Magnetic Resonance Microscopy (MRM) of Single Mammalian Myofibers and Myonuclei

PubMed Central

Lee, Choong H.; Bengtsson, Niclas; Chrzanowski, Stephen M.; Flint, Jeremy J.; Walter, Glenn A.; Blackband, Stephen J.

2017-01-01

Recently, the first magnetic resonance microscopy (MRM) images at the cellular level in isolated mammalian brain tissues were obtained using microsurface coils. These methods can elucidate the cellular origins of MR signals and describe how these signals change over the course of disease progression and therapy. In this work, we explore the capability of these microimaging techniques to visualize mouse muscle fibers and their nuclei. Isolated myofibers expressing lacZ were imaged with and without a stain for β-galactosidase activity (S-Gal + ferric ammonium citrate) that produces both optical and MR contrast. We found that MRM can be used to image single myofibers with 6-μm resolution. The ability to image single myofibers will serve as a valuable tool to study MR properties attributed to healthy and myopathic cells. The ability to image nuclei tagged with MR/Optical gene markers may also find wide use in cell lineage MRI studies. PMID:28045071

Distributed representation of visual objects by single neurons in the human brain.

PubMed

Valdez, André B; Papesh, Megan H; Treiman, David M; Smith, Kris A; Goldinger, Stephen D; Steinmetz, Peter N

2015-04-01

It remains unclear how single neurons in the human brain represent whole-object visual stimuli. While recordings in both human and nonhuman primates have shown distributed representations of objects (many neurons encoding multiple objects), recordings of single neurons in the human medial temporal lobe, taken as subjects' discriminated objects during multiple presentations, have shown gnostic representations (single neurons encoding one object). Because some studies suggest that repeated viewing may enhance neural selectivity for objects, we had human subjects discriminate objects in a single, more naturalistic viewing session. We found that, across 432 well isolated neurons recorded in the hippocampus and amygdala, the average fraction of objects encoded was 26%. We also found that more neurons encoded several objects versus only one object in the hippocampus (28 vs 18%, p < 0.001) and in the amygdala (30 vs 19%, p < 0.001). Thus, during realistic viewing experiences, typical neurons in the human medial temporal lobe code for a considerable range of objects, across multiple semantic categories. Copyright © 2015 the authors 0270-6474/15/355180-07$15.00/0.

Comparative analysis of European bat lyssavirus 1 pathogenicity in the mouse model.

PubMed

Eggerbauer, Elisa; Pfaff, Florian; Finke, Stefan; Höper, Dirk; Beer, Martin; Mettenleiter, Thomas C; Nolden, Tobias; Teifke, Jens-Peter; Müller, Thomas; Freuling, Conrad M

2017-06-01

European bat lyssavirus 1 is responsible for most bat rabies cases in Europe. Although EBLV-1 isolates display a high degree of sequence identity, different sublineages exist. In individual isolates various insertions and deletions have been identified, with unknown impact on viral replication and pathogenicity. In order to assess whether different genetic features of EBLV-1 isolates correlate with phenotypic changes, different EBLV-1 variants were compared for pathogenicity in the mouse model. Groups of three mice were infected intracranially (i.c.) with 102 TCID50/ml and groups of six mice were infected intramuscularly (i.m.) with 105 TCID50/ml and 102 TCID50/ml as well as intranasally (i.n.) with 102 TCID50/ml. Significant differences in survival following i.m. inoculation with low doses as well as i.n. inoculation were observed. Also, striking variations in incubation periods following i.c. inoculation and i.m. inoculation with high doses were seen. Hereby, the clinical picture differed between general symptoms, spasms and aggressiveness depending on the inoculation route. Immunohistochemistry of mouse brains showed that the virus distribution in the brain depended on the inoculation route. In conclusion, different EBLV-1 isolates differ in pathogenicity indicating variation which is not reflected in studies of single isolates.

Comparative analysis of European bat lyssavirus 1 pathogenicity in the mouse model

PubMed Central

Eggerbauer, Elisa; Pfaff, Florian; Finke, Stefan; Höper, Dirk; Beer, Martin; Mettenleiter, Thomas C.; Nolden, Tobias; Teifke, Jens-Peter; Müller, Thomas

2017-01-01

European bat lyssavirus 1 is responsible for most bat rabies cases in Europe. Although EBLV-1 isolates display a high degree of sequence identity, different sublineages exist. In individual isolates various insertions and deletions have been identified, with unknown impact on viral replication and pathogenicity. In order to assess whether different genetic features of EBLV-1 isolates correlate with phenotypic changes, different EBLV-1 variants were compared for pathogenicity in the mouse model. Groups of three mice were infected intracranially (i.c.) with 102 TCID50/ml and groups of six mice were infected intramuscularly (i.m.) with 105 TCID50/ml and 102 TCID50/ml as well as intranasally (i.n.) with 102 TCID50/ml. Significant differences in survival following i.m. inoculation with low doses as well as i.n. inoculation were observed. Also, striking variations in incubation periods following i.c. inoculation and i.m. inoculation with high doses were seen. Hereby, the clinical picture differed between general symptoms, spasms and aggressiveness depending on the inoculation route. Immunohistochemistry of mouse brains showed that the virus distribution in the brain depended on the inoculation route. In conclusion, different EBLV-1 isolates differ in pathogenicity indicating variation which is not reflected in studies of single isolates. PMID:28628617

Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin.

PubMed

Welch, Martha G; Welch-Horan, Thomas B; Anwar, Muhammad; Anwar, Nargis; Ludwig, Robert J; Ruggiero, David A

2005-01-01

Recent research points to the connection between behavioral and gut disorders. Early adverse events are associated with inflammatory bowel disease (IBD). In animal models, maternal deprivation and social isolation predispose to gastric erosion and brain pathology. This study examined (1) brain effects of chronic gastrointestinal inflammation in a rat model of acquired IBD and (2) whether such changes are resolved by individual secretin (S) or oxytocin (OT) peptide treatment. Neurological manifestations of IBD were mapped by c-fos gene expression in male Sprague-Dawley rats (n = 10) with trinitrobenzene sulfonic acid (TNBS)-induced IBD vs controls (n = 11). IBD was characterized by moderate/severe infiltration of inflammatory cells 10 d after TNBS infusion. Age-matched pairs were processed for immunocytochemical detection of Fos, expressed when neurons are stimulated. S or OT (100 mg/250 mL saline) or equivolume saline was administered iv by Alzet pump for 20 d after disease onset. Degree of resolution of colitis-induced brain activation was assessed by c-fos expression, and mean numbers of Fos-immunoreactive nuclei for each group were compared using Independent Samples T-test. Chronic IBD activated periventricular gray, hypothalamic/visceral thalamic stress axes and cortical domains, and septal/preoptic/amygdala, brain areas abnormal in autism. Single peptide treatment with S or OT did not alter the effects of inflammation on the brain. Brain areas concomitantly activated by visceral inflammation are those often abnormal in autism, suggesting that IBD could be a model for testing treatments of autism. Other single and combined peptide treatments of IBD should be tested. The clinical implications for treating autism, IBD, and concomitant sickness behaviors with peptide therapy, with or without maternal nurturing as a natural equivalent, are presented.

Toward multi-area distributed network of implanted neural interrogators

NASA Astrophysics Data System (ADS)

Powell, Marc P.; Hou, Xiaoxiao; Galligan, Craig; Ashe, Jeffrey; Borton, David A.

2017-08-01

As we aim to improve our understanding of the brain, it is critical that researchers have simultaneous multi-area, large-scale access to the brain. Information processing in the brain occurs through close and distant coupling of functional sub-domains, as opposed to within isolated single neurons. However, commercially available neural interfaces capable of sensing electrophysiology of single neurons, currently allow access to only a small, mm3 volume of cortical cells, are not scalable to recording from orders of magnitude more neurons, and leverage bulky, skull mounted hardware and cabling sensitive to relative movements of the skull and brain. In this work, we propose a system capable of recording from many individual distributed neural interrogator nodes, untethered from any external electronics. Using an array of epidural inductive coils to wirelessly power the implanted electronics, the system is intended to be agnostic to the surgical placement of any individual node. Here, we demonstrate the ability to transmit nearly 15mW of power with greater than 50% power transfer efficiency, benchtop testing of individual subcircuit system components showing successful digitization of neural signals, and wireless transmission currently supporting a data rate of 3.84Mbps. We leverage a software defined radio based RF receiver to demodulate the data which can be stored in memory for later retrieval. Finally, we introduce a packaging technology capable of isolating active electronics from the surrounding tissue while providing capability for electrical feed-through assemblies for external neural interfacing. We expect, based on the presented preliminary findings, that the system can be integrated into a platform technology for the study of the intricate interactions between cortical domains.

Preservation of mitochondrial functional integrity in mitochondria isolated from small cryopreserved mouse brain areas.

PubMed

Valenti, Daniela; de Bari, Lidia; De Filippis, Bianca; Ricceri, Laura; Vacca, Rosa Anna

2014-01-01

Studies of mitochondrial bioenergetics in brain pathophysiology are often precluded by the need to isolate mitochondria immediately after tissue dissection from a large number of brain biopsies for comparative studies. Here we present a procedure of cryopreservation of small brain areas from which mitochondrial enriched fractions (crude mitochondria) with high oxidative phosphorylation efficiency can be isolated. Small mouse brain areas were frozen and stored in a solution containing glycerol as cryoprotectant. Crude mitochondria were isolated by differential centrifugation from both cryopreserved and freshly explanted brain samples and were compared with respect to their ability to generate membrane potential and produce ATP. Intactness of outer and inner mitochondrial membranes was verified by polarographic ascorbate and cytochrome c tests and spectrophotometric assay of citrate synthase activity. Preservation of structural integrity and oxidative phosphorylation efficiency was successfully obtained in crude mitochondria isolated from different areas of cryopreserved mouse brain samples. Long-term cryopreservation of small brain areas from which intact and phosphorylating mitochondria can be isolated for the study of mitochondrial bioenergetics will significantly expand the study of mitochondrial defects in neurological pathologies, allowing large comparative studies and favoring interlaboratory and interdisciplinary analyses. Copyright © 2013 Elsevier Inc. All rights reserved.

Pituitary dysfunction and its association with quality of life in traumatic brain injury.

PubMed

Izzo, Giulia; Tirelli, Assunta; Angrisani, Elisabetta; Cannaviello, Giovanni; Cannaviello, Lucio; Puzziello, Alessandro; Vatrella, Alessandro; Vitale, Mario

2016-04-01

Traumatic brain injury (TBI) is a major cause of death and disability and may cause transient or persistent, isolated or multiple hypopituitarism in a variable percentage of cases. The primary aim of this study was to determine the incidence of isolated and multiple anterior pituitary hormone deficiency in subjects with TBI in a single institution. The secondary aim was to determine a correlation between pituitary deficiency and quality of life (QOL) after TBI. Thirty-five patients, aged between 18 and 63 years, were evaluated 6months to 5 years after TBI. We evaluated the QOL by SF-12(®) questionnaire and measured serum basal GH, IGF1, LH, FSH, testosterone (in males), 17-β-estradiol (in women), PRL, fT4 and TSH. In patients with low IGF1, a GHRH + Arginine test was performed. Single or multiple pituitary failure was found in 13 patients (37%). Low testosterone was found in 7 males, low FSH and/or LH in 4, low IGF1 in 7 patients. Hypogonadotropic hypogonadism and GH insufficiency assessed by GHRH + Arginine test were found respectively in 3 and 2 patients. One patient displayed a concomitant GH insufficiency and low TSH level. Twenty six patients showed a reduction in QOL. A correlations between altered QOL and hormonal deficiency was not observed. Isolated or multiple hypopituitarism resulting from TBI are frequent. Alterations in QOL and pituitary function resulting from TBI are not associated. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Alkamides from Echinacea angustifolia Interact with P-glycoprotein of primary brain capillary endothelial cells isolated from porcine brain blood vessels.

PubMed

Mahringer, Anne; Ardjomand-Woelkart, Karin; Bauer, Rudolf; Fricker, Gert; Efferth, Thomas

2013-03-01

The blood-brain barrier prevents the passage of toxic compounds from blood circulation into brain tissue. Unfortunately, drugs for the treatment of neurodegenerative diseases, brain tumors, and other diseases also do not cross the blood-brain barrier. In the present investigation, we used isolated porcine brain capillary endothelial cells and a flow cytometric calcein-AM assay to analyze inhibition of P-glycoprotein, a major constituent of the blood-brain barrier. We tested 8 alkamides isolated from Echinacea angustifolia and found that four of them inhibited P-glycoprotein-mediated calcein transport in porcine brain capillary endothelial cells. Georg Thieme Verlag KG Stuttgart · New York.

Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin.

PubMed

Huong, Nguyen Thi Thu; Murakami, Yukihisa; Tohda, Michihisa; Watanabe, Hiroshi; Matsumoto, Kinzo

2005-08-01

Stressors with a physical factor such as immobilization, electric foot shock, cold swim, etc., have been shown to produce oxidative damage to membrane lipids in the brain. In this study, we investigated the effect of protracted social isolation stress on lipid peroxidation activity in the mouse brain and elucidated the protective effect of majonoside-R2, a major saponin component of Vietnamese ginseng, in mice exposed to social isolation stress. Thiobarbituric acid reactive substance levels, one of the end products of lipid peroxidation reaction, were increased in the brains of mice subjected to 6-8 weeks of social isolation stress. Measurements of nitric oxide (NO) metabolites (NO(x)(-)) also revealed a significant increase of NO production in the brains of socially isolated mice. Moreover, the depletion of brain glutathione content, an endogenous antioxidant, in socially isolated animals occurred in association with the rise in lipid peroxidation. The intraperitoneal administration of majonoside-R2 (10-50 mg/kg) had no effect on thiobarbituric acid reactive substances (TBARS), NO, or glutathione levels in the brains of group-housed control mice but it significantly suppressed the increase in TBARS and NO levels and the decrease in glutathione levels caused by social isolation stress. These results suggest that mice subjected to 6-8 weeks of social isolation stress produces oxidative damage in the brain partly via enhancement of NO production, and that majonoside-R2 exerts a protective effect by modulating NO and glutathione systems in the brain.

Spatiotemporal analysis of single-trial EEG of emotional pictures based on independent component analysis and source location

NASA Astrophysics Data System (ADS)

Liu, Jiangang; Tian, Jie

2007-03-01

The present study combined the Independent Component Analysis (ICA) and low-resolution brain electromagnetic tomography (LORETA) algorithms to identify the spatial distribution and time course of single-trial EEG record differences between neural responses to emotional stimuli vs. the neutral. Single-trial multichannel (129-sensor) EEG records were collected from 21 healthy, right-handed subjects viewing the emotion emotional (pleasant/unpleasant) and neutral pictures selected from International Affective Picture System (IAPS). For each subject, the single-trial EEG records of each emotional pictures were concatenated with the neutral, and a three-step analysis was applied to each of them in the same way. First, the ICA was performed to decompose each concatenated single-trial EEG records into temporally independent and spatially fixed components, namely independent components (ICs). The IC associated with artifacts were isolated. Second, the clustering analysis classified, across subjects, the temporally and spatially similar ICs into the same clusters, in which nonparametric permutation test for Global Field Power (GFP) of IC projection scalp maps identified significantly different temporal segments of each emotional condition vs. neutral. Third, the brain regions accounted for those significant segments were localized spatially with LORETA analysis. In each cluster, a voxel-by-voxel randomization test identified significantly different brain regions between each emotional condition vs. the neutral. Compared to the neutral, both emotional pictures elicited activation in the visual, temporal, ventromedial and dorsomedial prefrontal cortex and anterior cingulated gyrus. In addition, the pleasant pictures activated the left middle prefrontal cortex and the posterior precuneus, while the unpleasant pictures activated the right orbitofrontal cortex, posterior cingulated gyrus and somatosensory region. Our results were well consistent with other functional imaging studies, while revealed temporal dynamics of emotional processing of specific brain structure with high temporal resolution.

Direct bisulfite sequencing for examination of DNA methylation with gene and nucleotide resolution from brain tissues.

PubMed

Parrish, R Ryley; Day, Jeremy J; Lubin, Farah D

2012-07-01

DNA methylation is an epigenetic modification that is essential for the development and mature function of the central nervous system. Due to the relevance of this modification to the transcriptional control of gene expression, it is often necessary to examine changes in DNA methylation patterns with both gene and single-nucleotide resolution. Here, we describe an in-depth basic protocol for direct bisulfite sequencing of DNA isolated from brain tissue, which will permit direct assessment of methylation status at individual genes as well as individual cytosine molecules/nucleotides within a genomic region. This method yields analysis of DNA methylation patterns that is robust, accurate, and reproducible, thereby allowing insights into the role of alterations in DNA methylation in brain tissue.

The Myth of Optimality in Clinical Neuroscience.

PubMed

Holmes, Avram J; Patrick, Lauren M

2018-03-01

Clear evidence supports a dimensional view of psychiatric illness. Within this framework the expression of disorder-relevant phenotypes is often interpreted as a breakdown or departure from normal brain function. Conversely, health is reified, conceptualized as possessing a single ideal state. We challenge this concept here, arguing that there is no universally optimal profile of brain functioning. The evolutionary forces that shape our species select for a staggering diversity of human behaviors. To support our position we highlight pervasive population-level variability within large-scale functional networks and discrete circuits. We propose that, instead of examining behaviors in isolation, psychiatric illnesses can be best understood through the study of domains of functioning and associated multivariate patterns of variation across distributed brain systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

NeuroGrid: recording action potentials from the surface of the brain.

PubMed

Khodagholy, Dion; Gelinas, Jennifer N; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G; Buzsáki, György

2015-02-01

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.

Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

PubMed

Napoli, Alessandro; Obeid, Iyad

2016-03-01

Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

Iron overload prevents oxidative damage to rat brain after chlorpromazine administration.

PubMed

Piloni, Natacha E; Caro, Andres A; Puntarulo, Susana

2018-05-15

The hypothesis tested is that Fe administration leads to a response in rat brain modulating the effects of later oxidative challenges such as chlorpromazine (CPZ) administration. Either a single dose (acute Fe overload) or 6 doses every second day (sub-chronic Fe overload) of 500 or 50 mg Fe-dextran/kg, respectively, were injected intraperitoneally (ip) to rats. A single dose of 10 mg CPZ/kg was injected ip 8 h after Fe treatment. DNA integrity was evaluated by quantitative PCR, lipid radical (LR · ) generation rate by electron paramagnetic resonance (EPR), and catalase (CAT) activity by UV spectrophotometry in isolated brains. The maximum increase in total Fe brain was detected after 6 or 2 h in the acute and sub-chronic Fe overload model, respectively. Mitochondrial and nuclear DNA integrity decreased after acute Fe overload at the time of maximal Fe content; the decrease in DNA integrity was lower after sub-chronic than after acute Fe overload. CPZ administration increased LR · generation rate in control rat brain after 1 and 2 h; however, CPZ administration after acute or sub-chronic Fe overload did not affect LR · generation rate. CPZ treatment did not affect CAT activity after 1-4 h neither in control rats nor in acute Fe-overloaded rats. However, CPZ administration to rats treated sub-chronically with Fe showed increased brain CAT activity after 2 or 4 h, as compared to control values. Fe supplementation prevented brain damage in both acute and sub-chronic models of Fe overload by selectively activating antioxidant pathways.

Isolation, structure, synthesis, and activity of a new member of the calcitonin gene-related peptide family from frog skin and molecular cloning of its precursor.

PubMed

Seon, A A; Pierre, T N; Redeker, V; Lacombe, C; Delfour, A; Nicolas, P; Amiche, M

2000-02-25

Calcitonin gene-related peptide has been extracted from the skin exudate of a single living specimen of the frog Phyllomedusa bicolor and purified to homogeneity by a two-step protocol. A total volume of 250 microl of exudate yielded 380 microg of purified peptide. Mass spectrometric analysis and gas phase sequencing of the purified peptide as well as chemical synthesis and cDNA analysis were consistent with the structure SCDTSTCATQRLADFLSRSGGIGSPDFVPTDVSANSF amide and the presence of a disulfide bridge linking Cys(2) and Cys(7). The skin peptide, named skin calcitonin gene-related peptide, differs significantly from all other members of the calcitonin gene-related peptide family of peptides at nine positions but binds with high affinity to calcitonin gene-related peptide receptors in the rat brain and acts as an agonist in the rat vas deferens bioassay with potencies equal to those of human CGRP. Reverse transcriptase-polymerase chain reaction coupled with cDNA cloning and sequencing demonstrated that skin calcitonin gene-related peptide isolated in the skin is identical to that present in the frog's central and enteric nervous systems. These data, which indicate for the first time the existence of calcitonin gene-related peptide in the frog skin, add further support to the brain-skin-gut triangle hypothesis as a useful tool in the identification and/or isolation of mammalian peptides that are present in the brain and other tissues in only minute quantities.

