creutzfelt-Jakob disease. Now, Prusiner's group at the University of California, San Francisco, has used genetic engineering techniques to recreate GSS by transplanting the mutated prion gene into mice. Not only will the animal model help neurobiologists answer the many remaining questions about prions and how they work, but it may also shed some light on other neurodegenerative diseases as well.

  14. Hierarchical modularity in human brain functional networks

    CERN Document Server

    Meunier, D; Fornito, A; Ersche, K D; Bullmore, E T; 10.3389/neuro.11.037.2009

    2010-01-01

    The idea that complex systems have a hierarchical modular organization originates in the early 1960s and has recently attracted fresh support from quantitative studies of large scale, real-life networks. Here we investigate the hierarchical modular (or "modules-within-modules") decomposition of human brain functional networks, measured using functional magnetic resonance imaging (fMRI) in 18 healthy volunteers under no-task or resting conditions. We used a customized template to extract networks with more than 1800 regional nodes, and we applied a fast algorithm to identify nested modular structure at several hierarchical levels. We used mutual information, 0 < I < 1, to estimate the similarity of community structure of networks in different subjects, and to identify the individual network that is most representative of the group. Results show that human brain functional networks have a hierarchical modular organization with a fair degree of similarity between subjects, I=0.63. The largest 5 modules at ...

  15. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

    2005-01-01

    Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

  16. Imaging Monoamine Oxidase in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-11-10

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets.

  17. Involvement of striatal lipid peroxidation and inhibition of calcium influx into brain slices in neurobehavioral alterations in a rat model of short-term oral exposure to manganese.

    Science.gov (United States)

    Avila, Daiana Silva; Gubert, Priscila; Fachinetto, Roselei; Wagner, Caroline; Aschner, Michael; Rocha, João Batista Teixeira; Soares, Félix Alexandre Antunes

    2008-11-01

    Manganese is an essential element for biological systems, nevertheless occupational exposure to high levels of Mn can lead to neurodegenerative disorder, characterized by excessive Mn accumulation, especially in astrocytes of basal ganglia and symptoms closely resembling idiopathic Parkinson's disease (PD). The purpose of this study was to evaluate behavioral and biochemical alterations in adult rats exposed for 30 days to 10 and 25mg/mL of MnCl(2) in their drinking water. MnCl(2) intoxicated rats showed impaired locomotor activity in comparison to control animals. Furthermore, lipid peroxidation were increased, delta-aminolevulinate dehydratase (delta-ALA-D, an enzyme sensitive to pro-oxidant situations) activity was inhibited and (45)Ca(2+) influx into striatal slices was decreased in rats exposed to 25mg/mL of Mn, indicating that this brain region was markedly affected by short-term Mn exposure. In contrast, Mn exposure was not associated with characteristic extrapyramidal effects and did not modify protein oxidation, suggesting that the striatal damage represents early stages of Mn-induced damage. In addition, treatment with Mn was associated with reduced body weight gain, but there were no discernible alterations in liver and kidney function. In conclusion, Mn caused increased oxidative stress and decreased (45)Ca(2+) influx into the striatum, which are likely linked to impaired locomotor activity, but not with the occurrence of orofacial dyskinesia.

  18. N-Methyl-d-aspartate Modulation of Nucleus Accumbens Dopamine Release by Metabotropic Glutamate Receptors: Fast Cyclic Voltammetry Studies in Rat Brain Slices in Vitro.

    Science.gov (United States)

    Yavas, Ersin; Young, Andrew M J

    2017-02-15

    The N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine, induces behavioral changes in rodents mimicking symptoms of schizophrenia, possibly mediated through dysregulation of glutamatergic control of mesolimbic dopamine release. We tested the hypothesis that NMDA receptor activation modulates accumbens dopamine release, and that phencyclidine pretreatment altered this modulation. NMDA caused a receptor-specific, dose-dependent decrease in electrically stimulated dopamine release in nucleus accumbens brain slices. This decrease was unaffected by picrotoxin, making it unlikely to be mediated through GABAergic neurones, but was decreased by the metabotropic glutamate receptor antagonist, (RS)-α-methyl-4-sulfonophenylglycine, indicating that NMDA activates mechanisms controlled by these receptors to decrease stimulated dopamine release. The effect of NMDA was unchanged by in vivo pretreatment with phencyclidine (twice daily for 5 days), with a washout period of at least 7 days before experimentation, which supports the hypothesis that there is no enduring direct effect of PCP at NMDA receptors after this pretreatment procedure. We propose that NMDA depression of accumbal dopamine release is mediated by metabotropic glutamate receptors located pre- or perisynaptically, and suggest that NMDA evoked increased extrasynaptic spillover of glutamate is sufficient to activate these receptors that, in turn, inhibit dopamine release. Furthermore, we suggest that enduring functional changes brought about by subchronic phencyclidine pretreatment, modeling deficits in schizophrenia, are downstream effects consequent on chronic blockade of NMDA receptors, rather than direct effects on NMDA receptors themselves.

  19. Brain stem slice conditioned medium contains endogenous BDNF and GDNF that affect neural crest boundary cap cells in co-culture.

    Science.gov (United States)

    Kaiser, Andreas; Kale, Ajay; Novozhilova, Ekaterina; Siratirakun, Piyaporn; Aquino, Jorge B; Thonabulsombat, Charoensri; Ernfors, Patrik; Olivius, Petri

    2014-05-30

    Conditioned medium (CM), made by collecting medium after a few days in cell culture and then re-using it to further stimulate other cells, is a known experimental concept since the 1950s. Our group has explored this technique to stimulate the performance of cells in culture in general, and to evaluate stem- and progenitor cell aptitude for auditory nerve repair enhancement in particular. As compared to other mediums, all primary endpoints in our published experimental settings have weighed in favor of conditioned culture medium, where we have shown that conditioned culture medium has a stimulatory effect on cell survival. In order to explore the reasons for this improved survival we set out to analyze the conditioned culture medium. We utilized ELISA kits to investigate whether brain stem (BS) slice CM contains any significant amounts of brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF). We further looked for a donor cell with progenitor characteristics that would be receptive to BDNF and GDNF. We chose the well-documented boundary cap (BC) progenitor cells to be tested in our in vitro co-culture setting together with cochlear nucleus (CN) of the BS. The results show that BS CM contains BDNF and GDNF and that survival of BC cells, as well as BC cell differentiation into neurons, were enhanced when BS CM were used. Altogether, we conclude that BC cells transplanted into a BDNF and GDNF rich environment could be suitable for treatment of a traumatized or degenerated auditory nerve. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Stimulant mechanisms of cathinones - effects of mephedrone and other cathinones on basal and electrically evoked dopamine efflux in rat accumbens brain slices.

    Science.gov (United States)

    Opacka-Juffry, Jolanta; Pinnell, Thomas; Patel, Nisha; Bevan, Melissa; Meintel, Meghan; Davidson, Colin

    2014-10-01

    Mephedrone, an erstwhile "legal high", and some non-abused cathinones (ethcathinone, diethylpropion and bupropion) were tested for stimulant effects in vitro, through assessing their abilities to increase basal and electrically evoked dopamine efflux in rat accumbens brain slices, and compared with cocaine and amphetamine. We also tested mephedrone against cocaine in a dopamine transporter binding study. Dopamine efflux was electrically evoked and recorded using voltammetry in the rat accumbens core. We constructed concentration response curves for these cathinones for effects on basal dopamine levels; peak efflux after local electrical stimulation and the time-constant of the dopamine decay phase, an index of dopamine reuptake. We also examined competition between mephedrone or cocaine and [(125)I]RTI121 at the dopamine transporter. Mephedrone was less potent than cocaine at displacing [(125)I]RTI121. Mephedrone and amphetamine increased basal levels of dopamine in the absence of electrical stimulation. Cocaine, bupropion, diethylpropion and ethcathinone all increased the peak dopamine efflux after electrical stimulation and slowed dopamine reuptake. Cocaine was more potent than bupropion and ethcathinone, while diethylpropion was least potent. Notably, cocaine had the fastest onset of action. These data suggest that, with respect to dopamine efflux, mephedrone is more similar to amphetamine than cocaine. These findings also show that cocaine was more potent than bupropion and ethcathinone while diethylpropion was least potent. Mephedrone's binding to the dopamine transporter is consistent with stimulant effects but its potency was lower than that of cocaine. These findings confirm and further characterize stimulant properties of mephedrone and other cathinones in adolescent rat brain.

  1. MRI and MRS of human brain tumors.

    Science.gov (United States)

    Hou, Bob L; Hu, Jiani

    2009-01-01

    The purpose of this chapter is to provide an introduction to magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of human brain tumors, including the primary applications and basic terminology involved. Readers who wish to know more about this broad subject should seek out the referenced books (1. Tofts (2003) Quantitative MRI of the brain. Measuring changes caused by disease. Wiley; Bradley and Stark (1999) 2. Magnetic resonance imaging, 3rd Edition. Mosby Inc; Brown and Semelka (2003) 3. MRI basic principles and applications, 3rd Edition. Wiley-Liss) or reviews (4. Top Magn Reson Imaging 17:127-36, 2006; 5. JMRI 24:709-724, 2006; 6. Am J Neuroradiol 27:1404-1411, 2006).MRI is the most popular means of diagnosing human brain tumors. The inherent difference in the magnetic resonance (MR) properties of water between normal tissues and tumors results in contrast differences on the image that provide the basis for distinguishing tumors from normal tissues. In contrast to MRI, which provides spatial maps or images using water signals of the tissues, proton MRS detects signals of tissue metabolites. MRS can complement MRI because the observed MRS peaks can be linked to inherent differences in biochemical profiles between normal tissues and tumors.The goal of MRI and MRS is to characterize brain tumors, including tumor core, edge, edema, volume, types, and grade. The commonly used brain tumor MRI protocol includes T2-weighted images and T1-weighted images taken both before and after the injection of a contrast agent (typically gadolinium: Gd). The commonly used MRS technique is either point-resolved spectroscopy (PRESS) or stimulated echo acquisition mode (STEAM).

  2. Functional testing of an inhalable nanoparticle based influenza vaccine using a human precision cut lung slice technique.

    Directory of Open Access Journals (Sweden)

    Vanessa Neuhaus

    Full Text Available Annual outbreaks of influenza infections, caused by new influenza virus subtypes and high incidences of zoonosis, make seasonal influenza one of the most unpredictable and serious health threats worldwide. Currently available vaccines, though the main prevention strategy, can neither efficiently be adapted to new circulating virus subtypes nor provide high amounts to meet the global demand fast enough. New influenza vaccines quickly adapted to current virus strains are needed. In the present study we investigated the local toxicity and capacity of a new inhalable influenza vaccine to induce an antigen-specific recall response at the site of virus entry in human precision-cut lung slices (PCLS. This new vaccine combines recombinant H1N1 influenza hemagglutinin (HAC1, produced in tobacco plants, and a silica nanoparticle (NP-based drug delivery system. We found no local cellular toxicity of the vaccine within applicable concentrations. However higher concentrations of NP (≥10(3 µg/ml dose-dependently decreased viability of human PCLS. Furthermore NP, not the protein, provoked a dose-dependent induction of TNF-α and IL-1β, indicating adjuvant properties of silica. In contrast, we found an antigen-specific induction of the T cell proliferation and differentiation cytokine, IL-2, compared to baseline level (152±49 pg/mg vs. 22±5 pg/mg, which could not be seen for the NP alone. Additionally, treatment with 10 µg/ml HAC1 caused a 6-times higher secretion of IFN-γ compared to baseline (602±307 pg/mg vs. 97±51 pg/mg. This antigen-induced IFN-γ secretion was further boosted by the adjuvant effect of silica NP for the formulated vaccine to a 12-fold increase (97±51 pg/mg vs. 1226±535 pg/mg. Thus we were able to show that the plant-produced vaccine induced an adequate innate immune response and re-activated an established antigen-specific T cell response within a non-toxic range in human PCLS at the site of virus entry.

  3. 31P-saturation-transfer nuclear-magnetic-resonance measurements of phosphocreatine turnover in guinea-pig brain slices.

    Science.gov (United States)

    Morris, P G; Feeney, J; Cox, D W; Bachelard, H S

    1985-05-01

    The technique of 31P saturation-transfer n.m.r. was used to determine the forward and the reverse rate constants of creatine phosphotransferase in superfused guinea-pig cerebral tissues in vitro. The calculated forward rate constant of 0.22 +/- 0.03s-1 compared well with a previously reported value for rat brain in vivo [Shoubridge, Briggs & Radda (1982) FEBS Lett. 140, 288-292]. The reverse rate constant was found to be 0.55 +/- 0.10s-1. 3. By using concentrations of ATP and phosphocreatine estimated previously for this superfused preparation [Cox, Morris, Feeney & Bachelard (1983) Biochem. J. 212, 365-370], forward and reverse flux rates were calculated to be 0.68 and 0.72 mumol X s-1 X g-1 respectively. The concordance of forward and reverse fluxes contrasts with the situation observed in vitro in other tissues, and suggests that the creatine phosphotransferase reaction is at equilibrium under the conditions used here. 4. Lowering the concentration of glucose in the superfusing medium from 10mM to 0.5mM had no significant effect on phosphocreatine concentration or on the forward (ATP-generating) flux through creatine phosphotransferase. The results indicate that a normal phosphocreatine content in the presence of lowered glucose availability is reflected by an unchanged turnover rate.

  4. A Hedonism Hub in the Human Brain

    Science.gov (United States)

    Zacharopoulos, G.; Lancaster, T. M.; Bracht, T.; Ihssen, N.; Maio, G. R.; Linden, D. E. J.

    2016-01-01

    Human values are abstract ideals that motivate behavior. The motivational nature of human values raises the possibility that they might be underpinned by brain structures that are particularly involved in motivated behavior and reward processing. We hypothesized that variation in subcortical hubs of the reward system and their main connecting pathway, the superolateral medial forebrain bundle (slMFB) is associated with individual value orientation. We conducted Pearson's correlation between the scores of 10 human values and the volumes of 14 subcortical structures and microstructural properties of the medial forebrain bundle in a sample of 87 participants, correcting for multiple comparisons (i.e.,190). We found a positive association between the value that people attach to hedonism and the volume of the left globus pallidus (GP).We then tested whether microstructural parameters (i.e., fractional anisotropy and myelin volume fraction) of the slMFB, which connects with the GP, are also associated to hedonism and found a significant, albeit in an uncorrected level, positive association between the myelin volume fraction within the left slMFB and hedonism scores. This is the first study to elucidate the relationship between the importance people attach to the human value of hedonism and structural variation in reward-related subcortical brain regions. PMID:27473322

  5. Perfusion harmonic imaging of the human brain

    Science.gov (United States)

    Metzler, Volker H.; Seidel, Guenter; Wiesmann, Martin; Meyer, Karsten; Aach, Til

    2003-05-01

    The fast visualisation of cerebral microcirculation supports diagnosis of acute cerebrovascular diseases. However, the commonly used CT/MRI-based methods are time consuming and, moreover, costly. Therefore we propose an alternative approach to brain perfusion imaging by means of ultrasonography. In spite of the low signal/noise-ratio of transcranial ultrasound and the high impedance of the skull, flow images of cerebral blood flow can be derived by capturing the kinetics of appropriate contrast agents by harmonic ultrasound image sequences. In this paper we propose three different methods for human brain perfusion imaging, each of which yielding flow images indicating the status of the patient's cerebral microcirculation by visualising local flow parameters. Bolus harmonic imaging (BHI) displays the flow kinetics of bolus injections, while replenishment (RHI) and diminution harmonic imaging (DHI) compute flow characteristics from contrast agent continuous infusions. RHI measures the contrast agents kinetics in the influx phase and DHI displays the diminution kinetics of the contrast agent acquired from the decay phase. In clinical studies, BHI- and RHI-parameter images were found to represent comprehensive and reproducible distributions of physiological cerebral blood flow. For DHI it is shown, that bubble destruction and hence perfusion phenomena principally can be displayed. Generally, perfusion harmonic imaging enables reliable and fast bedside imaging of human brain perfusion. Due to its cost efficiency it complements cerebrovascular diagnostics by established CT/MRI-based methods.

  6. Human microglial cells synthesize albumin in brain.

    Directory of Open Access Journals (Sweden)

    Sung-Min Ahn

    Full Text Available Albumin, an abundant plasma protein with multifunctional properties, is mainly synthesized in the liver. Albumin has been implicated in Alzheimer's disease (AD since it can bind to and transport amyloid beta (Abeta, the causative agent of AD; albumin is also a potent inhibitor of Abeta polymerization. Despite evidence of non-hepatic transcription of albumin in many tissues including kidney and pancreas, non-hepatic synthesis of albumin at the protein level has been rarely confirmed. In a pilot phase study of Human Brain Proteome Project, we found evidence that microglial cells in brain may synthesize albumin. Here we report, for the first time, the de novo synthesis of albumin in human microglial cells in brain. Furthermore, we demonstrate that the synthesis and secretion of albumin from microglial cells is enhanced upon microglial activation by Abeta(1-42- or lipopolysaccharide (LPS-treatment. These data indicate that microglial cells may play a beneficial role in AD by secreting albumin that not only inhibits Abeta polymerization but also increases its clearance.

  7. Central Administration of Lipopolysaccharide Induces Depressive-like Behavior in Vivo and Activates Brain Indoleamine 2,3 Dioxygenase In Murine Organotypic Hippocampal Slice Cultures

    Directory of Open Access Journals (Sweden)

    Kavelaars Annemieke

    2010-08-01

    Full Text Available Abstract Background Transient stimulation of the innate immune system by an intraperitoneal injection of lipopolysaccharide (LPS activates peripheral and central expression of the tryptophan degrading enzyme indoleamine 2,3 dioxygenase (IDO which mediates depressive-like behavior. It is unknown whether direct activation of the brain with LPS is sufficient to activate IDO and induce depressive-like behavior. Methods Sickness and depressive-like behavior in C57BL/6J mice were assessed by social exploration and the forced swim test, respectively. Expression of cytokines and IDO mRNA was measured by real-time RT-PCR and cytokine protein was measured by enzyme-linked immunosorbent assays (ELISAs. Enzymatic activity of IDO was estimated as the amount of kynurenine produced from tryptophan as determined by high pressure liquid chromatography (HPLC with electrochemical detection. Results Intracerebroventricular (i.c.v. administration of LPS (100 ng increased steady-state transcripts of TNFα, IL-6 and the inducible isoform of nitric oxide synthase (iNOS in the hippocampus in the absence of any change in IFNγ mRNA. LPS also increased IDO expression and induced depressive-like behavior, as measured by increased duration of immobility in the forced swim test. The regulation of IDO expression was investigated using in situ organotypic hippocampal slice cultures (OHSCs derived from brains of newborn C57BL/6J mice. In accordance with the in vivo data, addition of LPS (10 ng/ml to the medium of OHSCs induced steady-state expression of mRNA transcripts for IDO that peaked at 6 h and translated into increased IDO enzymatic activity within 8 h post-LPS. This activation of IDO by direct application of LPS was preceded by synthesis and secretion of TNFα and IL-6 protein and activation of iNOS while IFNγ expression was undetectable. Conclusion These data establish that activation of the innate immune system in the brain is sufficient to activate IDO and induce

  8. Voltage-sensitive dye recording from axons, dendrites and dendritic spines of individual neurons in brain slices.

    Science.gov (United States)

    Popovic, Marko; Gao, Xin; Zecevic, Dejan

    2012-11-29

    Understanding the biophysical properties and functional organization of single neurons and how they process information is fundamental for understanding how the brain works. The primary function of any nerve cell is to process electrical signals, usually from multiple sources. Electrical properties of neuronal processes are extraordinarily complex, dynamic, and, in the general case, impossible to predict in the absence of detailed measurements. To obtain such a measurement one would, ideally, like to be able to monitor, at multiple sites, subthreshold events as they travel from the sites of origin on neuronal processes and summate at particular locations to influence action potential initiation. This goal has not been achieved in any neuron due to technical limitations of measurements that employ electrodes. To overcome this drawback, it is highly desirable to complement the patch-electrode approach with imaging techniques that permit extensive parallel recordings from all parts of a neuron. Here, we describe such a technique - optical recording of membrane potential transients with organic voltage-sensitive dyes (V(m)-imaging) - characterized by sub-millisecond and sub-micrometer resolution. Our method is based on pioneering work on voltage-sensitive molecular probes (2). Many aspects of the initial technology have been continuously improved over several decades (3, 5, 11). Additionally, previous work documented two essential characteristics of V(m)-imaging. Firstly, fluorescence signals are linearly proportional to membrane potential over the entire physiological range (-100 mV to +100 mV; (10, 14, 16)). Secondly, loading neurons with the voltage-sensitive dye used here (JPW 3028) does not have detectable pharmacological effects. The recorded broadening of the spike during dye loading is completely reversible (4, 7). Additionally, experimental evidence shows that it is possible to obtain a significant number (up to hundreds) of recordings prior to any detectable

  9. Inferring human intentions from the brain data

    DEFF Research Database (Denmark)

    Stanek, Konrad

    The human brain is a massively complex organ composed of approximately a hundred billion densely interconnected, interacting neural cells. The neurons are not wired randomly - instead, they are organized in local functional assemblies. It is believed that the complex patterns of dynamic electric...... discharges across the neural tissue are responsible for emergence of high cognitive function, conscious perception and voluntary action. The brain’s capacity to exercise free will, or internally generated free choice, has long been investigated by philosophers, psychologists and neuroscientists. Rather than...... assuming a causal power of conscious will, the neuroscience of volition is based on the premise that "mental states rest on brain processes”, and hence by measuring spatial and temporal correlates of volition in carefully controlled experiments we can infer about their underlying mind processes, including...

  10. Mathematical logic in the human brain: semantics.

    Directory of Open Access Journals (Sweden)

    Roland M Friedrich

    Full Text Available As a higher cognitive function in humans, mathematics is supported by parietal and prefrontal brain regions. Here, we give an integrative account of the role of the different brain systems in processing the semantics of mathematical logic from the perspective of macroscopic polysynaptic networks. By comparing algebraic and arithmetic expressions of identical underlying structure, we show how the different subparts of a fronto-parietal network are modulated by the semantic domain, over which the mathematical formulae are interpreted. Within this network, the prefrontal cortex represents a system that hosts three major components, namely, control, arithmetic-logic, and short-term memory. This prefrontal system operates on data fed to it by two other systems: a premotor-parietal top-down system that updates and transforms (external data into an internal format, and a hippocampal bottom-up system that either detects novel information or serves as an access device to memory for previously acquired knowledge.

  11. Mathematical logic in the human brain: semantics.

    Science.gov (United States)

    Friedrich, Roland M; Friederici, Angela D

    2013-01-01

    As a higher cognitive function in humans, mathematics is supported by parietal and prefrontal brain regions. Here, we give an integrative account of the role of the different brain systems in processing the semantics of mathematical logic from the perspective of macroscopic polysynaptic networks. By comparing algebraic and arithmetic expressions of identical underlying structure, we show how the different subparts of a fronto-parietal network are modulated by the semantic domain, over which the mathematical formulae are interpreted. Within this network, the prefrontal cortex represents a system that hosts three major components, namely, control, arithmetic-logic, and short-term memory. This prefrontal system operates on data fed to it by two other systems: a premotor-parietal top-down system that updates and transforms (external) data into an internal format, and a hippocampal bottom-up system that either detects novel information or serves as an access device to memory for previously acquired knowledge.

  12. Tracking White Matter Fiber in Human Brain

    Institute of Scientific and Technical Information of China (English)

    KANGNing; ZHANGJun; EricSCarlson

    2004-01-01

    A new approach for noninvasively tracing brain white matter fiber tracts is presented using diffusion tensor magnetic resonance imaging (DT-MRI) data. This technique is based on successive anisotropic diffusion simulations over the human brain, which are utilized to construct three dimensional diffusion fronts. The fiber pathways are determined by evaluating the distance and orientation from fronts to their corresponding diffusion seeds. Real DT-MRI data are used to demonstrate the tracking scheme. It is shown that several major white matter fiber pathways can be reproduced noninvasively, with the tract branching being allowed. Since the diffusion simulation,which is a truly physical phenomenon reflecting the underlying architecture of cerebral tissues, makes full use of the entire diffusion tensor data, the proposed approach is expected to enhance robustness and reliability of the DT-MRI based fiber tracking techniques in white matter fiber reconstruction.

  13. Anatomical Location of LPA1 Activation and LPA Phospholipid Precursors in Rodent and Human Brain

    Science.gov (United States)

    González de San Román, E; Manuel, I; Giralt, MT; Chun, J; Estivill-Torrús, G; Rodriguez de Fonseca, F; Santín, LJ; Ferrer, I; Rodriguez-Puertas, R

    2016-01-01

    Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors (GPCRs): LPA1–LPA6. LPA evokes several responses in the CNS including cortical development and folding, growth of the axonal cone and its retraction process. Those cell processes involve survival, migration, adhesion proliferation, differentiation and myelination. The anatomical localization of LPA1 is incompletely understood, particularly with regard to LPA binding. Therefore, we have used functional [35S]GTPγS autoradiography to verify the anatomical distribution of LPA1 binding sites in adult rodent and human brain. The greatest activity was observed in myelinated areas of the white matter such as corpus callosum, internal capsule and cerebellum. MaLPA1-null mice (a variant of LPA1-null) lack [35S]GTPγS basal binding in white matter areas, where the LPA1 receptor is expressed at high levels, suggesting a relevant role of the activity of this receptor in the most myelinated brain areas. In addition, phospholipid precursors of LPA were localized by MALDI-IMS in both rodent and human brain slices identifying numerous species of phosphatides (PA) and phosphatidylcholines (PC). Both PA and PC species represent potential LPA precursors. The anatomical distribution of these precursors in rodent and human brain may indicate a metabolic relationship between LPA and LPA1 receptors. PMID:25857358

  14. Human brain lesion-deficit inference remapped.

    Science.gov (United States)

    Mah, Yee-Haur; Husain, Masud; Rees, Geraint; Nachev, Parashkev

    2014-09-01

    Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury-the commonest aetiology in lesion-deficit studies-where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant

  15. 人脑胶质瘤256层CT灌注成像%Perfusion 256-Slice CT Imaging of Human Gliomas

    Institute of Scientific and Technical Information of China (English)

    陆娜; Haleena Ramsahye; 冯晓源; 强金伟; 廖治河; 蒋玲

    2013-01-01

    Objective:To evaluate the feasibility of using perfusion 256-slice CT imaging in the examination of human gliomas and to investigate the perfusion characteristics of gliomas.Methods:From Jan 2010 to Feb 2012,among 55 subjects who underwent perfusion 256-slice CT imaging,there were 40 patients with gliomas(25 patients with high grade gliomas,15 patients with low grade gliomas) and 15 healthy volunteers served as controls.The raw data including cerebral blood flow(CBF),cerebral blood volume(CBV),mean transit time(MTT) and permeability surface-area product of region of interest(ROD were processed using CT perfusion software.The statistical analysis was performed to compare the difference among controls,low grade gliomas and high grade gliomas using ANOVA test.Results:A total of 40 patients with gliomas have been proved by the histopathological results.CBF,CBV and permeability surface-area product in high grade gliomas were (51.41 ± 11.60)mL/(100 g · min),(6.26 ± 1.67)mL/100 g and (5.71 ± 2.22)mL/(min · 100 g),respectively; in low grade gliomas they were (32.73 ± 7.06)mL/(100 g · min),(2.98 ± 0.73) mL/100 g and (2.33 ± 0.47) mL/(min · 100 g),respectively; and in controls they were (21.06 ± 2.06)mL/(100 g · min),(1.76 ± 0.17)mL/100 g and (0.90 ± 0.07)mL/(min · 100 g) respectively.Significant differences of CBF,CBV and permeability surface-area product were observed among high grade gliomas,low grade gliomas and controls(P all<0.01).There were no difference in MTT among 3 groups.When cutoff value of permeability surface-area product was 2.88 mL/(min · 100 g),the sensitivity and specificity were 96 % and 93 %.When cutoff value of CBV was 3.91 mL/100 g,the sensitivity and specificity were 92 % and 93 %.When cutoff value of CBF was 38.90 mL/(100g· min),the sensitivity and specificity were 92 % and 86 %.Conclusions:Perfusion 256-slice CT imaging can provide useful parameters for glioma hemodynamics.%目的:探讨人脑胶质瘤256层CT灌注

  16. Positive selection on gene expression in the human brain

    DEFF Research Database (Denmark)

    Khaitovich, Philipp; Tang, Kun; Franz, Henriette

    2006-01-01

    Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

  17. Effects of brain evolution on human nutrition and metabolism.

    Science.gov (United States)

    Leonard, William R; Snodgrass, J Josh; Robertson, Marcia L

    2007-01-01

    The evolution of large human brain size has had important implications for the nutritional biology of our species. Large brains are energetically expensive, and humans expend a larger proportion of their energy budget on brain metabolism than other primates. The high costs of large human brains are supported, in part, by our energy- and nutrient-rich diets. Among primates, relative brain size is positively correlated with dietary quality, and humans fall at the positive end of this relationship. Consistent with an adaptation to a high-quality diet, humans have relatively small gastrointestinal tracts. In addition, humans are relatively "undermuscled" and "over fat" compared with other primates, features that help to offset the high energy demands of our brains. Paleontological evidence indicates that rapid brain evolution occurred with the emergence of Homo erectus 1.8 million years ago and was associated with important changes in diet, body size, and foraging behavior.

  18. Diffusion Based Modeling of Human Brain Response to External Stimuli

    CERN Document Server

    Namazi, Hamidreza

    2012-01-01

    Human brain response is the overall ability of the brain in analyzing internal and external stimuli in the form of transferred energy to the mind/brain phase-space and thus, making the proper decisions. During the last decade scientists discovered about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research there was less effort which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling of human EEG signal, as an alert state of overall human brain activity monitoring, due to receiving external stimuli, based on fractional diffusion equation. The results of this modeling show very good agreement with the real human EEG signal and thus, this model can be used as a strong representative of the human brain activity.

  19. Physical biology of human brain development

    Directory of Open Access Journals (Sweden)

    Silvia eBudday

    2015-07-01

    Full Text Available Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view towards surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level towards form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

  20. Physical biology of human brain development.

    Science.gov (United States)

    Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

    2015-01-01

    Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level toward form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

  1. Automated regional behavioral analysis for human brain images

    National Research Council Canada - National Science Library

    Lancaster, Jack L; Laird, Angela R; Eickhoff, Simon B; Martinez, Michael J; Fox, P Mickle; Fox, Peter T

    2012-01-01

    Behavioral categories of functional imaging experiments along with standardized brain coordinates of associated activations were used to develop a method to automate regional behavioral analysis of human brain images...