Characterization of Streptococcus constellatus strains recovered from a brain abscess and periodontal pockets in an immunocompromised patient.

PubMed

Marques da Silva, Rafael; Caugant, Dominique A; Josefsen, Roger; Tronstad, Leif; Olsen, Ingar

2004-12-01

There have been a number of reports of brain abscesses suggesting an odontogenic etiology. However, no efforts have been made to compare brain abscess isolates with isolates from the oral cavity using highly discriminative methods. We report a brain abscess caused by Streptococcus constellatus in an immunocompromised patient where oral infection (periodontitis) was suspected to be implicated. The brain abscess and oral isolates were compared by means of one phenotypic and three genetic (restriction fragment length polymorphism [RFLP], ribotyping, and random amplified polymorphic DNA [RAPD]) fingerprinting techniques. The phenotypic method and RFLP showed identical profiles between brain and periodontal isolates, while ribotyping and RAPD showed very close similarity, with only one band difference in one of the three ribotypes and in one of the three polymorphic RAPD. Gene transfer by genetic recombinational events in the periodontal pocket might have been responsible for the emergence of a strain variant of S. constellatus that had the potential to cause an abscess at a distant site (brain). The importance of odontogenic sources as potential foci of infection for brain abscesses is discussed.

Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

PubMed

Khodaie, Babak; Lotfinia, Ahmad Ali; Ahmadi, Milad; Lotfinia, Mahmoud; Jafarian, Maryam; Karimzadeh, Fariba; Coulon, Philippe; Gorji, Ali

2015-02-01

Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI. Copyright © 2014 Elsevier B.V. All rights reserved.

Beyond functional architecture in cognitive neuropsychology: a reply to Coltheart (2010).

PubMed

Plaut, David C; Patterson, Karalyn

2010-01-01

We (Patterson & Plaut, 2009) argued that cognitive neuropsychology has had a limited impact on cognitive science due to a nearly exclusive reliance on (a) single-case studies, (b) dissociations in cognitive performance, and (c) shallow, box-and-arrow theorizing, and we advocated adopting a case-series methodology, considering associations as well as dissociations, and employing explicit computational modeling in studying "how the brain does its cognitive business." In reply, Coltheart (2010) claims that our concern is misplaced because cognitive neuropsychology is concerned only with studying the mind, in terms of its "functional architecture," without regard to how this is implemented in the brain. In this response, we do not dispute his characterization of cognitive neuropsychology as it has typically been practiced over the last 40 years, but we suggest that our understanding of brain structure and function has advanced to the point where studying the mind without regard to the brain is unwise and perpetuates the field's isolation. Copyright © 2009 Cognitive Science Society, Inc.

Kainic acid-induced albumin leak across the blood-brain barrier facilitates epileptiform hyperexcitability in limbic regions.

PubMed

Noé, Francesco M; Bellistri, Elisa; Colciaghi, Francesca; Cipelletti, Barbara; Battaglia, Giorgio; de Curtis, Marco; Librizzi, Laura

2016-06-01

Systemic administration of kainic acid (KA) is a widely used procedure utilized to develop a model of temporal lobe epilepsy (TLE). Despite its ability to induce status epilepticus (SE) in vivo, KA applied to in vitro preparations induces only interictal-like activity and/or isolated ictal discharges. The possibility that extravasation of the serum protein albumin from the vascular compartment enhances KA-induced brain excitability is investigated here. Epileptiform activity was induced by arterial perfusion of 6 μm KA in the in vitro isolated guinea pig brain preparation. Simultaneous field potential recordings were carried out bilaterally from limbic (CA1, dentate gyrus [DG], and entorhinal cortex) and extralimbic regions (piriform cortex and neocortex). Blood-brain barrier (BBB) breakdown associated with KA-induced epileptiform activity was assessed by parenchymal leakage of intravascular fluorescein-isothiocyanate albumin. Seizure-induced brain inflammation was evaluated by western blot analysis of interleukin (IL)-1β expression in brain tissue. KA infusion caused synchronized activity at 15-30 Hz in limbic (but not extralimbic) cortical areas, associated with a brief, single seizure-like event. A second bolus of KA, 60 min after the induction of the first ictal event, did not further enhance excitability. Perfusion of serum albumin between the two administrations of KA enhanced epileptiform discharges and allowed a recurrent ictal event during the second KA infusion. Our data show that arterial KA administration selectively alters the synchronization of limbic networks. However, KA is not sufficient to generate recurrent seizures unless serum albumin is co-perfused during KA administration. These findings suggest a role of serum albumin in facilitating acute seizure generation. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

The Complexity of Biomechanics Causing Primary Blast-Induced Traumatic Brain Injury: A Review of Potential Mechanisms

PubMed Central

Courtney, Amy; Courtney, Michael

2015-01-01

Primary blast-induced traumatic brain injury (bTBI) is a prevalent battlefield injury in recent conflicts, yet biomechanical mechanisms of bTBI remain unclear. Elucidating specific biomechanical mechanisms is essential to developing animal models for testing candidate therapies and for improving protective equipment. Three hypothetical mechanisms of primary bTBI have received the most attention. Because translational and rotational head accelerations are primary contributors to TBI from non-penetrating blunt force head trauma, the acceleration hypothesis suggests that blast-induced head accelerations may cause bTBI. The hypothesis of direct cranial transmission suggests that a pressure transient traverses the skull into the brain and directly injures brain tissue. The thoracic hypothesis of bTBI suggests that some combination of a pressure transient reaching the brain via the thorax and a vagally mediated reflex result in bTBI. These three mechanisms may not be mutually exclusive, and quantifying exposure thresholds (for blasts of a given duration) is essential for determining which mechanisms may be contributing for a level of blast exposure. Progress has been hindered by experimental designs, which do not effectively expose animal models to a single mechanism and by over-reliance on poorly validated computational models. The path forward should be predictive validation of computational models by quantitative confirmation with blast experiments in animal models, human cadavers, and biofidelic human surrogates over a range of relevant blast magnitudes and durations coupled with experimental designs, which isolate a single injury mechanism. PMID:26539158

Comparison of apoptosis in human primary pulmonary endothelial cells and a brain microvascular endothelial cell line co-cultured with Plasmodium falciparum field isolates.

PubMed

Essone, Jean Claude Biteghe Bi; N'Dilimabaka, Nadine; Ondzaga, Julien; Lekana-Douki, Jean Bernard; Mba, Dieudonné Nkoghe; Deloron, Philippe; Mazier, Dominique; Gay, Frédrérick; Touré Ndouo, Fousseyni S

2017-06-27

Plasmodium falciparum infection can progress unpredictably to severe forms including respiratory distress and cerebral malaria. The mechanisms underlying the variable natural course of malaria remain elusive. The cerebral microvascular endothelial cells-D3 and lung endothelial cells both from human were cultured separately and challenged with P. falciparum field isolates taken directly from malaria patients or 3D7 strain (in vitro maintained culture). The capacity of these P. falciparum isolates to induce endothelial cell apoptosis via cytoadherence or not was then assessed. Overall, 27 P. falciparum isolates were collected from patients with uncomplicated malaria (n = 25) or severe malaria (n = 2). About half the isolates (n = 17) were able to bind brain endothelial cells (12 isolates, 44%) or lung endothelial cells (17 isolates, 63%) or both (12 isolates, 44%). Sixteen (59%) of the 27 isolates were apoptogenic for brain and/or lung endothelial cells. The apoptosis stimulus could be cytoadherence, direct cell-cell contact without cytoadherence, or diffusible soluble factors. While some of the apoptogenic isolates used two stimuli (direct contact with or without cytoadherence, plus soluble factors) to induce apoptosis, others used only one. Among the 16 apoptogenic isolates, eight specifically targeted brain endothelial cells, one lung endothelial cells, and seven both. These results indicate that the brain microvascular cell line was more susceptible to apoptosis triggered by P. falciparum than the primary pulmonary endothelial cells and may have relevance to host-parasite interaction.

The in vitro isolated whole guinea pig brain as a model to study epileptiform activity patterns.

PubMed

de Curtis, Marco; Librizzi, Laura; Uva, Laura

2016-02-15

Research on ictogenesis is based on the study of activity between seizures and during seizures in animal models of epilepsy (chronic condition) or in in vitro slices obtained from naïve non-epileptic brains after treatment with pro-convulsive drugs, manipulations of the extracellular medium and specific stimulation protocols. The in vitro isolated guinea pig brain retains the functional connectivity between brain structures and maintains interactions between neuronal, glial and vascular compartments. It is a close-to-in vivo preparation that offers experimental advantages not achieved with the use of other experimental models. Neurophysiological and imaging techniques can be utilized in this preparation to study brain activity during and between seizures induced by pharmacological or functional manipulations. Cellular and network determinants of interictal and ictal discharges that reproduce abnormal patterns observed in human focal epilepsies and the associated changes in extracellular ion and blood-brain permeability can be identified and analyzed in the isolated guinea pig brain. Ictal and interictal patterns recorded in in vitro slices may show substantial differences from seizure activity recorded in vivo due to slicing procedure itself. The isolated guinea pig brain maintained in vitro by arterial perfusion combines the typical facilitated access of in vitro preparations, that are difficult to approach during in vivo experiments, with the preservation of larger neuronal networks. The in vitro whole isolated guinea pig brain preparation offers an unique experimental model to study systemic and neurovascular changes during ictogenesis. Published by Elsevier B.V.

Early Social Isolation Stress and Perinatal NMDA Receptor Antagonist Treatment Induce Changes in the Structure and Neurochemistry of Inhibitory Neurons of the Adult Amygdala and Prefrontal Cortex.

PubMed

Castillo-Gómez, Esther; Pérez-Rando, Marta; Bellés, María; Gilabert-Juan, Javier; Llorens, José Vicente; Carceller, Héctor; Bueno-Fernández, Clara; García-Mompó, Clara; Ripoll-Martínez, Beatriz; Curto, Yasmina; Sebastiá-Ortega, Noelia; Moltó, María Dolores; Sanjuan, Julio; Nacher, Juan

2017-01-01

The exposure to aversive experiences during early life influences brain development and leads to altered behavior. Moreover, the combination of these experiences with subtle alterations in neurodevelopment may contribute to the emergence of psychiatric disorders, such as schizophrenia. Recent hypotheses suggest that imbalances between excitatory and inhibitory (E/I) neurotransmission, especially in the prefrontal cortex and the amygdala, may underlie their etiopathology. In order to understand better the neurobiological bases of these alterations, we studied the impact of altered neurodevelopment and chronic early-life stress on these two brain regions. Transgenic mice displaying fluorescent excitatory and inhibitory neurons, received a single injection of MK801 (NMDAR antagonist) or vehicle solution at postnatal day 7 and/or were socially isolated from the age of weaning until adulthood (3 months old). We found that anxiety-related behavior, brain volume, neuronal structure, and the expression of molecules related to plasticity and E/I neurotransmission in adult mice were importantly affected by early-life stress. Interestingly, many of these effects were potentiated when the stress paradigm was applied to mice perinatally injected with MK801 ("double-hit" model). These results clearly show the impact of early-life stress on the adult brain, especially on the structure and plasticity of inhibitory networks, and highlight the double-hit model as a valuable tool to study the contribution of early-life stress in the emergence of neurodevelopmental psychiatric disorders, such as schizophrenia.

Risk of traumatic brain injuries in children younger than 24 months with isolated scalp hematomas.

PubMed

Dayan, Peter S; Holmes, James F; Schutzman, Sara; Schunk, Jeffrey; Lichenstein, Richard; Foerster, Lillian A; Hoyle, John; Atabaki, Shireen; Miskin, Michelle; Wisner, David; Zuspan, SallyJo; Kuppermann, Nathan

2014-08-01

We aimed to determine the association between scalp hematoma characteristics and traumatic brain injuries in young children with blunt head trauma who have no other symptoms or signs suggestive of traumatic brain injuries (defined as "isolated scalp hematomas"). This was a secondary analysis of children younger than 24 months with minor blunt head trauma from a prospective cohort study in 25 Pediatric Emergency Care Applied Research Network emergency departments. Treating clinicians completed a structured data form. For children with isolated scalp hematomas, we determined the prevalence of and association between scalp hematoma characteristics and (1) clinically important traumatic brain injury (death, neurosurgery for traumatic brain injury, intubation >24 hours for traumatic brain injury, or positive computed tomography (CT) scan in association with hospitalization ≥2 nights for traumatic brain injury); and (2) traumatic brain injury on CT. Of 10,659 patients younger than 24 months were enrolled, 2,998 of 10,463 (28.7%) with complete data had isolated scalp hematomas. Clinically important traumatic brain injuries occurred in 12 patients (0.4%; 95% confidence interval [CI] 0.2% to 0.7%); none underwent neurosurgery (95% CI 0% to 0.1%). Of 570 patients (19.0%) for whom CTs were obtained, 50 (8.8%; 95% CI 6.6% to 11.4%) had traumatic brain injuries on CT. Younger age, non-frontal scalp hematoma location, increased scalp hematoma size, and severe injury mechanism were independently associated with traumatic brain injury on CT. In patients younger than 24 months with isolated scalp hematomas, a minority received CTs. Despite the occasional presence of traumatic brain injuries on CT, the prevalence of clinically important traumatic brain injuries was very low, with no patient requiring neurosurgery. Clinicians should use patient age, scalp hematoma location and size, and injury mechanism to help determine which otherwise asymptomatic children should undergo neuroimaging after minor head trauma. Copyright © 2014 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

The burden of traumatic brain injury among adolescent and young adult workers in Washington State.

PubMed

Graves, Janessa M; Sears, Jeanne M; Vavilala, Monica S; Rivara, Frederick P

2013-06-01

This study describes injury characteristics and costs of work-related traumatic brain injury (WRTBI) among 16-24 year olds in Washington State between 1998 and 2008. WRTBIs were identified in the Washington Trauma Registry (WTR) and linked to workers' compensation (WC) claims data. Medical and time-loss compensation costs were compared between workers with isolated TBI and TBI with other trauma. Of 273 WRTBI cases identified, most (61.5%) were TBI with other trauma. One-third of WRTBI did not link to a WC claim. Medical costs averaged $88,307 (median $16,426) for isolated TBI cases, compared to $73,669 (median $41,167) for TBI with other trauma. Results highlight the financial impact of WRTBI among young workers. Multiple data sources provided a more comprehensive picture than a single data source alone. This linked-data approach holds great potential for future traumatic occupational injury research. TBI among young workers not only involves long-term health and psychological impacts, but is costly as well. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

How many music centers are in the brain?

PubMed

Altenmüller, E O

2001-06-01

When reviewing the literature on brain substrates of music processing, a puzzling variety of findings can be stated. The traditional view of a left-right dichotomy of brain organization--assuming that in contrast to language, music is primarily processed in the right hemisphere--was challenged 20 years ago, when the influence of music education on brain lateralization was demonstrated. Modern concepts emphasize the modular organization of music cognition. According to this viewpoint, different aspects of music are processed in different, although partly overlapping neuronal networks of both hemispheres. However, even when isolating a single "module," such as, for example, the perception of contours, the interindividual variance of brain substrates is enormous. To clarify the factors contributing to this variability, we conducted a longitudinal experiment comparing the effects of procedural versus explicit music teaching on brain networks. We demonstrated that cortical activation during music processing reflects the auditory "learning biography," the personal experiences accumulated over time. Listening to music, learning to play an instrument, formal instruction, and professional training result in multiple, in many instances multisensory, representations of music, which seem to be partly interchangeable and rapidly adaptive. In summary, as soon as we consider "real music" apart from laboratory experiments, we have to expect individually formed and quickly adaptive brain substrates, including widely distributed neuronal networks in both hemispheres.

Molecular characterization of Indian rabies virus isolates by partial sequencing of nucleoprotein (N) and phosphoprotein (P) genes.

PubMed

Reddy, G B Manjunatha; Singh, R; Singh, R P; Singh, K P; Gupta, P K; Mahadevan, Anita; Desai, Anita; Shankar, S K; Ramakrishnan, M A; Verma, Rishendra

2011-08-01

Rabies is endemic and an important zoonosis in India. There are very few reports available on molecular epidemiology of rabies virus of Indian origin. In this study to know the dynamics of rabies virus, a total of 41 rabies positive brain samples from dogs, cats, domestic animals, wildlife, and humans from 11 states were subjected to RT-PCR amplification of N gene between nucleotide N521-N1262 (742 bp) and P gene between nucleotide P239-P750 (512 bp). The N gene could be amplified from 30, while P gene from 41 samples, using specific sets of primers. The N gene-based phylogenetic analysis indicated that all Indian virus isolates are genetically closely related with a single cluster under arctic/arctic-like viruses. However, two distinct clusters were realized in P gene-based phylogeny viz., Rabies virus isolates of Punjab and Rabies virus isolates of remaining parts of India (other than Punjab). All the Indian rabies virus isolates were closely related to geography (>95% homology), but not to host species.

The Exosome Secretory Pathway Transports Amyloid Precursor Protein Carboxyl-terminal Fragments from the Cell into the Brain Extracellular Space*

PubMed Central

Perez-Gonzalez, Rocio; Gauthier, Sebastien A.; Kumar, Asok; Levy, Efrat

2012-01-01

In vitro studies have shown that neuronal cell cultures secrete exosomes containing amyloid-β precursor protein (APP) and the APP-processing products, C-terminal fragments (CTFs) and amyloid-β (Aβ). We investigated the secretion of full-length APP (flAPP) and APP CTFs via the exosome secretory pathway in vivo. To this end, we developed a novel protocol designed to isolate exosomes secreted into mouse brain extracellular space. Exosomes with typical morphology were isolated from freshly removed mouse brains and from frozen mouse and human brain tissues, demonstrating that exosomes can be isolated from post-mortem tissue frozen for long periods of time. flAPP, APP CTFs, and enzymes that cleave both flAPP and APP CTFs were identified in brain exosomes. Although higher levels of both flAPP and APP CTFs were observed in exosomes isolated from the brains of transgenic mice overexpressing human APP (Tg2576) compared with wild-type control mice, there was no difference in the number of secreted brain exosomes. These data indicate that the levels of flAPP and APP CTFs associated with exosomes mirror the cellular levels of flAPP and APP CTFs. Interestingly, exosomes isolated from the brains of both Tg2576 and wild-type mice are enriched with APP CTFs relative to flAPP. Thus, we hypothesize that the exosome secretory pathway plays a pleiotropic role in the brain: exosome secretion is beneficial to the cell, acting as a specific releasing system of neurotoxic APP CTFs and Aβ, but the secretion of exosomes enriched with APP CTFs, neurotoxic proteins that are also a source of secreted Aβ, is harmful to the brain. PMID:23129776

Brain abscess in the computed tomography era: A 10-year experience from Auckland, New Zealand

PubMed Central

Holland, DJ; Cooper, B; Garner, J; Ellis-Pegler, R; Mee, E

1993-01-01

Notes were reviewed for 68 patients with brain abscess diagnosed at Auckland Hospital, Auckland, New Zealand between 1978 and 1988. Mean age was 30 years (range one week to 74 years). There were 48 men and 40% were Maori or Pacific Island Polynesians. Seventy-two per cent of patients had headache, 54% had fever and 72% had lateralizing neurological signs. Thirty-one per cent of abscesses were associated with contiguous infection (otic, sinus, dental). Forty-four per cent were in the frontal lobe. Two abscesses were sterile; 197 bacterial isolates were cultured from the remainder. Fifty-four per cent contained obligate anaerobes, which were the only isolates in 22%. Streptococcus anginosus was the single most common isolate present in 22% of the abscesses. Amoxycillin plus metronidazole provided cover for approximately 95% of the total isolates on the basis of sensitivity testing. Treatment was with surgery and antibiotics in all but three patients, who were cured with antibiotics alone. Sixty per cent had a definitive regimen of penicillin (or ampicillin/amoxycillin) and/or metronidazole, always intravenous initially but subsequently often orally. Median duration of antibiotic treatment was 57 days (range 28 to 206). Seventy-five per cent had initial aspiration, 9% open drainage and 7% were excised initially. Seventy-one per cent had a good functional outcome. Mortality was 8.8%. Factors associated with a poor outcome were trauma as a cause, and delays after admission of more than seven days to diagnosis and/or operation. PMID:22346451

ALTERATIONS IN BRAIN CREATINE CONCENTRATIONS UNDER LONG-TERM SOCIAL ISOLATION (EXPERIMENTAL STUDY).

PubMed

Koshoridze, N; Kuchukashvili, Z; Menabde, K; Lekiashvili, Sh; Koshoridze, M

2016-02-01

Stress represents one of the main problems of modern humanity. This study was done for understanding more clearly alterations in creatine content of the brain under psycho-emotional stress induced by long-term social isolation. It was shown that under 30 days social isolation creatine amount in the brain was arisen, while decreasing concentrations of synthesizing enzymes (AGAT, GAMT) and creatine transporter protein (CrT). Another important point was that such changes were accompanied by down-regulation of creatine kinase (CK), therefore the enzyme's concentration was lowered. In addition, it was observed that content of phosphocreatine (PCr) and ATP were also reduced, thus indicating down-regulation of energy metabolism of brain that is really a crucial point for its normal functioning. To sum up the results it can be underlined that long-term social isolation has negative influence on energy metabolism of brain; and as a result reduce ATP content, while increase of free creatine concentration, supposedly maintaining maximal balance for ATP amount, but here must be also noted that up-regulated oxidative pathways might have impact on blood brain barrier, resulting on its permeability.