  2. GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance

    Science.gov (United States)

    Heppner, Kristy M.; Baquero, Arian F.; True, Cadence; Grove, Kevin L.

    2017-01-01

    Abstract Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action. Using ovariectomized mice, we found that GLP-producing fibers come in close apposition with ARC Kiss1 neurons; these neurons also contain Glp1r mRNA. Electrophysiological recordings revealed that liraglutide (a long-acting GLP-1R agonist) increased action potential firing and caused a direct membrane depolarization of ARC Kiss1 cells in brain slices. We determined that brainstem preproglucagon mRNA is decreased after a 48-h fast in mice, a negative energy state in which ARC Kiss1 expression and downstream GnRH/luteinizing hormone (LH) release are potently suppressed. However, activation of GLP-1R signaling in fasted mice with liraglutide was not sufficient to prevent LH inhibition. Furthermore, chronic central infusions of the GLP-1R antagonist, exendin(9–39), in ad libitum–fed mice did not alter ARC Kiss1 mRNA or plasma LH. As a whole, these data identify a novel interaction of the GLP-1 system with ARC Kiss1 neurons but indicate that CNS GLP-1R signaling alone is not critical for the maintenance of LH during fasting or normal feeding. PMID:28144621

  3. GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance.

    Science.gov (United States)

    Heppner, Kristy M; Baquero, Arian F; Bennett, Camdin M; Lindsley, Sarah R; Kirigiti, Melissa A; Bennett, Baylin; Bosch, Martha A; Mercer, Aaron J; Rønnekleiv, Oline K; True, Cadence; Grove, Kevin L; Smith, M Susan

    2017-01-01

    Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action. Using ovariectomized mice, we found that GLP-producing fibers come in close apposition with ARC Kiss1 neurons; these neurons also contain Glp1r mRNA. Electrophysiological recordings revealed that liraglutide (a long-acting GLP-1R agonist) increased action potential firing and caused a direct membrane depolarization of ARC Kiss1 cells in brain slices. We determined that brainstem preproglucagon mRNA is decreased after a 48-h fast in mice, a negative energy state in which ARC Kiss1 expression and downstream GnRH/luteinizing hormone (LH) release are potently suppressed. However, activation of GLP-1R signaling in fasted mice with liraglutide was not sufficient to prevent LH inhibition. Furthermore, chronic central infusions of the GLP-1R antagonist, exendin(9-39), in ad libitum-fed mice did not alter ARC Kiss1 mRNA or plasma LH. As a whole, these data identify a novel interaction of the GLP-1 system with ARC Kiss1 neurons but indicate that CNS GLP-1R signaling alone is not critical for the maintenance of LH during fasting or normal feeding.

  4. Effective range of electrical stimulation in brain silica preparation; No slice hyohon ni okeru denki shigeki koka han`i no kento

    Energy Technology Data Exchange (ETDEWEB)

    Takimori, T.; Ogawa, T.; Nishida, M. [Akita University, Akita (Japan)

    1997-08-20

    In order to examine the confines of electrical stimulation in layer 2/3 of visual cortex in the brain slice preparation, we estimated the effective range of the stimulation based on the excitatory postsynaptic potential (EPSP) evoked in layer V neuron which receives input from layer 2/3. For this purpose, we recorded and compared EPSPs amplitudes evoked by stimulations at directly over site of recording electrode and lateral site in layer 2/3. Since the EPSP increased linearly with stimulus intensity before the saturation, it was considered that the EPSP correlates with the number of projecting neurons in area directly excited with the stimulation. Then we formed the region model by which we can get the ratios between the neuron numbers in areas excited by different sites stimulations against the stimulus effective ranges. And in the stimulus intensity for action potential threshold of layer 5 neuron, we evaluated the effective range for the relative values of EPSPs to be produced with the stimulations of 250{mu}m lateral site and directory over site. In the model, the ratio increased monotonically with the effective range and in the case of 250{mu}m for the effective range, the ratio between those EPSPs was less than the value in the model. These results led the conclusion that the effective range of the intensity for layer 5 neuron to generate the output is confined within 250{mu}m from directly over site, that is, within layer 2/3. 7 refs., 11 figs., 1 tab.

  5. Fast optical imaging of human brain function

    Directory of Open Access Journals (Sweden)

    Gabriele Gratton

    2010-06-01

    Full Text Available Great advancements in brain imaging during the last few decades have opened a large number of new possibilities for neuroscientists. The most dominant methodologies (electrophysiological and magnetic resonance-based methods emphasize temporal and spatial information, respectively. However, theorizing about brain function has recently emphasized the importance of rapid (within 100 ms or so interactions between different elements of complex neuronal networks. Fast optical imaging, and in particular the event-related optical signal (EROS, a technology that has emerged over the last 15 years may provide descriptions of localized (to sub-cm level brain activity with a temporal resolution of less than 100 ms. The main limitations of EROS are its limited penetration, which allows us to image cortical structures not deeper than 3 cm from the surface of the head, and its low signal-to-noise ratio. Advantages include the fact that EROS is compatible with most other imaging methods, including electrophysiological, magnetic resonance, and trans-cranial magnetic stimulation techniques, with which can be recorded concurrently. In this paper we present a summary of the research that has been conducted so far on fast optical imaging, including evidence for the possibility of recording neuronal signals with this method, the properties of the signals, and various examples of applications to the study of human cognitive neuroscience. Extant issues, controversies, and possible future developments are also discussed.

  6. Human brain : biochemical lateralization in normal subjects.

    Directory of Open Access Journals (Sweden)

    Jayasundar R

    2002-07-01

    Full Text Available Chemical asymmetries in normal human brain were studied using the non-invasive technique of volume localized proton magnetic resonance spectroscopy (MRS. The technique of STEAM was used to acquire water-suppressed proton spectra from 8 ml voxels placed in bilaterally symmetrical positions in the two hemispheres of the brain. One hundred and sixty eight right-handed male volunteers were studied for six different regions in the brain (n=28, for each region. Parietal, occipital, temporal, frontal, thalamus and cerebellum regions were studied. The focus was on metabolites such as N-acetyl aspartate (NAA, creatine/phosphocreatine (Cr/PCr and choline (Cho containing compounds. Ratios of the peak areas were calculated for them. Quantitation of the metabolites were carried for data on 18 volunteers. Significant interhemispheric differences in the distribution of metabolites were observed for all the regions studied. There were statistically significant differences on right and left side for the metabolite ratios in all the regions studied. The study has shown the existence of significant lateralization in the distribution of proton MR visible metabolites for all the regions studied.

  7. BrainBank Metadata Specification for the Human Brain Project and Neuroinformatics

    OpenAIRE

    Lianglin, Hu; Yufang, Hou; Jianhui, Li; Ling, Yin; Wenwen, Shi

    2007-01-01

    Many databases and platforms for human brain data have been established in China over the years, and metadata plays an important role in understanding and using them. The BrainBank Metadata Specification for the Human Brain Project and Neuroinformatics provides a structure for describing the context and content information of BrainBank databases and services. It includes six parts: identification, method, data schema, distribution of the database, metadata extension, and metadata reference Th...

  8. Thick Slice and Thin Slice Teaching Evaluations

    Science.gov (United States)

    Tom, Gail; Tong, Stephanie Tom; Hesse, Charles

    2010-01-01

    Student-based teaching evaluations are an integral component to institutions of higher education. Previous work on student-based teaching evaluations suggest that evaluations of instructors based upon "thin slice" 30-s video clips of them in the classroom correlate strongly with their end of the term "thick slice" student evaluations. This study's…

  9. BrainBank Metadata Specification for the Human Brain Project and Neuroinformatics

    Directory of Open Access Journals (Sweden)

    Hu Lianglin

    2007-07-01

    Full Text Available Many databases and platforms for human brain data have been established in China over the years, and metadata plays an important role in understanding and using them. The BrainBank Metadata Specification for the Human Brain Project and Neuroinformatics provides a structure for describing the context and content information of BrainBank databases and services. It includes six parts: identification, method, data schema, distribution of the database, metadata extension, and metadata reference The application of the BrainBank Metadata Specification will promote conservation and management of BrainBank databases and platforms. it will also greatly facilitate the retrieval, evaluation, acquisition, and application of the data.

  10. Model human heart or brain signals

    CERN Document Server

    Tuncay, Caglar

    2008-01-01

    A new model is suggested and used to mimic various spatial or temporal designs in biological or non biological formations where the focus is on the normal or irregular electrical signals coming from human heart (ECG) or brain (EEG). The electrical activities in several muscles (EMG) or neurons or other organs of human or various animals, such as lobster pyloric neuron, guinea pig inferior olivary neuron, sepia giant axon and mouse neocortical pyramidal neuron and some spatial formations are also considered (in Appendix). In the biological applications, several elements (cells or tissues) in an organ are taken as various entries in a representative lattice (mesh) where the entries are connected to each other in terms of some molecular diffusions or electrical potential differences. The biological elements evolve in time (with the given tissue or organ) in terms of the mentioned connections (interactions) besides some individual feedings. The anatomical diversity of the species (or organs) is handled in terms o...

  11. Evolution of the human brain: changing brain size and the fossil record.

    Science.gov (United States)

    Park, Min S; Nguyen, Andrew D; Aryan, Henry E; U, Hoi Sang; Levy, Michael L; Semendeferi, Katerina

    2007-03-01

    Although the study of the human brain is a rapidly developing and expanding science, we must take pause to examine the historical and evolutionary events that helped shape the brain of Homo sapiens. From an examination of the human lineage to a discussion of evolutionary principles, we describe the basic principles and theories behind the evolution of the human brain. Specifically, we examine several theories concerning changes in overall brain size during hominid evolution and relate them to the fossil record. This overview is intended to provide a broad understanding of some of the controversial issues that are currently being debated in the multidisciplinary field of brain evolution research.

  12. The pedunculopontine tegmental nucleus: from basic neuroscience to neurosurgical applications: Arousal from slices to humans: implications for DBS

    OpenAIRE

    Garcia-Rill, Edgar; Simon, Christen; Smith, Kristen; Kezunovic, Nebosja; Hyde, James

    2010-01-01

    One element of the reticular activating system (RAS) is the pedunculopontine nucleus (PPN), which projects to the thalamus to trigger thalamocortical rhythms and the brainstem to modulate muscle tone and locomotion. The PPN is a posterior midbrain site known to induce locomotion in decerebrate animals when activated at 40–60 Hz, and has become a target for DBS in disorders involving gait deficits. We developed a research program using brainstem slices containing the PPN to study the cellular ...

  13. Comparative primate neuroimaging: insights into human brain evolution.

    Science.gov (United States)

    Rilling, James K

    2014-01-01

    Comparative neuroimaging can identify unique features of the human brain and teach us about human brain evolution. Comparisons with chimpanzees, our closest living primate relative, are critical in this endeavor. Structural magnetic resonance imaging (MRI) has been used to compare brain size development, brain structure proportions and brain aging. Positron emission tomography (PET) imaging has been used to compare resting brain glucose metabolism. Functional MRI (fMRI) has been used to compare auditory and visual system pathways, as well as resting-state networks of connectivity. Finally, diffusion-weighted imaging (DWI) has been used to compare structural connectivity. Collectively, these methods have revealed human brain specializations with respect to development, cortical organization, connectivity, and aging. These findings inform our knowledge of the evolutionary changes responsible for the special features of the modern human mind.

  14. [Neuroethics: Ethical Endowments of Human Brain].

    Science.gov (United States)

    López Moratalla, Natalia

    2015-01-01

    The neurobiological processes underlying moral judgement have been the focus of Neuroethics. Neurosciences demonstrate which cerebral areas are active and inactive whilst people decide how to act when facing a moral dilemma; in this way we know the correlation between determined cerebral areas and our human acts. We can explain how the ″ethical endowments″ of each person, common to all human beings, is ″embedded″ in the dynamic of cerebral flows. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion related areas of the brain contribute to moral judgement. The outcome of man's natural inclinations is on one hand linked to instinctive systems of animal survival and to basic emotions, and on the other, to the life of each individual human uninhibited by automatism of the biological laws, because he is governed by the laws of freedom. The capacity to formulate an ethical judgement is an innate asset of the human mind.

  15. Protective Effects of Chlorogenic Acid and its Metabolites on Hydrogen Peroxide-Induced Alterations in Rat Brain Slices: A Comparative Study with Resveratrol.

    Science.gov (United States)

    Gul, Zulfiye; Demircan, Celaleddin; Bagdas, Deniz; Buyukuysal, Rifat Levent

    2016-08-01

    The effectiveness of chlorogenic acid and its main metabolites, caffeic and quinic acids, against oxidative stress was investigated. Resveratrol, another natural phenolic compound, was also tested for comparison. Rat cortical slices were incubated with 200 μM H2O2 for 1 h, and alterations in oxidative stress parameters, such as 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and the production of both malondialdehyde (MDA) and reactive oxygen species (ROS), were assayed in the absence or presence of phenolic compounds. Additionally, the effectiveness of chlorogenic acid and other compounds on H2O2-induced increases in fluorescence intensities were also compared in slice-free incubation medium. Although quinic acid failed, chlorogenic and caffeic acids significantly ameliorated the H2O2-induced decline in TTC staining intensities. Although resveratrol also caused an increase in staining intensity, its effect was not dose-dependent; the high concentrations of resveratrol tested in the present study (10 and 100 μM) further lessened the staining of the slices. Additionally, all phenolic compounds significantly attenuated the H2O2-induced increases in MDA and ROS levels in cortical slices. When the IC50 values were compared to H2O2-induced alterations, chlorogenic acid was more potent than either its metabolites or resveratrol for all parameters studied under these experimental conditions. In slice-free experimental conditions, on the other hand, chlorogenic and caffeic acids significantly attenuated the fluorescence emission enhanced by H2O2 with a similar order of potency to that obtained in slice-containing physiological medium. These results indicate that chlorogenic acid is a more potent phenolic compound than resveratrol and its main metabolites caffeic and quinic acids against H2O2-induced alterations in oxidative stress parameters in rat cortical slices.

  16. A novel role for PHT1 in the disposition of l-histidine in brain: In vitro slice and in vivo pharmacokinetic studies in wildtype and Pht1 null mice.

    Science.gov (United States)

    Wang, Xiao-Xing; Hu, Yongjun; Keep, Richard F; Toyama-Sorimachi, Noriko; Smith, David E

    2017-01-15

    PHT1 (SLC15A4) is responsible for translocating l-histidine (l-His), di/tripeptides and peptide-like drugs across biological membranes. Previous studies have indicated that PHT1 is located in brain parenchyma, however, its role and significance in brain along with effect on the biodistribution of substrates is unknown. In this study, adult gender-matched Pht1-competent (wildtype) and Pht1-deficient (null) mice were used to investigate the effect of PHT1 on l-His brain disposition via in vitro slice and in vivo pharmacokinetic approaches. We also evaluated the serum clinical chemistry and expression levels of select transporters and enzymes in the two genotypes. No significant differences were observed between genotypes in serum chemistry, body weight, viability and fertility. PCR analyses indicated that Pept2 had a compensatory up-regulation in Pht1 null mice (about 2-fold) as compared to wildtype animals, which was consistent in different brain regions and confirmed by immunoblots. The uptake of l-His was reduced in brain slices by 50% during PHT1 ablation. The l-amino acid transporters accounted for 30% of the uptake, and passive (other) pathways for 20% of the uptake. During the in vivo pharmacokinetic studies, plasma concentration-time profiles of l-His were comparable between the two genotypes after intravenous administration. Still, biodistribution studies revealed that, when sampled 5min after dosing, l-His values were 28-48% lower in Pht1 null mice, as compared to wildtype animals, in brain parenchyma but not cerebrospinal fluid. These findings suggest that PHT1 may play an important role in histidine transport in brain, and resultant effects on histidine/histamine homeostasis and neuropeptide regulation.

  17. Brain-Computer Interfaces and Human-Computer Interaction

    NARCIS (Netherlands)

    Tan, Desney; Nijholt, Anton; Tan, Desney S.; Nijholt, Anton

    2010-01-01

    Advances in cognitive neuroscience and brain imaging technologies have started to provide us with the ability to interface directly with the human brain. This ability is made possible through the use of sensors that can monitor some of the physical processes that occur within the brain that correspo

  18. Brain-Computer Interfaces and Human-Computer Interaction

    NARCIS (Netherlands)

    Tan, Desney; Tan, Desney S.; Nijholt, Antinus

    2010-01-01

    Advances in cognitive neuroscience and brain imaging technologies have started to provide us with the ability to interface directly with the human brain. This ability is made possible through the use of sensors that can monitor some of the physical processes that occur within the brain that

  19. Dynamic analysis of the human brain with complex cerebral sulci.

    Science.gov (United States)

    Tseng, Jung-Ge; Huang, Bo-Wun; Ou, Yi-Wen; Yen, Ke-Tien; Wu, Yi-Te

    2016-07-03

    The brain is one of the most vulnerable organs inside the human body. Head accidents often appear in daily life and are easy to cause different level of brain damage inside the skull. Once the brain suffered intense locomotive impact, external injuries, falls, or other accidents, it will result in different degrees of concussion. This study employs finite element analysis to compare the dynamic characteristics between the geometric models of an assumed simple brain tissue and a brain tissue with complex cerebral sulci. It is aimed to understand the free vibration of the internal brain tissue and then to protect the brain from injury caused by external influences. Reverse engineering method is used for a Classic 5-Part Brain (C18) model produced by 3B Scientific Corporation. 3D optical scanner is employed to scan the human brain structure model with complex cerebral sulci and imported into 3D graphics software to construct a solid brain model to simulate the real complex brain tissue. Obtaining the normal mode analysis by inputting the material properties of the true human brain into finite element analysis software, and then to compare the simplified and the complex of brain models.

  20. Thresholding magnetic resonance images of human brain

    Institute of Scientific and Technical Information of China (English)

    Qing-mao HU; Wieslaw L NOWINSKI

    2005-01-01

    In this paper, methods are proposed and validated to determine low and high thresholds to segment out gray matter and white matter for MR images of different pulse sequences of human brain. First, a two-dimensional reference image is determined to represent the intensity characteristics of the original three-dimensional data. Then a region of interest of the reference image is determined where brain tissues are present. The non-supervised fuzzy c-means clustering is employed to determine: the threshold for obtaining head mask, the low threshold for T2-weighted and PD-weighted images, and the high threshold for T1-weighted, SPGR and FLAIR images. Supervised range-constrained thresholding is employed to determine the low threshold for T1-weighted, SPGR and FLAIR images. Thresholding based on pairs of boundary pixels is proposed to determine the high threshold for T2- and PD-weighted images. Quantification against public data sets with various noise and inhomogeneity levels shows that the proposed methods can yield segmentation robust to noise and intensity inhomogeneity. Qualitatively the proposed methods work well with real clinical data.

  1. Cristobalite and Hematite Particles in Human Brain.

    Science.gov (United States)

    Kopani, Martin; Kopaniova, A; Trnka, M; Caplovicova, M; Rychly, B; Jakubovsky, J

    2016-11-01

    Foreign substances get into the internal environment of living bodies and accumulate in various organs. Cristobalite and hematite particles in the glial cells of pons cerebri of human brain with diagnosis of Behhet disease with scanning electron microscopy (SEM), energy-dispersive microanalysis (EDX), and transmission electron microscopy (TEM) with diffraction were identified. SEM with EDX revealed the matter of irregular micrometer-sized particles sometimes forming polyhedrons with fibrilar or stratified structure. It was found in some particles Ti, Fe, and Zn. Some particles contained Cu. TEM and electron diffraction showed particles of cristobalite and hematite. The presence of the particles can be a result of environmental effect, disruption of normal metabolism, and transformation of physiologically iron-ferrihydrite into more stable form-hematite. From the size of particles can be drawn the long-term accumulation of elements in glial cells.

  2. Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain

    Directory of Open Access Journals (Sweden)

    Chongyuan Luo

    2016-12-01

    Full Text Available Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of the human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. Demethylated regions (74% of 35,627 identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed widespread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development.

  3. Stereological estimation of total brain numbers in humans

    Directory of Open Access Journals (Sweden)

    Solveig eWalloe

    2014-07-01

    Full Text Available Our knowledge of the relationship between brain structure and cognitive function is still limited. Human brains and individual cortical areas vary considerably in size and shape. Studies of brain cell numbers have historically been based on biased methods, which did not always result in correct estimates and were often very time-consuming. Within the last 20–30 years, it has become possible to rely on more advanced and unbiased methods. These methods have provided us with information about fetal brain development, differences in cell numbers between men and women, the effect of age on selected brain cell populations, and disease-related changes associated with a loss of function. In that this article concerns normal brain rather than brain disorders, it focuses on normal brain development in humans and age related changes in terms of cell numbers. For comparative purposes a few examples of neocortical neuron number in other mammals are also presented.

  4. Changes in cognitive state alter human functional brain networks

    Directory of Open Access Journals (Sweden)

    Malaak Nasser Moussa

    2011-08-01

    Full Text Available The study of the brain as a whole system can be accomplished using network theory principles. Research has shown that human functional brain networks during a resting state exhibit small-world properties and high degree nodes, or hubs, localized to brain areas consistent with the default mode network (DMN. However, the study of brain networks across different tasks and or cognitive states has been inconclusive. Research in this field is important because the underpinnings of behavioral output are inherently dependent on whether or not brain networks are dynamic. This is the first comprehensive study to evaluate multiple network metrics at a voxel-wise resolution in the human brain at both the whole brain and regional level under various conditions: resting state, visual stimulation, and multisensory (auditory and visual stimulation. Our results show that despite global network stability, functional brain networks exhibit considerable task-induced changes in connectivity, efficiency, and community structure at the regional level.

  5. "Messing with the Mind: Evolutionary Challenges to Human Brain Augmentation

    Directory of Open Access Journals (Sweden)

    ARTHUR eSANIOTIS

    2014-09-01

    Full Text Available The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to understand some of the basic concepts of cognition. Therefore, this article proposes that brain-machine interfacing and nootropics are not going to produce augmented brains because we do not understand enough about how evolutionary pressures have informed the neural networks which support human cognitive faculties.

  6. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

    Full Text Available Reverse transcriptase from avian myeloblastosis virus (AMV was the subject of the study, from which the investi- gations of the Department of biosynthesis of nucleic acids were started. Production of AMV in grams quantities and isolation of AMV reverse transcriptase were established in the laboratory during the seventies of the past cen- tury and this initiated research on the cDNA synthesis, cloning and investigation of the structure and functions of the eukaryotic genes. Structures of salmon insulin and insulin-like growth factor (IGF family genes and their transcripts were determined during long-term investigations. Results of two modern techniques, microarray-ba- sed hybridization and SAGE, were used for the identification of the genes differentially expressed in astrocytic gliomas and human normal brain. Comparison of SAGE results on the genes overexpressed in glioblastoma with the results of microarray analysis revealed a limited number of common genes. 105 differentially expressed genes, common to both methods, can be included in the list of candidates for the molecular typing of glioblastoma. The first experiments on the classification of glioblastomas based on the data of the 20 genes expression were conducted by using of artificial neural network analysis. The results of these experiments showed that the expression profiles of these genes in 224 glioblastoma samples and 74 normal brain samples could be according to the Koho- nen’s maps. The CHI3L1 and CHI3L2 genes of chitinase-like cartilage protein were revealed among the most overexpressed genes in glioblastoma, which could have prognostic and diagnostic potential. Results of in vitro experiments demonstrated that both proteins, CHI3L1 and CHI3L2, may initiate the phosphorylation of ERK1/ ERK2 and AKT kinases leading to the activation of MAPK/ERK1/2 and PI3K/AKT signaling cascades in human embryonic kidney 293 cells, human glioblastoma U87MG, and U373 cells. The new human cell line

  7. Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution.

    Science.gov (United States)

    Cunnane, Stephen C; Crawford, Michael A

    2014-12-01

    The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development.

  8. Human induced rotation and reorganization of the brain of domestic dogs.

    Directory of Open Access Journals (Sweden)

    Taryn Roberts

    Full Text Available Domestic dogs exhibit an extraordinary degree of morphological diversity. Such breed-to-breed variability applies equally to the canine skull, however little is known about whether this translates to systematic differences in cerebral organization. By looking at the paramedian sagittal magnetic resonance image slice of canine brains across a range of animals with different skull shapes (N = 13, we found that the relative reduction in skull length compared to width (measured by Cephalic Index was significantly correlated to a progressive ventral pitching of the primary longitudinal brain axis (r = 0.83, as well as with a ventral shift in the position of the olfactory lobe (r = 0.81. Furthermore, these findings were independent of estimated brain size or body weight. Since brachycephaly has arisen from generations of highly selective breeding, this study suggests that the remarkable diversity in domesticated dogs' body shape and size appears to also have led to human-induced adaptations in the organization of the canine brain.

  9. Sex differences in brain organization: implications for human communication.

    Science.gov (United States)

    Hanske-Petitpierre, V; Chen, A C

    1985-12-01

    This article reviews current knowledge in two major research domains: sex differences in neuropsychophysiology, and in human communication. An attempt was made to integrate knowledge from several areas of brain research with human communication and to clarify how such a cooperative effort may be beneficial to both fields of study. By combining findings from the area of brain research, a communication paradigm was developed which contends that brain-related sex differences may reside largely in the area of communication of emotion.

  10. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  11. Evolutionary origins of human brain and spirituality.

    Science.gov (United States)

    Henneberg, Maciej; Saniotis, Arthur

    2009-12-01

    Evolving brains produce minds. Minds operate on imaginary entities. Thus they can create what does not exist in the physical world. Spirits can be deified. Perception of spiritual entities is emotional--organic. Spirituality is a part of culture while culture is an adaptive mechanism of human groups as it allows for technology and social organization to support survival and reproduction. Humans are not rational, they are emotional. Most of explanations of the world, offered by various cultures, involve an element of "fiat", a will of a higher spiritual being, or a reference to some ideal. From this the rules of behaviour are deduced. These rules are necessary to maintain social peace and allow a complex unit consisting of individuals of both sexes and all ages to function in a way ensuring their reproductive success and thus survival. There is thus a direct biological benefit of complex ideological superstructure of culture. This complex superstructure most often takes a form of religion in which logic is mixed with appeals to emotions based on images of spiritual beings. God is a consequence of natural evolution. Whether a deity is a cause of this evolution is difficult to discover, but existence of a deity cannot be questioned.

  12. Anatomical location of LPA1 activation and LPA phospholipid precursors in rodent and human brain.

    Science.gov (United States)

    González de San Román, Estibaliz; Manuel, Iván; Giralt, María Teresa; Chun, Jerold; Estivill-Torrús, Guillermo; Rodríguez de Fonseca, Fernando; Santín, Luis Javier; Ferrer, Isidro; Rodríguez-Puertas, Rafael

    2015-08-01

    Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors: LPA1 -LPA6 . LPA evokes several responses in the CNS, including cortical development and folding, growth of the axonal cone and its retraction process. Those cell processes involve survival, migration, adhesion proliferation, differentiation, and myelination. The anatomical localization of LPA1 is incompletely understood, particularly with regard to LPA binding. Therefore, we have used functional [(35) S]GTPγS autoradiography to verify the anatomical distribution of LPA1 binding sites in adult rodent and human brain. The greatest activity was observed in myelinated areas of the white matter such as corpus callosum, internal capsule and cerebellum. MaLPA1 -null mice (a variant of LPA1 -null) lack [(35) S]GTPγS basal binding in white matter areas, where the LPA1 receptor is expressed at high levels, suggesting a relevant role of the activity of this receptor in the most myelinated brain areas. In addition, phospholipid precursors of LPA were localized by MALDI-IMS in both rodent and human brain slices identifying numerous species of phosphatides and phosphatidylcholines. Both phosphatides and phosphatidylcholines species represent potential LPA precursors. The anatomical distribution of these precursors in rodent and human brain may indicate a metabolic relationship between LPA and LPA1 receptors. Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors (GPCR), LPA1 to LPA6 . LPA evokes several responses in the central nervous system (CNS), including cortical development and folding, growth of the axonal cone and its retraction process. We used functional [(35) S]GTPγS autoradiography to verify the anatomical distribution of LPA1 -binding sites in adult rodent and human brain. The distribution of LPA1 receptors in rat, mouse and human brains show the highest activity in white matter myelinated areas. The basal and

  13. A Culture-Behavior-Brain Loop Model of Human Development.

    Science.gov (United States)

    Han, Shihui; Ma, Yina

    2015-11-01

    Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model.

  14. GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bonde, C; Kristensen, B W; Blaabjerg, M;

    2000-01-01

    The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN......-producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining. Both the addition of rhGDNF and NBN...

  15. Hominins and the emergence of the modern human brain.

    Science.gov (United States)

    de Sousa, Alexandra; Cunha, Eugénia

    2012-01-01

    Evidence used to reconstruct the morphology and function of the brain (and the rest of the central nervous system) in fossil hominin species comes from the fossil and archeological records. Although the details provided about human brain evolution are scarce, they benefit from interpretations informed by interspecific comparative studies and, in particular, human pathology studies. In recent years, new information has come to light about fossil DNA and ontogenetic trajectories, for which pathology research has significant implications. We briefly describe and summarize data from the paleoarcheological and paleoneurological records about the evolution of fossil hominin brains, including behavioral data most relevant to brain research. These findings are brought together to characterize fossil hominin taxa in terms of brain structure and function and to summarize brain evolution in the human lineage.

  16. Metabolic costs and evolutionary implications of human brain development.

    Science.gov (United States)

    Kuzawa, Christopher W; Chugani, Harry T; Grossman, Lawrence I; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R; Wildman, Derek E; Sherwood, Chet C; Leonard, William R; Lange, Nicholas

    2014-09-09

    The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain's glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain-body metabolic trade-offs using the ratios of brain glucose uptake to the body's resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.

  17. Human brain networks function in connectome-specific harmonic waves.

    Science.gov (United States)

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-21

    A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In this new frequency-specific representation of cortical activity, that we call 'connectome harmonics', oscillatory networks of the human brain at rest match harmonic wave patterns of certain frequencies. We demonstrate a neural mechanism behind the self-organization of connectome harmonics with a continuous neural field model of excitatory-inhibitory interactions on the connectome. Remarkably, the critical relation between the neural field patterns and the delicate excitation-inhibition balance fits the neurophysiological changes observed during the loss and recovery of consciousness.