Isolation of Neospora caninum from kidney and brain of a bovine foetus and molecular characterization in Brazil.

PubMed

Locatelli Dittrich, Rosangela; Regidor-Cerrillo, Javier; Ortega-Mora, Luis Miguel; Oliveira Koch, Marília de; Busch, Ana Paula B; Gonçalves, Kamila Alcalá; Cruz, Amilcar A

2018-02-01

Bovine neosporosis has become a disease of international concern as it is among the main causes of abortion in cattle. Viable N. caninum has been isolated from brains of fetuses and neonatal calves, and there is no report of isolation of tachyzoites from kidney. Also, detailed information about the genetic diversity of N. caninum is scarce. N. caninum tachyzoites were isolated from the kidney and the brain of an aborted 4-month-old bovine foetus. The parasite was confirmed to be N. caninum by PCR. The tachyzoites of the new isolate, named BNC-PR4, were propagated in Vero cell cultures. Pathogenicity of the parasite was examined in BALB/c mice. Mice inoculated intraperitoneally with BNC-PR4 failed to yield clinical signs of disease and did not induce severe brain lesions, suggesting a bovine isolate with low virulence. The N. caninum-positive DNA sample was further analyzed by multilocus microsatellite (MS) genotyping for MS4, MS5, MS6A, MS6B, MS7, MS8, MS10, MS12, and MS21. Multilocus-microsatellite genotyping revealed a unique genetic profile that differed from previously reported isolates. Published by Elsevier Inc.

Molecular testing of Klebsiella pneumoniae contaminating tissue allografts recovered from deceased donors.

PubMed

Ghalavand, Zohreh; Heidary Rouchi, Alireza; Bahraminasab, Hassan; Ravanasa, Elham; Mirsamadi, Elnaz Sadat; Nodeh Farahani, Narges; Nikmanesh, Bahram

2018-02-03

Microbiological screening of tissue allografts is crucial to prevent the transmission of bacterial and fungal infections to transplant recipients. Klebsiella was the most prevalent and resistant contaminating microorganism observed in our setting in the Iranian Tissue Bank. This study was conducted to determine the presence of extended-spectrum β-lactamase (ESBL) genes, antimicrobial resistance patterns of Klebsiella pneumoniae isolates, and their clonal relationships in allograft materials. K. pneumoniae contaminating bone and other tissue allografts recovered from deceased donors were identified and ESBL isolates were detected using a phenotypic confirmatory method. Antimicrobial susceptibility testing was carried out using the disk diffusion method. Distribution of ESBL genes and molecular typing were performed using polymerase chain reaction (PCR) and Repetitive-element (rep-PCR) methods. Of 3828 donated tissues, 51 (1.3%) were found contaminated by K. pneumoniae isolates. Compared to tissue allografts from brain-dead, heart-beating tissue donors, allografts from donors with circulatory cessation were associated with a higher risk of K. pneumoniae contamination [odds ratio (OR), 1.2 (CI 95% 0.9-2.3) (P value < 0.001)]. Half of the isolates produced ESBL, and the rate of susceptibility to cephalosporins was 51%. Among isolates, 22 (43.1%) harbored CTX-M, 31 (60.8%) SHV, and 9 (17.6%) harbored TEM types. The rep-dendrogram indicated that clones having identical or related strains with a similar antibiotype were isolated in the same period. This study provides evidence that a single clone of K. pneumoniae contaminated tissue allografts recovered from many different donors. A single clone found on tissues from several donors suggests contamination of tissues from a single source such as the tissue recovery process and environment. Genomic DNA testing and clonality of contaminating bacteria using molecular methods can focus the epidemiologic investigation on the tissue allograft recovery process including a search for contamination of the tissue recovery room environment, recovery staff, recovery equipment, reagents, solutions and supplies.

Trauma deaths in the first hour: are they all unsalvageable injuries?

PubMed

MacLeod, Jana B A; Cohn, Stephen M; Johnson, E William; McKenney, Mark G

2007-02-01

With the advent of trauma systems, time to definitive care has been decreased. We hypothesized that a subset of patients who are in extremis from the time of prehospital transport to arrival at the trauma center, and who ultimately die early after arrival, may in fact have a potentially salvageable single-organ injury. We reviewed all deaths that occurred in the first hour after hospital admission. Trauma registry, medical records, and autopsy reports for 556 patients were evaluated. The median time to arrival was 39 minutes, and the median Injury Severity Score was 29. Blunt injuries (53%) were most commonly auto-accident injuries (134 of 285 patients; 47%). Penetrating wounds (42%) were mostly gunshot wounds to the chest (73 of 233 patients; 31%). For patients with initial vital signs, the most common cause of death was isolated brain injury (26 patients; 28%). Possibly survivable injuries (single organ or vessel) occurred in 35 (38%) patients, of which 4 were isolated spleen injuries (4%). Some patients with potentially survivable single organ injuries did not have associated head injuries. An aggressive approach is warranted on patients with detectable vital signs on at least one occasion in the field but who arrive at the trauma center in extremis.

Molecular cloning and expression of rat brain endopeptidase 3.4.24.16.

PubMed

Dauch, P; Vincent, J P; Checler, F

1995-11-10

We have isolated by immunological screening of a lambda ZAPII cDNA library constructed from rat brain mRNAs a cDNA clone encoding endopeptidase 3.4.24.16. The longest open reading frame encodes a 704-amino acid protein with a theoretical molecular mass of 80,202 daltons and bears the consensus sequence of the zinc metalloprotease family. The sequence exhibits a 60.2% homology with those of another zinc metallopeptidase, endopeptidase 3.4.24.15. Northern blot analysis reveals two mRNA species of about 3 and 5 kilobases in rat brain, ileum, kidney, and testis. We have transiently transfected COS-7 cells with pcDNA3 containing the cloned cDNA and established the overexpression of a 70-75-kDa immunoreactive protein. This protein hydrolyzes QFS, a quenched fluorimetric substrate of endopeptidase 3.4.24.16, and cleaves neurotensin at a single peptide bond, leading to the formation of neurotensin (1-10) and neurotensin (11-13). QFS and neurotensin hydrolysis are potently inhibited by the selective endopeptidase 3.4.24.16 dipeptide blocker Pro-Ile and by dithiothreitol, while the enzymatic activity remains unaffected by phosphoramidon and captopril, the specific inhibitors of endopeptidase 3.4.24.11 and angiotensin-converting enzyme, respectively. Altogether, these physicochemical, biochemical, and immunological properties unambiguously identify endopeptidase 3.4.24.16 as the protein encoded by the isolated cDNA clone.

Nature's Anti-Alzheimer's Drug: Isolation and Structure Elucidation of Galantamine from "Leucojum Aestivum"

ERIC Educational Resources Information Center

Halpin, Catherine M.; Reilly, Ciara; Walsh, John J.

2010-01-01

The discovery that galantamine penetrates the blood-brain barrier has led to its clinical use in the treatment of choline-deficiency conditions in the brain, such as Alzheimer's disease. This experiment involves the isolation and structure elucidation of galantamine from "Leucojum aestivum". Isolation of the alkaloid constituents in "L. aestivum"…

Caspr2-reactive antibody cloned from a mother of an ASD child mediates an ASD-like phenotype in mice.

PubMed

Brimberg, L; Mader, S; Jeganathan, V; Berlin, R; Coleman, T R; Gregersen, P K; Huerta, P T; Volpe, B T; Diamond, B

2016-12-01

Autism spectrum disorder (ASD) occurs in 1 in 68 births, preferentially affecting males. It encompasses a group of neurodevelopmental abnormalities characterized by impaired social interaction and communication, stereotypic behaviors and motor dysfunction. Although recent advances implicate maternal brain-reactive antibodies in a causative role in ASD, a definitive assessment of their pathogenic potential requires cloning of such antibodies. Here, we describe the isolation and characterization of monoclonal brain-reactive antibodies from blood of women with brain-reactive serology and a child with ASD. We further demonstrate that male but not female mice exposed in utero to the C6 monoclonal antibody, binding to contactin-associated protein-like 2 (Caspr2), display abnormal cortical development, decreased dendritic complexity of excitatory neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as impairments in sociability, flexible learning and repetitive behavior. Anti-Caspr2 antibodies are frequent in women with brain-reactive serology and a child with ASD. Together these studies provide a methodology for obtaining monclonal brain-reactive antibodies from blood B cells, demonstrate that ASD can result from in utero exposure to maternal brain-reactive antibodies of single specificity and point toward the exciting possibility of prognostic and protective strategies.

Cronobacter sakazakii clinical isolates overcome host barriers and evade the immune response.

PubMed

Almajed, Faisal S; Forsythe, Stephen J

2016-01-01

Cronobacter sakazakii is the most frequently clinically isolated species of the Cronobacter genus. However the virulence factors of C. sakazakii including their ability to overcome host barriers remains poorly studied. In this study, ten clinical isolates of C. sakazakii were assessed for their ability to invade and translocate through human colonic carcinoma epithelial cells (Caco-2) and human brain microvascular endothelial cells (HBMEC). Their ability to avoid phagocytosis in human macrophages U937 and human brain microglial cells was investigated. Additionally, they were tested for serum sensitivity and the presence of the Cronobacter plasminogen activation gene (cpa) gene, which is reported to confer serum resistance. Our data showed that the clinical C. sakazakii strains invaded and translocated through Caco-2 and HBMEC cell lines and some strains showed significantly higher levels of invasion and translocation. Moreover, C. sakazakii was able to persist and even multiply in phagocytic macrophage and microglial cells. All strains, except one, were able to withstand human serum exposure, the single serum sensitive strain was also the only one which did not encode for the cpa gene. These results demonstrate that C. sakazakii clinical isolates are able to overcome host barriers and evade the host immune response indicating their capacity to cause diseases such as necrotizing enterocolitis (NEC) and meningitis. Our data showed for the first time the ability of C. sakazakii clinical isolates to survive and multiply within human microglial cells. Additionally, it was shown that C. sakazakii clinical strains have the capacity to translocate through the Caco-2 and HBMEC cell lines paracellularly. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early Social Isolation Stress and Perinatal NMDA Receptor Antagonist Treatment Induce Changes in the Structure and Neurochemistry of Inhibitory Neurons of the Adult Amygdala and Prefrontal Cortex

PubMed Central

Bellés, María; Gilabert-Juan, Javier; Llorens, José Vicente; Bueno-Fernández, Clara; Ripoll-Martínez, Beatriz; Curto, Yasmina; Sebastiá-Ortega, Noelia; Sanjuan, Julio

2017-01-01

Abstract The exposure to aversive experiences during early life influences brain development and leads to altered behavior. Moreover, the combination of these experiences with subtle alterations in neurodevelopment may contribute to the emergence of psychiatric disorders, such as schizophrenia. Recent hypotheses suggest that imbalances between excitatory and inhibitory (E/I) neurotransmission, especially in the prefrontal cortex and the amygdala, may underlie their etiopathology. In order to understand better the neurobiological bases of these alterations, we studied the impact of altered neurodevelopment and chronic early-life stress on these two brain regions. Transgenic mice displaying fluorescent excitatory and inhibitory neurons, received a single injection of MK801 (NMDAR antagonist) or vehicle solution at postnatal day 7 and/or were socially isolated from the age of weaning until adulthood (3 months old). We found that anxiety-related behavior, brain volume, neuronal structure, and the expression of molecules related to plasticity and E/I neurotransmission in adult mice were importantly affected by early-life stress. Interestingly, many of these effects were potentiated when the stress paradigm was applied to mice perinatally injected with MK801 ("double-hit" model). These results clearly show the impact of early-life stress on the adult brain, especially on the structure and plasticity of inhibitory networks, and highlight the double-hit model as a valuable tool to study the contribution of early-life stress in the emergence of neurodevelopmental psychiatric disorders, such as schizophrenia. PMID:28466069

Brain metastases as site of first and isolated recurrence of breast cancer: the role of systemic therapy after local treatment.

PubMed

Niwińska, Anna

2016-10-01

The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p < 0.001). In patients with a Karnofsky Performance Status ≥70 and those <70, survival was respectively 16 and 5.5 months (p < 0.001). The median survival from brain metastasis in patients with solitary brain metastasis, with and without systemic treatment after local therapy, was respectively 22 and 7 months (p = 0.003). Cox multivariate analysis demonstrated that good performance status, solitary brain metastasis and systemic therapy undertaken after local treatment were factors which prolonged survival. However patient survival was adversely affected by those having leptomeningeal metastasis associated with brain parenchymal lesions. Systemic therapy, undertaken after local treatment improved survival in those patients with breast cancer and brain metastases as the site of first and isolated recurrence. Further study is required in order to fully establish the role of systemic treatment for this patient group.

P-gp Protein Expression and Transport Activity in Rodent Seizure Models and Human Epilepsy.

PubMed

Hartz, Anika M S; Pekcec, Anton; Soldner, Emma L B; Zhong, Yu; Schlichtiger, Juli; Bauer, Bjoern

2017-04-03

A cure for epilepsy is currently not available, and seizure genesis, seizure recurrence, and resistance to antiseizure drugs remain serious clinical problems. Studies show that the blood-brain barrier is altered in animal models of epilepsy and in epileptic patients. In this regard, seizures increase expression of blood-brain barrier efflux transporters such as P-glycoprotein (P-gp), which is thought to reduce brain uptake of antiseizure drugs, and thus, contribute to antiseizure drug resistance. The goal of the current study was to assess the viability of combining in vivo and ex vivo preparations of isolated brain capillaries from animal models of seizures and epilepsy as well as from patients with epilepsy to study P-gp at the blood-brain barrier. Exposing isolated rat brain capillaries to glutamate ex vivo upregulated P-gp expression to levels that were similar to those in capillaries isolated from rats that had status epilepticus or chronic epilepsy. Moreover, the fold-increase in P-gp protein expression seen in animal models is consistent with the fold-increase in P-gp observed in human brain capillaries isolated from patients with epilepsy compared to age-matched control individuals. Overall, the in vivo/ex vivo approach presented here allows detailed analysis of the mechanisms underlying seizure-induced changes of P-gp expression and transport activity at the blood-brain barrier. This approach can be extended to other blood-brain barrier proteins that might contribute to drug-resistant epilepsy or other CNS disorders as well.

Coagulopathy and transfusion requirements in war related penetrating traumatic brain injury. A single centre study in a French role 3 medical treatment facility in Afghanistan.

PubMed

Bordes, J; Joubert, C; Esnault, P; Montcriol, A; Nguyen, C; Meaudre, E; Dulou, R; Dagain, A

2017-05-01

Traumatic brain injury associated coagulopathy is frequent, either in isolated traumatic brain injury in civilian practice and in combat traumatic brain injury. In war zone, it is a matter of concern because head and neck are the second most frequent site of wartime casualty burden. Data focusing on transfusion requirements in patients with war related TBI coagulopathy are limited. A descriptive analysis was conducted of 77 penetrating traumatic brain injuries referred to a French role 3 medical treatment facility in Kabul, Afghanistan, deployed on the Kabul International Airport (KaIA), over a 30 months period. On 77 patients, 23 died during the prehospital phase and were not included in the study. Severe traumatic brain injury represented 50% of patients. Explosions were the most common injury mechanism. Extracranial injuries were present in 72% of patients. Traumatic brain injury coagulopathy was diagnosed in 67% of patients at role 3 admission. Red blood cell units (RBCu) were transfused in 39 (72%) patients, French lyophilized plasma (FLYP) in 41 (76%), and fresh whole blood (FWB) in 17 (31%). The results of this study support previous observations of coagulopathy as a frequent complication of traumatic brain injury. The majority of patients with war related penetrating traumatic brain injury presented with extracranial lesions. Most of them required a high level of transfusion capacity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain.

PubMed

Schnydrig, Sabine; Korner, Lukas; Landweer, Svenja; Ernst, Beat; Walker, Gaby; Otten, Uwe; Kunz, Dieter

2007-12-11

Peripheral inflammation induced by intraperitoneal (i.p.) injection of Lipopolysaccharide (LPS) is known to cause functional impairments in the brain affecting memory and learning. One of mechanisms may be the interference with neurotrophin (NT) expression and function. In the current study we administered a single, high dose of LPS (3mg/kg, i.p.) into mice and investigated changes in brain-derived neurotrophic factor (BDNF) gene expression within 1-6 days after LPS injection. Crude synaptosomes were isolated from brain tissue and subjected to Western-blot analyses. We found transient reductions in synaptosomal proBDNF- and BDNF protein expression, with a maximal decrease at day 3 as compared to saline injected controls. The time course of reduction of BDNF mRNA in whole brain extracts parallels the decrease in protein levels in synaptosomes. LPS effects in the central nervous system (CNS) are known to crucially involve the activation of the hypothalamic-pituitary-adrenal (HPA) axis. We analysed the time course of corticotropin releasing hormone (CRH)- and proopiomelanocortin (POMC) mRNA expression. As observed for BDNF-, CRH- and POMC mRNA levels are also significantly reduced on day 3 indicating a comparable time course. These results suggest that peripheral inflammation causes a reduction of trophic supply in the brain, including BDNF at synaptic sites. The mechanisms involved could be a negative feedback of the activated HPA axis.

Utility of brain MRI in children with sleep-disordered breathing.

PubMed

Selvadurai, Sarah; Al-Saleh, Suhail; Amin, Reshma; Zweerink, Allison; Drake, James; Propst, Evan J; Narang, Indra

2017-02-01

To investigate the utility of a brain magnetic resonance imaging (MRI) in children with sleep-disordered breathing (SDB), classified as isolated obstructive sleep apnea (OSA) in the absence of adenotonsillar hypertrophy, persistent OSA following adenotonsillectomy, isolated central sleep apnea (CSA) of unclear etiology, OSA with coexisting CSA of unclear etiology, or unexplained nocturnal hypoventilation (NH). Retrospective chart review of polysomnography (PSG) and brain MRI data. Children with PSG evidence of SDB, as described above, and who subsequently had their first brain MRI, were included. PSG, MRI data, and subsequent interventions were recorded. A total of 59 of 6,087 (1%) children met inclusion criteria. Of those, 28 of 59 (47%) were nonsyndromic children and 31 of 59 (53%) were syndromic children with an underlying medical disorder. Abnormal brain MRI findings were observed in 19 of 59 (32%) children, where eight of 19 (42%) were nonsyndromic and 11 of 19 (58%) were syndromic. Abnormal brain MRI findings were most common in syndromic children with combined OSA and CSA without adenotonsillar hypertrophy. Isolated OSA was also a common PSG finding associated with an abnormal brain MRI. Of the nonsyndromic children with an abnormal brain MRI, the most common abnormal brain MRI finding was Chiari malformation (CM), observed in 88% of the group. A brainstem tumor was identified in one nonsyndromic child. Interventions following brain MRI included neurosurgery, chemotherapy, and noninvasive positive pressure ventilation (NiPPV). A brain MRI is an important diagnostic tool in syndromic and nonsyndromic children, especially in children with either isolated OSA or combined OSA and CSA without a clear etiology. 4. Laryngoscope, 2016 127:513-519, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress.

PubMed

Zelikowsky, Moriel; Hui, May; Karigo, Tomomi; Choe, Andrea; Yang, Bin; Blanco, Mario R; Beadle, Keith; Gradinaru, Viviana; Deverman, Benjamin E; Anderson, David J

2018-05-17

Chronic social isolation causes severe psychological effects in humans, but their neural bases remain poorly understood. 2 weeks (but not 24 hr) of social isolation stress (SIS) caused multiple behavioral changes in mice and induced brain-wide upregulation of the neuropeptide tachykinin 2 (Tac2)/neurokinin B (NkB). Systemic administration of an Nk3R antagonist prevented virtually all of the behavioral effects of chronic SIS. Conversely, enhancing NkB expression and release phenocopied SIS in group-housed mice, promoting aggression and converting stimulus-locked defensive behaviors to persistent responses. Multiplexed analysis of Tac2/NkB function in multiple brain areas revealed dissociable, region-specific requirements for both the peptide and its receptor in different SIS-induced behavioral changes. Thus, Tac2 coordinates a pleiotropic brain state caused by SIS via a distributed mode of action. These data reveal the profound effects of prolonged social isolation on brain chemistry and function and suggest potential new therapeutic applications for Nk3R antagonists. Copyright © 2018 Elsevier Inc. All rights reserved.

Recapitulating in vivo-like plasticity of glioma cell invasion along blood vessels and in astrocyte-rich stroma.

PubMed

Gritsenko, Pavlo; Leenders, William; Friedl, Peter

2017-10-01

Diffuse invasion of glioma cells into the brain parenchyma leads to nonresectable brain tumors and poor prognosis of glioma disease. In vivo, glioma cells can adopt a range of invasion strategies and routes, by moving as single cells, collective strands and multicellular networks along perivascular, perineuronal and interstitial guidance cues. Current in vitro assays to probe glioma cell invasion, however, are limited in recapitulating the modes and adaptability of glioma invasion observed in brain parenchyma, including collective behaviours. To mimic in vivo-like glioma cell invasion in vitro, we here applied three tissue-inspired 3D environments combining multicellular glioma spheroids and reconstituted microanatomic features of vascular and interstitial brain structures. Radial migration from multicellular glioma spheroids of human cell lines and patient-derived xenograft cells was monitored using (1) reconstituted basement membrane/hyaluronan interfaces representing the space along brain vessels; (2) 3D scaffolds generated by multi-layered mouse astrocytes to reflect brain interstitium; and (3) freshly isolated mouse brain slice culture ex vivo. The invasion patterns in vitro were validated using histological analysis of brain sections from glioblastoma patients and glioma xenografts infiltrating the mouse brain. Each 3D assay recapitulated distinct aspects of major glioma invasion patterns identified in mouse xenografts and patient brain samples, including individually migrating cells, collective strands extending along blood vessels, and multicellular networks of interconnected glioma cells infiltrating the neuropil. In conjunction, these organotypic assays enable a range of invasion modes used by glioma cells and will be applicable for mechanistic analysis and targeting of glioma cell dissemination.

Expression of Iron-Related Proteins at the Neurovascular Unit Supports Reduction and Reoxidation of Iron for Transport Through the Blood-Brain Barrier.

PubMed

Burkhart, Annette; Skjørringe, Tina; Johnsen, Kasper Bendix; Siupka, Piotr; Thomsen, Louiza Bohn; Nielsen, Morten Schallburg; Thomsen, Lars Lykke; Moos, Torben

2016-12-01

The mechanisms for iron transport through the blood-brain barrier (BBB) remain a controversy. We analyzed for expression of mRNA and proteins involved in oxidation and transport of iron in isolated brain capillaries from dietary normal, iron-deficient, and iron-reverted rats. The expression was also investigated in isolated rat brain endothelial cells (RBECs) and in immortalized rat brain endothelial (RBE4) cells grown as monoculture or in hanging culture inserts with defined BBB properties. Transferrin receptor 1, ferrireductases Steap 2 and 3, divalent metal transporter 1 (DMT1), ferroportin, soluble and glycosylphosphatidylinositol (GPI)-anchored ceruloplasmin, and hephaestin were all expressed in brain capillaries in vivo and in isolated RBECs and RBE4 cells. Gene expression of DMT1, ferroportin, and soluble and GPI-anchored ceruloplasmin were significantly higher in isolated RBECs with induced BBB properties. Primary pericytes and astrocytes both expressed ceruloplasmin and hephaestin, and RBECs, pericytes, and astrocytes all exhibited ferrous oxidase activity. The coherent protein expression of these genes was demonstrated by immunocytochemistry. The data show that brain endothelial cells provide the machinery for receptor-mediated uptake of ferric iron-containing transferrin. Ferric iron can then undergo reduction to ferrous iron by ferrireductases inside endosomes followed by DMT1-mediated pumping into the cytosol and subsequently cellular export by ferroportin. The expression of soluble ceruloplasmin by brain endothelial cells, pericytes, and astrocytes that together form the neurovascular unit (NVU) provides the ferroxidase activity necessary to reoxidize ferrous iron once released inside the brain.

Transformation of Primary Hamster Brain Cells with JC Virus and Its DNA

PubMed Central

Frisque, R. J.; Rifkin, D. B.; Walker, D. L.

1980-01-01

We transformed primary hamster brain cells with four isolates of JC virus and JC virus DNA. Several properties of these transformants were characterized and compared to those of simian virus 40 transformants isolated under identical conditions. Images PMID:6251275

Kinetic modeling of PET-FDG in the brain without blood sampling.

PubMed

Bentourkia, M'hamed

2006-12-01

The aim in this work is to report a new method to calculate parametric images from a single scan acquisition with positron emission tomography (PET) and fluorodeoxyglucose (FDG) in the human brain without blood sampling. It is usually practical for research or clinical purposes to inject the patient in an isolated room and to start the PET acquisition only for some 10-20 min, about 30 min after FDG injection. In order to calculate the cerebral metabolic rates for glucose (CMRG), usually several blood samples are required. The proposed method considers the relation between the uptake of the tracer in the cerebellum as a reference tissue and the population based input curve. Similar results were obtained for CMRG values with the present method in comparison to the usual autoradiographic and the non-linear least squares fitting of regions of interest.

Whole-brain ex-vivo quantitative MRI of the cuprizone mouse model

PubMed Central

Hurley, Samuel A.; Vernon, Anthony C.; Torres, Joel; Dell’Acqua, Flavio; Williams, Steve C.R.; Cash, Diana

2016-01-01

Myelin is a critical component of the nervous system and a major contributor to contrast in Magnetic Resonance (MR) images. However, the precise contribution of myelination to multiple MR modalities is still under debate. The cuprizone mouse is a well-established model of demyelination that has been used in several MR studies, but these have often imaged only a single slice and analysed a small region of interest in the corpus callosum. We imaged and analyzed the whole brain of the cuprizone mouse ex-vivo using high-resolution quantitative MR methods (multi-component relaxometry, Diffusion Tensor Imaging (DTI) and morphometry) and found changes in multiple regions, including the corpus callosum, cerebellum, thalamus and hippocampus. The presence of inflammation, confirmed with histology, presents difficulties in isolating the sensitivity and specificity of these MR methods to demyelination using this model. PMID:27833805

Toward a Neurology of Loneliness

PubMed Central

Cacioppo, Stephanie; Capitanio, John P.; Cacioppo, John T.

2016-01-01

Social isolation has been recognized as a major risk factor for morbidity and mortality in humans for more than a quarter century. The brain is the key organ of social connections and processes, however, and the same objective social relationship can be experienced as caring and protective or as exploitive and isolating. We review evidence that the perception of social isolation (i.e., loneliness) impacts brain and behavior and is a risk factor for broad-based morbidity and mortality. However, the causal role of loneliness on neural mechanisms and mortality is difficult to test conclusively in humans. Mechanistic animal studies provide a lens through which to evaluate the neurological effects of a member of a social species living chronically on the social perimeter. Experimental studies show that social isolation produces significant changes in brain structures and processes in adult social animals. These effects are not uniform across the brain or across species but instead are most evident in brain regions that reflect differences in the functional demands of solitary versus social living for a particular species. The human and animal literatures have developed independently, however, and significant gaps also exist. The current review underscores the importance of integrating human and animal research to delineate the mechanisms through which social relationships impact the brain, health, and well-being. PMID:25222636

Aging alters mRNA expression of amyloid transporter genes at the blood-brain barrier.

PubMed

Osgood, Doreen; Miller, Miles C; Messier, Arthur A; Gonzalez, Liliana; Silverberg, Gerald D

2017-09-01

Decreased clearance of potentially toxic metabolites, due to aging changes, likely plays a significant role in the accumulation of amyloid-beta (Aβ) peptides and other macromolecules in the brain of the elderly and in the patients with Alzheimer's disease (AD). Aging is the single most important risk factor for AD development. Aβ transport receptor proteins expressed at the blood-brain barrier are significantly altered with age: the efflux transporters lipoprotein receptor-related protein 1 and P-glycoprotein are reduced, whereas the influx transporter receptor for advanced glycation end products is increased. These receptors play an important role in maintaining brain biochemical homeostasis. We now report that, in a rat model of aging, gene transcription is altered in aging, as measured by Aβ receptor gene messenger RNA (mRNA) at 3, 6, 9, 12, 15, 20, 30, and 36 months. Gene mRNA expression from isolated cerebral microvessels was measured by quantitative polymerase chain reaction. Lipoprotein receptor-related protein 1 and P-glycoprotein mRNA were significantly reduced in aging, and receptor for advanced glycation end products was increased, in parallel with the changes seen in receptor protein expression. Transcriptional changes appear to play a role in aging alterations in blood-brain barrier receptor expression and Aβ accumulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuronal nuclei isolation from human postmortem brain tissue.

PubMed

Matevossian, Anouch; Akbarian, Schahram

2008-10-01

Neurons in the human brain become postmitotic largely during prenatal development, and thus maintain their nuclei throughout the full lifespan. However, little is known about changes in neuronal chromatin and nuclear organization during the course of development and aging, or in chronic neuropsychiatric disease. However, to date most chromatin and DNA based assays (other than FISH) lack single cell resolution. To this end, the considerable cellular heterogeneity of brain tissue poses a significant limitation, because typically various subpopulations of neurons are intermingled with different types of glia and other non-neuronal cells. One possible solution would be to grow cell-type specific cultures, but most CNS cells, including neurons, are ex vivo sustainable, at best, for only a few weeks and thus would provide an incomplete model for epigenetic mechanisms potentially operating across the full lifespan. Here, we provide a protocol to extract and purify nuclei from frozen (never fixed) human postmortem brain. The method involves extraction of nuclei in hypotonic lysis buffer, followed by ultracentrifugation and immunotagging with anti-NeuN antibody. Labeled neuronal nuclei are then collected separately using fluorescence-activated sorting. This method should be applicable to any brain region in a wide range of species and suitable for chromatin immunoprecipitation studies with site- and modification-specific anti-histone antibodies, and for DNA methylation and other assays.

Coding rate and duration of vocalizations of the frog, Xenopus laevis.

PubMed

Zornik, Erik; Yamaguchi, Ayako

2012-08-29

Vocalizations involve complex rhythmic motor patterns, but the underlying temporal coding mechanisms in the nervous system are poorly understood. Using a recently developed whole-brain preparation from which "fictive" vocalizations are readily elicited in vitro, we investigated the cellular basis of temporal complexity of African clawed frogs (Xenopus laevis). Male advertisement calls contain two alternating components--fast trills (∼300 ms) and slow trills (∼700 ms) that contain clicks repeated at ∼60 and ∼30 Hz, respectively. We found that males can alter the duration of fast trills without changing click rates. This finding led us to hypothesize that call rate and duration are regulated by independent mechanisms. We tested this by obtaining whole-cell patch-clamp recordings in the "fictively" calling isolated brain. We discovered a single type of premotor neuron with activity patterns correlated with both the rate and duration of fast trills. These "fast-trill neurons" (FTNs) exhibited long-lasting depolarizations (LLDs) correlated with each fast trill and action potentials that were phase-locked with motor output-neural correlates of call duration and rate, respectively. When depolarized without central pattern generator activation, FTNs produced subthreshold oscillations and action potentials at fast-trill rates, indicating FTN resonance properties are tuned to, and may dictate, the fast-trill rhythm. NMDA receptor (NMDAR) blockade eliminated LLDs in FTNs, and NMDAR activation in synaptically isolated FTNs induced repetitive LLDs. These results suggest FTNs contain an NMDAR-dependent mechanism that may regulate fast-trill duration. We conclude that a single premotor neuron population employs distinct mechanisms to regulate call rate and duration.

Brain Injury Differences in Frontal Impact Crash Using Different Simulation Strategies

PubMed Central

Ma, Chunsheng; Shen, Ming; Li, Peiyu; Zhang, Jinhuan

2015-01-01

In the real world crashes, brain injury is one of the leading causes of deaths. Using isolated human head finite element (FE) model to study the brain injury patterns and metrics has been a simplified methodology widely adopted, since it costs significantly lower computation resources than a whole human body model does. However, the degree of precision of this simplification remains questionable. This study compared these two kinds of methods: (1) using a whole human body model carried on the sled model and (2) using an isolated head model with prescribed head motions, to study the brain injury. The distribution of the von Mises stress (VMS), maximum principal strain (MPS), and cumulative strain damage measure (CSDM) was used to compare the two methods. The results showed that the VMS of brain mainly concentrated at the lower cerebrum and occipitotemporal region close to the cerebellum. The isolated head modelling strategy predicted higher levels of MPS and CSDM 5%, while the difference is small in CSDM 10% comparison. It suggests that isolated head model may not equivalently reflect the strain levels below the 10% compared to the whole human body model. PMID:26495029

Fatal cerebral mycoses caused by the ascomycete Chaetomium strumarium.

PubMed

Abbott, S P; Sigler, L; McAleer, R; McGough, D A; Rinaldi, M G; Mizell, G

1995-10-01

Three cases of fatal cerebral mycosis in males with prior histories of intravenous drug use from the United States and Australia are reported. Infection in each case was limited to brain abscess; no other sites of infection were observed. The fungus seen by histopathology and isolated from the brain tissue in each case was identified as Chaetomium strumarium. This is the first report of human infection by this species, and C. strumarium is the second species of Chaetomium known to cause primary brain infection. Chaetomium strumarium is unusual among members of the genus Chaetomium in forming ascocarps covered with pale, thin-walled, flexuous hairs, a feature leading to its original placement in the genus Achaetomium. Presence of pinkish exudate droplets and/or crystals associated with hyphae or ascocarps, sometimes accompanied by a pinkish diffusible pigment; good growth at 42 degrees C; and production of small conidia further distinguish this species. The brain abscess isolates were compared with isolates from prior cases of cerebral infection which had been identified as either Chaetomium atrobrunneum or Chaetomium globosum. With reidentification of one isolate originally identified as C. globosum to C. atrobrunneum, only C. strumarium and C. atrobrunneum have been confirmed to cause infection involving the brain.

Fatal cerebral mycoses caused by the ascomycete Chaetomium strumarium.

PubMed Central

Abbott, S P; Sigler, L; McAleer, R; McGough, D A; Rinaldi, M G; Mizell, G

1995-01-01

Three cases of fatal cerebral mycosis in males with prior histories of intravenous drug use from the United States and Australia are reported. Infection in each case was limited to brain abscess; no other sites of infection were observed. The fungus seen by histopathology and isolated from the brain tissue in each case was identified as Chaetomium strumarium. This is the first report of human infection by this species, and C. strumarium is the second species of Chaetomium known to cause primary brain infection. Chaetomium strumarium is unusual among members of the genus Chaetomium in forming ascocarps covered with pale, thin-walled, flexuous hairs, a feature leading to its original placement in the genus Achaetomium. Presence of pinkish exudate droplets and/or crystals associated with hyphae or ascocarps, sometimes accompanied by a pinkish diffusible pigment; good growth at 42 degrees C; and production of small conidia further distinguish this species. The brain abscess isolates were compared with isolates from prior cases of cerebral infection which had been identified as either Chaetomium atrobrunneum or Chaetomium globosum. With reidentification of one isolate originally identified as C. globosum to C. atrobrunneum, only C. strumarium and C. atrobrunneum have been confirmed to cause infection involving the brain. PMID:8567907

Social Isolation During Adolescence Strengthens Retention of Fear Memories and Facilitates Induction of Late-Phase Long-Term Potentiation.

PubMed

Liu, Ji-Hong; You, Qiang-Long; Wei, Mei-Dan; Wang, Qian; Luo, Zheng-Yi; Lin, Song; Huang, Lang; Li, Shu-Ji; Li, Xiao-Wen; Gao, Tian-Ming

2015-12-01

Social isolation during the vulnerable period of adolescence produces emotional dysregulation that often manifests as abnormal behavior in adulthood. The enduring consequence of isolation might be caused by a weakened ability to forget unpleasant memories. However, it remains unclear whether isolation affects unpleasant memories. To address this, we used a model of associative learning to induce the fear memories and evaluated the influence of isolation mice during adolescence on the subsequent retention of fear memories and its underlying cellular mechanisms. Following adolescent social isolation, we found that mice decreased their social interaction time and had an increase in anxiety-related behavior. Interestingly, when we assessed memory retention, we found that isolated mice were unable to forget aversive memories when tested 4 weeks after the original event. Consistent with this, we observed that a single train of high-frequency stimulation (HFS) enabled a late-phase long-term potentiation (L-LTP) in the hippocampal CA1 region of isolated mice, whereas only an early-phase LTP was observed with the same stimulation in the control mice. Social isolation during adolescence also increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus, and application of a tropomyosin-related kinase B (TrkB) receptor inhibitor ameliorated the facilitated L-LTP seen after isolation. Together, our results suggest that adolescent isolation may result in mental disorders during adulthood and that this may stem from an inability to forget the unpleasant memories via BDNF-mediated synaptic plasticity. These findings may give us a new strategy to prevent mental disorders caused by persistent unpleasant memories.

Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer's disease: prophylactic and therapeutic applications.

PubMed

Kou, Jinghong; Yang, Junling; Lim, Jeong-Eun; Pattanayak, Abhinandan; Song, Min; Planque, Stephanie; Paul, Sudhir; Fukuchi, Ken-Ichiro

2015-02-01

Accumulation of amyloid beta-peptide (Aβ) in the brain is hypothesized to be a causal event leading to dementia in Alzheimer's disease (AD). Aβ vaccination removes Aβ deposits from the brain. Aβ immunotherapy, however, may cause T cell- and/or Fc-receptor-mediated brain inflammation and relocate parenchymal Aβ deposits to blood vessels leading to cerebral hemorrhages. Because catalytic antibodies do not form stable immune complexes and Aβ fragments produced by catalytic antibodies are less likely to form aggregates, Aβ-specific catalytic antibodies may have safer therapeutic profiles than reversibly-binding anti-Aβ antibodies. Additionally, catalytic antibodies may remove Aβ more efficiently than binding antibodies because a single catalytic antibody can hydrolyze thousands of Aβ molecules. We previously isolated Aβ-specific catalytic antibody, IgVL5D3, with strong Aβ-hydrolyzing activity. Here, we evaluated the prophylactic and therapeutic efficacy of brain-targeted IgVL5D3 gene delivery via recombinant adeno-associated virus serotype 9 (rAAV9) in an AD mouse model. One single injection of rAAV9-IgVL5D3 into the right ventricle of AD model mice yielded widespread, high expression of IgVL5D3 in the unilateral hemisphere. IgVL5D3 expression was readily detectable in the contralateral hemisphere but to a much lesser extent. IgVL5D3 expression was also confirmed in the cerebrospinal fluid. Prophylactic and therapeutic injection of rAAV9-IgVL5D3 reduced Aβ load in the ipsilateral hippocampus of AD model mice. No evidence of hemorrhages, increased vascular amyloid deposits, increased proinflammatory cytokines, or infiltrating T-cells in the brains was found in the experimental animals. AAV9-mediated anti-Aβ catalytic antibody brain delivery can be prophylactic and therapeutic options for AD.

Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

PubMed

Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-06-01

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

Deletion of TLX and social isolation impairs exercise-induced neurogenesis in the adolescent hippocampus.

PubMed

Kozareva, Danka A; O'Leary, Olivia F; Cryan, John F; Nolan, Yvonne M

2018-01-01

Adolescence is a sensitive period of neurodevelopment during which life experiences can have profound effects on the brain. Hippocampal neurogenesis, the neurodevelopmental process of generating functional new neurons from neural stem cells, occurs throughout the lifespan and has been shown to play a role in learning, memory and in mood regulation. In adulthood it is influenced by extrinsic environmental factors such as exercise and stress. Intrinsic factors that regulate hippocampal neurogenesis include the orphan nuclear receptor TLX (Nr2e1) which is primarily expressed in the neurogenic niches of the brain. While mechanisms regulating adult hippocampal neurogenesis have been widely studied, less is known on how hippocampal neurogenesis is affected during adolescence. The aim of this study was to investigate the influence of both TLX and isolation stress on exercise-induced increases in neurogenesis in running and sedentary conditions during adolescence. Single- (isolation stress) wild type and Nr2e1 -/- mice or pair-housed wild type mice were housed in sedentary conditions or allowed free access to running wheels for 3 weeks during adolescence. A reduction of neuronal survival was evident in mice lacking TLX, and exercise did not increase hippocampal neurogenesis in these Nr2e1 -/- mice. This suggests that TLX is necessary for the pro-neurogenic effects of exercise during adolescence. Interestingly, although social isolation during adolescence did not affect hippocampal neurogenesis, it prevented an exercise-induced increase in neurogenesis in the ventral hippocampus. Together these data demonstrate the importance of intrinsic and extrinsic factors in promoting an exercise-induced increase in neurogenesis at this key point in life. © 2017 Wiley Periodicals, Inc.

A novel in vivo method for isolating antibodies from a phage display library by neuronal retrograde transport selectively yields antibodies against p75(NTR.).