  18. The immune response of the human brain to abdominal surgery

    DEFF Research Database (Denmark)

    Forsberg, Anton; Cervenka, Simon; Jonsson Fagerlund, Malin

    2017-01-01

    OBJECTIVE: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans....... This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. METHODS: Eight males undergoing prostatectomy under general...... to change in [(11) C]PBR28 binding (p = 0.027). INTERPRETATION: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may...

  19. Neuroglobin and Cytoglobin expression in the human brain

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Kelsen, Jesper; Hay-Schmidt, Anders

    2013-01-01

    expressed and up-regulated following stroke in the human brain. The present study aimed at confirming our previous observations in rodents using two post-mortem human brains. The anatomical localization of Neuroglobin and Cytoglobin in the human brain is much like what has been described for the rodent...... and Cytoglobin in the cerebral cortex, while no expression in the cerebellar cortex was detectable. We provide a neuroanatomical indication for a different role of Neuroglobin and Cytoglobin in the human brain.......Neuroglobin and Cytoglobin are new members of the heme-globin family. Both globins are primarily expressed in neurons of the brain and retina. Neuroglobin and Cytoglobin have been suggested as novel therapeutic targets in various neurodegenerative diseases based on their oxygen binding and cell...

  20. Mapping human whole-brain structural networks with diffusion MRI.

    Directory of Open Access Journals (Sweden)

    Patric Hagmann

    Full Text Available Understanding the large-scale structural network formed by neurons is a major challenge in system neuroscience. A detailed connectivity map covering the entire brain would therefore be of great value. Based on diffusion MRI, we propose an efficient methodology to generate large, comprehensive and individual white matter connectional datasets of the living or dead, human or animal brain. This non-invasive tool enables us to study the basic and potentially complex network properties of the entire brain. For two human subjects we find that their individual brain networks have an exponential node degree distribution and that their global organization is in the form of a small world.

  1. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    Science.gov (United States)

    Li, Guangye; Zhang, Dingguo

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

  2. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    Directory of Open Access Journals (Sweden)

    Guangye Li

    Full Text Available An all-chain-wireless brain-to-brain system (BTBS, which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP based brain-computer interface (BCI was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

  3. Mathematical modeling of human glioma growth based on brain topological structures: study of two clinical cases.

    Directory of Open Access Journals (Sweden)

    Cecilia Suarez

    Full Text Available Gliomas are the most common primary brain tumors and yet almost incurable due mainly to their great invasion capability. This represents a challenge to present clinical oncology. Here, we introduce a mathematical model aiming to improve tumor spreading capability definition. The model consists in a time dependent reaction-diffusion equation in a three-dimensional spatial domain that distinguishes between different brain topological structures. The model uses a series of digitized images from brain slices covering the whole human brain. The Talairach atlas included in the model describes brain structures at different levels. Also, the inclusion of the Brodmann areas allows prediction of the brain functions affected during tumor evolution and the estimation of correlated symptoms. The model is solved numerically using patient-specific parametrization and finite differences. Simulations consider an initial state with cellular proliferation alone (benign tumor, and an advanced state when infiltration starts (malign tumor. Survival time is estimated on the basis of tumor size and location. The model is used to predict tumor evolution in two clinical cases. In the first case, predictions show that real infiltrative areas are underestimated by current diagnostic imaging. In the second case, tumor spreading predictions were shown to be more accurate than those derived from previous models in the literature. Our results suggest that the inclusion of differential migration in glioma growth models constitutes another step towards a better prediction of tumor infiltration at the moment of surgical or radiosurgical target definition. Also, the addition of physiological/psychological considerations to classical anatomical models will provide a better and integral understanding of the patient disease at the moment of deciding therapeutic options, taking into account not only survival but also life quality.

  4. Sex beyond the genitalia: The human brain mosaic.

    Science.gov (United States)

    Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S; Liem, Franziskus; Hänggi, Jürgen; Jäncke, Lutz; Assaf, Yaniv

    2015-12-15

    Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains ("female brain" or "male brain"). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only "male" or only "female" features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the "maleness-femaleness" continuum are rare. Rather, most brains are comprised of unique "mosaics" of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain.

  5. Gender versus brain size effects on subcortical gray matter volumes in the human brain.

    Science.gov (United States)

    Tang, Tianyu; Jiao, Yun; Wang, Xunheng; Lu, Zuhong

    2013-11-27

    Previous studies had reported that volume differences of gray matter (GM) in subcortical regions of the human brain were mainly caused by gender. Meanwhile, other studies had found that the distribution of GM in the human brain varied based on individual brain sizes. Main effects of volume differences of GM in subcortical regions remain unclear. Therefore, the goals of this study are twofold, namely, to determine the main effects of volume differences of GM in subcortical regions of the human brain and to investigate the independent or joint contribution of gender and brain size to subcortical volume differences. In this study, 40 male and 40 female subjects with comparable brain sizes were selected from a population of 198 individuals. The sample was divided into the following four groups: male and female groups with comparably large brain sizes and male and female groups with comparably small brain sizes. The main effects of gender and of brain size and interactions between both factors in subcortical GM volumes were examined by analyses of covariance (ANCOVAs) using a 2×2 design matrix. Volumes of GM in subcortical regions were extracted and measured by an automatic segmentation method. Furthermore, we used two datasets to test the reliability of our methods. In both datasets, we found significant brain size effects in the right amygdala and the bilateral caudate nucleus and significant gender effects in the bilateral putamen. No interactions between brain size and gender were found. In conclusion, both gender and brain size independently contributed to volume distribution in different subcortical areas of the human brain.

  6. [Survival of the fattest: the key to human brain evolution].

    Science.gov (United States)

    Cunnane, Stephen C

    2006-01-01

    The circumstances of human brain evolution are of central importance to accounting for human origins, yet are still poorly understood. Human evolution is usually portrayed as having occurred in a hot, dry climate in East Africa where the earliest human ancestors became bipedal and evolved tool-making skills and language while struggling to survive in a wooded or savannah environment. At least three points need to be recognised when constructing concepts of human brain evolution : (1) The human brain cannot develop normally without a reliable supply of several nutrients, notably docosahexaenoic acid, iodine and iron. (2) At term, the human fetus has about 13 % of body weight as fat, a key form of energy insurance supporting brain development that is not found in other primates. (3) The genome of humans and chimpanzees is human brain become so much larger, and how was its present-day nutritional vulnerability circumvented during 5-6 million years of hominid evolution ? The abundant presence of fish bones and shellfish remains in many African hominid fossil sites dating to 2 million years ago implies human ancestors commonly inhabited the shores, but this point is usually overlooked in conceptualizing how the human brain evolved. Shellfish, fish and shore-based animals and plants are the richest dietary sources of the key nutrients needed by the brain. Whether on the shores of lakes, marshes, rivers or the sea, the consumption of most shore-based foods requires no specialized skills or tools. The presence of key brain nutrients and a rich energy supply in shore-based foods would have provided the essential metabolic and nutritional support needed to gradually expand the hominid brain. Abundant availability of these foods also provided the time needed to develop and refine proto-human attributes that subsequently formed the basis of language, culture, tool making and hunting. The presence of body fat in human babies appears to be the product of a long period of

  7. Genomic connectivity networks based on the BrainSpan atlas of the developing human brain

    Science.gov (United States)

    Mahfouz, Ahmed; Ziats, Mark N.; Rennert, Owen M.; Lelieveldt, Boudewijn P. F.; Reinders, Marcel J. T.

    2014-03-01

    The human brain comprises systems of networks that span the molecular, cellular, anatomic and functional levels. Molecular studies of the developing brain have focused on elucidating networks among gene products that may drive cellular brain development by functioning together in biological pathways. On the other hand, studies of the brain connectome attempt to determine how anatomically distinct brain regions are connected to each other, either anatomically (diffusion tensor imaging) or functionally (functional MRI and EEG), and how they change over development. A global examination of the relationship between gene expression and connectivity in the developing human brain is necessary to understand how the genetic signature of different brain regions instructs connections to other regions. Furthermore, analyzing the development of connectivity networks based on the spatio-temporal dynamics of gene expression provides a new insight into the effect of neurodevelopmental disease genes on brain networks. In this work, we construct connectivity networks between brain regions based on the similarity of their gene expression signature, termed "Genomic Connectivity Networks" (GCNs). Genomic connectivity networks were constructed using data from the BrainSpan Transcriptional Atlas of the Developing Human Brain. Our goal was to understand how the genetic signatures of anatomically distinct brain regions relate to each other across development. We assessed the neurodevelopmental changes in connectivity patterns of brain regions when networks were constructed with genes implicated in the neurodevelopmental disorder autism (autism spectrum disorder; ASD). Using graph theory metrics to characterize the GCNs, we show that ASD-GCNs are relatively less connected later in development with the cerebellum showing a very distinct expression of ASD-associated genes compared to other brain regions.

  8. Brain Prostheses as a Dynamic System (Immortalizing the Human Brain?)

    CERN Document Server

    Astakhov, Vadim

    2007-01-01

    Interest in development of brain prostheses, which might be proposed to recover mental functions lost due to neuron-degenerative disease or trauma, requires new methods in molecular engineering and nanotechnology to build artificial brain tissues. We develop a Dynamic Core model to analyze complexity of damaged biological neural network as well as transition and recovery of the system functionality due to changes in the system environment. We provide a method to model complexity of physical systems which might be proposed as an artificial tissue or prosthesis. Delocalization of Dynamic Core model is developed to analyze migration of mental functions in dynamic bio-systems which undergo architecture transition induced by trauma. Term Dynamic Core is used to define a set of causally related functions and Delocalization is used to describe the process of migration. Information geometry and topological formalisms are proposed to analyze information processes. A holographic model is proposed to construct dynamic e...

  9. New Heuristics for Interfacing Human Motor System using Brain Waves

    Directory of Open Access Journals (Sweden)

    Mohammed El-Dosuky

    2012-09-01

    Full Text Available There are many new forms of interfacing human users to machines. We persevere here electric-mechanical form of interaction between human and machine. The emergence of brain-computer interface allows mind-to-movement systems. The story of the Pied Piper inspired us to devise some new heuristics for interfacing human motor system using brain waves, by combining head helmet and LumbarMotionMonitor. For the simulation we use java GridGain. Brain responses of classified subjects during training indicates that Probe can be the best stimulus to rely on in distinguishing between knowledgeable and not knowledgeable

  10. Development of a Human Head FE Model and Impact Simulation on the Focal Brain Injury

    Science.gov (United States)

    Watanabe, Dai; Yuge, Kohei; Nishimoto, Tetsuya; Murakami, Shigeyuki; Takao, Hiroyuki

    In this paper, a three-dimensional digital human-head model was developed and several dynamic analyses on the head trauma were conducted. This model was built up by the VOXEL approach using 433 slice CT images (512×512 pixels) and made of 1.22 million parallelepiped finite elements with 10 anatomical tissue properties such as scalp, CSF, skull, brain, dura mater and so on. The numerical analyses were conducted using a finite element code the authors have developed. The main features of the code are 1) it is based on the explicit time integration method and 2) it uses the one point integration method to evaluate the equivalent nodal forces with the hourglass control proposed by Flanagan and Belytschko(1) and 3) it utilizes the parallel computation system based on MPI. In order to verify the developed model, the head impact experiment for a cadaver by Nahum et al.(2) was simulated. The calculated results showed good agreement with the experimental ones. A front and rear impact analyses were also performed to discuss on the characteristic measure of the brain injury, in which the von-Mises stress was high in the frontal lobe in both of the analyses because of the large deformations of a frontal cranial base. This result suggests that the von-Mises stress can be a good measure of the brain injury since it is empirically well known that the frontal lobe tends to get injured regardless of the impact positions.

  11. Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model

    OpenAIRE

    Zhang, Huaqiu; Xie, Minjie; Gary P. Schools; Feustel, Paul F.; Wang, Wei; Lei, Ting; Kimelberg, Harold K.; Zhou, Min

    2008-01-01

    Pretreatment of ovarectomized rats with estrogen shows long-term protection via activation of the estrogen receptor (ER). However, it remains unknown whether activation of the ER can provide protection against early neuronal damage when given acutely, we simulated ischemic conditions by applying oxygen and glucose deprived (OGD) solution to acute male rat hippocampal slices and examined the neuronal electrophysiological changes. Pyramidal neurons and interneurons showed a time-dependent membr...

  12. Neuronal activity and brain-derived neurotrophic factor regulate the density of inhibitory synapses in organotypic slice cultures of postnatal hippocampus.

    Science.gov (United States)

    Marty, S; Wehrlé, R; Sotelo, C

    2000-11-01

    Hippocampal interneurons inhibit pyramidal neurons through the release of the neurotransmitter GABA. Given the importance of this inhibition for the proper functioning of the hippocampus, the development of inhibitory synapses must be tightly regulated. In this study, the possibility that neuronal activity and neurotrophins regulate the density of GABAergic inhibitory synapses was investigated in organotypic slice cultures taken from postnatal day 7 rats. In hippocampal slices cultured for 13 d in the presence of the GABA(A) receptor antagonist bicuculline, the density of glutamic acid decarboxylase (GAD) 65-immunoreactive terminals was increased in the CA1 area when compared with control slices. Treatment with the glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione decreased the density of GAD65-immunoreactive terminals in the stratum oriens of CA1. These treatments had parallel effects on the density of GABA-immunoreactive processes. Electron microscopic analysis after postembedding immunogold labeling with antibodies against GABA indicated that bicuculline treatment increased the density of inhibitory but not excitatory synapses. Application of exogenous BDNF partly mimicked the stimulatory effect of bicuculline on GAD65-immunoreactive terminals. Finally, antibodies against BDNF, but not antibodies against nerve growth factor, decrease the density of GAD65-immunoreactive terminals in bicuculline-treated slices. Thus, neuronal activity regulates the density of inhibitory synapses made by postnatal hippocampal interneurons, and BDNF could mediate part of this regulation. This regulation of the density of inhibitory synapses could represent a feedback mechanism aimed at maintaining an appropriate level of activity in the developing hippocampal networks.

  13. Selection for smaller brains in Holocene human evolution

    OpenAIRE

    Hawks, John

    2011-01-01

    Background: Human populations during the last 10,000 years have undergone rapid decreases in average brain size as measured by endocranial volume or as estimated from linear measurements of the cranium. A null hypothesis to explain the evolution of brain size is that reductions result from genetic correlation of brain size with body mass or stature. Results: The absolute change of endocranial volume in the study samples was significantly greater than would be predicted from observed changes i...

  14. Stereological estimation of total brain numbers in humans

    OpenAIRE

    Solveig eWalloe; Bente ePakkenberg; Katrine eFabricius

    2014-01-01

    Our knowledge of the relationship between brain structure and cognitive function is still limited. Human brains and individual cortical areas vary considerably in size and shape. Studies of brain cell numbers have historically been based on biased methods, which did not always result in correct estimates and were often very time-consuming. Within the last 20–30 years, it has become possible to rely on more advanced and unbiased methods. These methods have provided us with information about fe...

  15. Common genetic variants influence human subcortical brain structures

    OpenAIRE

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro,; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume de...

  16. Cell diversity and network dynamics in photosensitive human brain organoids.

    Science.gov (United States)

    Quadrato, Giorgia; Nguyen, Tuan; Macosko, Evan Z; Sherwood, John L; Min Yang, Sung; Berger, Daniel R; Maria, Natalie; Scholvin, Jorg; Goldman, Melissa; Kinney, Justin P; Boyden, Edward S; Lichtman, Jeff W; Williams, Ziv M; McCarroll, Steven A; Arlotta, Paola

    2017-05-04

    In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (more than 9 months), allowing for the establishment of relatively mature features, including the formation of dendritic spines and spontaneously active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photosensitive cells, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli.

  17. Human-specific transcriptional networks in the brain.

    Science.gov (United States)

    Konopka, Genevieve; Friedrich, Tara; Davis-Turak, Jeremy; Winden, Kellen; Oldham, Michael C; Gao, Fuying; Chen, Leslie; Wang, Guang-Zhong; Luo, Rui; Preuss, Todd M; Geschwind, Daniel H

    2012-08-23

    Understanding human-specific patterns of brain gene expression and regulation can provide key insights into human brain evolution and speciation. Here, we use next-generation sequencing, and Illumina and Affymetrix microarray platforms, to compare the transcriptome of human, chimpanzee, and macaque telencephalon. Our analysis reveals a predominance of genes differentially expressed within human frontal lobe and a striking increase in transcriptional complexity specific to the human lineage in the frontal lobe. In contrast, caudate nucleus gene expression is highly conserved. We also identify gene coexpression signatures related to either neuronal processes or neuropsychiatric diseases, including a human-specific module with CLOCK as its hub gene and another module enriched for neuronal morphological processes and genes coexpressed with FOXP2, a gene important for language evolution. These data demonstrate that transcriptional networks have undergone evolutionary remodeling even within a given brain region, providing a window through which to view the foundation of uniquely human cognitive capacities.

  18. Preconditioning of brain slices against hypoxia induced injury by a Gynostemma pentaphyllum extract--stimulation of anti-oxidative enzyme expression.

    Science.gov (United States)

    Schild, L; Cotte, T; Keilhoff, G; Brödemann, R

    2012-06-15

    A short period of hypoxia/hypoglycaemia (oxygen and glucose deprivation, OGD) induced by perfusion with O(2)/glucose-free medium caused immediate loss and incomplete restoration of evoked field potentials in the CA1 region of transverse hippocampus slices. OGD-dependent decrease in evoked field potentials can be prevented by a proceeding short OGD event (preconditioning). We report about a study investigating the effect of an ethanolic Gynostemma pentaphyllum extract on evoked field potentials when administered before the OGD episode. Using this procedure, the extract completely protected the cells of the slices from functional injury. In an astroglia rich cell culture the ethanolic Gynostemma pentaphyllum extract caused within 48 h of cultivation increased protein and activity levels of the anti-oxidative enzymes manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase (GPx). Consequently, the cellular H(2)O(2) concentration remained at a low level. These data suggest that the Gynostemma pentaphyllum-mediated increase in antioxidative enzyme activities may contribute to the protection of transverse hippocampus slices from OGD induced functional injury. Our results demonstrate that the prophylactic administration of the ethanolic extract from Gynostemma pentaphyllum has a high potential to protect from ischemia/reperfusion injury. Copyright © 2012 Elsevier GmbH. All rights reserved.

  19. Initial experience of whole-brain perfusion imaging performed with 256-slice CT%256层螺旋CT全脑灌注成像的初步研究

    Institute of Scientific and Technical Information of China (English)

    唐健; 姜建威; 常军; 侯海燕; 姜旭栋; 堵红群

    2011-01-01

    目的:初步评价256层螺旋CT全脑灌注成像对正常脑血流动力学测定的可行性和价值.方法:从拟诊缺血性脑病行头颅平扫、头颅灌注成像及头颈部血管成像的114例患者中选取检查结果正常者35例,记录头颅灌注成像的辐射剂量,由两名高年资神经放射科医生分别对灌注图像进行分析,选择基底节层面和侧脑室体部层面的两侧大脑中动脉供血区的颞叶皮质进行测定,通过手动勾画选定层面的感兴趣区,CT灌注软件自动生成感兴趣区的脑血流量(CBF)、脑血容量(CBV)、平均通过时间(MTr)、达峰时间(TTP)值,测得的灌注参数均值进行单因素方差分析.结果:35例正常人的辐射剂量为(2.307±0.008)mSv.2名分析者所测得侧脑室体部层面和基底节层面的颞叶灰质的CBF、CBV、MTr、TTP值之间无明显统计学差异(P>0.05).2名分析者测得的两个层面的颞叶灰质的CBV、CBF值之间均有统计学差异(P<0.05).结论:256层螺旋CT全脑灌注成像辐射剂量低,脑灌注参数稳定,能够更真实的反应全脑血流动力学改变.%Objective;To preliminarily evaluate the feasibility and potential values of whole-brain perfusion imaging performed with 256-slice CT to assess normal adult cerebral hemodynamics. Methods; Thirty-five normal results were selected from one hundred and fourteen patients who underwent brain CT unenhanced scan.CT perfusion imaging and CT angiography in head and neck for suspicion of ischemic cerebrovascular disease. The radiation dosage of CT perfusion imaging was recorded. Two senior neuroradiologic doctors independently analyzed the CT perfusion maps. Region of interest (ROI) was placed on bilateral temporal gray matter of two slices (the basal ganglia slice and body of lateral cerebral ventricle slice) supplied by middle cerebral artery,and the cerebral blood flow(CBF),cerebral blood volume(CBV),mean transiting time(MTT), and time to peak(TTP) values of ROI

  20. Alcohol-related brain damage in humans.

    Directory of Open Access Journals (Sweden)

    Amaia M Erdozain

    Full Text Available Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann's area (BA 9 from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics.

  1. Outer brain barriers in rat and human development

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

    2015-01-01

    diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...

  2. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Puetz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Goering, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdes Hernandez, Maria C.; van't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Voelzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigat

  3. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); J.L. Stein; M.E. Rentería (Miguel); A. Arias-Vásquez (Alejandro); S. Desrivières (Sylvane); N. Jahanshad (Neda); R. Toro (Roberto); K. Wittfeld (Katharina); L. Abramovic (Lucija); M. Andersson (Micael); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); M. Bernard (Manon); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.A. Brown (Andrew); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); G. Cuellar-Partida (Gabriel); A. den Braber (Anouk); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); O. Grimm (Oliver); T. Guadalupe (Tulio); J. Hass (Johanna); G. Woldehawariat (Girma); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil H.); L.M. Olde Loohuis (Loes M.); M. Luciano (Michelle); C. MacAre (Christine); R. Mather; M. Mattheisen (Manuel); Y. Milaneschi (Yuri); K. Nho (Kwangsik); M. Papmeyer (Martina); A. Ramasamy (Adaikalavan); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); E.J. Rose (Emma); A. Salami (Alireza); P.G. Sämann (Philipp); L. Schmaal (Lianne); N.J. Schork (Nicholas); J. Shin (Jean); V.M. Strike (Vanessa); A. Teumer (Alexander); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); R.K. Walters (Raymond); L.T. Westlye (Lars); C.D. Whelan (Christopher); A.M. Winkler (Anderson); M.P. Zwiers (Marcel); S. Alhusaini (Saud); L. Athanasiu (Lavinia); S.M. Ehrlich (Stefan); M. Hakobjan (Marina); C.B. Hartberg (Cecilie B.); U.K. Haukvik (Unn); A.J.G.A.M. Heister (Angelien J. G. A. M.); D. Hoehn (David); D. Kasperaviciute (Dalia); D.C. Liewald (David C.); L.M. Lopez (Lorna); R.R.R. Makkinje (Remco R. R.); M. Matarin (Mar); M.A.M. Naber (Marlies A. M.); D. Reese McKay; M. Needham (Margaret); A.C. Nugent (Allison); B. Pütz (Benno); N.A. Royle (Natalie); L. Shen (Li); R. Sprooten (Roy); D. Trabzuni (Danyah); S.S.L. Van Der Marel (Saskia S. L.); K.J.E. Van Hulzen (Kimm J. E.); E. Walton (Esther); A. Björnsson (Asgeir); L. Almasy (Laura); D. Ames (David); S. Arepalli (Sampath); A.A. Assareh; M.E. Bastin (Mark); H. Brodaty (Henry); K. Bulayeva (Kazima); M.A. Carless (Melanie); S. Cichon (Sven); A. Corvin (Aiden); J.E. Curran (Joanne); M. Czisch (Michael); G.I. de Zubicaray (Greig); A. Dillman (Allissa); A. Duggirala (Aparna); M.D. Dyer (Matthew); S. Erk; I. Fedko (Iryna); L. Ferrucci (Luigi); T. Foroud (Tatiana); P.T. Fox (Peter); M. Fukunaga (Masaki); J. Raphael Gibbs; H.H.H. Göring (Harald H.); R.C. Green (Robert C.); S. Guelfi (Sebastian); N.K. Hansell (Narelle); C.A. Hartman (Catharina); K. Hegenscheid (Katrin); J. Heinz (Judith); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); P.J. Hoekstra (Pieter); F. Holsboer; G. Homuth (Georg); J.J. Hottenga (Jouke Jan); M. Ikeda (Masashi); C.R. Jack Jr. (Clifford); S. Jenkinson (Sarah); R. Johnson (Robert); R. Kanai (Ryota); M. Keil (Maria); J.W. Kent (Jack W.); P. Kochunov (Peter); J.B. Kwok (John B.); S. Lawrie (Stephen); X. Liu (Xinmin); D.L. Longo (Dan L.); K.L. Mcmahon (Katie); E. Meisenzahl (Eva); I. Melle (Ingrid); S. Mohnke (Sebastian); G.W. Montgomery (Grant); J.C. Mostert (Jeanette C.); T.W. Mühleisen (Thomas); M.A. Nalls (Michael); T.E. Nichols (Thomas); L.G. Nilsson; M.M. Nöthen (Markus); K. Ohi (Kazutaka); R.L. Olvera (Rene); R. Perez-Iglesias (Rocio); G. Bruce Pike; S.G. Potkin (Steven); I. Reinvang (Ivar); S. Reppermund; M. Rietschel (M.); N. Seiferth (Nina); G.D. Rosen (Glenn D.); D. Rujescu (Dan); K. Schnell (Kerry); C.J. Schofield (Christopher); C. Smith (Colin); V.M. Steen (Vidar); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); J. Turner (Jessica); M.C. Valdés Hernández (Maria); D. van 't Ent (Dennis); M.P. van der Brug (Marcel); N.J. van der Wee (Nic); M.J.D. van Tol (Marie-José); D.J. Veltman (Dick); A.M.J. Wassink (Annemarie); E. Westman (Eric); R.H. Zielke (Ronald H.); A.B. Zonderman (Alan B.); D.G. Ashbrook (David G.); R. Hager (Reinmar); L. Lu (Lu); F.J. Mcmahon (Francis J); D.W. Morris (Derek W); R.W. Williams (Robert W.); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan K.); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); G. Cavalleri (Gianpiero); B. Crespo-Facorro (Benedicto); A.M. Dale (Anders); G.E. Davies (Gareth); N. Delanty; C. Depondt (Chantal); S. Djurovic (Srdjan); D.A. Drevets (Douglas); T. Espeseth (Thomas); R.L. Gollub (Randy); B.C. Ho (Beng ); W. Hoffmann (Wolfgang)

    2015-01-01

    textabstractThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate

  4. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, D.P.; Stein, J.L.; Renteria, M.E.; Arias Vasquez, A.; Desrivieres, S.; Jahanshad, N.; Toro, R.; Wittfeld, K.; Abramovic, L.; Andersson, M.; Aribisala, B.S.; Armstrong, N.J.; Bernard, M.; Bohlken, M.M.; Boks, M.P.; Bralten, J.; Brown, A.A.; Chakravarty, M.M.; Chen, Q.; Ching, C.R.; Cuellar-Partida, G.; Braber, A.; Giddaluru, S.; Goldman, A.L.; Grimm, O.; Guadalupe, T.; Hass, J.; Woldehawariat, G.; Holmes, A.J.; Hoogman, M.; Janowitz, D.; Jia, T.; Kim, S.; Klein, M.; Kraemer, B.; Lee, P.H.; Olde Loohuis, L.M.; Luciano, M.; Macare, C.; Mather, K.A.; Mattheisen, M.; Milaneschi, Y.; Nho, K.; Papmeyer, M.; Ramasamy, A.; Risacher, S.L.; Roiz-Santianez, R.; Rose, E.J.; Salami, A.; Samann, P.G.; Schmaal, L.; Schork, A.J.; Shin, J.; Strike, L.T.; Teumer, A.; Donkelaar, M.M.J. van; Eijk, K.R. van; Walters, R.K.; Westlye, L.T.; Whelan, C.D.; Winkler, A.M.; Zwiers, M.P.; Alhusaini, S.; Athanasiu, L.; Ehrlich, S.; Hakobjan, M.M.; Hartberg, C.B.; Haukvik, U.K.; Heister, A.J.; Hoehn, D.; Kasperaviciute, D.; Liewald, D.C.; Lopez, L.M.; Makkinje, R.R.; Matarin, M.; Naber, M.; McKay, D.R.; Needham, M.; Nugent, A.C.; Putz, B.; Royle, N.A.; Shen, L.; Sprooten, E.; Trabzuni, D.; Marel, S.S. van der; Hulzen, K.J.E. van; Walton, E.; Wolf, C.; Almasy, L.; Ames, D.; Arepalli, S.; Assareh, A.A.; Bastin, M.E.; Brodaty, H.; Bulayeva, K.B.; Carless, M.A.; Cichon, S.; Corvin, A.; Curran, J.E.; Czisch, M.; Fisher, S.E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common

  5. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Puetz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Goering, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdes Hernandez, Maria C.; van't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Voelzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To

  6. An anatomically comprehensive atlas of the adult human brain transcriptome

    NARCIS (Netherlands)

    Hawrylycz, M.J.; Beckmann, Christian

    2012-01-01

    Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising

  7. Neuronal substrates of sensory gating within the human brain.

    NARCIS (Netherlands)

    Grunwald, T.; Boutros, N.N.; Pezer, N.; Oertzen, J. von; Fernandez, G.S.E.; Schaller, C.; Elger, C.E.

    2003-01-01

    BACKGROUND: For the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brain's electrical responses to repeated clicks: the P50 potential is normally reduced to the

  8. Neuronal substrates of sensory gating within the human brain.

    NARCIS (Netherlands)

    Grunwald, T.; Boutros, N.N.; Pezer, N.; Oertzen, J. von; Fernandez, G.S.E.; Schaller, C.; Elger, C.E.