PubMed

Tani, Hiroaki; Osbourn, Jane K; Walker, Edward H; Rush, Robert A; Ferguson, Ian A

2013-01-01

The neurotrophin receptor p75(NTR) is utilized by a variety of pathogens to gain entry into the central nervous system (CNS). We tested if this entry portal might be exploited using a phage display library to isolate internalizing antibodies that target the CNS in vivo. By applying a phage library that expressed human single chain variable fragment (scFv) antibodies on their surface to a transected sciatic nerve, we showed that (1) phage conjugated to anti-p75(NTR) antibody or phage scFv library pre-panned against p75(NTR) are internalized by neurons expressing p75(NTR); (2) subsequent retrograde axonal transport separates internalized phage from the applied phage; and, (3) internalized phage can be recovered from a proximal ligature made on a nerve. This approach resulted in 13-fold increase in the number of phage isolated from the injured nerve compared with the starting population, and isolation of 18 unique internalizing p75(NTR) antibodies that were transported from the peripheral nerve into the spinal cord, through the blood-brain barrier. In addition, antibodies recognizing other potentially internalized antigens were identified through in vivo selection using a fully diverse library. Because p75(NTR) expression is upregulated in motor neurons in response to injury and in disease, the p75(NTR) antibodies may have substantial potential for cell-targeted drug/gene delivery. In addition, this novel selection method provides the potential to generate panels of antibodies that could be used to identify further internalization targets, which could aid drug delivery across the blood-brain barrier.

A novel in vivo method for isolating antibodies from a phage display library by neuronal retrograde transport selectively yields antibodies against p75NTR

PubMed Central

Tani, Hiroaki; Osbourn, Jane K.; Walker, Edward H.; Rush, Robert A.; Ferguson, Ian A.

2013-01-01

The neurotrophin receptor p75NTR is utilized by a variety of pathogens to gain entry into the central nervous system (CNS). We tested if this entry portal might be exploited using a phage display library to isolate internalizing antibodies that target the CNS in vivo. By applying a phage library that expressed human single chain variable fragment (scFv) antibodies on their surface to a transected sciatic nerve, we showed that (1) phage conjugated to anti-p75NTR antibody or phage scFv library pre-panned against p75NTR are internalized by neurons expressing p75NTR; (2) subsequent retrograde axonal transport separates internalized phage from the applied phage; and, (3) internalized phage can be recovered from a proximal ligature made on a nerve. This approach resulted in 13-fold increase in the number of phage isolated from the injured nerve compared with the starting population, and isolation of 18 unique internalizing p75NTR antibodies that were transported from the peripheral nerve into the spinal cord, through the blood-brain barrier. In addition, antibodies recognizing other potentially internalized antigens were identified through in vivo selection using a fully diverse library. Because p75NTR expression is upregulated in motor neurons in response to injury and in disease, the p75NTR antibodies may have substantial potential for cell-targeted drug/gene delivery. In addition, this novel selection method provides the potential to generate panels of antibodies that could be used to identify further internalization targets, which could aid drug delivery across the blood-brain barrier. PMID:23549155

Isolation of viable Neospora caninum from brains of wild gray wolves (Canis lupus).

PubMed

Dubey, J P; Jenkins, M C; Ferreira, L R; Choudhary, S; Verma, S K; Kwok, O C H; Fetterer, R; Butler, E; Carstensen, M

2014-03-17

Neospora caninum is a common cause of abortion in cattle worldwide. Canids, including the dog and the dingo (Canis familiaris), the coyote (Canis latrans), and the gray wolf (Canis lupus) are its definitive hosts that can excrete environmentally resistant oocysts in the environment, but also can act as intermediate hosts, harboring tissue stages of the parasite. In an attempt to isolate viable N. caninum from tissues of naturally infected wolves, brain and heart tissue from 109 wolves from Minnesota were bioassayed in mice. Viable N. caninum (NcWolfMn1, NcWolfMn2) was isolated from the brains of two wolves by bioassays in interferon gamma gene knockout mice. DNA obtained from culture-derived N. caninum tachyzoites of the two isolates were analyzed by N. caninum-specific Nc5 polymerase chain reaction and confirmed diagnosis. This is the first report of isolation of N. caninum from tissues of any wild canid host. Published by Elsevier B.V.

The Clock gene clone and its circadian rhythms in Pelteobagrus vachelli

NASA Astrophysics Data System (ADS)

Qin, Chuanjie; Shao, Ting

2015-05-01

The Clock gene, a key molecule in circadian systems, is widely distributed in the animal kingdom. We isolated a 936-bp partial cDNA sequence of the Clock gene ( Pva-clock) from the darkbarbel catfish Pelteobagrus vachelli that exhibited high identity with Clock genes of other species of fish and animals (65%-88%). The putative domains included a basic helix-loop-helix (bHLH) domain and two period-ARNT-single-minded (PAS) domains, which were also similar to those in other species of fish and animals. Pva-Clock was primarily expressed in the brain, and was detected in all of the peripheral tissues sampled. Additionally, the pattern of Pva-Clock expression over a 24-h period exhibited a circadian rhythm in the brain, liver and intestine, with the acrophase at zeitgeber time 21:35, 23:00, and 23:23, respectively. Our results provide insight into the function of the molecular Clock of P. vachelli.

Molecular and antimicrobial susceptibility characterization of Globicatella sulfidifaciens isolated from sow's urinary tract infection.

PubMed

Matajira, Carlos E C; Moreno, Luisa Z; Gomes, Vasco T M; Silva, Ana Paula S; Mesquita, Renan E; Amigo, Cristina R; Christ, Ana Paula G; Sato, Maria Inês Z; Moreno, Andrea M

2017-12-01

The Globicatella genus comprises Gram-positive, facultative anaerobic, α-hemolytic and catalase negative cocci morphologically and phenotypically very similar to Streptococcus and Aerococcus genus which can lead to misidentification and underestimation of this pathogen. Globicatella species have already been isolated from human and animals with heart and brain disorders. Their clinical relevance in animals, and its zoonotic potential, remains unknown due to the difficulty in their identification. To present the isolation, phenotypic and molecular characterization of G. sulfidifaciens from urinary tract infection in sows. Urine samples from 140 sows of two swine herds located in São Paulo State (Brazil) yielded the isolation of three presumptive G. sulfidifaciens strains. Identification and species confirmation were done by MALDI-TOF MS and 16S rRNA sequencing. Strains were further characterized by single enzyme amplified fragments length polymorphism (SE-AFLP) and broth microdilution techniques. All three isolates were confirmed as G. sulfidifaciens. The SE-AFLP genotyping resulted in distinct fingerprint patterns for each strain. All isolates presented high MIC values to tetracycline, sulphonamides, aminoglycosides and tylosin tartrate, which present high usage in human and animal medicine. Globicatella sulfidifaciens could be related to sporadic urinary tract infections in swine and appear to present alarming antimicrobial susceptibility profile. It is necessary to differentiate Streptococcus-like microorganisms in routine laboratory diagnostics for the correct identification of underestimated species potentially pathogenic to animals.

Pharmacological Rescue of Long-Term Potentiation in Alzheimer Diseased Synapses

PubMed Central

Berchtold, Nicole C.; Lynch, Gary; Cotman, Carl W.

2017-01-01

Long-term potentiation (LTP) is an activity-dependent and persistent increase in synaptic transmission. Currently available techniques to measure LTP are time-intensive and require highly specialized expertise and equipment, and thus are not well suited for screening of multiple candidate treatments, even in animal models. To expand and facilitate the analysis of LTP, here we use a flow cytometry-based method to track chemically induced LTP by detecting surface AMPA receptors in isolated synaptosomes: fluorescence analysis of single-synapse long-term potentiation (FASS-LTP). First, we demonstrate that FASS-LTP is simple, sensitive, and models electrically induced LTP recorded in intact circuitries. Second, we conducted FASS-LTP analysis in two well-characterized Alzheimer's disease (AD) mouse models (3xTg and Tg2576) and, importantly, in cryopreserved human AD brain samples. By profiling hundreds of synaptosomes, our data provide the first direct evidence to support the idea that synapses from AD brain are intrinsically defective in LTP. Third, we used FASS-LTP for drug evaluation in human synaptosomes. Testing a panel of modulators of cAMP and cGMP signaling pathways, FASS-LTP identified vardenafil and Bay-73–6691 (phosphodiesterase-5 and -9 inhibitors, respectively) as potent enhancers of LTP in synaptosomes from AD cases. These results indicate that our approach could provide the basis for protocols to study LTP in both healthy and diseased human brains, a previously unattainable goal. SIGNIFICANCE STATEMENT Learning and memory depend on the ability of synapses to strengthen in response to activity. Long-term potentiation (LTP) is a rapid and persistent increase in synaptic transmission that is thought to be affected in Alzheimer's disease (AD). However, direct evidence of LTP deficits in human AD brain has been elusive, primarily due to methodological limitations. Here, we analyze LTP in isolated synapses from AD brain using a novel approach that allows testing LTP in cryopreserved brain. Our analysis of hundreds of synapses supports the idea that AD-diseased synapses are intrinsically defective in LTP. Further, we identified pharmacological agents that rescue LTP in AD, thus opening up a new avenue for drug screening and evaluation of strategies for alleviating memory impairments. PMID:27986924

Expressive electronic journal writing: freedom of communication for survivors of acquired brain injury.

PubMed

Fraas, Michael; Balz, Magdalen A

2008-03-01

In addition to the impaired ability to effectively communicate, adults with acquired brain injury (ABI) also experience high incidences of depression, social isolation, and decreased quality of life. Expressive writing programs have been shown to be effective in alleviating these concomitant impairments in other populations including incarcerated inmates (Lane, Writing as a road to self-discovery, F & W, Cincinnati 1993). In addition, computer applications such as email have been suggested as an effective means of improving communication and social isolation in adults with brain injury (Sohlberg et al. [2003]. Brain Injury, 17(7), 609-629). This investigation examines the effects of on-line expressive journal writing on the communication, emotional status, social integration and quality of life of individuals with brain injury.

Differentiation and characteristics of the enhanced green fluorescent protein gene transgenic goat neural stem cells cultured in attached and non-attached plates.

PubMed

Zheng, Yue-Mao; Dang, Yong-Hui; Qiu, Shuang; Qi, Ying-Pei; Xu, Yong-Ping; Sai, Wu-Jia-Fu

2011-08-01

The aims of this study were (i) to determine whether NSCs (neural stem cells) could be isolated from the brain of embryonic day 98 fetal goat, (ii) to determine if these stem cells have the capability of multipotent differentiation following transfection with a reporter gene, EGFP (enhanced green fluorescent protein) and (iii) to study the characteristics of the stem cells cultured in attached and non-attached plates. NSCs were isolated from embryonic day 98 fetal goat brain, transfected with EGFP gene using lipofection, and subcultured in attached and non-attached plates respectively. The transgenic stem cells were induced to differentiate into osteogenic and endothelial cells in vitro respectively. Markers associated with undifferentiated NSCs and their differentiated cells were tested by RT-PCR (reverse transcription-PCR). The results demonstrated that stem cells could be isolated from embryonic day 98 fetal goat brain, and EGFP gene could be transfected into the cells. The transgenic NSCs were capable of self-renewal, a defining property of stem cells, and were grown as free-floating neurospheres in non-attached plates. When the neurospheres were transferred and cultured in attached plates, cells migrate from the neurospheres and are grown as spindle cells. The stem cells were grown as quasi-circular cells when the single stem cells were cultured in attached plates. Both the NSCs cultured in non-attached and attached plates could express Hes1 (hairy and enhancer of split 1), Oct4 (octamer-binding protein 4), Nanog, Sox2 [SRY (sex-determining region Y)-box 2] and Nestin, while following differentiation cells expressed markers for osteogenic cells (Osteocalcin+ and Osteonectin+) and endothelium (CD34+ and eNOS+). The results demonstrated that the goat EGFP gene transgenic NSCs have the capability of multipotent differentiation, which means that the transgenic NSCs may be useful in cell transplantation studies in future.

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage.

PubMed

Chang, Ronald; Folkerson, Lindley E; Sloan, Duncan; Tomasek, Jeffrey S; Kitagawa, Ryan S; Choi, H Alex; Wade, Charles E; Holcomb, John B

2017-02-01

Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large-animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. "Early plasma" was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P = .08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71-1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20-9.35). Although early plasma transfusion was not associated with improved in-hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in-hospital survival in those with multifocal intracranial hemorrhage. Copyright © 2016 Elsevier Inc. All rights reserved.

Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy.

PubMed

Rempe, Ralf G; Hartz, Anika M S; Soldner, Emma L B; Sokola, Brent S; Alluri, Satya R; Abner, Erin L; Kryscio, Richard J; Pekcec, Anton; Schlichtiger, Juli; Bauer, Björn

2018-05-02

The blood-brain barrier is dysfunctional in epilepsy, thereby contributing to seizure genesis and resistance to antiseizure drugs. Previously, several groups reported that seizures increase brain glutamate levels, which leads to barrier dysfunction. One critical component of barrier dysfunction is brain capillary leakage. Based on our preliminary data, we hypothesized that glutamate released during seizures mediates an increase in matrix-metalloproteinase (MMP) expression and activity levels, thereby contributing to barrier leakage. To test this hypothesis, we exposed isolated brain capillaries from male Sprague Dawley rats to glutamate ex vivo and used an in vivo / ex vivo approach of isolated brain capillaries from female Wistar rats that experienced status epilepticus as an acute seizure model. We found that exposing isolated rat brain capillaries to glutamate increased MMP-2 and MMP-9 protein and activity levels, and decreased tight junction protein levels, which resulted in barrier leakage. We confirmed these findings in vivo in rats after status epilepticus and in brain capillaries from male mice lacking cytosolic phospholipase A 2 Together, our data support the hypothesis that glutamate released during seizures signals an increase in MMP-2 and MMP-9 protein expression and activity levels, resulting in blood-brain barrier leakage. SIGNIFICANCE STATEMENT The mechanism leading to seizure-mediated blood-brain barrier dysfunction in epilepsy is poorly understood. In the present study, we focused on defining this mechanism in the brain capillary endothelium. We demonstrate that seizures trigger a pathway that involves glutamate signaling through cytosolic phospholipase A 2 , which increases MMP levels and decreases tight junction protein expression levels, resulting in barrier leakage. These findings may provide potential therapeutic avenues within the blood-brain barrier to limit barrier dysfunction in epilepsy and decrease seizure burden. Copyright © 2018 the authors 0270-6474/18/384301-15$15.00/0.

Pig Brain Mitochondria as a Biological Model for Study of Mitochondrial Respiration.

PubMed

Fišar, Z; Hroudová, J

2016-01-01

Oxidative phosphorylation is a key process of intracellular energy transfer by which mitochondria produce ATP. Isolated mitochondria serve as a biological model for understanding the mitochondrial respiration control, effects of various biologically active substances, and pathophysiology of mitochondrial diseases. The aim of our study was to evaluate pig brain mitochondria as a proper biological model for investigation of activity of the mitochondrial electron transport chain. Oxygen consumption rates of isolated pig brain mitochondria were measured using high-resolution respirometry. Mitochondrial respiration of crude mitochondrial fraction, mitochondria purified in sucrose gradient, and mitochondria purified in Percoll gradient were assayed as a function of storage time. Oxygen flux and various mitochondrial respiratory control ratios were not changed within two days of mitochondria storage on ice. Leak respiration was found higher and Complex I-linked respiration lower in purified mitochondria compared to the crude mitochondrial fraction. Damage to both outer and inner mitochondrial membrane caused by the isolation procedure was the greatest after purification in a sucrose gradient. We confirmed that pig brain mitochondria can serve as a biological model for investigation of mitochondrial respiration. The advantage of this biological model is the stability of respiratory parameters for more than 48 h and the possibility to isolate large amounts of mitochondria from specific brain areas without the need to kill laboratory animals. We suggest the use of high-resolution respirometry of pig brain mitochondria for research of the neuroprotective effects and/or mitochondrial toxicity of new medical drugs.

Intercellular signaling through secreted proteins induces free-energy gradient-directed cell movement.

PubMed

Kravchenko-Balasha, Nataly; Shin, Young Shik; Sutherland, Alex; Levine, R D; Heath, James R

2016-05-17

Controlling cell migration is important in tissue engineering and medicine. Cell motility depends on factors such as nutrient concentration gradients and soluble factor signaling. In particular, cell-cell signaling can depend on cell-cell separation distance and can influence cellular arrangements in bulk cultures. Here, we seek a physical-based approach, which identifies a potential governed by cell-cell signaling that induces a directed cell-cell motion. A single-cell barcode chip (SCBC) was used to experimentally interrogate secreted proteins in hundreds of isolated glioblastoma brain cancer cell pairs and to monitor their relative motions over time. We used these trajectories to identify a range of cell-cell separation distances where the signaling was most stable. We then used a thermodynamics-motivated analysis of secreted protein levels to characterize free-energy changes for different cell-cell distances. We show that glioblastoma cell-cell movement can be described as Brownian motion biased by cell-cell potential. To demonstrate that the free-energy potential as determined by the signaling is the driver of motion, we inhibited two proteins most involved in maintaining the free-energy gradient. Following inhibition, cell pairs showed an essentially random Brownian motion, similar to the case for untreated, isolated single cells.

Autonomic regulation of hepatic glucose production.

PubMed

Bisschop, Peter H; Fliers, Eric; Kalsbeek, Andries

2015-01-01

Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system to communicate with peripheral organs. Within the brain, the hypothalamus is the key region to integrate signals on energy status, including signals from lipid, glucose, and hormone sensing cells, with afferent neural signals from the internal and external milieu. In turn, the hypothalamus regulates metabolism in peripheral organs, including the liver, not only via the anterior pituitary gland but also via multiple neuropeptidergic pathways in the hypothalamus that have been identified as regulators of hepatic glucose metabolism. These pathways comprise preautonomic neurons projecting to nuclei in the brain stem and spinal cord, which relay signals from the hypothalamus to the liver via the autonomic nervous system. The neuroendocrine and neuronal outputs of the hypothalamus are not separate entities. They appear to act as a single integrated regulatory system, far more subtle, and complex than when each is viewed in isolation. Consequently, hypothalamic regulation should be viewed as a summation of both neuroendocrine and neural influences. As a result, our endocrine-based understanding of diseases such as diabetes and obesity should be expanded by integration of neural inputs into our concept of the pathophysiological process. © 2014 American Physiological Society.

Mitochondrial dysfunction contribute to diabetic neurotoxicity induced by streptozocin in mice: protective effect of Urtica dioica and pioglitazone.

PubMed

Shokrzadeh, Mohammad; Mirshafa, Atefeh; Yekta Moghaddam, Niusha; Birjandian, Behnoosh; Shaki, Fatemeh

2018-04-18

Uncontrolled chronic hyperglycemia in diabetic patients could result in various complications, including neurotoxicity. Urtica dioica L. (UD) is known for its hypoglycemic and antioxidant effects. In this study, we evaluated the efficacy of UD and pioglitazone (PIO) in reduction of neurotoxicity and oxidative stress in streptozocin-induced diabetic mice. Male mice were divided into seven groups: control, diabetic, dimethyl sulfoxide-treated control, PIO-treated, UD-treated, UD-PIO-treated, and vitamin E-treated. For induction of diabetes, streptozocin was injected in a single dose (65 mg/kg, i.p.). All treatments were performed for 5 weeks. Neurotoxicity was evaluated through hot plate and formalin test. Then, animals were killed, brain tissue was separated and the mitochondrial fraction was isolated with different centrifuge technique. Also, oxidative stress markers (reactive oxygen species, lipid peroxidation, protein carbonyl, glutathione) were measured in brain. Mitochondrial function was evaluated by MTT test in brain isolated mitochondria. Elevation of oxidative stress markers and mitochondrial damage were observed in diabetic mice compared to control group. Administration of PIO and UD ameliorated the oxidative stress and mitochondrial damage (p < 0.05) in diabetic mice. Also increase in pain score was shown in diabetic mice that treatment with UD and PIO diminished elevation of pain score in diabetic mice. Interestingly, simultaneous administration of PIO and UD showed synergism effect in attenuation of oxidative stress and hyperglycemia. UD showed a therapeutic potential for the attenuation of oxidative stress and diabetes-induced hyperglycemia that can be considered as co-treatment in treatment of diabetic neurotoxicity.

Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue.

PubMed

Tamashiro, Tami T; Dalgard, Clifton Lee; Byrnes, Kimberly R

2012-08-15

Microglia account for approximately 12% of the total cellular population in the mammalian brain. While neurons and astrocytes are considered the major cell types of the nervous system, microglia play a significant role in normal brain physiology by monitoring tissue for debris and pathogens and maintaining homeostasis in the parenchyma via phagocytic activity. Microglia are activated during a number of injury and disease conditions, including neurodegenerative disease, traumatic brain injury, and nervous system infection. Under these activating conditions, microglia increase their phagocytic activity, undergo morpohological and proliferative change, and actively secrete reactive oxygen and nitrogen species, pro-inflammatory chemokines and cytokines, often activating a paracrine or autocrine loop. As these microglial responses contribute to disease pathogenesis in neurological conditions, research focused on microglia is warranted. Due to the cellular heterogeneity of the brain, it is technically difficult to obtain sufficient microglial sample material with high purity during in vivo experiments. Current research on the neuroprotective and neurotoxic functions of microglia require a routine technical method to consistently generate pure and healthy microglia with sufficient yield for study. We present, in text and video, a protocol to isolate pure primary microglia from mixed glia cultures for a variety of downstream applications. Briefly, this technique utilizes dissociated brain tissue from neonatal rat pups to produce mixed glial cell cultures. After the mixed glial cultures reach confluency, primary microglia are mechanically isolated from the culture by a brief duration of shaking. The microglia are then plated at high purity for experimental study. The principle and protocol of this methodology have been described in the literature. Additionally, alternate methodologies to isolate primary microglia are well described. Homogenized brain tissue may be separated by density gradient centrifugation to yield primary microglia. However, the centrifugation is of moderate length (45 min) and may cause cellular damage and activation, as well as, cause enriched microglia and other cellular populations. Another protocol has been utilized to isolate primary microglia in a variety of organisms by prolonged (16 hr) shaking while in culture. After shaking, the media supernatant is centrifuged to isolate microglia. This longer two-step isolation method may also perturb microglial function and activation. We chiefly utilize the following microglia isolation protocol in our laboratory for a number of reasons: (1) primary microglia simulate in vivo biology more faithfully than immortalized rodent microglia cell lines, (2) nominal mechanical disruption minimizes potential cellular dysfunction or activation, and (3) sufficient yield can be obtained without passage of the mixed glial cell cultures. It is important to note that this protocol uses brain tissue from neonatal rat pups to isolate microglia and that using older rats to isolate microglia can significantly impact the yield, activation status, and functional properties of isolated microglia. There is evidence that aging is linked with microglia dysfunction, increased neuroinflammation and neurodegenerative pathologies, so previous studies have used ex vivo adult microglia to better understand the role of microglia in neurodegenerative diseases where aging is important parameter. However, ex vivo microglia cannot be kept in culture for prolonged periods of time. Therefore, while this protocol extends the life of primary microglia in culture, it should be noted that the microglia behave differently from adult microglia and in vitro studies should be carefully considered when translated to an in vivo setting.

Single-cell isolation by a modular single-cell pipette for RNA-sequencing.

PubMed

Zhang, Kai; Gao, Min; Chong, Zechen; Li, Ying; Han, Xin; Chen, Rui; Qin, Lidong

2016-11-29

Single-cell transcriptome sequencing highly requires a convenient and reliable method to rapidly isolate a live cell into a specific container such as a PCR tube. Here, we report a modular single-cell pipette (mSCP) consisting of three modular components, a SCP-Tip, an air-displacement pipette (ADP), and ADP-Tips, that can be easily assembled, disassembled, and reassembled. By assembling the SCP-Tip containing a hydrodynamic trap, the mSCP can isolate single cells from 5-10 cells per μL of cell suspension. The mSCP is compatible with microscopic identification of captured single cells to finally achieve 100% single-cell isolation efficiency. The isolated live single cells are in submicroliter volumes and well suitable for single-cell PCR analysis and RNA-sequencing. The mSCP possesses merits of convenience, rapidness, and high efficiency, making it a powerful tool to isolate single cells for transcriptome analysis.

Albumin elicits calcium signals from astrocytes in brain slices from neonatal rat cortex

PubMed Central

Nadal, Angel; Sul, Jai-Yoon; Valdeolmillos, Miguel; McNaughton, Peter A

1998-01-01

Albumin causes calcium signals and mitosis in cultured astrocytes, but it has not been established whether astrocytes in intact brain also respond to albumin. The effect of albumin on intracellular calcium concentration ([Ca2+]i) in single cells was therefore studied in acutely isolated cortical brain slices from the neonatal rat.Physiological concentrations of albumin from plasma and from serum produced an increase in [Ca2+]i in a subpopulation of cortical cells. Trains of transient elevations in [Ca2+]i (Ca2+ spikes) were seen in 41 % of these cells.The cells responding to albumin are identified as astrocytes because the neurone-specific agonist NMDA caused much smaller and slower responses in these cells. On the other hand NMDA-responsive cells, which are probably neurones, exhibited only small and slow responses to albumin. The residual responses of astrocytes to NMDA and neurones to albumin are likely to be due to crosstalk with adjacent neurones and astrocytes, respectively.Methanol extraction of albumin removes a polar lipid and abolishes the ability of albumin to increase intracellular calcium.Astrocyte calcium signalling caused by albumin may have important physiological consequences when the blood-brain barrier breaks down and allows albumin to enter the CNS. PMID:9596793

Vitamins and neural and cognitive developmental outcomes in children.

PubMed

Benton, David

2012-02-01

The role of vitamin status in the development of the brain and the subsequent functioning of the brain was considered. There are data with a range of vitamins, from animal studies and human studies in developing countries, suggesting that a clinical deficiency during the critical period when the brain is developing causes permanent damage. To date there is, however, with the exception of cases of clinical deficiency such as those that might be associated with a vegan diet, little evidence that variations in the diet of those living in industrialised countries have a lasting developmental influence. Similarly, later in life clinical deficiencies of various vitamins disrupt cognition although there is to date limited evidence that variations in the intake of single vitamins in industrialised societies influence functioning. It may well be, however, unreasonable to expect that vitamins examined in isolation will be associated with differences in cognitive functioning. The output of the brain reflects millions of metabolic processes, each potentially susceptible to any of a range of vitamins. A diet poor in one respect is likely to be poor in other respects as well. As such, the preliminary reports in double-blind placebo-controlled trials that aspects of cognition and behaviour respond to supplementation with multi-micronutrients may indicate the way forward.

Cysteine-rich whey protein isolate (Immunocal®) ameliorates deficits in the GFAP.HMOX1 mouse model of schizophrenia.

PubMed

Song, Wei; Tavitian, Ayda; Cressatti, Marisa; Galindez, Carmela; Liberman, Adrienne; Schipper, Hyman M

2017-09-01

Schizophrenia is a neuropsychiatric disorder that features neural oxidative stress and glutathione (GSH) deficits. Oxidative stress is augmented in brain tissue of GFAP.HMOX1 transgenic mice which exhibit schizophrenia-relevant characteristics. The whey protein isolate, Immunocal® serves as a GSH precursor upon oral administration. In this study, we treated GFAP.HMOX1 transgenic mice daily with either Immunocal (33mg/ml drinking water) or equivalent concentrations of casein (control) between the ages of 5 and 6.5 months. Immunocal attenuated many of the behavioral, neurochemical and redox abnormalities observed in GFAP.HMOX1 mice. In addition to restoring GSH homeostasis in the CNS of the transgenic mice, the whey protein isolate augmented GSH reserves in the brains of wild-type animals. These results demonstrate that consumption of whey protein isolate augments GSH stores and antioxidant defenses in the healthy and diseased mammalian brain. Whey protein isolate supplementation (Immunocal) may constitute a safe and effective modality for the management of schizophrenia, an unmet clinical imperative. Copyright © 2017 Elsevier Inc. All rights reserved.

Salmonella as a biological "Trojan horse" for neoplasia: future possibilities including brain cancer.

PubMed

Mlynarczyk, Gregory S A; Berg, Carrie A; Withrock, Isabelle C; Fick, Meghan E; Anderson, Stephen J; Laboissonniere, Lauren A; Jefferson, Matthew A; Brewer, Matthew T; Stock, Matthew L; Lange, Jennifer K; Luna, K C; Acharya, Sreemoyee; Kanuri, Sriharsha; Sharma, Shaunik; Kondru, Naveen C; McCormack, Garrett R; Carlson, Steve A

2014-09-01

This manuscript considers available evidence that a specific Salmonella strain could be used as an effective orally-administered option for cancer therapy involving the brain. It has been established that Salmonella preferentially colonizes neoplastic tissue and thrives as a facultative anaerobe in the intra-tumor environment. Although Salmonella accumulates in tumors by passive processes, it is still possible for lipopolysaccharide to cause sepsis and endotoxic shock during the migration of bacteria to the tumor site. An LPS-free version of a recently identified Salmonella isolate may have the capability to circumvent the blood brain barrier and provide a safer method of reaching brain tumors. This isolate merits further research as a "Trojan horse" for future oral biotherapy of brain cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influence of Pre-reproductive Maternal Enrichment on Coping Response to Stress and Expression of c-Fos and Glucocorticoid Receptors in Adolescent Offspring

PubMed Central

Cutuli, Debora; Berretta, Erica; Pasqualini, Greta; De Bartolo, Paola; Caporali, Paola; Laricchiuta, Daniela; Sampedro-Piquero, Patricia; Gelfo, Francesca; Pesoli, Matteo; Foti, Francesca; Begega, Azucena; Petrosini, Laura

2017-01-01

Environmental enrichment (EE) is an experimental setting broadly used for investigating the effects of complex social, cognitive, and sensorimotor stimulations on brain structure and function. Recent studies point out that parental EE experience, even occurring in the pre-reproductive phase, affects neural development and behavioral trajectories of the offspring. In the present study we investigated the influences of pre-reproductive EE of female rats on maternal behavior and adolescent male offspring's coping response to an inescapable stressful situation after chronic social isolation. For this purpose female Wistar rats were housed from weaning to breeding age in enriched or standard environments. Subsequently, all females were mated and housed in standard conditions until offspring weaning. On the first post partum day (ppd 1), mother-pup interactions in undisturbed conditions were recorded. Further, after weaning the male pups were reared for 2 weeks under social isolation or in standard conditions, and then submitted or not to a single-session Forced Swim Test (FST). Offspring's neuronal activation and plastic changes were identified by immunohistochemistry for c-Fos and glucocorticoid receptors (GRs), and assessed by using stereological analysis. The biochemical correlates were measured in the hippocampus, amygdala and cingulate cortex, structures involved in hypothalamic-pituitary-adrenocortical axis regulation. Enriched dams exhibited increased Crouching levels in comparison to standard reared dams. In the offspring of both kinds of dams, social isolation reduced body weight, decreased Immobility, and increased Swimming during FST. Moreover, isolated offspring of enriched dams exhibited higher levels of Climbing in comparison to controls. Interestingly, in the amygdala of both isolated and control offspring of enriched dams we found a lower number of c-Fos immunopositive cells in response to FST and a higher number of GRs in comparison to the offspring of standard dams. These results highlight the profound influence of a stressful condition, such as the social isolation, on the brain of adolescent rats, and underline intergenerational effects of maternal experiences in regulating the offspring response to stress. PMID:28536510

Novel Replication-Competent Circular DNA Molecules from Healthy Cattle Serum and Milk and Multiple Sclerosis-Affected Human Brain Tissue

PubMed Central

Whitley, Corinna; Gunst, Karin; Müller, Hermann; Funk, Mathis; zur Hausen, Harald

2014-01-01

Epidemiological data point to the involvement of a cow milk factor in the etiology of multiple sclerosis (MS). Eleven circular DNA molecules closely related to transmissible spongiform encephalopathy (TSE)-associated isolate Sphinx 1.76 were isolated from healthy cattle serum, cow milk, and serum and brain tissue from MS patients. PMID:25169859

Sex differences in the outcome of juvenile social isolation on HPA axis function in rats.

PubMed

Pisu, M G; Garau, A; Boero, G; Biggio, F; Pibiri, V; Dore, R; Locci, V; Paci, E; Porcu, P; Serra, M

2016-04-21

Women are more likely than men to suffer from anxiety disorders and major depression. These disorders share hyperresponsiveness to stress as an etiological factor. Thus, sex differences in brain arousal systems and their regulation by chronic stress may account for the increased vulnerability to these disorders in women. Social isolation is a model of early life stress that results in neurobiological alterations leading to increased anxiety-like and depressive-like behaviors. Here we investigated the sex difference in the effects of post-weaning social isolation on acute stress sensitivity and behavior in rats. In both sexes, social isolation at weaning reduced basal levels of the neuroactive steroid allopregnanolone in the brain and of corticosterone in plasma. Moreover, acute stress increased plasma corticosterone levels in both group-housed and socially isolated male and female rats; however this effect was greater in male than female rats subjected to social isolation. Intriguingly, group-housed female rats showed no change in plasma and brain levels of allopregnanolone after acute foot-shock stress. The absence of stress-induced effects on allopregnanolone synthesis might be due to the physiologically higher levels of this hormone in females vs. males. Accordingly, increasing allopregnanolone levels in male rats blunted the response to foot-shock stress in these animals. Socially isolated male, but not female, rats also display depressive-like behavior and increased hippocampal brain-derived neurotrophic factor (BDNF). The ovarian steroids could "buffer" the effect of this adverse experience in females on these parameters. Finally, the dexamethasone (DEX) suppression test indicated that the chronic stress associated with social isolation impairs feedback inhibition in both sexes in which an increase in the abundance of glucocorticoid receptors (GRs) in the hippocampus was found. Altogether, these results demonstrate that social isolation affects neuroendocrine reactivity to stress, plasticity and emotionality in a sexually dimorphic manner. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Contralateral Superior Cerebellar Artery Syndrome: A Consequence of Brain Herniation

PubMed Central

Mohseni, Meysam; Habibi, Zohreh; Nejat, Farideh

2017-01-01

Vascular compromise is a well-known consequence of brain herniation syndromes. Transtentorial brain herniation most often involves posterior cerebral arteries. However, isolated involvement of contralateral superior cerebellar artery (SCA) during unilateral impending brain herniation is reported only once and we present another case of this exceedingly rare entity. A 24-year-old man was referred to us with impending herniation due to a multiloculated hydrocephalus, and during the course of illness, he developed an isolated SCA ischemia in the opposite side of the most dilated entrapped horn. In the current article we discuss the probable pathophysiologic mechanisms of this phenomenon, as well as recommending more inclusive brain studies in cases suspected of Kernohan-Woltman notch phenomenon in unilateral brain herniation. The rationale for this commentary is that contralateral SCA transient ischemia or infarct might be the underdiagnosed underlying pathomechanism of ipsilateral hemiparesis occurring in many cases of this somehow vague phenomenon. PMID:28490164

Vaccine-induced rabies in a red fox (Vulpes vulpes): isolation of vaccine virus in brain tissue and salivary glands.

PubMed

Hostnik, Peter; Picard-Meyer, Evelyne; Rihtarič, Danijela; Toplak, Ivan; Cliquet, Florence

2014-04-01

Oral vaccination campaigns to eliminate fox rabies were initiated in Slovenia in 1995. In May 2012, a young fox (Vulpes vulpes) with typical rabies signs was captured. Its brain and salivary gland tissues were found to contain vaccine strain SAD B19. The Basic Logical Alignment Search Tool alignment of 589 nucleotides determined from the N gene of the virus isolated from the brain and salivary glands of the affected fox was 100% identical to the GenBank reference SAD B19 strain. Sequence analysis of the N and M genes (4,351 nucleotides) showed two nucleotide modifications at position 1335 (N gene) and 3114 (M gene) in the KC522613 isolate identified in the fox compared to SAD B19.

Relationships among North American and Japanese Laetiporus isolates inferred from molecular phylogenetics and single-spore incompatibility reactions

Treesearch

Mark T. Banik; Daniel L. Lindner; Yuko Ota; Tsutomu Hattori

2010-01-01

Relationships were investigated among North American and Japanese isolates of Laetiporus using phylogenetic analysis of ITS sequences and single-spore isolate incompatibility. Single-spore isolate pairings revealed no significant compatibility between North American and Japanese isolates. ITS analysis revealed 12 clades within the core ...

Behavioral and Functional Neuroanatomical Correlates of Anterograde Autobiographical Memory in Isolated Retrograde Amnesic Patient M. L.

ERIC Educational Resources Information Center

Levine, Brian; Svoboda, Eva; Turner, Gary R.; Mandic, Marina; Mackey, Allison

2009-01-01

Patient M. L. [Levine, B., Black, S. E., Cabeza, R., Sinden, M., Mcintosh, A. R., Toth, J. P., et al. (1998). "Episodic memory and the self in a case of isolated retrograde amnesia." "Brain", "121", 1951-1973], lost memory for events occurring before his severe traumatic brain injury, yet his anterograde (post-injury) learning and memory appeared…

Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment.

PubMed

Franke, Cornelia; Nöldner, Michael; Abdel-Kader, Reham; Johnson-Anuna, Leslie N; Gibson Wood, W; Müller, Walter E; Eckert, Gunter P

2007-02-01

The present study determined if chronic simvastatin administration in vivo would provide neuroprotection in brain cells isolated from guinea pigs after challenge with the Bcl-2 inhibitor HA 14-1 or the NO donor sodium nitroprusside (SNP). Bcl-2 levels were significantly increased in brains of simvastatin-treated guinea pigs while levels of the pro-apoptotic protein Bax were significantly reduced. The ratio of Bax/Bcl-2, being a critical factor of the apoptotic state of cells, was significantly reduced in simvastatin-treated animals. Cholesterol levels in the brain remained unchanged in the simvastatin group. Brain cells isolated from simvastatin-treated guinea pigs were significantly less vulnerable to mitochondrial dysfunction and caspase-activation. These results provide new insight into potential mechanisms for the protective actions of statins within the CNS where programmed cell death has been implicated.

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline

PubMed Central

Tsao, May N.; Rades, Dirk; Wirth, Andrew; Lo, Simon S.; Danielson, Brita L.; Gaspar, Laurie E.; Sperduto, Paul W.; Vogelbaum, Michael A.; Radawski, Jeffrey D.; Wang, Jian Z.; Gillin, Michael T.; Mohideen, Najeeb; Hahn, Carol A.; Chang, Eric L.

2012-01-01

Purpose To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and Materials Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. Results The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Conclusions Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone). PMID:25925626

Isolation and genetic characterization of Toxoplasma gondii from striped dolphin (Stenella coeruleoalba) from Costa Rica.

PubMed

Dubey, J P; Morales, J A; Sundar, N; Velmurugan, G V; González-Barrientos, C R; Hernández-Mora, G; Su, C

2007-06-01

Toxoplasma gondii infection in marine mammals is of interest because of mortality and mode of transmission. It has been suggested that marine mammals become infected with T. gondii oocysts washed from land to the sea. We report the isolation and genetic characterization of viable T. gondii from a striped dolphin (Stenella coeruleoalba), the first time from this host. An adult female dolphin was found stranded on the Pacific Coast of Costa Rica, and the animal died the next day. The dolphin had a high (1:6400) antibody titer to T. gondii in the modified agglutination test. Severe nonsuppurative meningoencephalomyelitis was found in its brain and spinal cord, but T. gondii was not found in histological sections of the dolphin. Portions of its brain and the heart were bioassayed in mice for the isolation of T. gondii. Viable T. gondii was isolated from the brain, but not from the heart, of the dolphin. A cat fed mice infected with the dolphin isolate (designated TgSdCol) shed oocysts. Genomic DNA from tachyzoites of this isolate was used for genotyping at 10 genetic loci, including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico, and this TgSdCo1 isolate was found to be Type II.

A hierarchical model of the evolution of human brain specializations

PubMed Central

Barrett, H. Clark

2012-01-01

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. PMID:22723350

Ruminant Rhombencephalitis-Associated Listeria monocytogenes Alleles Linked to a Multilocus Variable-Number Tandem-Repeat Analysis Complex ▿ †

PubMed Central

Balandyté, Lina; Brodard, Isabelle; Frey, Joachim; Oevermann, Anna; Abril, Carlos

2011-01-01

Listeria monocytogenes is among the most important food-borne pathogens and is well adapted to persist in the environment. To gain insight into the genetic relatedness and potential virulence of L. monocytogenes strains causing central nervous system (CNS) infections, we used multilocus variable-number tandem-repeat analysis (MLVA) to subtype 183 L. monocytogenes isolates, most from ruminant rhombencephalitis and some from human patients, food, and the environment. Allelic-profile-based comparisons grouped L. monocytogenes strains mainly into three clonal complexes and linked single-locus variants (SLVs). Clonal complex A essentially consisted of isolates from human and ruminant brain samples. All but one rhombencephalitis isolate from cattle were located in clonal complex A. In contrast, food and environmental isolates mainly clustered into clonal complex C, and none was classified as clonal complex A. Isolates of the two main clonal complexes (A and C) obtained by MLVA were analyzed by PCR for the presence of 11 virulence-associated genes (prfA, actA, inlA, inlB, inlC, inlD, inlE, inlF, inlG, inlJ, and inlC2H). Virulence gene analysis revealed significant differences in the actA, inlF, inlG, and inlJ allelic profiles between clinical isolates (complex A) and nonclinical isolates (complex C). The association of particular alleles of actA, inlF, and newly described alleles of inlJ with isolates from CNS infections (particularly rhombencephalitis) suggests that these virulence genes participate in neurovirulence of L. monocytogenes. The overall absence of inlG in clinical complex A and its presence in complex C isolates suggests that the InlG protein is more relevant for the survival of L. monocytogenes in the environment. PMID:21984240

[Magnetic Resonance Imaging Conversion Predictors of Clinically Isolated Syndrome to Multiple Sclerosis].