    2003-01-01

    BACKGROUND: For the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brain's electrical responses to repeated clicks: the P50 potential is normally reduced to the sec

  9. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); J.L. Stein; M.E. Rentería (Miguel); A. Arias-Vásquez (Alejandro); S. Desrivières (Sylvane); N. Jahanshad (Neda); R. Toro (Roberto); K. Wittfeld (Katharina); L. Abramovic; M. Andersson (Micael); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); M. Bernard (Manon); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.A. Brown (Andrew); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); G. Cuellar-Partida (Gabriel); A. den Braber (Anouk); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); O. Grimm (Oliver); T. Guadalupe (Tulio); J. Hass (Johanna); G. Woldehawariat (Girma); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil H.); L.M. Olde Loohuis (Loes M.); M. Luciano (Michelle); C. MacAre (Christine); R. Mather; M. Mattheisen (Manuel); Y. Milaneschi (Yuri); K. Nho (Kwangsik); M. Papmeyer (Martina); A. Ramasamy (Adaikalavan); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); E.J. Rose (Emma); A. Salami (Alireza); P.G. Sämann (Philipp); L. Schmaal (Lianne); N.J. Schork (Nicholas); J. Shin (Jean); V.M. Strike (Vanessa); A. Teumer (Alexander); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); R.K. Walters (Raymond); L.T. Westlye (Lars); C.D. Whelan (Christopher); A.M. Winkler (Anderson); M.P. Zwiers (Marcel); S. Alhusaini (Saud); L. Athanasiu (Lavinia); S.M. Ehrlich (Stefan); M. Hakobjan (Marina); C.B. Hartberg (Cecilie B.); U.K. Haukvik (Unn); A.J.G.A.M. Heister (Angelien J. G. A. M.); D. Hoehn (David); D. Kasperaviciute (Dalia); D.C. Liewald (David C.); L.M. Lopez (Lorna); R.R.R. Makkinje (Remco R. R.); M. Matarin (Mar); M.A.M. Naber (Marlies A. M.); D. Reese McKay; M. Needham (Margaret); A.C. Nugent (Allison); B. Pütz (Benno); N.A. Royle (Natalie); L. Shen (Li); R. Sprooten (Roy); D. Trabzuni (Danyah); S.S.L. Van Der Marel (Saskia S. L.); K.J.E. Van Hulzen (Kimm J. E.); E. Walton (Esther); A. Björnsson (Asgeir); L. Almasy (Laura); D. Ames (David); S. Arepalli (Sampath); A.A. Assareh; M.E. Bastin (Mark); H. Brodaty (Henry); K. Bulayeva (Kazima); M.A. Carless (Melanie); S. Cichon (Sven); A. Corvin (Aiden); J.E. Curran (Joanne); M. Czisch (Michael); G.I. de Zubicaray (Greig); A. Dillman (Allissa); A. Duggirala (Aparna); M.D. Dyer (Matthew); S. Erk; I. Fedko (Iryna); L. Ferrucci (Luigi); T. Foroud (Tatiana); P.T. Fox (Peter); M. Fukunaga (Masaki); J. Raphael Gibbs; H.H.H. Göring (Harald H.); R.C. Green (Robert C.); S. Guelfi (Sebastian); N.K. Hansell (Narelle); C.A. Hartman (Catharina); K. Hegenscheid (Katrin); J. Heinz (Judith); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); P.J. Hoekstra (Pieter); F. Holsboer; G. Homuth (Georg); J.J. Hottenga (Jouke Jan); M. Ikeda (Masashi); C.R. Jack Jr. (Clifford); S. Jenkinson (Sarah); R. Johnson (Robert); R. Kanai (Ryota); M. Keil (Maria); J.W. Kent (Jack W.); P. Kochunov (Peter); J.B. Kwok (John B.); S. Lawrie (Stephen); X. Liu (Xinmin); D.L. Longo (Dan L.); K.L. Mcmahon (Katie); E. Meisenzahl (Eva); I. Melle (Ingrid); S. Mohnke (Sebastian); G.W. Montgomery (Grant); J.C. Mostert (Jeanette C.); T.W. Mühleisen (Thomas); M.A. Nalls (Michael); T.E. Nichols (Thomas); L.G. Nilsson; M.M. Nöthen (Markus); K. Ohi (Kazutaka); R.L. Olvera (Rene); R. Perez-Iglesias (Rocio); G. Bruce Pike; S.G. Potkin (Steven); I. Reinvang (Ivar); S. Reppermund; M. Rietschel (M.); N. Seiferth (Nina); G.D. Rosen (Glenn D.); D. Rujescu (Dan); K. Schnell (Kerry); C.J. Schofield (Christopher); C. Smith (Colin); V.M. Steen (Vidar); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); J. Turner (Jessica); M.C. Valdés Hernández (Maria); D. van 't Ent (Dennis); M.P. van der Brug (Marcel); N.J. van der Wee (Nic); M.J.D. van Tol (Marie-José); D.J. Veltman (Dick); A.M.J. Wassink (Annemarie); E. Westman (Eric); R.H. Zielke (Ronald H.); A.B. Zonderman (Alan B.); D.G. Ashbrook (David G.); R. Hager (Reinmar); L. Lu (Lu); F.J. Mcmahon (Francis J); D.W. Morris (Derek W); R.W. Williams (Robert W.); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan K.); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); G. Cavalleri (Gianpiero); B. Crespo-Facorro (Benedicto); A.M. Dale (Anders); G.E. Davies (Gareth); N. Delanty; C. Depondt (Chantal); S. Djurovic (Srdjan); D.A. Drevets (Douglas); T. Espeseth (Thomas); R.L. Gollub (Randy); B.C. Ho (Beng ); W. Hoffmann (Wolfgang); N. Hosten (Norbert); R. Kahn; S. Le Hellard (Stephanie); A. Meyer-Lindenberg; B. Müller-Myhsok (B.); M. Nauck (Matthias); L. Nyberg (Lars); M. Pandolfo (Massimo); B.W.J.H. Penninx (Brenda); J.L. Roffman (Joshua); S.M. Sisodiya (Sanjay); J.W. Smoller; H. van Bokhoven (Hans); N.E.M. van Haren (Neeltje E.); H. Völzke (Henry); H.J. Walter (Henrik); M.W. Weiner (Michael); W. Wen (Wei); T.J.H. White (Tonya); I. Agartz (Ingrid); O.A. Andreassen (Ole A.); J. Blangero (John); D.I. Boomsma (Dorret); R.M. Brouwer (Rachel); D.M. Cannon (Dara); M.R. Cookson (Mark); E.J.C. de Geus (Eco); I.J. Deary (Ian J.); D.J. Donohoe (Dennis); G. Fernandez (Guillén); S.E. Fisher (Simon); C. Francks (Clyde); D.C. Glahn (David); H.J. Grabe (Hans Jörgen); O. Gruber (Oliver); J. Hardy (John); R. Hashimoto (Ryota); H.E. Hulshoff Pol (Hilleke); E.G. Jönsson (Erik); I. Kloszewska (Iwona); S. Lovestone (Simon); V.S. Mattay (Venkata S.); P. Mecocci (Patrizia); C. McDonald (Colm); A.M. McIntosh (Andrew); R.A. Ophoff (Roel); T. Paus (Tomas); Z. Pausova (Zdenka); M. Ryten (Mina); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); A. Simmons (Andrew); A. Singleton (Andrew); H. Soininen (H.); J.M. Wardlaw (J.); M.E. Weale (Michael); D.R. Weinberger (Daniel); H.H.H. Adams (Hieab); L.J. Launer (Lenore); S. Seiler (Stephan); R. Schmidt (Reinhold); G. Chauhan (Ganesh); C.L. Satizabal (Claudia L.); J.T. Becker (James); L.R. Yanek (Lisa); S. van der Lee (Sven); M. Ebling (Maritza); B. Fischl (Bruce); W.T. Longstreth Jr; D. Greve (Douglas); R. Schmidt (Reinhold); P. Nyquist (Paul); L.N. Vinke (Louis N.); C.M. van Duijn (Cock); L. Xue (Luting); B. Mazoyer (Bernard); J.C. Bis (Joshua); V. Gudnason (Vilmundur); S. Seshadri (Sudha); M.A. Ikram (Arfan); N.G. Martin (Nicholas); M.J. Wright (Margaret); G. Schumann (Gunter); B. Franke (Barbara); P.M. Thompson (Paul); S.E. Medland (Sarah Elizabeth)

    2015-01-01

    textabstractThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate h

  10. Forthergillian Lecture. Imaging human brain function.

    Science.gov (United States)

    Frackowiak, R S

    The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning

  11. Entrainment of perceptually relevant brain oscillations by non-invasive rhythmic stimulation of the human brain

    Directory of Open Access Journals (Sweden)

    Gregor eThut

    2011-07-01

    Full Text Available The notion of driving brain oscillations by directly stimulating neuronal elements with rhythmic stimulation protocols has become increasingly popular in research on brain rhythms. Induction of brain oscillations in a controlled and functionally meaningful way would likely prove highly beneficial for the study of brain oscillations, and their therapeutic control. We here review conventional and new non-invasive brain stimulation protocols as to their suitability for controlled intervention into human brain oscillations. We focus on one such type of intervention, the direct entrainment of brain oscillations by a periodic external drive. We review highlights of the literature on entraining brain rhythms linked to perception and attention, and point out controversies. Behaviourally, such entrainment seems to alter specific aspects of perception depending on the frequency of stimulation, informing models on the functional role of oscillatory activity. This indicates that human brain oscillations and function may be promoted in a controlled way by focal entrainment, with great potential for probing into brain oscillations and their causal role.

  12. Entrainment of perceptually relevant brain oscillations by non-invasive rhythmic stimulation of the human brain.

    Science.gov (United States)

    Thut, Gregor; Schyns, Philippe G; Gross, Joachim

    2011-01-01

    The notion of driving brain oscillations by directly stimulating neuronal elements with rhythmic stimulation protocols has become increasingly popular in research on brain rhythms. Induction of brain oscillations in a controlled and functionally meaningful way would likely prove highly beneficial for the study of brain oscillations, and their therapeutic control. We here review conventional and new non-invasive brain stimulation protocols as to their suitability for controlled intervention into human brain oscillations. We focus on one such type of intervention, the direct entrainment of brain oscillations by a periodic external drive. We review highlights of the literature on entraining brain rhythms linked to perception and attention, and point out controversies. Behaviourally, such entrainment seems to alter specific aspects of perception depending on the frequency of stimulation, informing models on the functional role of oscillatory activity. This indicates that human brain oscillations and function may be promoted in a controlled way by focal entrainment, with great potential for probing into brain oscillations and their causal role.

  13. Toward discovery science of human brain function.

    Science.gov (United States)

    Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian; Gohel, Suril; Kelly, Clare; Smith, Steve M; Beckmann, Christian F; Adelstein, Jonathan S; Buckner, Randy L; Colcombe, Stan; Dogonowski, Anne-Marie; Ernst, Monique; Fair, Damien; Hampson, Michelle; Hoptman, Matthew J; Hyde, James S; Kiviniemi, Vesa J; Kötter, Rolf; Li, Shi-Jiang; Lin, Ching-Po; Lowe, Mark J; Mackay, Clare; Madden, David J; Madsen, Kristoffer H; Margulies, Daniel S; Mayberg, Helen S; McMahon, Katie; Monk, Christopher S; Mostofsky, Stewart H; Nagel, Bonnie J; Pekar, James J; Peltier, Scott J; Petersen, Steven E; Riedl, Valentin; Rombouts, Serge A R B; Rypma, Bart; Schlaggar, Bradley L; Schmidt, Sein; Seidler, Rachael D; Siegle, Greg J; Sorg, Christian; Teng, Gao-Jun; Veijola, Juha; Villringer, Arno; Walter, Martin; Wang, Lihong; Weng, Xu-Chu; Whitfield-Gabrieli, Susan; Williamson, Peter; Windischberger, Christian; Zang, Yu-Feng; Zhang, Hong-Ying; Castellanos, F Xavier; Milham, Michael P

    2010-03-09

    Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

  14. Artificial Brain Based on Credible Neural Circuits in a Human Brain

    CERN Document Server

    Burger, John Robert

    2010-01-01

    Neurons are individually translated into simple gates to plan a brain with human psychology and intelligence. State machines, assumed previously learned in subconscious associative memory are shown to enable equation solving and rudimentary thinking using nanoprocessing within short term memory.

  15. Astrocytes and the evolution of the human brain.

    Science.gov (United States)

    Robertson, James M

    2014-02-01

    Cells within the astroglial lineage are proposed as the origin of human brain evolution. It is now widely accepted that they direct mammalian fetal neurogenesis, gliogenesis, laminar cytoarchitectonics, synaptic connectivity and neuronal network formation. Furthermore, genetic, anatomical and functional studies have recently identified multiple astrocyte exaptations that strongly suggest a direct relation to the increased size and complexity of the human brain. Copyright © 2013 The Author. Published by Elsevier Ltd.. All rights reserved.

  16. Quantitation of glial fibrillary acidic protein in human brain tumours

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...... amounts of GFA, up to 85 times the concentration in parietal grey substance of normal human brain. GFA was not found in neurinomas, meningiomas, adenomas of the hypophysis, or in a single case of metastasis of adenocarcinoma. Non-glial tumours of craniopharyngioma and haemangioblastoma were infiltrated...

  17. Optogenetic control of human neurons in organotypic brain cultures

    DEFF Research Database (Denmark)

    Andersson, My; Avaliani, Natalia; Svensson, Andreas

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof......-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies....

  18. Integrated RF/shim coil array for parallel reception and localized B0 shimming in the human brain.

    Science.gov (United States)

    Truong, Trong-Kha; Darnell, Dean; Song, Allen W

    2014-12-01

    The purpose of this work was to develop a novel integrated radiofrequency and shim (RF/shim) coil array that can perform parallel reception and localized B0 shimming in the human brain with the same coils, thereby maximizing both the signal-to-noise ratio and shimming efficiency. A 32-channel receive-only head coil array was modified to enable both RF currents (for signal reception) and direct currents (for B0 shimming) to flow in individual coil elements. Its in vivo performance was assessed in the frontal brain region, which is affected by large susceptibility-induced B0 inhomogeneities. The coil modifications did not reduce their quality factor or signal-to-noise ratio. Axial B0 maps and echo-planar images acquired in vivo with direct currents optimized to shim specific slices showed substantially reduced B0 inhomogeneities and image distortions in the frontal brain region. The B0 root-mean-square error in the anterior half of the brain was reduced by 60.3% as compared to that obtained with second-order spherical harmonic shimming. These results demonstrate that the integrated RF/shim coil array can perform parallel reception and localized B0 shimming in the human brain and provide a much more effective shimming than conventional spherical harmonic shimming alone, without taking up additional space in the magnet bore and without compromising the signal-to-noise ratio or shimming performance.

  19. Understanding complexity in the human brain.

    Science.gov (United States)

    Bassett, Danielle S; Gazzaniga, Michael S

    2011-05-01

    Although the ultimate aim of neuroscientific enquiry is to gain an understanding of the brain and how its workings relate to the mind, the majority of current efforts are largely focused on small questions using increasingly detailed data. However, it might be possible to successfully address the larger question of mind-brain mechanisms if the cumulative findings from these neuroscientific studies are coupled with complementary approaches from physics and philosophy. The brain, we argue, can be understood as a complex system or network, in which mental states emerge from the interaction between multiple physical and functional levels. Achieving further conceptual progress will crucially depend on broad-scale discussions regarding the properties of cognition and the tools that are currently available or must be developed in order to study mind-brain mechanisms.

  20. Increased morphological asymmetry, evolvability and plasticity in human brain evolution.

    Science.gov (United States)

    Gómez-Robles, Aida; Hopkins, William D; Sherwood, Chet C

    2013-06-22

    The study of hominin brain evolution relies mostly on evaluation of the endocranial morphology of fossil skulls. However, only some general features of external brain morphology are evident from endocasts, and many anatomical details can be difficult or impossible to examine. In this study, we use geometric morphometric techniques to evaluate inter- and intraspecific differences in cerebral morphology in a sample of in vivo magnetic resonance imaging scans of chimpanzees and humans, with special emphasis on the study of asymmetric variation. Our study reveals that chimpanzee-human differences in cerebral morphology are mainly symmetric; by contrast, there is continuity in asymmetric variation between species, with humans showing an increased range of variation. Moreover, asymmetric variation does not appear to be the result of allometric scaling at intraspecific levels, whereas symmetric changes exhibit very slight allometric effects within each species. Our results emphasize two key properties of brain evolution in the hominine clade: first, evolution of chimpanzee and human brains (and probably their last common ancestor and related species) is not strongly morphologically constrained, thus making their brains highly evolvable and responsive to selective pressures; second, chimpanzee and, especially, human brains show high levels of fluctuating asymmetry indicative of pronounced developmental plasticity. We infer that these two characteristics can have a role in human cognitive evolution.

  1. DUF1220 domains, cognitive disease, and human brain evolution.

    Science.gov (United States)

    Dumas, L; Sikela, J M

    2009-01-01

    We have established that human genome sequences encoding a novel protein domain, DUF1220, show a dramatically elevated copy number in the human lineage (>200 copies in humans vs. 1 in mouse/rat) and may be important to human evolutionary adaptation. Copy-number variations (CNVs) in the 1q21.1 region, where most DUF1220 sequences map, have now been implicated in numerous diseases associated with cognitive dysfunction, including autism, autism spectrum disorder, mental retardation, schizophrenia, microcephaly, and macrocephaly. We report here that these disease-related 1q21.1 CNVs either encompass or are directly flanked by DUF1220 sequences and exhibit a dosage-related correlation with human brain size. Microcephaly-producing 1q21.1 CNVs are deletions, whereas macrocephaly-producing 1q21.1 CNVs are duplications. Similarly, 1q21.1 deletions and smaller brain size are linked with schizophrenia, whereas 1q21.1 duplications and larger brain size are associated with autism. Interestingly, these two diseases are thought to be phenotypic opposites. These data suggest a model which proposes that (1) DUF1220 domain copy number may be involved in influencing human brain size and (2) the evolutionary advantage of rapidly increasing DUF1220 copy number in the human lineage has resulted in favoring retention of the high genomic instability of the 1q21.1 region, which, in turn, has precipitated a spectrum of recurrent human brain and developmental disorders.

  2. Effects of ketamine,midazolam,thiopental,and propofol on brain ischemia injury in rat cerebral cortical slices%氯胺酮,咪唑安定,硫喷妥钠和异丙酚对大鼠皮层脑片缺血性损伤的作用

    Institute of Scientific and Technical Information of China (English)

    薛庆生; 于布为; 王泽剑; 陈红专

    2004-01-01

    AIM: To compare the effects of ketamine, midazolam, thiopental, and propofol on brain ischemia by the model of oxygen-glucose deprivation (OGD) in rat cerebral cortical slices. METHODS: Cerebral cortical slices were incubated in 2 % 2,3,5-triphenyltetrazolium chloride (TTC) solution after OGD, the damages and effects of ketamine,midazolam, thiopental, and propofol were quantitativlye evaluated by ELISA reader of absorbance (A) at 490 nm,which indicated the red formazan extracted from slices, lactic dehydrogenase (LDH) releases in the incubated supernate were also measured. RESULTS: Progressive prolongation of OGD resulted in decreases of TTC staining.The percentage of tissue injury had a positive correlation with LDH releases, r=0.9609, P<0.01. Two hours of reincubation aggravated the decrease of TTC staining compared with those slices stained immediately after OGD (P<0.01). These four anesthetics had no effects on the TTC staining of slices. Ketamine completely inhibited the decrease of A value induced by 10 min of OGD injury. High concentrations of midazolam (10 μmol/L) and thiopental (400 μmol/L)partly attenuated this decrease. Propofol at high concentration (100 μmol/L) enhanced the decrease of A value induced by 10 min of OGD injury (P<0.01). CONCLUSION: Ketamine, high concentration of midazolam and thiopental have neuroprotective effects against OGD injury in rat cerebral cortical slices, while high concentration of propofol augments OGD injury in rat cerebral cortical slices.

  3. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Conscious brain-to-brain communication in humans using non-invasive technologies.

    Directory of Open Access Journals (Sweden)

    Carles Grau

    Full Text Available Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI. These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B communication between subjects (hyperinteraction. Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG changes with a CBI inducing the conscious perception of phosphenes (light flashes through neuronavigated, robotized transcranial magnetic stimulation (TMS, with special care taken to block sensory (tactile, visual or auditory cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

  5. Conscious brain-to-brain communication in humans using non-invasive technologies.

    Science.gov (United States)

    Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L; Pascual-Leone, Alvaro; Ruffini, Giulio

    2014-01-01

    Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

  6. Transcriptomic insights into human brain evolution: acceleration, neutrality, heterochrony.

    Science.gov (United States)

    Somel, Mehmet; Rohlfs, Rori; Liu, Xiling

    2014-12-01

    Primate brain transcriptome comparisons within the last 12 years have yielded interesting but contradictory observations on how the transcriptome evolves, and its adaptive role in human cognitive evolution. Since the human-chimpanzee common ancestor, the human prefrontal cortex transcriptome seems to have evolved more than that of the chimpanzee. But at the same time, most expression differences among species, especially those observed in adults, appear as consequences of neutral evolution at cis-regulatory sites. Adaptive expression changes in the human brain may be rare events involving timing shifts, or heterochrony, in specific neurodevelopmental processes. Disentangling adaptive and neutral expression changes, and associating these with human-specific features of the brain require improved methods, comparisons across more species, and further work on comparative development.

  7. Cryopreserved Human Precision-Cut Lung Slices as a Bioassay for Live Tissue Banking. A Viability Study of Bronchodilation with Bitter-Taste Receptor Agonists.

    Science.gov (United States)

    Bai, Yan; Krishnamoorthy, Nandini; Patel, Kruti R; Rosas, Ivan; Sanderson, Michael J; Ai, Xingbin

    2016-05-01

    Human precision-cut lung slices (hPCLSs) provide a unique ex vivo model for translational research. However, the limited and unpredictable availability of human lung tissue greatly impedes their use. Here, we demonstrate that cryopreservation of hPCLSs facilitates banking of live human lung tissue for routine use. Our results show that cryopreservation had little effect on overall cell viability and vital functions of immune cells, including phagocytes and T lymphocytes. In addition, airway contraction and relaxation in response to specific agonists and antagonists, respectively, were unchanged after cryopreservation. At the subcellular level, cryopreserved hPCLSs maintained Ca(2+)-dependent regulatory mechanisms for the control of airway smooth muscle cell contractility. To exemplify the use of cryopreserved hPCLSs in smooth muscle research, we provide evidence that bitter-taste receptor (TAS2R) agonists relax airways by blocking Ca(2+) oscillations in airway smooth muscle cells. In conclusion, the banking of cryopreserved hPCLSs provides a robust bioassay for translational research of lung physiology and disease.

  8. Human brain activity with functional NIR optical imager

    Science.gov (United States)

    Luo, Qingming

    2001-08-01

    In this paper we reviewed the applications of functional near infrared optical imager in human brain activity. Optical imaging results of brain activity, including memory for new association, emotional thinking, mental arithmetic, pattern recognition ' where's Waldo?, occipital cortex in visual stimulation, and motor cortex in finger tapping, are demonstrated. It is shown that the NIR optical method opens up new fields of study of the human population, in adults under conditions of simulated or real stress that may have important effects upon functional performance. It makes practical and affordable for large populations the complex technology of measuring brain function. It is portable and low cost. In cognitive tasks subjects could report orally. The temporal resolution could be millisecond or less in theory. NIR method will have good prospects in exploring human brain secret.

  9. Leveraging Human Brain Activity to Improve Object Classification

    OpenAIRE

    Fong, Ruth Catherine

    2015-01-01

    Today, most object detection algorithms differ drastically from how humans tackle visual problems. In this thesis, I present a new paradigm for improving machine vision algorithms by designing them to better mimic how humans approach these tasks. Specifically, I demonstrate how human brain activity from functional magnetic resonance imaging (fMRI) can be leveraged to improve object classification. Inspired by the graduated manner in which humans learn, I present a novel algorithm that sim...

  10. Functional network organization of the human brain.

    Science.gov (United States)

    Power, Jonathan D; Cohen, Alexander L; Nelson, Steven M; Wig, Gagan S; Barnes, Kelly Anne; Church, Jessica A; Vogel, Alecia C; Laumann, Timothy O; Miezin, Fran M; Schlaggar, Bradley L; Petersen, Steven E

    2011-11-17

    Real-world complex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks that eliminates potentially artificial short-distance relationships. These graphs contain many subgraphs in good agreement with known functional brain systems. Other subgraphs lack established functional identities; we suggest possible functional characteristics for these subgraphs. Further, graph measures of the areal network indicate that the default mode subgraph shares network properties with sensory and motor subgraphs: it is internally integrated but isolated from other subgraphs, much like a "processing" system. The modified voxelwise graph also reveals spatial motifs in the patterning of systems across the cortex.

  11. Effects of isoflurane and sevoflurane postconditioning and changes in JNK1/2 pathway activity on rat brain slices subjected to oxygen and glucose deprivation in vitro

    Institute of Scientific and Technical Information of China (English)

    Sheng Wang; Zhigang Dai; Xiwei Dong; Suxiang Guo; Yang Liu; Shan Jiang; Zhiping Wang

    2011-01-01

    Recent research shows that the JNK1/2 signaling pathway plays a neuroprotective role against ischemia-reperfusion injury by cross-talk with other pathways. The present study investigated the effects of isoflurane and sevoflurane postconditioning on JNK1/2 pathway activity and neuronal cell viability after oxygen and glucose deprivation injury in hippocampal slices in vitro. Techniques used included population spike analysis, propidium iodide fluorescent staining, western blot assay, and the use of JNK1/2-specific pharmacological tools such as anisomycin (agonist) and SP600125 (inhibitor). We found that both isoflurane and sevoflurane inhibited JNK pathway activity and had neuroprotective effects against oxygen and glucose deprivation injury in slices of rat hippocampus in vitro. Postconditioning with volatile anesthetics exerted neuroprotective effects on nerve cells and preserved the function of the CA1 region by inhibiting JNK1/2 phosphorylation. This suppression of JNK1/2 activity could underlie the observed synergistic neuroprotective effect produced by volatile anesthetic postconditioning.

  12. Phaco slice and separate.

    Science.gov (United States)

    Arshinoff, S A

    1999-04-01

    Phaco slice and separate retains the advantages of the chopping techniques of Nagahara, Koch, and Fukasaku but replaces chopping or snapping with slicing across the center of the phaco-tip-stabilized nucleus using a Nagahara chopper and then repositioning the chopper to optimally separate the divided lens halves. As the lens is rotated in the capsular bag, small pieces of the nuclear pie are sliced off, separated, emulsified, and aspirated. Emulsification and aspiration can alternatively be left until most or all the slices have been made. This technique works with a broader range of lens densities than other chopping techniques and uses no sculpting and very little phaco time. The phaco time required for this technique is relatively independent of nuclear density compared with a sculpting technique.

  13. Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

    Science.gov (United States)

    Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

    2017-03-01

    Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Slice hyperholomorphic Schur analysis

    CERN Document Server

    Alpay, Daniel; Sabadini, Irene

    2016-01-01

    This book defines and examines the counterpart of Schur functions and Schur analysis in the slice hyperholomorphic setting. It is organized into three parts: the first introduces readers to classical Schur analysis, while the second offers background material on quaternions, slice hyperholomorphic functions, and quaternionic functional analysis. The third part represents the core of the book and explores quaternionic Schur analysis and its various applications. The book includes previously unpublished results and provides the basis for new directions of research.

  15. The effect of head size∕shape, miscentering, and bowtie filter on peak patient tissue doses from modern brain perfusion 256-slice CT: how can we minimize the risk for deterministic effects?

    Science.gov (United States)

    Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis; Papadakis, Antonios E; Damilakis, John

    2013-01-01

    To determine patient-specific absorbed peak doses to skin, eye lens, brain parenchyma, and cranial red bone marrow (RBM) of adult individuals subjected to low-dose brain perfusion CT studies on a 256-slice CT scanner, and investigate the effect of patient head size∕shape, head position during the examination and bowtie filter used on peak tissue doses. The peak doses to eye lens, skin, brain, and RBM were measured in 106 individual-specific adult head phantoms subjected to the standard low-dose brain perfusion CT on a 256-slice CT scanner using a novel Monte Carlo simulation software dedicated for patient CT dosimetry. Peak tissue doses were compared to corresponding thresholds for induction of cataract, erythema, cerebrovascular disease, and depression of hematopoiesis, respectively. The effects of patient head size∕shape, head position during acquisition and bowtie filter used on resulting peak patient tissue doses were investigated. The effect of eye-lens position in the scanned head region was also investigated. The effect of miscentering and use of narrow bowtie filter on image quality was assessed. The mean peak doses to eye lens, skin, brain, and RBM were found to be 124, 120, 95, and 163 mGy, respectively. The effect of patient head size and shape on peak tissue doses was found to be minimal since maximum differences were less than 7%. Patient head miscentering and bowtie filter selection were found to have a considerable effect on peak tissue doses. The peak eye-lens dose saving achieved by elevating head by 4 cm with respect to isocenter and using a narrow wedge filter was found to approach 50%. When the eye lies outside of the primarily irradiated head region, the dose to eye lens was found to drop to less than 20% of the corresponding dose measured when the eye lens was located in the middle of the x-ray beam. Positioning head phantom off-isocenter by 4 cm and employing a narrow wedge filter results in a moderate reduction of signal-to-noise ratio

  16. The effect of head size/shape, miscentering, and bowtie filter on peak patient tissue doses from modern brain perfusion 256-slice CT: How can we minimize the risk for deterministic effects?

    Energy Technology Data Exchange (ETDEWEB)

    Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis; Papadakis, Antonios E.; Damilakis, John [Department of Medical Physics, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion 71003, Crete (Greece); Medical Diagnostic Center ' Ayios Therissos,' P.O. Box 28405, Nicosia 2033, Cyprus and Department of Medical Physics, Medical School, Democritus University of Thrace, Panepistimioupolis, Dragana 68100, Alexandroupolis (Greece); Department of Medical Physics, University Hospital of Heraklion, P.O. Box 1352, Heraklion 71110, Crete (Greece); Department of Medical Physics, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion 71003, Crete (Greece)

    2013-01-15

    Purpose: To determine patient-specific absorbed peak doses to skin, eye lens, brain parenchyma, and cranial red bone marrow (RBM) of adult individuals subjected to low-dose brain perfusion CT studies on a 256-slice CT scanner, and investigate the effect of patient head size/shape, head position during the examination and bowtie filter used on peak tissue doses. Methods: The peak doses to eye lens, skin, brain, and RBM were measured in 106 individual-specific adult head phantoms subjected to the standard low-dose brain perfusion CT on a 256-slice CT scanner using a novel Monte Carlo simulation software dedicated for patient CT dosimetry. Peak tissue doses were compared to corresponding thresholds for induction of cataract, erythema, cerebrovascular disease, and depression of hematopoiesis, respectively. The effects of patient head size/shape, head position during acquisition and bowtie filter used on resulting peak patient tissue doses were investigated. The effect of eye-lens position in the scanned head region was also investigated. The effect of miscentering and use of narrow bowtie filter on image quality was assessed. Results: The mean peak doses to eye lens, skin, brain, and RBM were found to be 124, 120, 95, and 163 mGy, respectively. The effect of patient head size and shape on peak tissue doses was found to be minimal since maximum differences were less than 7%. Patient head miscentering and bowtie filter selection were found to have a considerable effect on peak tissue doses. The peak eye-lens dose saving achieved by elevating head by 4 cm with respect to isocenter and using a narrow wedge filter was found to approach 50%. When the eye lies outside of the primarily irradiated head region, the dose to eye lens was found to drop to less than 20% of the corresponding dose measured when the eye lens was located in the middle of the x-ray beam. Positioning head phantom off-isocenter by 4 cm and employing a narrow wedge filter results in a moderate reduction of

  17. On Expression Patterns and Developmental Origin of Human Brain Regions.

    Science.gov (United States)

    Kirsch, Lior; Chechik, Gal

    2016-08-01

    Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions.

  18. BrainScope: interactive visual exploration of the spatial and temporal human brain transcriptome.

    Science.gov (United States)

    Huisman, Sjoerd M H; van Lew, Baldur; Mahfouz, Ahmed; Pezzotti, Nicola; Höllt, Thomas; Michielsen, Lieke; Vilanova, Anna; Reinders, Marcel J T; Lelieveldt, Boudewijn P F

    2017-06-02

    Spatial and temporal brain transcriptomics has recently emerged as an invaluable data source for molecular neuroscience. The complexity of such data poses considerable challenges for analysis and visualization. We present BrainScope: a web portal for fast, interactive visual exploration of the Allen Atlases of the adult and developing human brain transcriptome. Through a novel methodology to explore high-dimensional data (dual t-SNE), BrainScope enables the linked, all-in-one visualization of genes and samples across the whole brain and genome, and across developmental stages. We show that densities in t-SNE scatter plots of the spatial samples coincide with anatomical regions, and that densities in t-SNE scatter plots of the genes represent gene co-expression modules that are significantly enriched for biological functions. We also show that the topography of the gene t-SNE maps reflect brain region-specific gene functions, enabling hypothesis and data driven research. We demonstrate the discovery potential of BrainScope through three examples: (i) analysis of cell type specific gene sets, (ii) analysis of a set of stable gene co-expression modules across the adult human donors and (iii) analysis of the evolution of co-expression of oligodendrocyte specific genes over developmental stages. BrainScope is publicly accessible at www.brainscope.nl. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Progress on the paternal brain: theory, animal models, human brain research, and mental health implications.

    Science.gov (United States)

    Swain, J E; Dayton, C J; Kim, P; Tolman, R M; Volling, B L

    2014-01-01

    With a secure foundation in basic research across mammalian species in which fathers participate in the raising of young, novel brain-imaging approaches are outlining a set of consistent brain circuits that regulate paternal thoughts and behaviors in humans. The newest experimental paradigms include increasingly realistic baby-stimuli to provoke paternal cognitions and behaviors with coordinated hormone measures to outline brain networks that regulate motivation, reflexive caring, emotion regulation, and social brain networks with differences and similarities to those found in mothers. In this article, on the father brain, we review all brain-imaging studies on PubMed to date on the human father brain and introduce the topic with a selection of theoretical models and foundational neurohormonal research on animal models in support of the human work. We discuss potentially translatable models for the identification and treatment of paternal mood and father-child relational problems, which could improve infant mental health and developmental trajectories with potentially broad public health importance. © 2014 Michigan Association for Infant Mental Health.

  20. Toward discovery science of human brain function.

    NARCIS (Netherlands)

    Biswal, B.B.; Mennes, M.J.J.; Zuo, X.N.; Gohel, S.; Kelly, C.; Smith, S.M.; Beckmann, C.F.; Adelstein, J.S.; Buckner, R.L.; Colcombe, S.; Dogonowski, A.M.; Ernst, M.; Fair, D.; Hampson, M.; Hoptman, M.J.; Hyde, J.S.; Kiviniemi, V.J.; Kotter, R.; Li, S.J.; Lin, C.P.; Lowe, M.J.; Mackay, C.; Madden, D.J.; Madsen, K.H.; Margulies, D.S.; Mayberg, H.S.; McMahon, K.; Monk, C.S.; Mostofsky, S.H.; Nagel, B.J.; Pekar, J.J.; Peltier, S.J.; Petersen, S.E.; Riedl, V.; Rombouts, S.A.R.B.; Rypma, B.; Schlaggar, B.L.; Schmidt, S.; Seidler, R.D.; Siegle, G.J.; Sorg, C.; Teng, G.J.; Veijola, J.; Villringer, A.; Walter, M.; Wang, L.; Weng, X.C.; Whitfield-Gabrieli, S.; Williamson, P.; Windischberger, C.; Zang, Y.F.; Zhang, H.Y.; Castellanos, F.X.; Milham, M.P.

    2010-01-01

    Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a

  1. Toward discovery science of human brain function.

    NARCIS (Netherlands)

    Biswal, B.B.; Mennes, M.; Zuo, X.N.; Gohel, S.; Kelly, C.; Smith, S.M.; Beckmann, C.F.; Adelstein, J.S.; Buckner, R.L.; Colcombe, S.; Dogonowski, A.M.; Ernst, M.; Fair, D.; Hampson, M.; Hoptman, M.J.; Hyde, J.S.; Kiviniemi, V.J.; Kotter, R.; Li, S.J.; Lin, C.P.; Lowe, M.J.; Mackay, C.; Madden, D.J.; Madsen, K.H.; Margulies, D.S.; Mayberg, H.S.; McMahon, K.; Monk, C.S.; Mostofsky, S.H.; Nagel, B.J.; Pekar, J.J.; Peltier, S.J.; Petersen, S.E.; Riedl, V.; Rombouts, S.A.; Rypma, B.; Schlaggar, B.L.; Schmidt, S.; Seidler, R.D.; Siegle, G.J.; Sorg, C.; Teng, G.J.; Veijola, J.; Villringer, A.; Walter, M.; Wang, L.; Weng, X.C.; Whitfield-Gabrieli, S.; Williamson, P.; Windischberger, C.; Zang, Y.F.; Zhang, H.Y.; Castellanos, F.X.; Milham, M.P.

    2010-01-01

    Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a pr

  2. Toward discovery science of human brain function

    DEFF Research Database (Denmark)

    Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian

    2010-01-01

    Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a...

  3. Weight lifting in the human brain

    NARCIS (Netherlands)

    Lange, F.P. de

    2006-01-01

    The world, just like us, is constantly changing. Making predictions about what will happen to you when you do something (and correcting these predictions based on what is actually happening) is therefore of vital importance. An influential theory states that the brain solves this challenge by using

  4. Shortcomings of the Human Brain and Remedial Action by Religion

    Science.gov (United States)

    Reich, K. Helmut

    2010-01-01

    There is no consensus as to whether, and if so, in which regard and to what extent science and religion is needed for human survival. Here a circumscribed domain is taken up: the sovereignty and sufficiency of the human brain in this context. Several of its shortcomings are pointed out. Religion and other aspects of culture are needed for remedial…

  5. Sibling rivalry among paralogs promotes evolution of the human brain.

    Science.gov (United States)

    Tyler-Smith, Chris; Xue, Yali

    2012-05-11

    Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution.

  6. Shortcomings of the Human Brain and Remedial Action by Religion

    Science.gov (United States)

    Reich, K. Helmut

    2010-01-01

    There is no consensus as to whether, and if so, in which regard and to what extent science and religion is needed for human survival. Here a circumscribed domain is taken up: the sovereignty and sufficiency of the human brain in this context. Several of its shortcomings are pointed out. Religion and other aspects of culture are needed for remedial…

  7. Development of human brain structural networks through infancy and childhood.

    Science.gov (United States)

    Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

    2015-05-01

    During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Gene expression in the aging human brain: an overview.

    Science.gov (United States)

    Mohan, Adith; Mather, Karen A; Thalamuthu, Anbupalam; Baune, Bernhard T; Sachdev, Perminder S

    2016-03-01

    The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

  9. Evolution of the human brain: when bigger is better.

    Directory of Open Access Journals (Sweden)

    Michel A. Hofman

    2014-03-01

    Full Text Available Comparative studies of the brain in mammals suggest that there are general architectural principles governing its growth and evolutionary development. We are beginning to understand the geometric, biophysical and energy constraints that have governed the evolution and functional organization of the brain and its underlying neuronal network. The object of this review is to present current perspectives on primate brain evolution, especially in humans, and to examine some hypothetical organizing principles that underlie the brain’s complex organization. Some of the design principles and operational modes that underlie the information processing capacity of the cerebral cortex in primates will be explored. It is shown that the development of the cortex coordinates folding with connectivity in a way that produces smaller and faster brains, then otherwise would have been possible. In view of the central importance placed on brain evolution in explaining the success of our own species, one may wonder whether there are physical limits that constrain its processing power and evolutionary potential. It will be argued that at a brain size of about 3500 cm3, corresponding to a brain volume two to three times that of modern man, the brain seems to reach its maximum processing capacity. The larger the brain grows beyond this critical size, the less efficient it will become, thus limiting any improvement in cognitive power.

  10. Expression of iron-related genes in human brain and brain tumors

    Directory of Open Access Journals (Sweden)

    Britton Robert S

    2009-04-01

    Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

  11. The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

    Science.gov (United States)

    Miller, Geoffrey F.; Penke, Lars

    2007-01-01

    Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

  12. The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

    Science.gov (United States)

    Miller, Geoffrey F.; Penke, Lars

    2007-01-01

    Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

  13. A HYBRID DYNAMIC PROGRAM SLICING

    Institute of Scientific and Technical Information of China (English)

    Yi Tong; Wu Fangjun

    2005-01-01

    This letter proposes a hybrid method for computing dynamic program slicing. The key element is to construct a Coverage-Testing-based Dynamic Dependence Graph (CTDDG),which makes use of both dynamic and static information to get execution status. The approach overcomes the limitations of previous dynamic slicing methods, which have to redo slicing if slice criterion changes.

  14. The bilingual brain: Flexibility and control in the human cortex

    Science.gov (United States)

    Buchweitz, Augusto; Prat, Chantel

    2013-12-01

    The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.

  15. Three-dimensional morphology of the human embryonic brain

    Directory of Open Access Journals (Sweden)

    N. Shiraishi

    2015-09-01

    Full Text Available The morphogenesis of the cerebral vesicles and ventricles was visualized in 3D movies using images derived from human embryo specimens between Carnegie stage 13 and 23 from the Kyoto Collection. These images were acquired with a magnetic resonance microscope equipped with a 2.35-T superconducting magnet. Three-dimensional images using the same scale demonstrated brain development and growth effectively. The non-uniform thickness of the brain tissue, which may indicate brain differentiation, was visualized with thickness-based surface color mapping. A closer view was obtained of the unique and complicated differentiation of the rhombencephalon, especially with regard to the internal view and thickening of the brain tissue. The present data contribute to a better understanding of brain and cerebral ventricle development.

  16. Electrical Guidance of Human Stem Cells in the Rat Brain

    Directory of Open Access Journals (Sweden)

    Jun-Feng Feng

    2017-07-01

    Full Text Available Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

  17. Design principles of the human brain: an evolutionary perspective.

    Science.gov (United States)

    Hofman, Michel A

    2012-01-01

    The evolution of the brain in mammals has been accompanied by a reorganization of the brain as a result of differential growth of certain brain regions. Consequently, the geometry of the brain, and especially the size and shape of the cerebral cortex, has changed notably during evolution. Comparative studies of the cerebral cortex suggest that there are general architectural principles governing its growth and evolutionary development and that the primate neocortex is uniformly organized and composed of neural processing units. We are beginning to understand the geometric, biophysical, and energy constraints that have governed the evolution of these neuronal networks. In this review, some of the design principles and operational modes will be explored that underlie the information processing capacity of the cerebral cortex in primates, and it will be argued that with the evolution of the human brain we have nearly reached the limits of biological intelligence.

  18. Genetic contributions to human brain morphology and intelligence

    DEFF Research Database (Denmark)

    Hulshoff Pol, HE; Schnack, HG; Posthuma, D

    2006-01-01

    Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...... of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images.......55). Intelligence shared a common genetic origin with superior occipitofrontal, callosal, and left optical radiation WM and frontal, occipital, and parahippocampal GM (phenotypic correlations up to 0.35). These findings point to a neural network that shares a common genetic origin with human intelligence...

  19. Decade of the Brain 1990--2000: Maximizing human potential

    Energy Technology Data Exchange (ETDEWEB)

    1991-04-01

    The US Decade of the Brain offers scientists throughout the Federal Government a unique opportunity to advance and apply scientific knowledge about the brain and nervous system. During the next 10 years, scientists hope to maximize human potential through studies of human behavior, senses and communication, learning and memory, genetic/chemical alterations, and environmental interactions. Progress in these areas should lead to reductions in mortality from brain and nervous system disorders and to improvements in the quality of life. This report identifies nine research areas that could form the basis of an integrated program in the brain and behavioral sciences. A chart summarizing the Federal activities in these nine areas may be found at the back of the report. In addition, three areas that span the nine research areas -- basic research, technology and international activities -- are considered.

  20. Brain and Social Networks: Fundamental Building Blocks of Human Experience.

    Science.gov (United States)

    Falk, Emily B; Bassett, Danielle S

    2017-09-01

    How do brains shape social networks, and how do social ties shape the brain? Social networks are complex webs by which ideas spread among people. Brains comprise webs by which information is processed and transmitted among neural units. While brain activity and structure offer biological mechanisms for human behaviors, social networks offer external inducers or modulators of those behaviors. Together, these two axes represent fundamental contributors to human experience. Integrating foundational knowledge from social and developmental psychology and sociology on how individuals function within dyads, groups, and societies with recent advances in network neuroscience can offer new insights into both domains. Here, we use the example of how ideas and behaviors spread to illustrate the potential of multilayer network models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  2. Gene expression analysis of precision-cut human liver slices indicate stable expression of hepatotoxicity related genes

    NARCIS (Netherlands)

    Elferink, Maria; Olinga, Peter; van Leeuwen, E. M.; Bauerschmidt, S.; Polman, J.; Schoonen, W. G.; Heisterkamp, S. H.; Groothuis, Genoveva

    2011-01-01

    In the process of drug development it is of high importance to test the safety of new drugs with predictive value for human toxicity. A promising approach of toxicity testing is based on changes in the gene expression profile of the liver. Toxicity screening based on animal liver cells cannot be dir

  3. Gene expression analysis of precision cut human liver slices indicate stable expression of ADME-Tox related genes

    NARCIS (Netherlands)

    Elferink, M.; Olinga, P.; Van Leeuwen, E.; Bauerschmidt, S.; Polman, J.; Schoonen, W.; Heisterkamp, S.; Groothuis, G.

    2010-01-01

    In the process of drug development it is of high importance to test the safety of new drugs with predictive value for human toxicity. Currently, for toxicity studies toxicogenomic analysis of changes in gene expression profile of the liver is increasingly applied. Toxicity screening based on animal

  4. Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes

    NARCIS (Netherlands)

    Elferink, M. G. L.; Olinga, P.; van Leeuwen, E. M.; Bauerschmidt, S.; Polman, J.; Schoonen, W. G.; Heisterkamp, S. H.; Groothuis, G. M. M.

    2011-01-01

    In the process of drug development it is of high importance to test the safety of new drugs with predictive value for human toxicity. A promising approach of toxicity testing is based on shifts in gene expression profiling of the liver. Toxicity screening based on animal liver cells cannot be direct

  5. Organ slices as an in vitro test system for drug metabolism in human liver, lung and kidney

    NARCIS (Netherlands)

    Olinga, Peter; de Jager, M.H; Meijer, D.K F; Groothuis, Geny; Merema, M.T.

    1999-01-01

    Metabolism of xenobiotics occurs mainly in the liver, but in addition, the lungs and kidneys may contribute considerably. The choice of the animal species during drug development as a predictive model for the human condition is often inadequate due to large interspecies differences. Therefore, a

  6. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    Science.gov (United States)

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.

  7. Three-dimensional microtomographic imaging of human brain cortex

    CERN Document Server

    Mizutania, Ryuta; Uesugi, Kentaro; Ohyama, Masami; Takekoshi, Susumu; Osamura, R Yoshiyuki; Suzuki, Yoshio

    2016-01-01

    This paper describes an x-ray microtomographic technique for imaging the three-dimensional structure of the human cerebral cortex. Neurons in the brain constitute a neural circuit as a three-dimensional network. The brain tissue is composed of light elements that give little contrast in a hard x-ray transmission image. The contrast was enhanced by staining neural cells with metal compounds. The obtained structure revealed the microarchitecture of the gray and white matter regions of the frontal cortex, which is responsible for the higher brain functions.

  8. Immunohistochemical localization of oxytocin receptors in human brain.

    Science.gov (United States)

    Boccia, M L; Petrusz, P; Suzuki, K; Marson, L; Pedersen, C A

    2013-12-03

    The neuropeptide oxytocin (OT) regulates rodent, primate and human social behaviors and stress responses. OT binding studies employing (125)I-d(CH2)5-[Tyr(Me)2,Thr4,Tyr-NH2(9)] ornithine vasotocin ((125)I-OTA), has been used to locate and quantify OT receptors (OTRs) in numerous areas of the rat brain. This ligand has also been applied to locating OTRs in the human brain. The results of the latter studies, however, have been brought into question because of subsequent evidence that (125)I-OTA is much less selective for OTR vs. vasopressin receptors in the primate brain. Previously we used a monoclonal antibody directed toward a region of the human OTR to demonstrate selective immunostaining of cell bodies and fibers in the preoptic-anterior hypothalamic area and ventral septum of a cynomolgus monkey (Boccia et al., 2001). The present study employed the same monoclonal antibody to study the location of OTRs in tissue blocks containing cortical, limbic and brainstem areas dissected from fixed adult, human female brains. OTRs were visualized in discrete cell bodies and/or fibers in the central and basolateral regions of the amygdala, medial preoptic area (MPOA), anterior and ventromedial hypothalamus, olfactory nucleus, vertical limb of the diagonal band, ventrolateral septum, anterior cingulate and hypoglossal and solitary nuclei. OTR staining was not observed in the hippocampus (including CA2 and CA3), parietal cortex, raphe nucleus, nucleus ambiguus or pons. These results suggest that there are some similarities, but also important differences, in the locations of OTRs in human and rodent brains. Immunohistochemistry (IHC) utilizing a monoclonal antibody provides specific localization of OTRs in the human brain and thereby provides opportunity to further study OTR in human development and psychiatric conditions. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Regional distribution of serotonin transporter protein in postmortem human brain

    Energy Technology Data Exchange (ETDEWEB)

    Kish, Stephen J. [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)]. E-mail: Stephen_Kish@CAMH.net; Furukawa, Yoshiaki [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Chang Lijan [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Tong Junchao [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Ginovart, Nathalie [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Wilson, Alan [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Meyer, Jeffrey H. [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

    2005-02-01

    Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met.

  10. Pain perception and its genesis in the human brain

    Institute of Scientific and Technical Information of China (English)

    Andrew CN CHEN

    2008-01-01

    In the past two decades, pain perception in the human brain has been studied with EEG/MEG brain topography and PET/ fMRI neuroimaging techniques. A host of cortical and subeortical loci can be activated by various nociceptive conditions. The activation in pain perception can be induced by physical (electrical, thermal, mechanical), chemical (capsacin, ascoric acid), psychological (anxiety, stress, nocebo) means, and pathological (e.g. migraine, neuropathic) diseases. This article deals mainly on the activation, but not modulation, of human pain in the brain. The brain areas identified are named pain representation, matrix, neuraxis, or signature. The sites are not uniformly isolated across various studies, but largely include a set of cores sites: thalamus and primary somatic area (SI), second somatic area (SII), insular cortex (IC), prefrontal cortex (PFC), cingnlate, and parietal cortices. Other areas less reported and considered important in pain perception include brainstem, hippocampus, amygdala and supplementary motor area (SMA). The issues of pain perception basically encompass both the site and the mode of brain function. Although the site issue is delineared to a large degree, the mode issue has been much less explored. From the temporal dynamics, IC can be considered as the initial stage in genesis of pain perception as conscious suffering, the unique aversion in the human brain.

  11. Distribution of vesicular glutamate transporters in the human brain

    Directory of Open Access Journals (Sweden)

    Erika eVigneault

    2015-03-01

    Full Text Available Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3 are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

  12. Pain perception and its genesis in the human brain.

    Science.gov (United States)

    C N Chen, Andrew

    2008-10-25

    In the past two decades, pain perception in the human brain has been studied with EEG/MEG brain topography and PET/fMRI neuroimaging techniques. A host of cortical and subcortical loci can be activated by various nociceptive conditions. The activation in pain perception can be induced by physical (electrical, thermal, mechanical), chemical (capsacin, ascoric acid), psychological (anxiety, stress, nocebo) means, and pathological (e.g. migraine, neuropathic) diseases. This article deals mainly on the activation, but not modulation, of human pain in the brain. The brain areas identified are named pain representation, matrix, neuraxis, or signature. The sites are not uniformly isolated across various studies, but largely include a set of cores sites: thalamus and primary somatic area (SI), second somatic area (SII), insular cortex (IC), prefrontal cortex (PFC), cingulate, and parietal cortices. Other areas less reported and considered important in pain perception include brainstem, hippocampus, amygdala and supplementary motor area (SMA). The issues of pain perception basically encompass both the site and the mode of brain function. Although the site issue is delineared to a large degree, the mode issue has been much less explored. From the temporal dynamics, IC can be considered as the initial stage in genesis of pain perception as conscious suffering, the unique aversion in the human brain.

  13. Cell lineage analysis in human brain using endogenous retroelements.

    Science.gov (United States)

    Evrony, Gilad D; Lee, Eunjung; Mehta, Bhaven K; Benjamini, Yuval; Johnson, Robert M; Cai, Xuyu; Yang, Lixing; Haseley, Psalm; Lehmann, Hillel S; Park, Peter J; Walsh, Christopher A

    2015-01-07

    Somatic mutations occur during brain development and are increasingly implicated as a cause of neurogenetic disease. However, the patterns in which somatic mutations distribute in the human brain are unknown. We used high-coverage whole-genome sequencing of single neurons from a normal individual to identify spontaneous somatic mutations as clonal marks to track cell lineages in human brain. Somatic mutation analyses in >30 locations throughout the nervous system identified multiple lineages and sublineages of cells marked by different LINE-1 (L1) retrotransposition events and subsequent mutation of poly-A microsatellites within L1. One clone contained thousands of cells limited to the left middle frontal gyrus, whereas a second distinct clone contained millions of cells distributed over the entire left hemisphere. These patterns mirror known somatic mutation disorders of brain development and suggest that focally distributed mutations are also prevalent in normal brains. Single-cell analysis of somatic mutation enables tracing of cell lineage clones in human brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. A quantitative transcriptome reference map of the normal human brain.

    Science.gov (United States)

    Caracausi, Maria; Vitale, Lorenza; Pelleri, Maria Chiara; Piovesan, Allison; Bruno, Samantha; Strippoli, Pierluigi

    2014-10-01

    We performed an innovative systematic meta-analysis of 60 gene expression profiles of whole normal human brain, to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 39,250 known, mapped and 26,026 uncharacterized (unmapped) transcripts. To this aim, we used the software named Transcriptome Mapper (TRAM), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the brain transcriptome with those derived from human foetal brain gene expression, from a pool of human tissues (except the brain) and from the two normal human brain regions cerebellum and cerebral cortex, which are two of the main regions severely affected when cognitive impairment occurs, as happens in the case of trisomy 21. Data were downloaded from microarray databases, processed and analyzed using TRAM software and validated in vitro by assaying gene expression through several magnitude orders by 'real-time' reverse transcription polymerase chain reaction (RT-PCR). The excellent agreement between in silico and experimental data suggested that our transcriptome maps may be a useful quantitative reference benchmark for gene expression studies related to the human brain. Furthermore, our analysis yielded biological insights about those genes which have an intrinsic over-/under-expression in the brain, in addition offering a basis for the regional analysis of gene expression. This could be useful for the study of chromosomal alterations associated to cognitive impairment, such as trisomy 21, the most common genetic cause of intellectual disability.

  15. The heritability of chimpanzee and human brain asymmetry.

    Science.gov (United States)

    Gómez-Robles, Aida; Hopkins, William D; Schapiro, Steven J; Sherwood, Chet C

    2016-12-28

    Human brains are markedly asymmetric in structure and lateralized in function, which suggests a relationship between these two properties. The brains of other closely related primates, such as chimpanzees, show similar patterns of asymmetry, but to a lesser degree, indicating an increase in anatomical and functional asymmetry during hominin evolution. We analysed the heritability of cerebral asymmetry in chimpanzees and humans using classic morphometrics, geometric morphometrics, and quantitative genetic techniques. In our analyses, we separated directional asymmetry and fluctuating asymmetry (FA), which is indicative of environmental influences during development. We show that directional patterns of asymmetry, those that are consistently present in most individuals in a population, do not have significant heritability when measured through simple linear metrics, but they have marginally significant heritability in humans when assessed through three-dimensional configurations of landmarks that reflect variation in the size, position, and orientation of different cortical regions with respect to each other. Furthermore, genetic correlations between left and right hemispheres are substantially lower in humans than in chimpanzees, which points to a relatively stronger environmental influence on left-right differences in humans. We also show that the level of FA has significant heritability in both species in some regions of the cerebral cortex. This suggests that brain responsiveness to environmental influences, which may reflect neural plasticity, has genetic bases in both species. These results have implications for the evolvability of brain asymmetry and plasticity among humans and our close relatives.

  16. Notch receptor expression in human brain arteriovenous malformations.

    Science.gov (United States)

    Hill-Felberg, Sandra; Wu, Hope Hueizhi; Toms, Steven A; Dehdashti, Amir R

    2015-08-01

    The roles of the Notch pathway proteins in normal adult vascular physiology and the pathogenesis of brain arteriovenous malformations are not well-understood. Notch 1 and 4 have been detected in human and mutant mice vascular malformations respectively. Although mutations in the human Notch 3 gene caused a genetic form of vascular stroke and dementia, its role in arteriovenous malformations development has been unknown. In this study, we performed immunohistochemistry screening on tissue microarrays containing eight surgically resected human brain arteriovenous malformations and 10 control surgical epilepsy samples. The tissue microarrays were evaluated for Notch 1-4 expression. We have found that compared to normal brain vascular tissue Notch-3 was dramatically increased in brain arteriovenous malformations. Similarly, Notch 4 labelling was also increased in vascular malformations and was confirmed by western blot analysis. Notch 2 was not detectable in any of the human vessels analysed. Using both immunohistochemistry on microarrays and western blot analysis, we have found that Notch-1 expression was detectable in control vessels, and discovered a significant decrease of Notch 1 expression in vascular malformations. We have demonstrated that Notch 3 and 4, and not Notch 1, were highly increased in human arteriovenous malformations. Our findings suggested that Notch 4, and more importantly, Notch 3, may play a role in the development and pathobiology of human arteriovenous malformations.

  17. Optimizing full-brain coverage in human brain MRI through population distributions of brain size

    NARCIS (Netherlands)

    Mennes, M.; Jenkinson, M.; Valabregue, R.; Buitelaar, J.; Beckmann, C.; Smith, S.

    2014-01-01

    When defining an MRI protocol, brain researchers need to set multiple interdependent parameters that define repetition time (TR), voxel size, field-of-view (FOV), etc. Typically, researchers aim to image the full brain, making the expected FOV an important parameter to consider. Especially in 2D-EPI

  18. Measuring dopamine release in the human brain with PET

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York at Stony Brook, Stony Brook, NY (United States). Dept. of Psychiatry; Fowler, J.S.; Logan, J.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States)

    1995-12-01

    The dopamine system is involved in the regulation of brain regions that subserve motor, cognitive and motivational behaviors. Disruptions of dopamine (DA) function have ben implicated in neurological and psychiatric illnesses including substance abuse as well as on some of the deficits associated with aging of the human brain. This has made the DA system an important topic in research in the neurosciences and neuroimaging as well as an important molecular target for drug development. Positron Emission Tomography (PET), was the first technology that enabled direct measurement of components of the DA system in the living human brain. Imaging studies of DA in the living brain have been indirect, relying on the development of radiotracers to label DA receptors, DA transporters, compounds which have specificity for the enzymes which degrade synaptic DA. Additionally, through the use of tracers that provide information on regional brain activity (ie brain glucose metabolism and cerebral blood flow) and of appropriate pharmacological interventions, it has been possible to assess the functional consequences of changes in brain DA activity. DA specific ligands have been useful in the evaluation of patients with neuropsychiatric illnesses as well as to investigate receptor blockade by antipsychotic drugs. A limitation of strategies that rely on the use of DA specific ligands is that the measures do not necessarily reflect the functional state of the dopaminergic system and that there use to study the effects of drugs is limited to the investigation of receptor or transporter occupancy. Newer strategies have been developed in an attempt to provide with information on dopamine release and on the functional responsivity of the DA system in the human brain. This in turn allows to investigate the effects of pharmacological agent in an analogous way to what is done with microdialysis techniques.

  19. The immune response of the human brain to abdominal surgery.

    Science.gov (United States)

    Forsberg, Anton; Cervenka, Simon; Jonsson Fagerlund, Malin; Rasmussen, Lars S; Zetterberg, Henrik; Erlandsson Harris, Helena; Stridh, Pernilla; Christensson, Eva; Granström, Anna; Schening, Anna; Dymmel, Karin; Knave, Nina; Terrando, Niccolò; Maze, Mervyn; Borg, Jacqueline; Varrone, Andrea; Halldin, Christer; Blennow, Kaj; Farde, Lars; Eriksson, Lars I

    2017-04-01

    Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [(11) C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Patients showed a global downregulation of gray matter [(11) C]PBR28 binding of 26 ± 26% (mean ± standard deviation) at 3 to 4 days postoperatively compared to baseline (p = 0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-α in blood displayed a reduction (41 ± 39%) on the 3rd to 4th postoperative day, corresponding to changes in [(11) C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [(11) C]PBR28 binding (p = 0.027). This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. Ann Neurol 2017;81:572-582. © 2017 American Neurological Association.