PubMed

Peixoto, Sara; Abreu, Pedro

2016-11-01

Clinically isolated syndrome may be the first manifestation of multiple sclerosis, a chronic demyelinating disease of the central nervous system, and it is defined by a single clinical episode suggestive of demyelination. However, patients with this syndrome, even with long term follow up, may not develop new symptoms or demyelinating lesions that fulfils multiple sclerosis diagnostic criteria. We reviewed, in clinically isolated syndrome, what are the best magnetic resonance imaging findings that may predict its conversion to multiple sclerosis. A search was made in the PubMed database for papers published between January 2010 and June 2015 using the following terms: 'clinically isolated syndrome', 'cis', 'multiple sclerosis', 'magnetic resonance imaging', 'magnetic resonance' and 'mri'. In this review, the following conventional magnetic resonance imaging abnormalities found in literature were included: lesion load, lesion location, Barkhof's criteria and brain atrophy related features. The non conventional magnetic resonance imaging techniques studied were double inversion recovery, magnetization transfer imaging, spectroscopy and diffusion tensor imaging. The number and location of demyelinating lesions have a clear role in predicting clinically isolated syndrome conversion to multiple sclerosis. On the other hand, more data are needed to confirm the ability to predict this disease development of non conventional techniques and remaining neuroimaging abnormalities. In forthcoming years, in addition to the established predictive value of the above mentioned neuroimaging abnormalities, different clinically isolated syndrome neuroradiological findings may be considered in multiple sclerosis diagnostic criteria and/or change its treatment recommendations.

Asymptomatic solitary cerebral metastasis from papillary carcinoma thyroid: 131I SPECT/CT for accurate staging.

PubMed

Jain, Tarun Kumar; Karunanithi, Sellam; Sharma, Punit; Vijay, Maneesh Kumar; Ballal, Sanjana; Bal, Chandrasekhar

2014-11-01

Isolated asymptomatic brain metastasis in papillary carcinoma thyroid (PCT) is extremely rare. We here present such a case of a 48-year-old woman with PCT. SPECT/CT localized the 131I radiotracer concentration seen on whole-body scan in this patient to the right posterior parietal cortex, suggesting brain metastasis. Contrast-enhanced MRI and 18F-FDG PET/CT confirmed the diagnosis and the patient was taken for gamma-knife radiosurgery. 131I SPECT/CT in this case accurately restaged the patient by detecting asymptomatic isolated brain metastasis and correctly directed the management strategy.

A miniaturized multipurpose platform for rapid, label-free, and simultaneous separation, patterning, and in vitro culture of primary and rare cells.

PubMed

Didar, Tohid Fatanat; Bowey, Kristen; Almazan, Guillermina; Tabrizian, Maryam

2014-02-01

Given that current cell isolation techniques are expensive, time consuming, yield low isolation purities, and/or alter target cell properties, a versatile, cost effective, and easy-to-operate microchip with the capability to simultaneously separate, capture, pattern, and culture rare and primary cells in vitro is developed. The platform is based on target cell adhesion onto the micro-fabricated interfaces produced by microcontact printing of cell-specific antibodies. Results show over 95% separation efficiency in less than 10 min for the separation of oligodendrocyte progenitor cells (OPCs) and cardiomyocytes from rat brain and heart mixtures, respectively. Target cell attachment and single cell spreading can be precisely controlled on the basis of the designed patterns. Both cell types can maintain their biofunctionality. Indeed, isolated OPCs can proliferate and differentiate into mature oligodendrocytes, while isolated cardiomyocytes retain their contractile properties on the separation platform. Successful separation of two dissimilar cell types present in varying concentrations in their respective cell mixtures and the demonstration of their integrity after separation open new avenues for time and cost-effective sorting of various cell types using the developed miniaturized platform. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of single spore isolates of Agaricus bisporus (Lange) Imbach using conventional and molecular methods.

PubMed

Sharma, Manju; Suman, B C; Gupta, Dharmesh

2014-10-01

Strains A-15, S11, S-140, and U3 of Agaricus bisporus (Lange) Imbach, were used as parent strains for raising single spore homokaryotic isolates. Out of total 1,642 single spore isolates, only 36 single spore isolates were homokaryons and exhibited slow mycelial growth rate (≤2.0 mm/day) and appressed colony morphology. All these SSIs failed to produce pinheads in Petri plates even after 65 days of incubation, whereas the strandy slow growing SSIs along with parent strains were able to form the fructification in petriplates after 30 days. Out of 24, six ISSR primers, exhibited scorable bands. In the ISSR fingerprints, single spore isolates, homokaryons, lacked amplification products at multiple loci; they grow slowly and all of them had appressed types of colony morphology. The study revealed losses of ISSR polymorphic patterns in non-fertile homokaryotic single spore isolates compared to the parental control or fertile heterokaryotic single spore isolates.

Biological characterisation of Sarcocystis neurona isolated from a Southern sea otter (Enhydra lutris nereis)

USGS Publications Warehouse

Lindsay, D.S.; Thomas, N.J.; Dubey, J.P.

2000-01-01

Sarcocystis neurona was isolated from the brain of a juvenile, male southern sea otter (Enhydra lutris nereis) suffering from CNS disease. Schizonts and merozoites in tissue sections of the otter's brain reacted with anti-S. neurona antiserum immunohistochemically. Development in cell culture was by endopolyogeny and mature schizonts were first observed at 3 days postinoculation. PCR of merozoite DNA using primer pairs JNB33/JNB54 and restriction enzyme digestion of the 1100 bp product with Dra I indicated the organism was S. neurona. Four of four interferon-γ gene knockout mice inoculated with merozoites developed S. neurona-associated encephalitis. Antibodies to S. neurona but not Sarcocystis falcatula, Toxoplasma gondii, or Neospora caninum were present in the serum of inoculated mice. This is the first isolation of S. neurona from the brain of a non-equine host.

Simultaneous real-time monitoring of multiple cortical systems.

PubMed

Gupta, Disha; Jeremy Hill, N; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L; Schalk, Gerwin

2014-10-01

Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. We study these questions using electrocorticographic signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (six for offline parameter optimization, six for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main Results: Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelopes. These decoders were trained separately and executed simultaneously in real time. This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple independent brain systems. Our comparison of univariate and multivariate decoding strategies, and our analysis of the influence of their decoding parameters, provides benchmarks and guidelines for future research on this topic.

Simultaneous Real-Time Monitoring of Multiple Cortical Systems

PubMed Central

Gupta, Disha; Hill, N. Jeremy; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L.; Schalk, Gerwin

2014-01-01

Objective Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor, or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. Approach We study these questions using electrocorticographic (ECoG) signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (6 for offline parameter optimization, 6 for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main results Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelope. These decoders were trained separately and executed simultaneously in real time. Significance This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple independent brain systems. Our comparison of univariate and multivariate decoding strategies, and our analysis of the influence of their decoding parameters, provides benchmarks and guidelines for future research on this topic. PMID:25080161

A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing.

PubMed

Murakami, Tatsuya C; Mano, Tomoyuki; Saikawa, Shu; Horiguchi, Shuhei A; Shigeta, Daichi; Baba, Kousuke; Sekiya, Hiroshi; Shimizu, Yoshihiro; Tanaka, Kenji F; Kiyonari, Hiroshi; Iino, Masamitsu; Mochizuki, Hideki; Tainaka, Kazuki; Ueda, Hiroki R

2018-04-01

A three-dimensional single-cell-resolution mammalian brain atlas will accelerate systems-level identification and analysis of cellular circuits underlying various brain functions. However, its construction requires efficient subcellular-resolution imaging throughout the entire brain. To address this challenge, we developed a fluorescent-protein-compatible, whole-organ clearing and homogeneous expansion protocol based on an aqueous chemical solution (CUBIC-X). The expanded, well-cleared brain enabled us to construct a point-based mouse brain atlas with single-cell annotation (CUBIC-Atlas). CUBIC-Atlas reflects inhomogeneous whole-brain development, revealing a significant decrease in the cerebral visual and somatosensory cortical areas during postnatal development. Probabilistic activity mapping of pharmacologically stimulated Arc-dVenus reporter mouse brains onto CUBIC-Atlas revealed the existence of distinct functional structures in the hippocampal dentate gyrus. CUBIC-Atlas is shareable by an open-source web-based viewer, providing a new platform for whole-brain cell profiling.

Exploring the Use of Isolated Expressions and Film Clips to Evaluate Emotion Recognition by People with Traumatic Brain Injury

PubMed Central

Zupan, Barbra; Neumann, Dawn

2016-01-01

The current study presented 60 people with traumatic brain injury (TBI) and 60 controls with isolated facial emotion expressions, isolated vocal emotion expressions, and multimodal (i.e., film clips) stimuli that included contextual cues. All stimuli were presented via computer. Participants were required to indicate how the person in each stimulus was feeling using a forced-choice format. Additionally, for the film clips, participants had to indicate how they felt in response to the stimulus, and the level of intensity with which they experienced that emotion. PMID:27213280

Oxytocin-Induced Changes in Monoamine Level in Symmetric Brain Structures of Isolated Aggressive C57Bl/6 Mice.

PubMed

Karpova, I V; Mikheev, V V; Marysheva, V V; Bychkov, E R; Proshin, S N

2016-03-01

Changes in activity of monoaminergic systems of the left and right brain hemispheres after administration of saline and oxytocin were studied in male C57Bl/6 mice subjected to social isolation. The concentrations of dopamine, norepinephrine, serotonin, and their metabolites dihydroxyphenylacetic, homovanillic, and 5-hydroxyindoleacetic acids were measured in the cerebral cortex, hippocampus, olfactory tubercle, and striatum of the left and right brain hemispheres by HPLC. In isolated aggressive males treated intranasally with saline, the content of serotonin and 5-hydroxyindoleacetic acid was significantly higher in the right hippocampus. Oxytocin reduces aggression caused by long-term social isolation, but has no absolute ability to suppress this type of behavior. Oxytocin reduced dopamine content in the left cortex and serotonin content in the right hippocampus and left striatum. Furthermore, oxytocin evened the revealed asymmetry in serotonin and 5-hydroxyindoleacetic acid concentrations in the hippocampus. At the same time, asymmetry in dopamine concentration appeared in the cortex with predominance of this transmitter in the right hemisphere. The data are discussed in the context of lateralization of neurotransmitter systems responsible for intraspecific aggression caused by long-term social isolation.

Isolation, properties and P content of the human brain myosin.

PubMed

Fazekas, S; Ováry, I; Horváth, E; Székessy-Hermann, V; Juhász, P

1982-01-01

KCl-, and NaCl-myosins were prepared from different parts of the central nervous system (CNS). Throughout these experiments P and lipid contents were higher in NaCl-myosins than in KCl-preparations. Both KCl-, and NaCl-myosins have increased lipid and P contents compared with skeletal muscle myosins. When the specimens were separated by a molecular sieve, it was found by chromatographic technique on Sepharose 4B column that the cerebral and cerebellar myosins were composed of two fractions of different molecular mass while the brain stem and spinal cord myosins revealed only a single peak. The myosin fractions' Ca-ATPase activity could be augmented by rabbit muscle actin. The myosin preparations developed filamentous systems and aggregates which could be shown by scanning electron microscopy. All the CNS-myosin preparations could be phosphorylated; however, they were saturated to a different degree and were influenced by the presence or absence of serotonin. The kinetic studies revealed that the phosphate saturation of the brain stem, cerebellar and cerebral myosins depended on the ATP concentration and incubation time. The alkaline hydrolysates of lipid-free human brain myosin preparations contained amino acid phosphates, P-Arg, P-Lys and P-His in different amounts depending on their sources. In response to a phosphorylating mixture only the amount of P-Arg was elevated in the cerebral myosins, P-Arg and P-His in the brain stem preparations, and P-Arg, P-His and the amounts of unidentified compounds in the cerebellar ones.

Isolation and molecular typing of Naegleria fowleri from the brain of a cow that died of primary amebic meningoencephalitis.

PubMed

Visvesvara, Govinda S; De Jonckheere, Johan F; Sriram, Rama; Daft, Barbara

2005-08-01

Naegleria fowleri causes an acute and rapidly fatal central nervous system infection called primary amebic meningoencephalitis (PAM) in healthy children and young adults. We describe here the identification of N. fowleri isolated from the brain of one of several cows that died of PAM based on sequencing of the internal transcribed spacers, including the 5.8S rRNA genes.

Whole-Genome Sequence of a Suid Herpesvirus-1 Strain Isolated from the Brain of a Hunting Dog in Italy

PubMed Central

Pizzurro, Federica; Mangone, Iolanda; Zaccaria, Guendalina; De Luca, Eliana; Malatesta, Daniela; Innocenti, Marco; Carmine, Irene; Cito, Francesca; Marcacci, Maurilia; Di Sabatino, Daria

2016-01-01

Suid herpesvirus-1 (SHV-1), a DNA virus of the family Herpesviridae, causes a severe and fatal disease in a wide range of mammals. Here, we report the whole-genome sequence of an SHV-1 isolated in Italy in 2014 from the brain of a hunting dog that suffered from an acute and severe disease. PMID:27908993

Isolated spinal cord contusion in rats induces chronic brain neuroinflammation, neurodegeneration, and cognitive impairment. Involvement of cell cycle activation.

PubMed

Wu, Junfang; Stoica, Bogdan A; Luo, Tao; Sabirzhanov, Boris; Zhao, Zaorui; Guanciale, Kelsey; Nayar, Suresh K; Foss, Catherine A; Pomper, Martin G; Faden, Alan I

2014-01-01

Cognitive dysfunction has been reported in patients with spinal cord injury (SCI), but it has been questioned whether such changes may reflect concurrent head injury, and the issue has not been addressed mechanistically or in a well-controlled experimental model. Our recent rodent studies examining SCI-induced hyperesthesia revealed neuroinflammatory changes not only in supratentorial pain-regulatory sites, but also in other brain regions, suggesting that additional brain functions may be impacted following SCI. Here we examined effects of isolated thoracic SCI in rats on cognition, brain inflammation, and neurodegeneration. We show for the first time that SCI causes widespread microglial activation in the brain, with increased expression of markers for activated microglia/macrophages, including translocator protein and chemokine ligand 21 (C-C motif). Stereological analysis demonstrated significant neuronal loss in the cortex, thalamus, and hippocampus. SCI caused chronic impairment in spatial, retention, contextual, and fear-related emotional memory-evidenced by poor performance in the Morris water maze, novel objective recognition, and passive avoidance tests. Based on our prior work implicating cell cycle activation (CCA) in chronic neuroinflammation after SCI or traumatic brain injury, we evaluated whether CCA contributed to the observed changes. Increased expression of cell cycle-related genes and proteins was found in hippocampus and cortex after SCI. Posttraumatic brain inflammation, neuronal loss, and cognitive changes were attenuated by systemic post-injury administration of a selective cyclin-dependent kinase inhibitor. These studies demonstrate that chronic brain neurodegeneration occurs after isolated SCI, likely related to sustained microglial activation mediated by cell cycle activation.

Isolated spinal cord contusion in rats induces chronic brain neuroinflammation, neurodegeneration, and cognitive impairment

PubMed Central

Wu, Junfang; Stoica, Bogdan A; Luo, Tao; Sabirzhanov, Boris; Zhao, Zaorui; Guanciale, Kelsey; Nayar, Suresh K; Foss, Catherine A; Pomper, Martin G; Faden, Alan I

2014-01-01

Cognitive dysfunction has been reported in patients with spinal cord injury (SCI), but it has been questioned whether such changes may reflect concurrent head injury, and the issue has not been addressed mechanistically or in a well-controlled experimental model. Our recent rodent studies examining SCI-induced hyperesthesia revealed neuroinflammatory changes not only in supratentorial pain-regulatory sites, but also in other brain regions, suggesting that additional brain functions may be impacted following SCI. Here we examined effects of isolated thoracic SCI in rats on cognition, brain inflammation, and neurodegeneration. We show for the first time that SCI causes widespread microglial activation in the brain, with increased expression of markers for activated microglia/macrophages, including translocator protein and chemokine ligand 21 (C–C motif). Stereological analysis demonstrated significant neuronal loss in the cortex, thalamus, and hippocampus. SCI caused chronic impairment in spatial, retention, contextual, and fear-related emotional memory—evidenced by poor performance in the Morris water maze, novel objective recognition, and passive avoidance tests. Based on our prior work implicating cell cycle activation (CCA) in chronic neuroinflammation after SCI or traumatic brain injury, we evaluated whether CCA contributed to the observed changes. Increased expression of cell cycle-related genes and proteins was found in hippocampus and cortex after SCI. Posttraumatic brain inflammation, neuronal loss, and cognitive changes were attenuated by systemic post-injury administration of a selective cyclin-dependent kinase inhibitor. These studies demonstrate that chronic brain neurodegeneration occurs after isolated SCI, likely related to sustained microglial activation mediated by cell cycle activation. PMID:25483194

Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prody, C.A.; Zevin-Sonkin, D.; Gnatt, A.

1987-06-01

To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase and Torpedo electric organ true acetylcholinesterase. Using these probes, the authors isolated several cDNA clones from lambdagt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. Inmore » RNA blots of poly(A)/sup +/ RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These finding demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species.« less

c-Fos expression in the paternal mouse brain induced by communicative interaction with maternal mates.

PubMed

Zhong, Jing; Liang, Mingkun; Akther, Shirin; Higashida, Chiharu; Tsuji, Takahiro; Higashida, Haruhiro

2014-09-11

Appropriate parental care by fathers greatly facilitates health in human family life. Much less is known from animal studies regarding the factors and neural circuitry that affect paternal behavior compared with those affecting maternal behavior. We recently reported that ICR mouse sires displayed maternal-like retrieval behavior when they were separated from pups and caged with their mates (co-housing) because the sires receive communicative interactions via ultrasonic and pheromone signals from the dams. We investigated the brain structures involved in regulating this activity by quantifying c-Fos-immunoreactive cells as neuronal activation markers in the neural pathway of male parental behavior. c-Fos expression in the medial preoptic area (mPOA) was significantly higher in sires that exhibited retrieval behavior (retrievers) than those with no such behavior (non-retrievers). Identical increased expression was found in the mPOA region in the retrievers stimulated by ultrasonic vocalizations or pheromones from their mates. Such increases in expression were not observed in the ventral tegmental area (VTA), nucleus accumbens (NAcc) or ventral palladium (VP). On the following day that we identified the families of the retrievers or non-retrievers, c-Fos expression in neuronal subsets in the mPOA, VTA, NAcc and VP was much higher in the retriever sires when they isolated together with their mates in new cages. This difference was not observed in the singly isolated retriever sires in new cages. The non-retriever sires did not display expression changes in the four brain regions that were assessed. The mPOA neurons appeared to be activated by direct communicative interactions with mate dams, including ultrasonic vocalizations and pheromones. The mPOA-VTA-NAcc-VP neural circuit appears to be involved in paternal retrieval behavior.

Glutamic Acid Signal Synchronizes Protein Synthesis Kinetics in Hepatocytes from Old Rats for the Following Several Days. Cell Metabolism Memory.

PubMed

Brodsky, V Y; Malchenko, L A; Lazarev, D S; Butorina, N N; Dubovaya, T K; Zvezdina, N D

2018-03-01

The kinetics of protein synthesis was investigated in primary cultures of hepatocytes from old rats in serum-free medium. The rats were fed mixed fodder supplemented with glutamic acid and then transferred to a regular mixed fodder. The amplitude of protein synthesis rhythm in hepatocytes isolated from these rats increased on average 2-fold in comparison with the rats not receiving glutamic acid supplement. Based on this indicator reflecting the degree of cell-cell interactions, the cells from old rats were not different from those of young rats. The effect was preserved for 3-4 days. These results are discussed in connection with our previous data on preservation of the effect of single administration of gangliosides, noradrenaline, serotonin, and other synchronizers on various cell populations. In contrast to the other investigated factors, glutamic acid is capable of penetrating the blood-brain barrier, which makes its effect possible not only in the case of hepatocytes and other non-brain cells, but also in neurons.

The effect of brain lesions on sound localization in complex acoustic environments.

PubMed

Zündorf, Ida C; Karnath, Hans-Otto; Lewald, Jörg

2014-05-01

Localizing sound sources of interest in cluttered acoustic environments--as in the 'cocktail-party' situation--is one of the most demanding challenges to the human auditory system in everyday life. In this study, stroke patients' ability to localize acoustic targets in a single-source and in a multi-source setup in the free sound field were directly compared. Subsequent voxel-based lesion-behaviour mapping analyses were computed to uncover the brain areas associated with a deficit in localization in the presence of multiple distracter sound sources rather than localization of individually presented sound sources. Analyses revealed a fundamental role of the right planum temporale in this task. The results from the left hemisphere were less straightforward, but suggested an involvement of inferior frontal and pre- and postcentral areas. These areas appear to be particularly involved in the spectrotemporal analyses crucial for effective segregation of multiple sound streams from various locations, beyond the currently known network for localization of isolated sound sources in otherwise silent surroundings.