  20. Voice processing in monkey and human brains.

    Science.gov (United States)

    Scott, Sophie K

    2008-09-01

    Studies in humans have indicated that the anterior superior temporal sulcus has an important role in the processing of information about human voices, especially the identification of talkers from their voice. A new study using functional magnetic resonance imaging (fMRI) with macaques provides strong evidence that anterior auditory fields, part of the auditory 'what' pathway, preferentially respond to changes in the identity of conspecifics, rather than specific vocalizations from the same individual.

  1. Neural stem cells improve neuronal survival in cultured postmortem brain tissue from aged and Alzheimer patients.

    Science.gov (United States)

    Wu, L; Sluiter, A A; Guo, Ho-Fu; Balesar, R A; Swaab, D F; Zhou, Jiang-Ning; Verwer, R W H

    2008-01-01

    Neurodegenerative diseases are progressive and incurable and are becoming ever more prevalent. To study whether neural stem cell can reactivate or rescue functions of impaired neurons in the human aging and neurodegenerating brain, we co-cultured postmortem slices from Alzheimer patients and control participants with rat embryonic day 14 (E14) neural stem cells. Viability staining based on the exclusion of ethidium bromide by intact plasma membranes showed that there were strikingly more viable cells and fewer dead cells in slices co-cultured with neural stem cells than in untreated slices. The presence of Alzheimer pathology in the brain slices did not influence this effect, although the slices from Alzheimer patients, in general, contained fewer viable cells. Co-culturing with rat E14 fibroblasts did not improve the viability of neurons in the human brain slices. Since the human slices and neural stem cells were separated by a membrane during co-culturing our data show for the first time that neural stem cells release diffusible factors that may improve the survival of aged and degenerating neurons in human brains.

  2. Neurospin Seminar: From the Proton to the Human Brain

    CERN Document Server

    CERN. Geneva

    2016-01-01

    From the Proton to the Human Brain Speaker: Prof Denis Le Bihan Abstract: The understanding of the human brain is one of the main scientific challenges of the 21st century. In the early 2000s the French Atomic Energy Commission (CEA) launched a program to conceive and build a “human brain explorer”, the first human MRI scanner operating at 11.7T. This scanner was envisioned to be part of the ambitious Iseult project, bridging together industrial and academic partners to push the limits of molecular neuroimaging, from mouse to man, using Ultra-High Field (UHF) MRI. In this seminar a summary of the main features of this magnet, and the neuroscience and medical targets of NeuroSpin where this outstanding instrument will be installed in 2017 will be surveyed. The unprecedented resolution and the new contrasts allowed by such UHF magnets, in combination with innovative concepts in physics and neurobiology, will allow to explore the human brain at a mesoscale at which everything remains to d...

  3. Common genetic variants influence human subcortical brain structures.

    Science.gov (United States)

    Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy

    2015-04-01

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

  4. Comprehensive cellular-resolution atlas of the adult human brain.

    Science.gov (United States)

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. Copyright © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  5. Energetics and the evolution of human brain size.

    Science.gov (United States)

    Navarrete, Ana; van Schaik, Carel P; Isler, Karin

    2011-11-09

    The human brain stands out among mammals by being unusually large. The expensive-tissue hypothesis explains its evolution by proposing a trade-off between the size of the brain and that of the digestive tract, which is smaller than expected for a primate of our body size. Although this hypothesis is widely accepted, empirical support so far has been equivocal. Here we test it in a sample of 100 mammalian species, including 23 primates, by analysing brain size and organ mass data. We found that, controlling for fat-free body mass, brain size is not negatively correlated with the mass of the digestive tract or any other expensive organ, thus refuting the expensive-tissue hypothesis. Nonetheless, consistent with the existence of energy trade-offs with brain size, we find that the size of brains and adipose depots are negatively correlated in mammals, indicating that encephalization and fat storage are compensatory strategies to buffer against starvation. However, these two strategies can be combined if fat storage does not unduly hamper locomotor efficiency. We propose that human encephalization was made possible by a combination of stabilization of energy inputs and a redirection of energy from locomotion, growth and reproduction.

  6. Comprehensive cellular‐resolution atlas of the adult human brain

    Science.gov (United States)

    Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  7. A glass capillary microelectrode based on capillarity and its application to the detection of L-glutamate release from mouse brain slices.

    Science.gov (United States)

    Nakajima, Kumiko; Yamagiwa, Takashi; Hirano, Ayumi; Sugawara, Masao

    2003-01-01

    A new glass capillary microelectrode for L-glutamate is described using pulled glass capillaries (tip size, approximately 12.5 microm) with a very small volume (approximately 2 microl) of inner solution containing glutamate oxidase (GluOx) and ascorbate oxidase. The operation of the electrode is based on capillary action that samples L-glutamate into the inner solution. The enzyme reaction by GluOx generates hydrogen peroxide that is detected at an Os-gel-HRP polymer modified Pt electrode in a three-electrode configuration. The amperometric response behavior of the electrode was characterized in terms of the capillarity, response time, sensitivity and selectivity for measurements of L-glutamate. The currents at 0 V vs. Ag/AgCl increased linearly with the L-glutamate concentration from 10 to 150 microM for in vitro and in situ calibrations. The response was highly selective to L-glutamate over ascorbate, dopamine, serotonin and other amino acids. The detection of L-glutamate in the extracellular fluids of different regions of mouse hippocampal slices under stimulation of KCl was demonstrated.

  8. Addiction circuitry in the human brain (*).

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.

    2011-09-27

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.

  9. Mathematical logic in the human brain: syntax.

    Directory of Open Access Journals (Sweden)

    Roland Friedrich

    Full Text Available Theory predicts a close structural relation of formal languages with natural languages. Both share the aspect of an underlying grammar which either generates (hierarchically structured expressions or allows us to decide whether a sentence is syntactically correct or not. The advantage of rule-based communication is commonly believed to be its efficiency and effectiveness. A particularly important class of formal languages are those underlying the mathematical syntax. Here we provide brain-imaging evidence that the syntactic processing of abstract mathematical formulae, written in a first order language, is, indeed efficient and effective as a rule-based generation and decision process. However, it is remarkable, that the neural network involved, consisting of intraparietal and prefrontal regions, only involves Broca's area in a surprisingly selective way. This seems to imply that despite structural analogies of common and current formal languages, at the neural level, mathematics and natural language are processed differently, in principal.

  10. Mathematical logic in the human brain: syntax.

    Science.gov (United States)

    Friedrich, Roland; Friederici, Angela D

    2009-05-28

    Theory predicts a close structural relation of formal languages with natural languages. Both share the aspect of an underlying grammar which either generates (hierarchically) structured expressions or allows us to decide whether a sentence is syntactically correct or not. The advantage of rule-based communication is commonly believed to be its efficiency and effectiveness. A particularly important class of formal languages are those underlying the mathematical syntax. Here we provide brain-imaging evidence that the syntactic processing of abstract mathematical formulae, written in a first order language, is, indeed efficient and effective as a rule-based generation and decision process. However, it is remarkable, that the neural network involved, consisting of intraparietal and prefrontal regions, only involves Broca's area in a surprisingly selective way. This seems to imply that despite structural analogies of common and current formal languages, at the neural level, mathematics and natural language are processed differently, in principal.

  11. A hierarchical model of the evolution of human brain specializations.

    Science.gov (United States)

    Barrett, H Clark

    2012-06-26

    The study of information-processing adaptations in the brain is controversial, in part because of disputes about the form such adaptations might take. Many psychologists assume that adaptations come in two kinds, specialized and general-purpose. Specialized mechanisms are typically thought of as innate, domain-specific, and isolated from other brain systems, whereas generalized mechanisms are developmentally plastic, domain-general, and interactive. However, if brain mechanisms evolve through processes of descent with modification, they are likely to be heterogeneous, rather than coming in just two kinds. They are likely to be hierarchically organized, with some design features widely shared across brain systems and others specific to particular processes. Also, they are likely to be largely developmentally plastic and interactive with other brain systems, rather than canalized and isolated. This article presents a hierarchical model of brain specialization, reviewing evidence for the model from evolutionary developmental biology, genetics, brain mapping, and comparative studies. Implications for the search for uniquely human traits are discussed, along with ways in which conventional views of modularity in psychology may need to be revised.

  12. The modular and integrative functional architecture of the human brain.

    Science.gov (United States)

    Bertolero, Maxwell A; Yeo, B T Thomas; D'Esposito, Mark

    2015-12-01

    Network-based analyses of brain imaging data consistently reveal distinct modules and connector nodes with diverse global connectivity across the modules. How discrete the functions of modules are, how dependent the computational load of each module is to the other modules' processing, and what the precise role of connector nodes is for between-module communication remains underspecified. Here, we use a network model of the brain derived from resting-state functional MRI (rs-fMRI) data and investigate the modular functional architecture of the human brain by analyzing activity at different types of nodes in the network across 9,208 experiments of 77 cognitive tasks in the BrainMap database. Using an author-topic model of cognitive functions, we find a strong spatial correspondence between the cognitive functions and the network's modules, suggesting that each module performs a discrete cognitive function. Crucially, activity at local nodes within the modules does not increase in tasks that require more cognitive functions, demonstrating the autonomy of modules' functions. However, connector nodes do exhibit increased activity when more cognitive functions are engaged in a task. Moreover, connector nodes are located where brain activity is associated with many different cognitive functions. Connector nodes potentially play a role in between-module communication that maintains the modular function of the brain. Together, these findings provide a network account of the brain's modular yet integrated implementation of cognitive functions.

  13. Kisspeptin modulates sexual and emotional brain processing in humans

    Science.gov (United States)

    Comninos, Alexander N.; Wall, Matthew B.; Demetriou, Lysia; Shah, Amar J.; Clarke, Sophie A.; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K.; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M.; Jayasena, Channa N.; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A.; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Wilson, Steven Ray; Brown, Rachel C.; Thomas, Sarah A.; Bloom, Stephen R.; Dhillo, Waljit S.

    2017-01-01

    BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin’s enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC). PMID:28112678

  14. Unveiling the mystery of visual information processing in human brain.

    Science.gov (United States)

    Diamant, Emanuel

    2008-08-15

    It is generally accepted that human vision is an extremely powerful information processing system that facilitates our interaction with the surrounding world. However, despite extended and extensive research efforts, which encompass many exploration fields, the underlying fundamentals and operational principles of visual information processing in human brain remain unknown. We still are unable to figure out where and how along the path from eyes to the cortex the sensory input perceived by the retina is converted into a meaningful object representation, which can be consciously manipulated by the brain. Studying the vast literature considering the various aspects of brain information processing, I was surprised to learn that the respected scholarly discussion is totally indifferent to the basic keynote question: "What is information?" in general or "What is visual information?" in particular. In the old days, it was assumed that any scientific research approach has first to define its basic departure points. Why was it overlooked in brain information processing research remains a conundrum. In this paper, I am trying to find a remedy for this bizarre situation. I propose an uncommon definition of "information", which can be derived from Kolmogorov's Complexity Theory and Chaitin's notion of Algorithmic Information. Embracing this new definition leads to an inevitable revision of traditional dogmas that shape the state of the art of brain information processing research. I hope this revision would better serve the challenging goal of human visual information processing modeling.

  15. Expression of epidermal growth factor receptors in human brain tumors.

    Science.gov (United States)

    Libermann, T A; Razon, N; Bartal, A D; Yarden, Y; Schlessinger, J; Soreq, H

    1984-02-01

    The expression of receptors for epidermal growth factor (EGF-R) was determined in 29 samples of brain tumors from 22 patients. Primary gliogenous tumors, of various degrees of cancer, five meningiomas, and two neuroblastomas were examined. Tissue samples were frozen in liquid nitrogen immediately after the operation and stored at -70 degrees until use. Cerebral tissue samples from 11 patients who died from diseases not related to the central nervous system served as controls. Immunoprecipitation of functional EGF-R-kinase complexes revealed high levels of EGF-R in all of the brain tumors of nonneuronal origin that were examined. The level of EGF-R varied between tumors from different patients and also between specimens prelevated from different areas of the same tumor. In contrast, the levels of EGF-R from control specimens were invariably low. The biochemical properties of EGF-R in brain tumor specimens were found to be indistinguishable from those of the well-characterized EGF-R from the A-431 cell line, derived from human epidermoid carcinomas. Human brain EGF-R displays a molecular weight of 170,000 by polyacrylamide-sodium dodecyl sulfate gel electrophoresis. It is phosphorylated mainly in tyrosine residues and shows a 2-dimensional phosphopeptide map similar to that obtained with the phosphorylated EGF-R from membranes of A-431 cells. Our observations suggest that induction of EGF-R expression may accompany the malignant transformation of human brain cells of nonneuronal origin.

  16. New perspectives on corpora amylacea in the human brain

    Science.gov (United States)

    Augé, Elisabet; Cabezón, Itsaso; Pelegrí, Carme; Vilaplana, Jordi

    2017-01-01

    Corpora amylacea are structures of unknown origin and function that appear with age in human brains and are profuse in selected brain areas in several neurodegenerative conditions. They are constituted of glucose polymers and may contain waste elements derived from different cell types. As we previously found on particular polyglucosan bodies in mouse brain, we report here that corpora amylacea present some neo-epitopes that can be recognized by natural antibodies, a certain kind of antibodies that are involved in tissue homeostasis. We hypothesize that corpora amylacea, and probably some other polyglucosan bodies, are waste containers in which deleterious or residual products are isolated to be later eliminated through the action of the innate immune system. In any case, the presence of neo-epitopes on these structures and the existence of natural antibodies directed against them could become a new focal point for the study of both age-related and degenerative brain processes. PMID:28155917

  17. 肌肽对大鼠脑片缺氧缺糖/再灌损伤的保护作用%Neuroprotective of carnosine on oxygen-glucose deprivation/reperfusion induced injury in rat brain slices

    Institute of Scientific and Technical Information of China (English)

    方超; 李晴; 鲁美丽; 黄国兴; 杨菁

    2015-01-01

    目的:在离体脑片缺氧缺糖/再灌损伤模型上,评价肌肽对脑组织的保护作用。方法肌肽预处理后,用缺氧缺糖/再灌(oxygen glucose deprivation/reperfusion,OGD/RP)来制备大鼠离体脑片损伤模型。以2,3,5-三苯基氯化四氮唑(2,3,5-triphenyl tetrazolium chloride,TTC)染色法检测脑片活性;HPLC法检测海马脑片中ATP、ADP、AMP含量;荧光法检测脑组织活性氧( reactive oxygen species,ROS)。结果与对照组相比,缺氧缺糖/再灌损伤可以明显损伤大鼠海马脑片,TTC染色颜色变浅,A490 nm明显下降, ATP和ADP含量明显降低,而AMP含量明显升高,ROS明显升高,差异均具有统计学意义(P<0.01)。与模型组相比,缺氧缺糖/再灌损伤前预先加入1000、200、40μg/mL肌肽预处理15 min可显著抑制缺氧缺糖/再灌引起的损伤,TTC染色颜色加深,A490 nm明显升高,ATP、ADP、AMP含量升高,ROS含量降低,差异均具有统计学意义( P<0.01)。结论肌肽可减轻缺氧缺糖/再灌导致的损伤,其机制可能与其改善脑组织能量代谢,增强抗氧化能力有关。%Objective To investigate effect of carnosine on oxygen glucose deprivation/reperfusion ( OGD/RP) induced injury in rat brain slices. Methods Injury of brain slices was determined by TTC methods.The contents of ATP, ADP and AMP were determined by high performance liquid chromatography.Reactive Oxygen species ( ROS) were determined by fluorescence methods.Results Compared with control group, rat hippocampal slices were significantly damaged by OGD/RP, indicated by light color and decreased A490 nm value of TTC staining.Meanwhile the contents of ATP and ADP were significantly decreased, and the content of AMP and ROS were significantly increased, the difference between two group was significant ( P<0.01).Pre-incubation with Carnosine (1000, 200, 40 μg/mL) significantly inhibited the

  18. A chain of suprasegmental neuroscillatory circuits: a human brain theory.

    Science.gov (United States)

    Deshmukh, V D

    1988-01-01

    A novel electrophysiological model of human brain electrical activity and functions is proposed. It views the human central nervous system as a chain of three suprasegmental neuroscillatory circuits, namely prosencephalic, mesencephalic, and rhombencephalic. Each circuit consists of a network of periventricular paracrine core neurons, efferent motor plate neurons, and sensory-associative alar plate neurons mediating suprasegmental electroclinical phenomena. The model is based on the exponential analyses of well established human data from the fields of electroencephalography, evoked potentials, wake-sleep spectrum, stages of anesthesia, and a variety of human tremors. This neuroscillatory chain is functionally analogous to the chain of cardiac pacemaker neurons.

  19. Visual dictionaries as intermediate features in the human brain

    Directory of Open Access Journals (Sweden)

    Kandan eRamakrishnan

    2015-01-01

    Full Text Available The human visual system is assumed to transform low level visual features to object and scene representations via features of intermediate complexity. How the brain computationally represents intermediate features is still unclear. To further elucidate this, we compared the biologically plausible HMAX model and Bag of Words (BoW model from computer vision. Both these computational models use visual dictionaries, candidate features of intermediate complexity, to represent visual scenes, and the models have been proven effective in automatic object and scene recognition. These models however differ in the computation of visual dictionaries and pooling techniques. We investigated where in the brain and to what extent human fMRI responses to short video can be accounted for by multiple hierarchical levels of the HMAX and BoW models. Brain activity of 20 subjects obtained while viewing a short video clip was analyzed voxel-wise using a distance-based variation partitioning method. Results revealed that both HMAX and BoW explain a significant amount of brain activity in early visual regions V1, V2 and V3. However BoW exhibits more consistency across subjects in accounting for brain activity compared to HMAX. Furthermore, visual dictionary representations by HMAX and BoW explain significantly some brain activity in higher areas which are believed to process intermediate features. Overall our results indicate that, although both HMAX and BoW account for activity in the human visual system, the BoW seems to more faithfully represent neural responses in low and intermediate level visual areas of the brain.

  20. Visual dictionaries as intermediate features in the human brain.

    Science.gov (United States)

    Ramakrishnan, Kandan; Scholte, H Steven; Groen, Iris I A; Smeulders, Arnold W M; Ghebreab, Sennay

    2014-01-01

    The human visual system is assumed to transform low level visual features to object and scene representations via features of intermediate complexity. How the brain computationally represents intermediate features is still unclear. To further elucidate this, we compared the biologically plausible HMAX model and Bag of Words (BoW) model from computer vision. Both these computational models use visual dictionaries, candidate features of intermediate complexity, to represent visual scenes, and the models have been proven effective in automatic object and scene recognition. These models however differ in the computation of visual dictionaries and pooling techniques. We investigated where in the brain and to what extent human fMRI responses to short video can be accounted for by multiple hierarchical levels of the HMAX and BoW models. Brain activity of 20 subjects obtained while viewing a short video clip was analyzed voxel-wise using a distance-based variation partitioning method. Results revealed that both HMAX and BoW explain a significant amount of brain activity in early visual regions V1, V2, and V3. However, BoW exhibits more consistency across subjects in accounting for brain activity compared to HMAX. Furthermore, visual dictionary representations by HMAX and BoW explain significantly some brain activity in higher areas which are believed to process intermediate features. Overall our results indicate that, although both HMAX and BoW account for activity in the human visual system, the BoW seems to more faithfully represent neural responses in low and intermediate level visual areas of the brain.

  1. Brain size at birth throughout human evolution: a new method for estimating neonatal brain size in hominins.

    Science.gov (United States)

    DeSilva, Jeremy M; Lesnik, Julie J

    2008-12-01

    An increase in brain size is a hallmark of human evolution. Questions regarding the evolution of brain development and obstetric constraints in the human lineage can be addressed with accurate estimates of the size of the brain at birth in hominins. Previous estimates of brain size at birth in fossil hominins have been calculated from regressions of neonatal body or brain mass to adult body mass, but this approach is problematic for two reasons: modern humans are outliers for these regressions, and hominin adult body masses are difficult to estimate. To accurately estimate the brain size at birth in extinct human ancestors, an equation is needed for which modern humans fit the anthropoid regression and one in which the hominin variable entered into the regression equation has limited error. Using phylogenetically sensitive statistics, a resampling approach, and brain-mass data from the literature and from National Primate Research Centers on 362 neonates and 2802 adults from eight different anthropoid species, we found that the size of the adult brain can strongly predict the size of the neonatal brain (r2=0.97). This regression predicts human brain size, indicating that humans have precisely the brain size expected as an adult given the size of the brain at birth. We estimated the size of the neonatal brain in fossil hominins from a reduced major axis regression equation using published cranial capacities of 89 adult fossil crania. We suggest that australopiths gave birth to infants with cranial capacities that were on average 180cc (95% CI: 158-205cc), slightly larger than the average neonatal brain size of chimpanzees. Neonatal brain size increased in early Homo to 225cc (95% CI: 198-257cc) and in Homo erectus to approximately 270cc (95% CI: 237-310cc). These results have implications for interpreting the evolution of the birth process and brain development in all hominins from the australopiths and early Homo, through H. erectus, to Homo sapiens.

  2. Unveiling the mystery of visual information processing in human brain

    CERN Document Server

    Diamant, Emanuel

    2008-01-01

    It is generally accepted that human vision is an extremely powerful information processing system that facilitates our interaction with the surrounding world. However, despite extended and extensive research efforts, which encompass many exploration fields, the underlying fundamentals and operational principles of visual information processing in human brain remain unknown. We still are unable to figure out where and how along the path from eyes to the cortex the sensory input perceived by the retina is converted into a meaningful object representation, which can be consciously manipulated by the brain. Studying the vast literature considering the various aspects of brain information processing, I was surprised to learn that the respected scholarly discussion is totally indifferent to the basic keynote question: "What is information?" in general or "What is visual information?" in particular. In the old days, it was assumed that any scientific research approach has first to define its basic departure points. ...

  3. Endurance training enhances BDNF release from the human brain

    DEFF Research Database (Denmark)

    Seifert, Thomas; Brassard, Patrice; Wissenberg, Mads

    2010-01-01

    the human brain as detected from arterial and internal jugular venous blood samples. In a randomized controlled study, 12 healthy sedentary males carried out 3 mo of endurance training (n = 7) or served as controls (n = 5). Before and after the intervention, blood samples were obtained at rest and during...... in the hippocampus (4.5 + or - 1.6 vs. 1.4 + or - 1.1 mRNA/ssDNA; P human brain following training suggest......The circulating level of brain-derived neurotrophic factor (BDNF) is reduced in patients with major depression and type-2 diabetes. Because acute exercise increases BDNF production in the hippocampus and cerebral cortex, we hypothesized that endurance training would enhance the release of BDNF from...

  4. Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

    Science.gov (United States)

    Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

    2017-06-22

    Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Genetic control of human brain transcript expression in Alzheimer disease.

    Science.gov (United States)

    Webster, Jennifer A; Gibbs, J Raphael; Clarke, Jennifer; Ray, Monika; Zhang, Weixiong; Holmans, Peter; Rohrer, Kristen; Zhao, Alice; Marlowe, Lauren; Kaleem, Mona; McCorquodale, Donald S; Cuello, Cindy; Leung, Doris; Bryden, Leslie; Nath, Priti; Zismann, Victoria L; Joshipura, Keta; Huentelman, Matthew J; Hu-Lince, Diane; Coon, Keith D; Craig, David W; Pearson, John V; Heward, Christopher B; Reiman, Eric M; Stephan, Dietrich; Hardy, John; Myers, Amanda J

    2009-04-01

    We recently surveyed the relationship between the human brain transcriptome and genome in a series of neuropathologically normal postmortem samples. We have now analyzed additional samples with a confirmed pathologic diagnosis of late-onset Alzheimer disease (LOAD; final n = 188 controls, 176 cases). Nine percent of the cortical transcripts that we analyzed had expression profiles correlated with their genotypes in the combined cohort, and approximately 5% of transcripts had SNP-transcript relationships that could distinguish LOAD samples. Two of these transcripts have been previously implicated in LOAD candidate-gene SNP-expression screens. This study shows how the relationship between common inherited genetic variants and brain transcript expression can be used in the study of human brain disorders. We suggest that studying the transcriptome as a quantitative endo-phenotype has greater power for discovering risk SNPs influencing expression than the use of discrete diagnostic categories such as presence or absence of disease.

  6. Ubiquity and specificity of reinforcement signals throughout the human brain.

    Science.gov (United States)

    Vickery, Timothy J; Chun, Marvin M; Lee, Daeyeol

    2011-10-06

    Reinforcements and punishments facilitate adaptive behavior in diverse domains ranging from perception to social interactions. A conventional approach to understanding the corresponding neural substrates focuses on the basal ganglia and its dopaminergic projections. Here, we show that reinforcement and punishment signals are surprisingly ubiquitous in the gray matter of nearly every subdivision of the human brain. Humans played either matching-pennies or rock-paper-scissors games against computerized opponents while being scanned using fMRI. Multivoxel pattern analysis was used to decode previous choices and their outcomes, and to predict upcoming choices. Whereas choices were decodable from a confined set of brain structures, their outcomes were decodable from nearly all cortical and subcortical structures. In addition, signals related to both reinforcements and punishments were recovered reliably in many areas and displayed patterns not consistent with salience-based explanations. Thus, reinforcement and punishment might play global modulatory roles in the entire brain.

  7. Visual dictionaries as intermediate features in the human brain

    NARCIS (Netherlands)

    Ramakrishnan, K.; Scholte, H.S.; Groen, I.I.A.; Smeulders, A.W.M.; Ghebreab, S.

    2015-01-01

    The human visual system is assumed to transform low level visual features to object and scene representations via features of intermediate complexity. How the brain computationally represents intermediate features is still unclear. To further elucidate this, we compared the biologically plausible

  8. Stem Cells Expand Insights into Human Brain Evolution.

    Science.gov (United States)

    Dyer, Michael A

    2016-04-07

    Substantial expansion in the number of cerebral cortex neurons is thought to underlie cognitive differences between humans and other primates, although the mechanisms underlying this expansion are unclear. Otani et al. (2016) utilize PSC-derived brain organoids to study how species-specific differences in cortical progenitor proliferation may underlie cortical evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Mapping Human Brain Function with MRI at 7 Tesla

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ In the past decade, the most significant development in MRI is the introduction of fMRI, which permits the mapping of human brain function with exquisite details noninvasively. Functional mapping can be achieved by measuring changes in the blood oxygenation level (I.e. The BOLD contrast) or cerebral blood flow.

  10. Mapping the calcitonin receptor in human brain stem

    DEFF Research Database (Denmark)

    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

    2016-01-01

    understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...

  11. Exploring human brain lateralization with molecular genetics and genomics.

    Science.gov (United States)

    Francks, Clyde

    2015-11-01

    Lateralizations of brain structure and motor behavior have been observed in humans as early as the first trimester of gestation, and are likely to arise from asymmetrical genetic-developmental programs, as in other animals. Studies of gene expression levels in postmortem tissue samples, comparing the left and right sides of the human cerebral cortex, have generally not revealed striking transcriptional differences between the hemispheres. This is likely due to lateralization of gene expression being subtle and quantitative. However, a recent re-analysis and meta-analysis of gene expression data from the adult superior temporal and auditory cortex found lateralization of transcription of genes involved in synaptic transmission and neuronal electrophysiology. Meanwhile, human subcortical mid- and hindbrain structures have not been well studied in relation to lateralization of gene activity, despite being potentially important developmental origins of asymmetry. Genetic polymorphisms with small effects on adult brain and behavioral asymmetries are beginning to be identified through studies of large datasets, but the core genetic mechanisms of lateralized human brain development remain unknown. Identifying subtly lateralized genetic networks in the brain will lead to a new understanding of how neuronal circuits on the left and right are differently fine-tuned to preferentially support particular cognitive and behavioral functions. © 2015 New York Academy of Sciences.

  12. Endogenous control of waking brain rhythms induces neuroplasticity in humans.

    NARCIS (Netherlands)

    Ros, T.; Munneke, M.; Ruge, D.; Gruzelier, J.H.; Rothwell, J.C.

    2010-01-01

    This study explores the possibility of noninvasively inducing long-term changes in human corticomotor excitability by means of a brain-computer interface, which enables users to exert internal control over the cortical rhythms recorded from the scalp. We demonstrate that self-regulation of electroen

  13. Visual dictionaries as intermediate features in the human brain

    NARCIS (Netherlands)

    K. Ramakrishnan; H.S. Scholte; I.I.A. Groen; A.W.M. Smeulders; S. Ghebreab

    2015-01-01

    The human visual system is assumed to transform low level visual features to object and scene representations via features of intermediate complexity. How the brain computationally represents intermediate features is still unclear. To further elucidate this, we compared the biologically plausible HM

  14. Simultaneous multi-slice Turbo-FLASH imaging with CAIPIRINHA for whole brain distortion-free pseudo-continuous arterial spin labeling at 3 and 7 T.

    Science.gov (United States)

    Wang, Yi; Moeller, Steen; Li, Xiufeng; Vu, An T; Krasileva, Kate; Ugurbil, Kamil; Yacoub, Essa; Wang, Danny J J

    2015-06-01

    Simultaneous multi-slice (SMS) or multiband (MB) imaging has recently been attempted for arterial spin labeled (ASL) perfusion MRI in conjunction with echo-planar imaging (EPI) readout. It was found that SMS-EPI can reduce the T1 relaxation effect of the label and improve image coverage and resolution with little penalty in signal-to-noise ratio (SNR). However, EPI still suffers from geometric distortion and signal dropout from field inhomogeneity effects especially at high and ultrahigh magnetic fields. Here we present a novel scheme for achieving high fidelity distortion-free quantitative perfusion imaging by combining pseudo-continuous ASL (pCASL) with SMS Turbo-FLASH (TFL) readout at both 3 and 7 T. Bloch equation simulation was performed to characterize and optimize the TFL-based pCASL perfusion signal. Two MB factors (3 and 5) were implemented in SMS-TFL pCASL and compared with standard 2D TFL and EPI pCASL sequences. The temporal SNR of SMS-TFL pCASL relative to that of standard TFL pCASL was 0.76 ± 0.10 and 0.74 ± 0.11 at 7 T and 0.70 ± 0.05 and 0.65 ± 0.05 at 3T for MB factor of 3 and 5, respectively. By implementing background suppression in conjunction with SMS-TFL at 3T, the relative temporal SNR improved to 0.84 ± 0.09 and 0.79 ± 0.10 for MB factor of 3 and 5, respectively. Compared to EPI pCASL, significantly increased temporal SNR (pbrain distortion-free quantitative mapping of cerebral blood flow at high and ultrahigh magnetic fields.

  15. Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model.

    Science.gov (United States)

    Zhang, Huaqiu; Xie, Minjie; Schools, Gary P; Feustel, Paul F; Wang, Wei; Lei, Ting; Kimelberg, Harold K; Zhou, Min

    2009-01-09

    Pretreatment of ovarectomized rats with estrogen shows long-term protection via activation of the estrogen receptor (ER). However, it remains unknown whether activation of the ER can provide protection against early neuronal damage when given acutely. We simulated ischemic conditions by applying oxygen and glucose deprived (OGD) solution to acute male rat hippocampal slices and examined the neuronal electrophysiological changes. Pyramidal neurons and interneurons showed a time-dependent membrane potential depolarization and reduction in evoked action potential frequency and amplitude over a 10 to 15 min OGD exposure. These changes were largely suppressed by 10 microM TAM. The TAM effect was neuron-specific as the OGD-induced astrocytic membrane potential depolarization was not altered. The TAM effect was mediated through ER activation because it could be simulated by 17beta-estradiol and was completely inhibited by the ER inhibitor ICI 182, 780, and is therefore an example of TAM's selective estrogen receptor modulator (SERM) action. We further show that TAM's effects on OGD-induced impairment of neuronal excitability was largely due to activation of neuroprotective BK channels, as the TAM effect was markedly attenuated by the BK channel inhibitor paxilline at 10 microM. TAM also significantly reduced the frequency and amplitude of AMPA receptor mediated spontaneous excitatory postsynaptic currents (sEPSCs) in pyramidal neurons which is an early consequence of OGD. Altogether, this study demonstrates that both 17beta-estradiol and TAM attenuate neuronal excitability impairment early on in a simulated ischemia model via ER activation mediated potentiation of BK K(+) channels and reduction in enhanced neuronal AMPA/NMDA receptor-mediated excitotoxicity.

  16. Microscopic computation in human brain evolution.

    Science.gov (United States)

    Wallace, R

    1995-04-01

    When human psychological performance is viewed in terms of cognitive modules, our species displays remarkable differences in computational power. Algorithmically simple computations are generally difficult to perform, whereas optimal routing or "Traveling Salesman" Problems (TSP) of far greater complexity are solved on an everyday basis. It is argued that even "simple" instances of TSP are not purely Euclidian problems in human computations, but involve emotional, autonomic, and cognitive constraints. They therefore require a level of parallel processing not possible in a macroscopic system to complete the algorithm within a brief period of time. A microscopic neurobiological model emphasizing the computational power of excited atoms within the neuronal membrane is presented as an alternative to classical connectionist approaches. The evolution of the system is viewed in terms of specific natural selection pressures driving satisfying computations toward global optimization. The relationship of microscopic computation to the nature of consciousness is examined, and possible mathematical models as a basis for simulation studies are briefly discussed.

  17. The functional brain architecture of human morality.

    Science.gov (United States)

    Funk, Chadd M; Gazzaniga, Michael S

    2009-12-01

    Human morality provides the foundation for many of the pillars of society, informing political legislation and guiding legal decisions while also governing everyday social interactions. In the past decade, researchers in the field of cognitive neuroscience have made tremendous progress in the effort to understand the neural basis of human morality. The emerging insights from this research point toward a model in which automatic processing in parallel neural circuits, many of which are associated with social emotions, evaluate the actions and intentions of others. Through various mechanisms of competition, only a subset of these circuits ultimately causes a decision or an action. This activity is experienced consciously as a subjective moral sense of right or wrong, and an interpretive process offers post hoc explanations designed to link the social stimulus with the subjective moral response using whatever explicit information is available.

  18. Direct Electrical Stimulation in the Human Brain Disrupts Melody Processing.

    Science.gov (United States)

    Garcea, Frank E; Chernoff, Benjamin L; Diamond, Bram; Lewis, Wesley; Sims, Maxwell H; Tomlinson, Samuel B; Teghipco, Alexander; Belkhir, Raouf; Gannon, Sarah B; Erickson, Steve; Smith, Susan O; Stone, Jonathan; Liu, Lynn; Tollefson, Trenton; Langfitt, John; Marvin, Elizabeth; Pilcher, Webster H; Mahon, Bradford Z

    2017-09-11

    Prior research using functional magnetic resonance imaging (fMRI) [1-4] and behavioral studies of patients with acquired or congenital amusia [5-8] suggest that the right posterior superior temporal gyrus (STG) in the human brain is specialized for aspects of music processing (for review, see [9-12]). Intracranial electrical brain stimulation in awake neurosurgery patients is a powerful means to determine the computations supported by specific brain regions and networks [13-21] because it provides reversible causal evidence with high spatial resolution (for review, see [22, 23]). Prior intracranial stimulation or cortical cooling studies have investigated musical abilities related to reading music scores [13, 14] and singing familiar songs [24, 25]. However, individuals with amusia (congenitally, or from a brain injury) have difficulty humming melodies but can be spared for singing familiar songs with familiar lyrics [26]. Here we report a detailed study of a musician with a low-grade tumor in the right temporal lobe. Functional MRI was used pre-operatively to localize music processing to the right STG, and the patient subsequently underwent awake intraoperative mapping using direct electrical stimulation during a melody repetition task. Stimulation of the right STG induced "music arrest" and errors in pitch but did not affect language processing. These findings provide causal evidence for the functional segregation of music and language processing in the human brain and confirm a specific role of the right STG in melody processing. VIDEO ABSTRACT. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Common genetic variants influence human subcortical brain structures

    Science.gov (United States)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  20. Topological isomorphisms of human brain and financial market networks

    Directory of Open Access Journals (Sweden)

    Petra E Vértes

    2011-09-01

    Full Text Available Although metaphorical and conceptual connections between the human brain and the financial markets have often been drawn, rigorous physical or mathematical underpinnings of this analogy remain largely unexplored. Here, we apply a statistical and graph theoretic approach to the study of two datasets - the timeseries of 90 stocks from the New York Stock Exchange over a three-year period, and the fMRI-derived timeseries acquired from 90 brain regions over the course of a 10 min-long functional MRI scan of resting brain function in healthy volunteers. Despite the many obvious substantive differences between these two datasets, graphical analysis demonstrated striking commonalities in terms of global network topological properties. Both the human brain and the market networks were non-random, small-world, modular, hierarchical systems with fat-tailed degree distributions indicating the presence of highly connected hubs. These properties could not be trivially explained by the univariate time series statistics of stock price returns. This degree of topological isomorphism suggests that brains and markets can be regarded broadly as members of the same family of networks. The two systems, however, were not topologically identical. The financial market was more efficient and more modular - more highly optimised for information processing - than the brain networks; but also less robust to systemic disintegration as a result of hub deletion. We conclude that the conceptual connections between brains and markets are not merely metaphorical; rather these two information processing systems can be rigorously compared in the same mathematical language and turn out often to share important topological properties in common to some degree. There will be interesting scientific arbitrage opportunities in further work at the graph theoretically-mediated interface between systems neuroscience and the statistical physics of financial markets.

  1. Topological isomorphisms of human brain and financial market networks.

    Science.gov (United States)

    Vértes, Petra E; Nicol, Ruth M; Chapman, Sandra C; Watkins, Nicholas W; Robertson, Duncan A; Bullmore, Edward T

    2011-01-01

    Although metaphorical and conceptual connections between the human brain and the financial markets have often been drawn, rigorous physical or mathematical underpinnings of this analogy remain largely unexplored. Here, we apply a statistical and graph theoretic approach to the study of two datasets - the time series of 90 stocks from the New York stock exchange over a 3-year period, and the fMRI-derived time series acquired from 90 brain regions over the course of a 10-min-long functional MRI scan of resting brain function in healthy volunteers. Despite the many obvious substantive differences between these two datasets, graphical analysis demonstrated striking commonalities in terms of global network topological properties. Both the human brain and the market networks were non-random, small-world, modular, hierarchical systems with fat-tailed degree distributions indicating the presence of highly connected hubs. These properties could not be trivially explained by the univariate time series statistics of stock price returns. This degree of topological isomorphism suggests that brains and markets can be regarded broadly as members of the same family of networks. The two systems, however, were not topologically identical. The financial market was more efficient and more modular - more highly optimized for information processing - than the brain networks; but also less robust to systemic disintegration as a result of hub deletion. We conclude that the conceptual connections between brains and markets are not merely metaphorical; rather these two information processing systems can be rigorously compared in the same mathematical language and turn out often to share important topological properties in common to some degree. There will be interesting scientific arbitrage opportunities in further work at the graph-theoretically mediated interface between systems neuroscience and the statistical physics of financial markets.

  2. Regional mechanical properties of human brain tissue for computational models of traumatic brain injury.

    Science.gov (United States)

    Finan, John D; Sundaresh, Sowmya N; Elkin, Benjamin S; McKhann, Guy M; Morrison, Barclay

    2017-06-01

    To determine viscoelastic shear moduli, stress relaxation indentation tests were performed on samples of human brain tissue resected in the course of epilepsy surgery. Through the use of a 500µm diameter indenter, regional mechanical properties were measured in cortical grey and white matter and subregions of the hippocampus. All regions were highly viscoelastic. Cortical grey matter was significantly more compliant than the white matter or hippocampus which were similar in modulus. Although shear modulus was not correlated with the age of the donor, cortex from male donors was significantly stiffer than from female donors. The presented material properties will help to populate finite element models of the brain as they become more anatomically detailed. We present the first mechanical characterization of fresh, post-operative human brain tissue using an indentation loading mode. Indentation generates highly localized data, allowing structure-specific mechanical properties to be determined from small tissue samples resected during surgery. It also avoids pitfalls of cadaveric tissue and allows data to be collected before degenerative processes alter mechanical properties. To correctly predict traumatic brain injury, finite element models must calculate intracranial deformation during head impact. The functional consequences of injury depend on the anatomical structures injured. Therefore, morbidity depends on the distribution of deformation across structures. Accurate prediction of structure-specific deformation requires structure-specific mechanical properties. This data will facilitate deeper understanding of the physical mechanisms that lead to traumatic brain injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Distribution of cysteinyl leukotriene receptor 2 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    Hua HU; Er-qing WEI; Gao CHEN; Jian-min ZHANG; Wei-ping ZHANG; Lei ZHANG; Qiu-fu GE; Hong-tian YAO; Wei DING; Zhong CHEN

    2005-01-01

    Aim: To determine the distribution of cysteinyl leukotriene receptor 2 (CysLT2),one of the cysteinyl leukotriene receptors, in human brains with traumatic injury and tumors. Methods: Brain specimens were obtained from patients who underwent brain surgery. CysLT2 in brain tissues was examined using immunohistochemical analysis. Results: CysLT2 was expressed in the smooth muscle cells (not in the endothelial cells) of arteries and veins. CysLT2 was also expressed in the granulocytes in both vessels and in the brain parenchyma. In addition, CysLT2 was detected in neuron- and glial-appearing cells in either the late stages of traumatic injury or in the area surrounding the tumors. Microvessels regenerated 8 d after trauma and CysLT2 expression was recorded in their endothelial cells.Conclusion: CysLT2 is distributed in vascular smooth muscle cells and granulocytes, and brain trauma and tumor can induce its expression in vascular endothelial cells and in a number of other cells.

  4. Comparison of Cone Beam Computed Tomography and Multi Slice Computed Tomography Image Quality of Human Dried Mandible using 10 Anatomical Landmarks

    Science.gov (United States)

    Saati, Samira; Kaveh, Fatemeh

    2017-01-01

    Introduction Cone Beam Computed Tomography (CBCT) has gained a broad acceptance in dentomaxillofacial imaging. Computed Tomography (CT) is another imaging modality for diagnosis and preoperative assessments of the head and neck region. Aim Considering the increased radiation exposure and high cost of CT, this study sought to subjectively assess the image quality of CBCT and Multi Slice CT (MSCT). Materials and Methods A dry human mandible was scanned by five CBCT systems (New Tom 3G, Scanora, CRANEX 3D, Promax and Galileos) and one MSCT system. Three independent oral and maxillofacial radiologists reviewed the CBCT and MSCT scans for the quality of 10 landmarks namely mental foramen, trabecular bone, Periodontal Ligament (PDL), dentin, incisive canal, mandibular canal, dental pulp, enamel, lamina dura and cortical bone using a five-point scale. Results Significant differences were found between MSCT and CBCT and among the five CBCT systems (p<0.05) in visualization of different anatomical structures. A fine structure such as the incisive canal was significantly less visible and more variable among the systems in comparison with other anatomical landmarks such as the mental foramen, mandibular canal, cortical bone, dental pulp, enamel and dentin (p<0.05). The Cranex 3D and Promax systems were superior to MSCT and all other CBCT systems in visualizing anatomical structures. Conclusion The CBCT image quality was superior to that of MSCT even though some variability existed among different CBCT systems in visualizing fine structures. Considering the low radiation dose and high resolution, CBCT may be beneficial for dentomaxillofacial imaging. PMID:28384972

  5. Automated regional behavioral analysis for human brain images.

    Science.gov (United States)

    Lancaster, Jack L; Laird, Angela R; Eickhoff, Simon B; Martinez, Michael J; Fox, P Mickle; Fox, Peter T

    2012-01-01

    Behavioral categories of functional imaging experiments along with standardized brain coordinates of associated activations were used to develop a method to automate regional behavioral analysis of human brain images. Behavioral and coordinate data were taken from the BrainMap database (http://www.brainmap.org/), which documents over 20 years of published functional brain imaging studies. A brain region of interest (ROI) for behavioral analysis can be defined in functional images, anatomical images or brain atlases, if images are spatially normalized to MNI or Talairach standards. Results of behavioral analysis are presented for each of BrainMap's 51 behavioral sub-domains spanning five behavioral domains (Action, Cognition, Emotion, Interoception, and Perception). For each behavioral sub-domain the fraction of coordinates falling within the ROI was computed and compared with the fraction expected if coordinates for the behavior were not clustered, i.e., uniformly distributed. When the difference between these fractions is large behavioral association is indicated. A z-score ≥ 3.0 was used to designate statistically significant behavioral association. The left-right symmetry of ~100K activation foci was evaluated by hemisphere, lobe, and by behavioral sub-domain. Results highlighted the classic left-side dominance for language while asymmetry for most sub-domains (~75%) was not statistically significant. Use scenarios were presented for anatomical ROIs from the Harvard-Oxford cortical (HOC) brain atlas, functional ROIs from statistical parametric maps in a TMS-PET study, a task-based fMRI study, and ROIs from the ten "major representative" functional networks in a previously published resting state fMRI study. Statistically significant behavioral findings for these use scenarios were consistent with published behaviors for associated anatomical and functional regions.

  6. Extensive nuclear sphere generation in the human Alzheimer's brain.

    Science.gov (United States)

    Kolbe, Katharina; Bukhari, Hassan; Loosse, Christina; Leonhardt, Gregor; Glotzbach, Annika; Pawlas, Magdalena; Hess, Katharina; Theiss, Carsten; Müller, Thorsten

    2016-12-01

    Nuclear spheres are protein aggregates consisting of FE65, TIP60, BLM, and other yet unknown proteins. Generation of these structures in the cellular nucleus is putatively modulated by the amyloid precursor protein (APP), either by its cleavage or its phosphorylation. Nuclear spheres were preferentially studied in cell culture models and their existence in the human brain had not been known. Existence of nuclear spheres in the human brain was studied using immunohistochemistry. Cell culture experiments were used to study regulative mechanisms of nuclear sphere generation. The comparison of human frontal cortex brain samples from Alzheimer's disease (AD) patients to age-matched controls revealed a dramatically and highly significant enrichment of nuclear spheres in the AD brain. Costaining demonstrated that neurons are distinctly affected by nuclear spheres, but astrocytes never are. Nuclear spheres were predominantly found in neurons that were negative for threonine 668 residue in APP phosphorylation. Cell culture experiments revealed that JNK3-mediated APP phosphorylation reduces the amount of sphere-positive cells. The study suggests that nuclear spheres are a new APP-derived central hallmark of AD, which might be of crucial relevance for the molecular mechanisms in neurodegeneration.

  7. Xanthine oxidase activity regulates human embryonic brain cells growth

    Directory of Open Access Journals (Sweden)

    Kevorkian G. A.

    2011-10-01

    Full Text Available Aim. Involvement of Xanthine Oxidase (XO; EC1.1.3.22 in cellular proliferation and differentiation has been suggested by the numerous investigations. We have proposed that XO might have undoubtedly important role during the development, maturation as well as the death of human embryos brain cells. Methods. Human abortion material was utilized for the cultivation of brain cells (E90. XO activity was measured by the formation of uric acid in tissue. Cell death was detected by the utility of Trypan Blue dye. Results. Allopurinol suppressed the XO activity in the brain tissue (0.12 ± 0.02; 0.20 ± 0.03 resp., p < 0.05. On day 12th the number of cells in the culture treated with the Allopurinol at the early stage of development was higher in comparison with the Control (2350.1 ± 199.0 vs 2123 ± 96 and higher in comparison with the late period of treatment (1479.6 ± 103.8, p < < 0.05. In all groups, the number of the dead cells was less than in Control, indicating the protective nature of Allopurinol as an inhibitor of XO. Conclusions. Allopurinol initiates cells proliferation in case of the early treatment of the human brain derived cell culture whereas at the late stages it has an opposite effect.

  8. Luria: a unitary view of human brain and mind.

    Science.gov (United States)

    Mecacci, Luciano

    2005-12-01

    Special questions the eminent Russian psychologist and neuropsychologist Aleksandr R. Luria (1902-1977) dealt with in his research regarded the relationship between animal and human brain, child and adult mind, normal and pathological, theory and rehabilitation, clinical and experimental investigation. These issues were integrated in a unitary theory of cerebral and psychological processes, under the influence of both different perspectives active in the first half of the Nineteenth century (psychoanalysis and historical-cultural school, first of all) and the growing contribution of neuropsychological research on brain-injured patients.

  9. Cholinergic enhancement of visual attention and neural oscillations in the human brain.

    Science.gov (United States)

    Bauer, Markus; Kluge, Christian; Bach, Dominik; Bradbury, David; Heinze, Hans Jochen; Dolan, Raymond J; Driver, Jon

    2012-03-06

    Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Neocortical glial cell numbers in human brains

    DEFF Research Database (Denmark)

    Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.

    2008-01-01

    and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons...... while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males......, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex. (C) 2007 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/11...

  11. A human-specific de novo protein-coding gene associated with human brain functions.

    Directory of Open Access Journals (Sweden)

    Chuan-Yun Li

    2010-03-01

    Full Text Available To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203. Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

  12. A human-specific de novo protein-coding gene associated with human brain functions.

    Directory of Open Access Journals (Sweden)

    Chuan-Yun Li

    2010-03-01

    Full Text Available To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203. Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

  13. Chromosome conformation elucidates regulatory relationships in developing human brain.

    Science.gov (United States)

    Won, Hyejung; de la Torre-Ubieta, Luis; Stein, Jason L; Parikshak, Neelroop N; Huang, Jerry; Opland, Carli K; Gandal, Michael J; Sutton, Gavin J; Hormozdiari, Farhad; Lu, Daning; Lee, Changhoon; Eskin, Eleazar; Voineagu, Irina; Ernst, Jason; Geschwind, Daniel H

    2016-10-27

    Three-dimensional physical interactions within chromosomes dynamically regulate gene expression in a tissue-specific manner. However, the 3D organization of chromosomes during human brain development and its role in regulating gene networks dysregulated in neurodevelopmental disorders, such as autism or schizophrenia, are unknown. Here we generate high-resolution 3D maps of chromatin contacts during human corticogenesis, permitting large-scale annotation of previously uncharacterized regulatory relationships relevant to the evolution of human cognition and disease. Our analyses identify hundreds of genes that physically interact with enhancers gained on the human lineage, many of which are under purifying selection and associated with human cognitive function. We integrate chromatin contacts with non-coding variants identified in schizophrenia genome-wide association studies (GWAS), highlighting multiple candidate schizophrenia risk genes and pathways, including transcription factors involved in neurogenesis, and cholinergic signalling molecules, several of which are supported by independent expression quantitative trait loci and gene expression analyses. Genome editing in human neural progenitors suggests that one of these distal schizophrenia GWAS loci regulates FOXG1 expression, supporting its potential role as a schizophrenia risk gene. This work provides a framework for understanding the effect of non-coding regulatory elements on human brain development and the evolution of cognition, and highlights novel mechanisms underlying neuropsychiatric disorders.

  14. ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size

    OpenAIRE

    Rotem Kadir; Tamar Harel; Barak Markus; Yonatan Perez; Anna Bakhrat; Idan Cohen; Michael Volodarsky; Miora Feintsein-Linial; Elana Chervinski; Joel Zlotogora; Sara Sivan; Birnbaum, Ramon Y; Uri Abdu; Stavit Shalev; Birk, Ohad S.

    2016-01-01

    Author Summary One of the major events in human evolution is the significant increase in brain volume in the transition from primates to humans. The molecular pathways determining the larger size of the human brain are not fully understood. Hereditary primary microcephaly, a neurodevelopmental disorder in which infants are born with small head circumference and reduced brain volume with intellectual disability, offers insights to the embryonic molecular pathways determining human brain size. ...

  15. Listening to humans walking together activates the social brain circuitry.

    Science.gov (United States)

    Saarela, Miiamaaria V; Hari, Riitta

    2008-01-01

    Human footsteps carry a vast amount of social information, which is often unconsciously noted. Using functional magnetic resonance imaging, we analyzed brain networks activated by footstep sounds of one or two persons walking. Listening to two persons walking together activated brain areas previously associated with affective states and social interaction, such as the subcallosal gyrus bilaterally, the right temporal pole, and the right amygdala. These areas seem to be involved in the analysis of persons' identity and complex social stimuli on the basis of auditory cues. Single footsteps activated only the biological motion area in the posterior STS region. Thus, hearing two persons walking together involved a more widespread brain network than did hearing footsteps from a single person.

  16. Brain-Computer Interfaces Revolutionizing Human-Computer Interaction

    CERN Document Server

    Graimann, Bernhard; Allison, Brendan

    2010-01-01

    A brain-computer interface (BCI) establishes a direct output channel between the human brain and external devices. BCIs infer user intent via direct measures of brain activity and thus enable communication and control without movement. This book, authored by experts in the field, provides an accessible introduction to the neurophysiological and signal-processing background required for BCI, presents state-of-the-art non-invasive and invasive approaches, gives an overview of current hardware and software solutions, and reviews the most interesting as well as new, emerging BCI applications. The book is intended not only for students and young researchers, but also for newcomers and other readers from diverse backgrounds keen to learn about this vital scientific endeavour.

  17. Silhouette-Slice Theorems

    Science.gov (United States)

    1987-03-20

    with standard expressions of spherical trigonometry is sinr)0 = cos0 sini//0 (4.37) which is consistent with the results obtained previously with...theorems for discrete transforms. However, sampling questions inlroduce difficult obstacles in the develop- ment of a discrete theory. First, sampling...additional obstacle to discrete represen- tations of the CT. An example of qualitative predication of the shape of silhouettes with the Silhouette-Slice

  18. Distribution of cellular HSV-1 receptor expression in human brain.

    Science.gov (United States)

    Lathe, Richard; Haas, Juergen G

    2016-12-15

    Herpes simplex virus type 1 (HSV-1) is a neurotropic virus linked to a range of acute and chronic neurological disorders affecting distinct regions of the brain. Unusually, HSV-1 entry into cells requires the interaction of viral proteins glycoprotein D (gD) and glycoprotein B (gB) with distinct cellular receptor proteins. Several different gD and gB receptors have been identified, including TNFRSF14/HVEM and PVRL1/nectin 1 as gD receptors and PILRA, MAG, and MYH9 as gB receptors. We investigated the expression of these receptor molecules in different areas of the adult and developing human brain using online transcriptome databases. Whereas all HSV-1 receptors showed distinct expression patterns in different brain areas, the Allan Brain Atlas (ABA) reported increased expression of both gD and gB receptors in the hippocampus. Specifically, for PVRL1, TNFRFS14, and MYH9, the differential z scores for hippocampal expression, a measure of relative levels of increased expression, rose to 2.9, 2.9, and 2.5, respectively, comparable to the z score for the archetypical hippocampus-enriched mineralocorticoid receptor (NR3C2, z = 3.1). These data were confirmed at the Human Brain Transcriptome (HBT) database, but HBT data indicate that MAG expression is also enriched in hippocampus. The HBT database allowed the developmental pattern of expression to be investigated; we report that all HSV1 receptors markedly increase in expression levels between gestation and the postnatal/adult periods. These results suggest that differential receptor expression levels of several HSV-1 gD and gB receptors in the adult hippocampus are likely to underlie the susceptibility of this brain region to HSV-1 infection.

  19. Human Brain Stem Structures Respond Differentially to Noxious Heat

    Directory of Open Access Journals (Sweden)

    Alexander eRitter

    2013-09-01

    Full Text Available Concerning the physiological correlates of pain, the brain stem is considered to be one core region that is activated by noxious input. In animal studies, different slopes of skin heating (SSH with noxious heat led to activation in different columns of the midbrain periaqueductal grey (PAG. The present study aimed at finding a method for differentiating structures in PAG and other brain stem structures, which are associated with different qualities of pain in humans according to the structures that were associated with different behavioral significances to noxious thermal stimulation in animals. Brain activity was studied by fMRI in healthy subjects in response to steep and shallow SSH with noxious heat. We found differential activation to different SSH in the PAG and the rostral ventromedial medulla (RVM. In a second experiment we demonstrate that the different SSH were associated with different pain qualities. Our experiments provide evidence that brainstem structures, i.e. the PAG and the RVM, become differentially activated by different SSH. Therefore, different SSH can be utilized when brain stem structures are investigated and when it is aimed to activate these structures differentially. Moreover, percepts of first pain were elicited by shallow SSH whereas percepts of second pain were elicited by steep SSH. The stronger activation of these brain stem structures to SSH, eliciting percepts of second vs. first pain, might be of relevance for activating different coping strategies in response to the noxious input with the two types of SSH.

  20. Blood-Brain Barrier Breakdown in the Aging Human Hippocampus

    Science.gov (United States)

    Montagne, Axel; Barnes, Samuel R.; Sweeney, Melanie D.; Halliday, Matthew R.; Sagare, Abhay P.; Zhao, Zhen; Toga, Arthur W.; Jacobs, Russell E.; Liu, Collin Y.; Amezcua, Lilyana; Harrington, Michael G.; Chui, Helena C.; Law, Meng; Zlokovic, Berislav V.

    2014-01-01

    Summary The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens and cells into the brain that is essential for normal neuronal functioning and information processing. Post-mortem tissue analysis indicates BBB damage in Alzheimer’s disease (AD). The timing of BBB breakdown remains, however, elusive. Using an advanced dynamic contrast-enhanced magnetic resonance imaging protocol with high spatial and temporal resolutions to quantify regional BBB permeability in the living human brain, we show an age-dependent BBB breakdown in the hippocampus, a region critical for learning and memory that is affected early in AD. The BBB breakdown in the hippocampus and its CA1 and dentate gyrus subdivisions worsened with mild cognitive impairment that correlated with injury to BBB-associated pericytes, as shown by the cerebrospinal fluid analysis. Our data suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment. PMID:25611508

  1. Human plasma DNP level after severe brain injury

    Institute of Scientific and Technical Information of China (English)

    GAO Yi-lu; XIN Hui-ning; FENG Yi; FAN Ji-wei

    2006-01-01

    Objective: To determine the relationship between DNP level after human severe brain injury and hyponatremia as well as isorrhea.Methods: The peripheral venous plasma as control was collected from 8 volunteers. The peripheral venous plasma from 14 severe brain injury patients were collected in the 1, 3, 7 days after injury. Radioimmunoassay was used to detect the DNP concentration. Meanwhile, daily plasma and urine electrolytes, osmotic pressure as well as 24 h liquid intake and output volume were detected.Results: The normal adult human plasma DNP level was 62. 46 pg/ml ± 27. 56 pg/ml. In the experimental group, the plasma DNP levels were higher from day 1 today 3 in 8 of the 14 patients than those in the control group (P1 =0.05, P3 =0.03). Negative fluid balance occurred in 8 patients and hyponatremia in 7 patients. The increase of plasma DNP level was significantly correlated with the development of a negative fluid balance (r=-0.69,P<0.01) and hyponatremia (x2 =4.38, P<0.05).Conclusions: The increase of plasma DNP level is accompanied by the enhancement of natriuretic and diuretic responses in severe brain-injured patients, which is associated with the development of a negative fluid balance and hyponatremia after brain injury.

  2. Drug delivery to the human brain via the cerebrospinal fluid

    Energy Technology Data Exchange (ETDEWEB)

    Howden, L.; Aroussi, A. [Univ. of Nottingham, School of Mechanical, Material, Manufacturing Engineering and Managements, Nottingham (United Kingdom)]. E-mail: eaxljh@nottingham.ac.uk; Vloeberghs, M. [Queens Medical Centre, Dept. of Child Health, Nottingham (United Kingdom)

    2003-07-01

    This Study investigates the flow of Cerebrospinal Fluid (CSF) inside the human ventricular system with particular emphasis on drug path flow for the purpose of medical drug injections. The investigation is conducted using the computational fluid dynamics package FLUENT. The role of the ventricular system is very important in protecting the brain from injury by cushioning it against the cranium during sudden movements. If for any reason the passage of CSF through the ventricular system is blocked (usually by stenosis) then a condition known as Hydrocephalus occurs, where by the blocked CSF causes the Intra Cranial Pressure (ICP) inside the brain to rise. If this is not treated then severe brain damage and death can occur. Previous work conducted by the authors on this subject has focused on the technique of ventriculostomy to treat hydrocephalus. The present study carries on from the previous work but focuses on delivering medical drugs to treat brain tumors that are conventionally not accessible and which require complicated surgical procedures to remove them. The study focuses on the possible paths for delivering drugs to tumors in the human nervous system through conventionally accessible locations without major surgery. The results of the investigation have shown that it is possible to reach over 95% of the ventricular system by injection of drugs however the results also show that there are many factors that can affect the drug flow paths through the ventricular system and thus the areas reachable, by these drugs. (author)

  3. Neuron enriched nuclear proteome isolated from human brain.

    Science.gov (United States)

    Dammer, Eric B; Duong, Duc M; Diner, Ian; Gearing, Marla; Feng, Yue; Lah, James J; Levey, Allan I; Seyfried, Nicholas T

    2013-07-05

    The brain consists of diverse cell types including neurons, astrocytes, oligodendrocytes, and microglia. The isolation of nuclei from these distinct cell populations provides an opportunity to identify cell-type-specific nuclear proteins, histone modifications, and regulation networks that are altered with normal brain aging or neurodegenerative disease. In this study, we used a method by which intact neuronal and non-neuronal nuclei were purified from human post-mortem brain employing a modification of fluorescence activated cell sorting (FACS) termed fluorescence activated nuclei sorting (FANS). An antibody against NeuN, a neuron specific splicing factor, was used to isolate neuronal nuclei. Utilizing mass spectrometry (MS) based label-free quantitative proteomics, we identified 1755 proteins from sorted NeuN-positive and negative nuclear extracts. Approximately 20% of these proteins were significantly enriched or depleted in neuronal versus non-neuronal populations. Immunoblots of primary cultured rat neuron, astrocyte, and oligodendrocyte extracts confirmed that distinct members of the major nucleocytoplasmic structural linkage complex (LINC), nesprin-1 and nesprin-3, were differentially enriched in neurons and astrocytes, respectively. These comparative proteomic data sets also reveal a number of transcription and splicing factors that are selectively enriched in a cell-type-specific manner in human brain.

  4. The Speculative Neuroscience of the Future Human Brain

    Directory of Open Access Journals (Sweden)

    Robert A. Dielenberg

    2013-05-01

    Full Text Available The hallmark of our species is our ability to hybridize symbolic thinking with behavioral output. We began with the symmetrical hand axe around 1.7 mya and have progressed, slowly at first, then with greater rapidity, to producing increasingly more complex hybridized products. We now live in the age where our drive to hybridize has pushed us to the brink of a neuroscientific revolution, where for the first time we are in a position to willfully alter the brain and hence, our behavior and evolution. Nootropics, transcranial direct current stimulation (tDCS, transcranial magnetic stimulation (TMS, deep brain stimulation (DBS and invasive brain mind interface (BMI technology are allowing humans to treat previously inaccessible diseases as well as open up potential vistas for cognitive enhancement. In the future, the possibility exists for humans to hybridize with BMIs and mobile architectures. The notion of self is becoming increasingly extended. All of this to say: are we in control of our brains, or are they in control of us?

  5. 64排CT用于创伤性颅脑损伤诊断中的价值%Value of Applying 64-slice CT to Diagnosis of Traumatic Brain Injury

    Institute of Scientific and Technical Information of China (English)

    刘光祖

    2016-01-01

    Objective To research and analyze the value of applying 64-slice CT to diagnosis of traumatic brain injury. Methods 100 patients with traumatic brain injury were selected as main survey samples randomly. All patients received CT examination when they were admitted to the hospital. The patients with negative examination result received CT reexamination in 1 day. If the examination results were negative, the patients needed to receive CT examination for the third day. CT image features of 100 patients were analyzed carefully, and were divided into three types according to the actual characteristics of CT image. The condition of different injury classiifcations was analyzed. Results The sensitivity of the patients for the admission to hospital (30~180 minute), in one day and in 2~3 day was 69.00%, 73.00%and 100.00%. The light, medium and severe brain injury had different prognostic effect. The severer the injury, the higher disability rate and fatality rate, which had evident statistical signiifcance, P<0.05. Conclusion 64-slice CT achieves evident effect for diagnosing brain injury.%目的:研究分析64排CT用于创伤性颅脑损伤诊断中的价值。方法随机选取创伤性颅脑损伤患者100例作为主要的调查样本,在患者入院时均接受CT检查,对于检查结果为阴性的患者,在1天之内完成CT复查;若其检查结果还是阴性的患者,则需要在第2-3天之内第三天接受CT检查。对100例患者的CT影像特点进行缜密分析,严格按照CT影像的实际特点完成轻、中、重三型划分,对不同损伤分型影响预后的情况进行针对分析。结果刚刚入院时候(30~180分钟)、1天之内、2~3天内患者的灵敏度分别为69.00%、73.00%、100.00%。轻型、中型以及重型颅脑损伤存在不同的预后效果,即损伤越严重就会有越高的致残率以及致死率,具有明显的统计学意义,P<0.05。结论64排CT在诊断颅脑损伤优势的过程中可以取得非常明显的效果。

  6. Ventral tegmental area/substantia nigra and prefrontal cortex rodent organotypic brain slices as an integrated model to study the cellular changes induced by oxygen/glucose deprivation and reperfusion: effect of neuroprotective agents.

    Science.gov (United States)

    Colombo, Laura; Parravicini, Chiara; Lecca, Davide; Dossi, Elena; Heine, Claudia; Cimino, Mauro; Wanke, Enzo; Illes, Peter; Franke, Heike; Abbracchio, Maria P

    2014-01-01

    Unveiling the roles of distinct cell types in brain response to insults is a partially unsolved challenge and a key issue for new neuroreparative approaches. In vivo models are not able to dissect the contribution of residential microglia and infiltrating blood-borne monocytes/macrophages, which are fundamentally undistinguishable; conversely, cultured cells lack original tissue anatomical and functional complexity, which profoundly alters reactivity. Here, we tested whether rodent organotypic co-cultures from mesencephalic ventral tegmental area/substantia nigra and prefrontal cortex (VTA/SN-PFC) represent a suitable model to study changes induced by oxygen/glucose deprivation and reperfusion (OGD/R). OGD/R induced cytotoxicity to both VTA/SN and PFC slices, with higher VTA/SN susceptibility. Neurons were highly affected, with astrocytes and oligodendrocytes undergoing very mild damage. Marked reactive astrogliosis was also evident. Notably, OGD/R triggered the activation of CD68-expressing microglia and increased expression of Ym1 and Arg1, two markers of "alternatively" activated beneficial microglia. Treatment with two well-known neuroprotective drugs, the anticonvulsant agent valproic acid and the purinergic P2-antagonist PPADS, prevented neuronal damage. Thus, VTA/SN-PFC cultures are an integrated model to investigate OGD/R-induced effects on distinct cells and easily screen neuroprotective agents. The model is particularly adequate to dissect the microglia phenotypic shift in the lack of a functional vascular compartment.

  7. Human precision-cut liver tumor slices as a tumor patient-individual predictive test system for oncolytic measles vaccine viruses

    NARCIS (Netherlands)

    Zimmermann, Martina; Armeanu, Sorin; Smirnow, Irina; Kupka, Susan; Wagner, Silvia; Wehrmann, Manfred; Rots, Marianne G.; Groothuis, Geny M. M.; Weiss, Thomas S.; Koenigsrainer, Alfred; Gregor, Michael; Bitzer, Michael; Lauer, Ulrich M.

    2009-01-01

    Availability of an individualized preselection of oncolytic viruses to be used for virotherapy of tumor patients would be of great help. Using primary liver tumor resection specimens we evaluated the precision-cut liver slice (PCLS) technology as a novel in vitro test system for characterization of

  8. Human functional neuroimaging of brain changes associated with practice

    OpenAIRE

    GARAVAN, HUGH PATRICK

    2005-01-01

    PUBLISHED The discovery that experience-driven changes in the human brain can occur from a neural to a cortical level throughout the lifespan has stimulated a proliferation of research into how neural function changes in response to experience, enabled by neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging. Studies attempt to characterize these changes by examining how practice on a task affects the functional anatomy underlying performance. ...

  9. Evaluation of 128-slice spiral CT whole brain perfusion imaging in grading infiltrating astrocytomas%128层螺旋CT全脑灌注对浸润性星形细胞瘤的分级评估

    Institute of Scientific and Technical Information of China (English)

    曾文兵; 王毅; 汪明全; 吴炅; 刘兴华; 罗江平; 温云

    2011-01-01

    目的:评价128层螺旋CT全脑灌注(CTP)对浸润性星形细胞瘤分级定性诊断的价值.方法:选择我院90例脑肿瘤患者进行CTP检查,经手术和病理学证实为浸润性星形细胞瘤(Ⅱ~Ⅳ级)者46例纳入本研究对象.CTP采用SOMATOM Definition AS型128层螺旋CT机进行灌注扫描,应用后处理工作站对原始数据进行后处理.获得时间-密度曲线(TDC).测定肿瘤区和对侧正常组织的脑血流量(CBF)、脑血容量(CBV)、毛细血管表面通透性(PS)及对比剂达峰值时间(TTP),并对灌注参数进行统计学分析.结果:在所有病例中,全脑灌注图像平均视觉评价分数明显高于传统灌注图(P<0 01).且对病变定位更为精确.星形细胞肿瘤高级别组的CBF、CBV和PS值均显著高于低级别组(P<0.01).而TTP值的差异无统计学意义(P>0.05).ROC曲线分析表明,CBF、CBV和PS值对鉴别高、低级别星形细胞肿瘤的ROC曲线下面积分别为0.925、0.897和0.954.采用CBF≥72.052ml/min/100g,CBV≥4.293ml/100g和PS≥6.337ml/min/100g作为分界点对鉴别高低级别星形细胞肿瘤的敏感性均为87.2%,特异性分别是83.5%、83.5%和93.0%.结论:128层螺旋CT全脑灌注有利于脑肿瘤的术前整体评估和精确定位;CTP参数CBF、CBV及PS值及TDC曲线对鉴别高、低级别星形细胞肿瘤具有较高的敏感性和特异性.%Objective:To evaluate the value of 128-slicc spiral CT whole brain perfusion (CTP) imaging in grading infil-traiing astrocytomas. Methods: Ninety patients with brain rumors underwent CTP examination and forty-six of them with astrocytic tumors (Ⅱ -Ⅳ) confirmed by operation and pathology were selected as the object of this study. 128-slice helical CT whole brain perfusion imaging was performed in the 46 patients, and the data were analyzed by the software. Cerebral blood flow (CBF). Cerebral blood volume (CBV). Time to peak (TTP) and permeability surface (PS> on the maximum perfusion area

  10. Investigation of G72 (DAOA expression in the human brain

    Directory of Open Access Journals (Sweden)

    Hirsch Steven

    2008-12-01

    Full Text Available Abstract Background Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO, supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions. Methods The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth in silico analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability. Results Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala, spinal cord or testis. A detailed in silico analysis provides several lines of evidence that support the apparent low or absent expression of G72. Conclusion Our results suggest that native G72 protein is not normally present in the tissues that we analysed

  11. Brain tumors induced in rats by human adenovirus type 12

    Directory of Open Access Journals (Sweden)

    Murao,Tsuyoshi

    1974-02-01

    Full Text Available Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33 in SpragueDawley and 56% (14/25 in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.

  12. 5-HT4-receptors modulate induction of long-term depression but not potentiation at hippocampal output synapses in acute rat brain slices.

    Directory of Open Access Journals (Sweden)

    Matthias Wawra

    Full Text Available The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD. In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4 receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1, 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output.

  13. Effect of therapeutic ionizing radiation on the human brain.

    Science.gov (United States)

    Steen, R G; Spence, D; Wu, S; Xiong, X; Kun, L E; Merchant, T E

    2001-12-01

    We test a hypothesis that fractionated radiation therapy within a therapeutic dose range is associated with a dose-related change in normal brain, detectable by quantitative magnetic resonance imaging. A total of 33 patients were examined by quantitative magnetic resonance imaging to measure brain tissue spin-lattice relaxation time (T1) before treatment, and at various times during and after radiation therapy. A T1 map was generated at each time point, and radiation therapy isodose contours were superimposed on the corresponding segmented T1 map. Changes in white matter and gray matter T1 were analyzed as a function of radiation therapy dose and time since treatment, controlling for patient age and tumor site. In white matter, a dose level of more than 20 Gy was associated with a dose-dependent decrease in T1 over time, which became significant 6 months after treatment. There was no significant change in T1 of gray matter over time, at radiation therapy doses of less than 60 Gy. However, GM in close proximity to the tumor had a lower T1 before therapy. Our results represent the first radiation dose-response data derived from pediatric brain in vivo. These findings confirm that white matter is more vulnerable to radiation-induced change than is gray matter, and suggest that T1 mapping is sensitive to radiation-related changes over a broad dose range (20 to 60 Gy). Human white matter T1 is not sensitive to radiation therapy of less than 20 Gy, and gray matter T1 is unchanged over the dose range used to treat human brain tumor. The reduction of gray matter T1 near the tumor could result from compression of cortical parenchyma near the growing tumor mass, or from tumor cell invasion directly into the parenchyma. If brain T1 is a surrogate for radiation effect, reducing the volume of normal white matter receiving more than 20 Gy could be an important treatment planning goal.

  14. Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution.

    Science.gov (United States)

    Shi, Lei; Hu, Enzhi; Wang, Zhenbo; Liu, Jiewei; Li, Jin; Li, Ming; Chen, Hua; Yu, Chunshui; Jiang, Tianzi; Su, Bing

    2017-02-01

    Human evolution is marked by a continued enlargement of the brain. Previous studies on human brain evolution focused on identifying sequence divergences of brain size regulating genes between humans and nonhuman primates. However, the evolutionary pattern of the brain size regulating genes during recent human evolution is largely unknown. We conducted a comprehensive analysis of the brain size regulating gene CASC5 and found that in recent human evolution, CASC5 has accumulated many modern human specific amino acid changes, including two fixed changes and six polymorphic changes. Among human populations, 4 of the 6 amino acid polymorphic sites have high frequencies of derived alleles in East Asians, but are rare in Europeans and Africans. We proved that this between-population allelic divergence was caused by regional Darwinian positive selection in East Asians. Further analysis of brain image data of Han Chinese showed significant associations of the amino acid polymorphic sites with gray matter volume. Hence, CASC5 may contribute to the morphological and structural changes of the human brain during recent evolution. The observed between-population divergence of CASC5 variants was driven by natural selection that tends to favor a larger gray matter volume in East Asians.

  15. Two sexually dimorphic cell groups in the human brain.

    Science.gov (United States)

    Allen, L S; Hines, M; Shryne, J E; Gorski, R A

    1989-02-01

    A quantitative analysis of the volume of 4 cell groups in the preoptic-anterior hypothalamic area (PO-AHA) and of the supraoptic nucleus (SON) of the human brain was performed in 22 age-matched male and female individuals. We suggest the term Interstitial Nuclei of the Anterior Hypothalamus (INAH 1-4) to identify these 4 previously undescribed cell groups in the PO-AHA. While 2 INAH and the SON were not sexually dimorphic, gender-related differences were found in the other 2 cell groups. One nucleus (INAH-3) was 2.8 times larger in the male brain than in the female brain irrespective of age. The other cell group (INAH-2) was twice as large in the male brain, but also appeared to be related in women to circulating steroid hormone levels. Since the PO-AHA influences gonadotropin secretion, maternal behavior, and sexual behavior in several mammalian species, these results suggest that functional sex differences in the hypothalamus may be related to sex differences in neural structure.

  16. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B

    1999-01-01

    Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...... brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (r......CBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water...

  17. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B;

    1999-01-01

    Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...... brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (r......CBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water...

  18. A new microcontroller-based human brain hypothermia system.

    Science.gov (United States)

    Kapidere, Metin; Ahiska, Raşit; Güler, Inan

    2005-10-01

    Many studies show that artificial hypothermia of brain in conditions of anesthesia with the rectal temperature lowered down to 33 degrees C produces pronounced prophylactic effect protecting the brain from anoxia. Out of the methods employed now in clinical practice for reducing the oxygen consumption by the cerebral tissue, the most efficacious is craniocerebral hypothermia (CCH). It is finding even more extensive application in cardiovascular surgery, neurosurgery, neurorenimatology and many other fields of medical practice. In this study, a microcontroller-based designed human brain hypothermia system (HBHS) is designed and constructed. The system is intended for cooling and heating the brain. HBHS consists of a thermoelectric hypothermic helmet, a control and a power unit. Helmet temperature is controlled by 8-bit PIC16F877 microcontroller which is programmed using MPLAB editor. Temperature is converted to 10-bit digital and is controlled automatically by the preset values which have been already entered in the microcontroller. Calibration is controlled and the working range is tested. Temperature of helmet is controlled between -5 and +46 degrees C by microcontroller, with the accuracy of +/-0.5 degrees C.

  19. Distribution of immunoreactive glutamine synthetase in the adult human and mouse brain. Qualitative and quantitative observations with special emphasis on extra-astroglial protein localization.

    Science.gov (United States)

    Bernstein, Hans-Gert; Bannier, Jana; Meyer-Lotz, Gabriela; Steiner, Johann; Keilhoff, Gerburg; Dobrowolny, Henrik; Walter, Martin; Bogerts, Bernhard

    2014-11-01

    Glutamine synthetase catalyzes the ATP-dependent condensation of ammonia and glutamate to form glutamine, thus playing a pivotal role in glutamate and glutamine homoeostasis. Despite a plethora of studies on this enzyme, knowledge about the regional and cellular distribution of this enzyme in human brain is still fragmentary. Therefore, we mapped fourteen post-mortem brains of psychically healthy individuals for the distribution of the glutamine synthetase immunoreactive protein. It was found that glutamine synthetase immunoreactivity is expressed in multiple gray and white matter astrocytes, but also in oligodendrocytes, ependymal cells and certain neurons. Since a possible extra-astrocytic expression of glutamine synthetase is highly controversial, we paid special attention to its appearance in oligodendrocytes and neurons. By double immunolabeling of mouse brain slices and cultured mouse brain cells for glutamine synthetase and cell-type-specific markers we provide evidence that besides astrocytes subpopulations of oligodendrocytes, microglial cells and neurons express glutamine synthetase. Moreover, we show that glutamine synthetase-immunopositive neurons are not randomly distributed throughout human and mouse brain, but represent a subpopulation of nitrergic (i.e. neuronal nitric oxide synthase expressing) neurons. Possible functional implications of an extra-astrocytic localization of glutamine synthetase are discussed.

  20. Adenosine receptors in post-mortem human brain.

    Science.gov (United States)

    James, S; Xuereb, J H; Askalan, R; Richardson, P J

    1992-01-01

    1. Adenosine A2-like binding sites were characterized in post-mortem human brain membranes by examining several compounds for their ability to displace [3H]-CGS 21680 (2[p-(2 carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine) binding. 2. Two A2-like binding sites were identified in the striatum. 3. The more abundant striatal site was similar to the A2a receptor previously described in rat striatum, both in its pharmacological profile and striatal localization. 4. The less abundant striatal site had a pharmacological profile similar to that of the binding site characterized in the other brain regions examined. This was intermediate in character between A1 and A2 and may represent another adenosine receptor subtype. 5. The co-purification of [3H]-CGS 21680 binding during immunoisolation of human striatal cholinergic membranes was used to assess the possible cholinergic localization of A2-like binding sites in the human striatum. Only the more abundant striatal site co-purified with cholinergic membranes. This suggests that this A2a-like site is present on cholinergic neurones in the human striatum.

  1. Canonical Genetic Signatures of the Adult Human Brain

    Science.gov (United States)

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  2. Brain burdens of aluminum, iron, and copper and their relationships with amyloid-β pathology in 60 human brains.

    Science.gov (United States)

    Exley, Christopher; House, Emily; Polwart, Anthony; Esiri, Margaret M

    2012-01-01

    The deposition in the brain of amyloid-β as beta sheet conformers associated with senile plaques and vasculature is frequently observed in Alzheimer’s disease. While metals, primarily aluminum, iron, zinc, and copper, have been implicated in amyloid-β deposition in vivo, there are few data specifically relating brain metal burden with extent of amyloid pathologies in human brains. Herein brain tissue content of aluminum, iron, and copper are compared with burdens of amyloid-β, as senile plaques and as congophilic amyloid angiopathy, in 60 aged human brains. Significant observations were strong negative correlations between brain copper burden and the degree of severity of both senile plaque and congophilic amyloid angiopathy pathologies with the relationship with the former reaching statistical significance. While we did not have access to the dementia status of the majority of the 60 brain donors, this knowledge for just 4 donors allowed us to speculate that diagnosis of dementia might be predicted by a combination of amyloid pathology and a ratio of the brain burden of copper to the brain burden of aluminum. Taking into account only those donor brains with either senile plaque scores ≥4 and/or congophilic amyloid angiopathy scores ≥12, a Cu:Al ratio of <20 would predict that at least 39 of the 60 donors would have been diagnosed as suffering from dementia. Future research should test the hypothesis that, in individuals with moderate to severe amyloid pathology, low brain copper is a predisposition to developing dementia.

  3. Memory-related brain lateralisation in birds and humans.

    Science.gov (United States)

    Moorman, Sanne; Nicol, Alister U

    2015-03-01

    Visual imprinting in chicks and song learning in songbirds are prominent model systems for the study of the neural mechanisms of memory. In both systems, neural lateralisation has been found to be involved in memory formation. Although many processes in the human brain are lateralised--spatial memory and musical processing involves mostly right hemisphere dominance, whilst language is mostly left hemisphere dominant--it is unclear what the function of lateralisation is. It might enhance brain capacity, make processing more efficient, or prevent occurrence of conflicting signals. In both avian paradigms we find memory-related lateralisation. We will discuss avian lateralisation findings and propose that birds provide a strong model for studying neural mechanisms of memory-related lateralisation. Copyright © 2014. Published by Elsevier Ltd.

  4. Predicting human brain activity associated with the meanings of nouns.

    Science.gov (United States)

    Mitchell, Tom M; Shinkareva, Svetlana V; Carlson, Andrew; Chang, Kai-Min; Malave, Vicente L; Mason, Robert A; Just, Marcel Adam

    2008-05-30

    The question of how the human brain represents conceptual knowledge has been debated in many scientific fields. Brain imaging studies have shown that different spatial patterns of neural activation are associated with thinking about different semantic categories of pictures and words (for example, tools, buildings, and animals). We present a computational model that predicts the functional magnetic resonance imaging (fMRI) neural activation associated with words for which fMRI data are not yet available. This model is trained with a combination of data from a trillion-word text corpus and observed fMRI data associated with viewing several dozen concrete nouns. Once trained, the model predicts fMRI activation for thousands of other concrete nouns in the text corpus, with highly significant accuracies over the 60 nouns for which we currently have fMRI data.

  5. A theoretical model of phase transitions in the human brain.

    Science.gov (United States)

    Jirsa, V K; Friedrich, R; Haken, H; Kelso, J A

    1994-01-01

    An experiment using a multisensor SQUID (superconducting quantum interference device) array was performed by Kelso and colleagues (1992) which combined information from three different sources: perception, motor response, and brain signals. When an acoustic stimulus frequency is changed systematically, a spontaneous transition in coordination occurs at a critical frequency in both motor behavior and brain signals. Qualitatively analogous transitions are known for physical and biological systems such as changes in the coordination of human hand movements (Kelso 1981, 1984). In this paper we develop a theoretical model based on methods from the interdisciplinary field of synergetics (Haken 1983, 1987) and nonlinear oscillator theory that reproduces the main experimental features very well and suggests a formulation of a fundamental biophysical coupling.

  6. The evolution of distributed association networks in the human brain.

    Science.gov (United States)

    Buckner, Randy L; Krienen, Fenna M

    2013-12-01

    The human cerebral cortex is vastly expanded relative to other primates and disproportionately occupied by distributed association regions. Here we offer a hypothesis about how association networks evolved their prominence and came to possess circuit properties vital to human cognition. The rapid expansion of the cortical mantle may have untethered large portions of the cortex from strong constraints of molecular gradients and early activity cascades that lead to sensory hierarchies. What fill the gaps between these hierarchies are densely interconnected networks that widely span the cortex and mature late into development. Limitations of the tethering hypothesis are discussed as well as its broad implications for understanding critical features of the human brain as a byproduct of size scaling. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Microtesla MRI of the human brain with simultaneous MEG

    CERN Document Server

    Zotev, V S; Matlashov, A N; Savukov, I M; Espy, M A; Mosher, J C; Gómez, J J; Kraus, R H

    2007-01-01

    Magnetic resonance imaging at ultra-low fields (ULF MRI) uses SQUIDs (superconducting quantum interference devices) to measure spin precession at a microtesla-range field after sample magnetization is enhanced by a stronger pre-polarizing field. Here, the first ULF images of the human head acquired at 46 microtesla measurement field with pre-polarization at 30 mT are reported. The imaging was performed with 3 mm x 3 mm x 6 mm resolution using the seven-channel SQUID system designed for both ULF MRI and magnetoencephalography (MEG). Auditory MEG signals were measured immediately after the imaging while the human subject remained inside the system. These results demonstrate that ULF MRI of the human brain is feasible and can be naturally combined with MEG.

  8. [Molecular imaging of histamine receptors in the human brain].

    Science.gov (United States)

    Tashiro, Manabu; Yanai, Kazuhiko

    2007-03-01

    Brain histamine is involved in a wide range of physiological functions such as regulation of sleep-wake cycle, arousal, appetite control, cognition, learning and memory mainly through the 4 receptor subtypes: H1, H2, H3 and H4. Neurons producing histamine, histaminergic neurons, are exclusively located in the tuberomammillary nucleus of the posterior hypothalamus and are transmitting histamine to almost all regions of the brain. Roles of brain histamine have been studied using animals including knock-out mice and human subjects. For clinical studies, molecular imaging technique such as positron emission tomography (PET), with ligands such as [11C]doxepin and [11C]pyrilamine, has been a useful tool. A series of clinical studies on histamine H1 antagonists, or antihistamines, have demonstrated that antihistamines can be classified into sedative, mildly-sedative and non-sedative drugs according to their blood-brain barrier (BBB) permeability, showing apparent clinical usefulness regarding QOL, work efficiency and traffic safety of allergic patients. PET has also been used for elucidation of aging effects and pathophysiological roles of histaminergic nervous system in various neuropsychiatric disorders such as Alzheimer's disease, schizophrenia and depression, where H1 receptor binding potentials were lower than age-matched healthy controls. It has been also demonstrated that brain histamine functions as an endogenous anti-epileptic. In addition, H3 receptors are located in the presynaptic sites of not only histaminergic nerves but also in other nervous systems such as serotonergic, cholinergic and dopaminergic systems, and to be regulating secretion of various neurotransmitters. Nowadays, H3 receptors have been thought to be a new target of drug treatment of various neuropsychiatric disorders. There are still many research topics to be investigated regarding molecular imaging of histamine and histamine receptors. The authors hope that this line of research contributes

  9. Expression of muscarinic binding sites in primary human brain tumors.

    Science.gov (United States)

    Gurwitz, D; Razon, N; Sokolovsky, M; Soreq, H

    1984-05-01

    The expression of muscarinic binding sites was examined in a collection of primary brain tumors of different cellular origins and various degrees of dedifferentiation, as compared to control specimens. Eleven gliogenous tumors were examined, all of which contained substantial amounts of muscarinic binding sites. Most of the other tumor types examined did not display detectable binding of [3H]N-methyl-4-piperidyl benzilate ([3H]4NMPB). Scatchard analysis indicated the existence of homogeneous antagonist sites in both normal forebrain and glioblastoma multiforme, with Kd values of 1.2 nM and 0.9 nM, respectively. The density of muscarinic binding sites varied between tumors from different patients, and also between specimens prelevated from different areas of the same tumor. This variability, as well as the average density of binding sites, appeared to be larger in highly malignant tumors than in less malignant ones. In contrast, the density of muscarinic receptors from control specimens was invariably high, but within the same order of magnitude. To test whether the muscarinic binding activity in the brain tumors is correlated to other cholinoceptive properties, cholinesterase activity was also examined. Individual data for density of [3H]4NMPB binding sites were then plotted against corresponding values of cholinesterase activity. The pattern of distribution of these values was clearly different in tumor specimens, when compared to that observed in samples derived from non-malignant brain. Our observations indicate that human brain cells of gliogenous origin are capable of expressing muscarinic binding sites, and that, if a correlation exists between muscarinic receptors and cholinesterase levels in gliogenous tumors, it differs from that of non-malignant brain tissue.

  10. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alcendor Donald J

    2012-05-01

    Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

  11. SiRNA Inhibits Replication of Langat Virus, a Member of the Tick-Borne Encephalitis Virus Complex in Organotypic Rat Brain Slices

    Science.gov (United States)

    Maffioli, Carola; Grandgirard, Denis; Leib, Stephen L.; Engler, Olivier

    2012-01-01

    Tick-borne encephalitis virus is the causative agent of tick-borne encephalitis, a potentially fatal neurological infection. Tick-borne encephalitis virus belongs to the family of flaviviruses and is transmitted by infected ticks. Despite the availability of vaccines, approximately 2000–3000 cases of tick-borne encephalitis occur annually in Europe for which no curative therapy is available. The antiviral effects of RNA mediated interference by small interfering RNA (siRNA) was evaluated in cell culture and organotypic hippocampal cultures. Langat virus, a flavivirus highly related to Tick-borne encephalitis virus exhibits low pathogenicity for humans but retains neurovirulence for rodents. Langat virus was used for the establishment of an in vitro model of tick-borne encephalitis. We analyzed the efficacy of 19 siRNA sequences targeting different regions of the Langat genome to inhibit virus replication in the two in vitro systems. The most efficient suppression of virus replication was achieved by siRNA sequences targeting structural genes and the 3′ untranslated region. When siRNA was administered to HeLa cells before the infection with Langat virus, a 96.5% reduction of viral RNA and more than 98% reduction of infectious virus particles was observed on day 6 post infection, while treatment after infection decreased the viral replication by more than 98%. In organotypic hippocampal cultures the replication of Langat virus was reduced by 99.7% by siRNA sequence D3. Organotypic hippocampal cultures represent a suitable in vitro model to investigate neuronal infection mechanisms and treatment strategies in a preserved three-dimensional tissue architecture. Our results demonstrate that siRNA is an efficient approach to limit Langat virus replication in vitro. PMID:22984545

  12. Multi-dimensional dynamics of human electromagnetic brain activity

    Directory of Open Access Journals (Sweden)

    Tetsuo eKida

    2016-01-01

    Full Text Available Magnetoencephalography (MEG and electroencephalography (EEG are invaluable neuroscientific tools for unveiling human neural dynamics in three dimensions (space, time, and frequency, which are associated with a wide variety of perceptions, cognition, and actions. MEG/EEG also provides different categories of neuronal indices including activity magnitude, connectivity, and network properties along the three dimensions. In the last 20 years, interest has increased in inter-regional connectivity and complex network properties assessed by various sophisticated scientific analyses. We herein review the definition, computation, short history, and pros and cons of connectivity and complex network (graph-theory analyses