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

NASA Astrophysics Data System (ADS)

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.

A Triple Culture Model of the Blood-Brain Barrier Using Porcine Brain Endothelial cells, Astrocytes and Pericytes.

PubMed

Thomsen, Louiza Bohn; Burkhart, Annette; Moos, Torben

2015-01-01

In vitro blood-brain barrier (BBB) models based on primary brain endothelial cells (BECs) cultured as monoculture or in co-culture with primary astrocytes and pericytes are useful for studying many properties of the BBB. The BECs retain their expression of tight junction proteins and efflux transporters leading to high trans-endothelial electric resistance (TEER) and low passive paracellular permeability. The BECs, astrocytes and pericytes are often isolated from small rodents. Larger species as cows and pigs however, reveal a higher yield, are readily available and have a closer resemblance to humans, which make them favorable high-throughput sources for cellular isolation. The aim of the present study has been to determine if the preferable combination of purely porcine cells isolated from the 6 months old domestic pigs, i.e. porcine brain endothelial cells (PBECs) in co-culture with porcine astrocytes and pericytes, would compare with PBECs co-cultured with astrocytes and pericytes isolated from newborn rats with respect to TEER value and low passive permeability. The astrocytes and pericytes were grown both as contact and non-contact co-cultures as well as in triple culture to examine their effects on the PBECs for barrier formation as revealed by TEER, passive permeability, and expression patterns of tight junction proteins, efflux transporters and the transferrin receptor. This syngenic porcine in vitro BBB model is comparable to triple cultures using PBECs, rat astrocytes and rat pericytes with respect to TEER formation, low passive permeability, and expression of hallmark proteins signifying the brain endothelium (tight junction proteins claudin 5 and occludin, the efflux transporters P-glycoprotein (PgP) and breast cancer related protein (BCRP), and the transferrin receptor).

Isolated Cortical Vein Thrombosis - The Cord Sign

PubMed Central

Sharma, Vijay K.; Teoh, Hock L

2009-01-01

Isolated cortical vein thrombosis is an uncommon condition and often difficult to diagnose, both clinically and radiologically. We report a case of a 38 years old man who presented with headache of new onset and clinical examination was unremarkable. The unenhanced brain CT did not reveal any abnormality. In view of unrelenting headache and partial seizures, we performed magnetic resonance imaging (with axial T1, T2 and gradient echo sequences, coronal FLAIR, diffusion weighted imaging as well as Gadolinium contrast-enhanced images) and magnetic resonance venography of the brain that revealed an isolated parietal cortical vein thrombosis with the rarely reported 'cord sign'. We report the clinical and radiological findings in our patient with isolated parietal cortical vein thrombosis. PMID:22470649

A conformal transceive array for 7 T neuroimaging.

PubMed

Gilbert, Kyle M; Belliveau, Jean-Guy; Curtis, Andrew T; Gati, Joseph S; Klassen, L Martyn; Menon, Ravi S

2012-05-01

The first 16-channel transceive surface-coil array that conforms to the human head and operates at 298 MHz (7 T) is described. Individual coil elements were decoupled using circumferential shields around each element that extended orthogonally from the former. This decoupling method allowed elements to be constructed with arbitrary shape, size, and location to create a three-dimensional array. Radiofrequency shimming achieved a transmit-field uniformity of 20% over the whole brain and 14% over a single axial slice. During radiofrequency transmission, coil elements couple tightly to the head and reduce the amount of power necessary to achieve a mean 90° flip angle (660-μs and 480-μs pulse lengths were required for a 1-kW hard pulse when shimming over the whole brain and a single axial slice, respectively). During reception, the close proximity of coil elements to the head increases the signal-to-noise ratio in the periphery of the brain, most notably at the superior aspect of the head. The sensitivity profile of each element is localized beneath the respective shield. When combined with the achieved isolation between elements, this results in the capacity for low geometry factors during both transmit and receive: 1.04/1.06 (mean) and 1.25/1.54 (maximum) for 3-by-3 acceleration in the axial/sagittal plane. High cortical signal-to-noise ratio and parallel imaging performance make the conformal coil ideal for the study of high temporal and/or spatial cortical architecture and function. Copyright © 2011 Wiley Periodicals, Inc.

Nomadic Political Ontology and Transnational Academic Mobility

ERIC Educational Resources Information Center

Metcalfe, Amy Scott

2017-01-01

Transnational academic mobility is often characterized in relation to terms such as "brain drain", "brain gain", or "brain circulation"--terms that isolate researchers' minds from their bodies, while saying nothing about their political identities as foreign nationals. In this paper, I explore the possibilities of a…

Isolated brain stem lesion in children: is it acute disseminated encephalomyelitis or not?

PubMed

Alper, G; Sreedher, G; Zuccoli, G

2013-01-01

Isolated brain stem lesions presenting with acute neurologic findings create a major diagnostic dilemma in children. Although the brain stem is frequently involved in ADEM, solitary brain stem lesions are unusual. We performed a retrospective review in 6 children who presented with an inflammatory lesion confined to the brain stem. Two children were diagnosed with connective tissue disorder, CNS lupus, and localized scleroderma. The etiology could not be determined in 1, and clinical features suggested monophasic demyelination in 3. In these 3 children, initial lesions demonstrated vasogenic edema; all showed dramatic response to high-dose corticosteroids and made a full clinical recovery. Follow-up MRI showed complete resolution of lesions, and none had relapses at >2 years of follow-up. In retrospect, these cases are best regarded as a localized form of ADEM. We conclude that though ADEM is typically a disseminated disease with multifocal lesions, it rarely presents with monofocal demyelination confined to the brain stem.

Differing effects of cyclosporin a on swelling amplitude and time constant of mitochondria from normal and ischemic rat brain.

PubMed

Wu, Li-Ping; Shen, Fang; Lu, Yuan; Bruce, Iain; Xia, Qiang

2005-01-01

The purpose of this study was to investigate the effect of cyclosporin A on swelling amplitude and time constant of mitochondria isolated from normal and ischemic rat brain and to observe the possible role of the mitochondrial ATP-sensitive potassium channel on mitochondrial permeability transition. Mitochondrial swelling was evaluated by spectrophotometry. Cyclosporin A at 0.5 or 1 microM and diazoxide at 30 microM significantly decreased the swelling amplitude and attenuated the reduction of time constant of mitochondria isolated from normal brain mitochondria induced by 200 microM calcium, an effect abolished by atractyloside at 100 microM. However, cyclosporin A at 5 microM did not affect mitochondrial swelling. In mitochondria from ischemic brain, cyclosporin A at 0.5 microM but not 1 microM significantly decreased mitochondrial swelling amplitude and attenuated the reduction of time constant, which was abolished by atractyloside. Diazoxide had an effect similar to cyclosporin A at 0.5 microM, which was blocked by atractyloside or 5-hydroxydecanoate at 100 microM and 200 microM. Compared with mitochondria isolated from normal brain, those from ischemic brain were more sensitive to cyclosporin A. Activation of the mitochondrial ATP-sensitive potassium channel may be one of the mechanisms by which opening of the mitochondrial permeability transition pore is inhibited.

Characteristics of allelic gene expression in human brain cells from single-cell RNA-seq data analysis.

PubMed

Zhao, Dejian; Lin, Mingyan; Pedrosa, Erika; Lachman, Herbert M; Zheng, Deyou

2017-11-10

Monoallelic expression of autosomal genes has been implicated in human psychiatric disorders. However, there is a paucity of allelic expression studies in human brain cells at the single cell and genome wide levels. In this report, we reanalyzed a previously published single-cell RNA-seq dataset from several postmortem human brains and observed pervasive monoallelic expression in individual cells, largely in a random manner. Examining single nucleotide variants with a predicted functional disruption, we found that the "damaged" alleles were overall expressed in fewer brain cells than their counterparts, and at a lower level in cells where their expression was detected. We also identified many brain cell type-specific monoallelically expressed genes. Interestingly, many of these cell type-specific monoallelically expressed genes were enriched for functions important for those brain cell types. In addition, function analysis showed that genes displaying monoallelic expression and correlated expression across neuronal cells from different individual brains were implicated in the regulation of synaptic function. Our findings suggest that monoallelic gene expression is prevalent in human brain cells, which may play a role in generating cellular identity and neuronal diversity and thus increasing the complexity and diversity of brain cell functions.

High-resolution mapping and sequence analysis of 597 cDNA clones transcribed from the 1 Mb region in human chromosome 4q16.3 containing Huntington disease gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hadano, S.; Ishida, Y.; Tomiyasu, H.

1994-09-01

To complete a transcription map of the 1 Mb region in human chromosome 4p16.3 containing the Huntington disease (HD) gene, the isolation of cDNA clones are being performed throughout. Our method relies on a direct screening of the cDNA libraries probed with single copy microclones from 3 YAC clones spanning 1 Mbp of the HD gene region. AC-DNAs were isolated by a preparative pulsed-field gel electrophoresis, amplified by both a single unique primer (SUP)-PCR and a linker ligation PCR, and 6 microclone-DNA libraries were generated. Then, 8,640 microclones from these libraries were independently amplified by PCR, and arrayed onto themore » membranes. 800-900 microclones that were not cross-hybridized with total human and yeast genomic DNA, TAC vector DNA, and ribosomal cDNA on a dot hybridization (putatively carrying single copy sequences) were pooled to make 9 probe pools. A total of {approximately}1.8x10{sup 7} plaques from the human brain cDNA libraries was screened with 9 pool-probes, and then 672 positive cDNA clones were obtained. So far, 597 cDNA clones were defined and arrayed onto a map of the 1 Mbp of the HD gene region by hybridization with HD region-specific cosmid contigs and YAC clones. Further characterization including a DNA sequencing and Northern blot analysis is currently underway.« less

Osteoporosis Self-Assessment Tool for Asians Can Predict Neurologic Prognosis in Patients with Isolated Moderate Traumatic Brain Injury

PubMed Central

Chan, Hon-Man; Huang, Shiuh-Lin; Lin, Chih-Lung; Kwan, Aij-Lie; Lou, Yun-Ting; Chen, Chao-Wen

2015-01-01

Objectives Osteoporosis Self-Assessment Tool for Asians (OSTA) has been proved to be a simple and effective tool for recognizing osteoporosis risk. Our previous study has demonstrated that the preoperative OSTA index was a good prognostic predictor for stage II and III colon cancer patients after surgery. We aim to evaluate the value of OSTA index in prognostication of isolated traumatic brain injury with moderate severity (GCS 9-13). Methods We retrospectively reviewed all patients visiting Kaohsiung Medical University Hospital emergency department due to isolated moderate traumatic brain injury from Jan. 2010 to Dec. 2012. Background data (including the OSTA index), clinical presentations, management and outcomes (ICU admission days, total admission days, complications, Glasgow outcome score (GOS) at discharge, mortality) of the patients were recorded for further analysis. Our major outcome was good neurologic recovery defined as GOS of 5. Pearson chi-square test and the Mann-Whitney U test were used to compare demographic features. Multiple logistic regression was used to identify independent risk factors. Results 107 isolated moderate TBI patients were studied. 40 patients (37.4%) showed good recovery and 10 (9.3%) died at discharge. The univariate analysis revealed that younger age, higher OSTA index, lower ISS, lower AIS-H, and avoidance to neurosurgery were associated with better neurologic outcome for all moderate TBI patients. Multivariate analysis revealed that lower ISS, higher OSTA, and the avoidance of neurosurgery were independent risk factors predicting good neurologic recovery. Conclusion Higher ISS, lower OSTA index and exposure to neurosurgery were the independent risk factors for poorer recovery from isolated moderate TBI. In addition to labeling the cohort harboring osteoporotic risk, OSTA index could predict neurologic prognosis in patients with isolated moderate traumatic brain injury. PMID:26186582

Brain regional differences in social encounter-induced Fos expression in male and female rats after post-weaning social isolation.

PubMed

Ahern, Megan; Goodell, Dayton J; Adams, Jessica; Bland, Sondra T

2016-01-01

Early life adversity has been related to a number of psychological disorders including mood and other disorders that can manifest as inappropriate or aggressive responses to social challenges. The present study used post-weaning social isolation (PSI) in rats, a model of early life adversity, to examine its effects on Fos protein expression produced by exposure to a novel social encounter. We have previously reported that the social encounter-induced increase in Fos expression in the medial prefrontal cortex observed in group-housed controls (GRP) was attenuated in rats that had experienced PSI. Here we assessed Fos expression in other brain regions thought to be involved in emotion regulation and social behavior. Male and female rats were housed in same-sex groups or in isolation (ISO) for 4 weeks beginning on postnatal day (P) 21 and were exposed to a single 15 min social encounter with a novel same-sex conspecific on P49. Fos positive cells were assessed using immunohistochemistry in 16 regions within the forebrain. Exposure to a novel conspecific increased Fos expression in the forebrain of GRP rats in a region- and sex-specific fashion. This increase was blunted or absent in ISO rats within many regions including cortical regions, thalamus, habenula, dentate gyrus, lateral septum, and basolateral amygdala. In several regions, the increase in Fos was greater in male than in female group housed rats. Negative relationships were observed between social interactions and Fos in some regions. Forebrain hypofunction produced by early-life adversity may be involved in socially inappropriate behavior. Copyright © 2015 Elsevier B.V. All rights reserved.

Isolation and Molecular Typing of Naegleria fowleri from the Brain of a Cow That Died of Primary Amebic Meningoencephalitis

PubMed Central

Visvesvara, Govinda S.; De Jonckheere, Johan F.; Sriram, Rama; Daft, Barbara

2005-01-01

Naegleria fowleri causes an acute and rapidly fatal central nervous system infection called primary amebic meningoencephalitis (PAM) in healthy children and young adults. We describe here the identification of N. fowleri isolated from the brain of one of several cows that died of PAM based on sequencing of the internal transcribed spacers, including the 5.8S rRNA genes. PMID:16081978

Thyroxine (T4) Transfer from Blood to Cerebrospinal Fluid in Sheep Isolated Perfused Choroid Plexus: Role of Multidrug Resistance-Associated Proteins and Organic Anion Transporting Polypeptides

PubMed Central

Zibara, Kazem; Zein, Nabil El; Sabra, Mirna; Hneino, Mohammad; Harati, Hayat; Mohamed, Wael; Kobeissy, Firas H.; Kassem, Nouhad

2017-01-01

Thyroxine (T4) enters the brain either directly across the blood–brain barrier (BBB) or indirectly via the choroid plexus (CP), which forms the blood–cerebrospinal fluid barrier (B-CSF-B). In this study, using isolated perfused CP of the sheep by single-circulation paired tracer and steady-state techniques, T4 transport mechanisms from blood into lateral ventricle CP has been characterized as the first step in the transfer across the B-CSF-B. After removal of sheep brain, the CPs were perfused with 125I-T4 and 14C-mannitol. Unlabeled T4 was applied during single tracer technique to assess the mode of maximum uptake (Umax) and the net uptake (Unet) on the blood side of the CP. On the other hand, in order to characterize T4 protein transporters, steady-state extraction of 125I-T4 was measured in presence of different inhibitors such as probenecid, verapamil, BCH, or indomethacin. Increasing the concentration of unlabeled-T4 resulted in a significant reduction in Umax%, which was reflected by a complete inhibition of T4 uptake into CP. In fact, the obtained Unet% decreased as the concentration of unlabeled-T4 increased. The addition of probenecid caused a significant inhibition of T4 transport, in comparison to control, reflecting the presence of a carrier mediated process at the basolateral side of the CP and the involvement of multidrug resistance-associated proteins (MRPs: MRP1 and MRP4) and organic anion transporting polypeptides (Oatp1, Oatp2, and Oatp14). Moreover, verapamil, the P-glycoprotein (P-gp) substrate, resulted in ~34% decrease in the net extraction of T4, indicating that MDR1 contributes to T4 entry into CSF. Finally, inhibition in the net extraction of T4 caused by BCH or indomethacin suggests, respectively, a role for amino acid “L” system and MRP1/Oatp1 in mediating T4 transfer. The presence of a carrier-mediated transport mechanism for cellular uptake on the basolateral membrane of the CP, mainly P-gp and Oatp2, would account for the efficient T4 transport from blood to CSF. The current study highlights a carrier-mediated transport mechanism for T4 movement from blood to brain at the basolateral side of B-CSF-B/CP, as an alternative route to BBB. PMID:28588548

Isolating dividing neural and brain tumour cells for gene expression profiling.

PubMed

Endaya, Berwini; Cavanagh, Brenton; Alowaidi, Faisal; Walker, Tom; de Pennington, Nicholas; Ng, Jin-Ming A; Lam, Paula Y P; Mackay-Sim, Alan; Neuzil, Jiri; Meedeniya, Adrian C B

2016-01-15

The characterisation of dividing brain cells is fundamental for studies ranging from developmental and stem cell biology, to brain cancers. Whilst there is extensive anatomical data on these dividing cells, limited gene transcription data is available due to technical constraints. We focally isolated dividing cells whilst conserving RNA, from culture, primary neural tissue and xenografted glioma tumours, using a thymidine analogue that enables gene transcription analysis. 5-ethynyl-2-deoxyuridine labels the replicating DNA of dividing cells. Once labelled, cultured cells and tissues were dissociated, fluorescently tagged with a revised click chemistry technique and the dividing cells isolated using fluorescence-assisted cell sorting. RNA was extracted and analysed using real time PCR. Proliferation and maturation related gene expression in neurogenic tissues was demonstrated in acutely and 3 day old labelled cells, respectively. An elevated expression of marker and pathway genes was demonstrated in the dividing cells of xenografted brain tumours, with the non-dividing cells showing relatively low levels of expression. BrdU "immune-labelling", the most frequently used protocol for detecting cell proliferation, causes complete denaturation of RNA, precluding gene transcription analysis. This EdU labelling technique, maintained cell integrity during dissociation, minimized copper exposure during labelling and used a cell isolation protocol that avoided cell lysis, thus conserving RNA. The technique conserves RNA, enabling the definition of cell proliferation-related changes in gene transcription of neural and pathological brain cells in cells harvested immediately after division, or following a period of maturation. Copyright © 2015 Elsevier B.V. All rights reserved.

What the cerveau isolé preparation tells us nowadays about sleep-wake mechanisms?

PubMed

Gottesmann, C

1988-01-01

The intercollicular transected preparation opened a rich field for investigations of sleep-wake mechanisms. Initial results showed that brain stem ascending influences are essential for maintaining an activated cortex. It was subsequently shown that the forebrain also develops activating influences, since EEG desynchronization of the cortex reappears in the chronic cerveau isolé preparation, and continuous or almost continuous theta rhythm is able to occur in the acute cerveau isolé preparation. A brief "intermediate stage" of sleep occurs during natural sleep just prior to and after paradoxical sleep. It is characterized by cortical spindle bursts, hippocampal low frequency theta activity (two patterns of the acute cerveau isolé preparation) and is accompanied by a very low thalamic transmission level, suggesting a cerveau isolé-like state. The chronic cerveau isolé preparation also demonstrates that the executive processes of paradoxical sleep are located in the lower brain stem, while the occurrence of this sleep stage seems to be modulated by forebrain structures.

Developmental social isolation affects adult behavior, social interaction, and dopamine metabolite levels in zebrafish.

PubMed

Shams, Soaleha; Amlani, Shahid; Buske, Christine; Chatterjee, Diptendu; Gerlai, Robert

2018-01-01

The zebrafish is a social vertebrate and an excellent translational model for a variety of human disorders. Abnormal social behavior is a hallmark of several human brain disorders. Social behavioral problems can arise as a result of adverse early social environment. Little is known about the effects of early social isolation in adult zebrafish. We compared zebrafish that were isolated for either short (7 days) or long duration (180 days) to socially housed zebrafish, testing their behavior across ontogenesis (ages 10, 30, 60, 90, 120, 180 days), and shoal cohesion and whole-brain monoamines and their metabolites in adulthood. Long social isolation increased locomotion and decreased shoal cohesion and anxiety in the open-field in adult. Additionally, both short and long social isolation reduced dopamine metabolite levels in response to social stimuli. Thus, early social isolation has lasting effects in zebrafish, and may be employed to generate zebrafish models of human neuropsychiatric conditions. © 2017 Wiley Periodicals, Inc.

In vitro studies of the blood-brain barrier using isolated brain capillaries and cultured endothelial cells.

PubMed

Goldstein, G W; Betz, A L; Bowman, P D; Dorovini-Zis, K

1986-01-01

The endothelial cells in brain capillaries are the anatomic site of the blood-brain barrier. To learn more about the biology of these specialized cells, we developed methods to prepare suspensions of purified brain microvessels as well as primary cultures of endothelial cells in monolayer. These two preparations allow for direct investigation of the metabolism, transport properties, and receptor content of the brain capillary. We used isolated brain microvessels to study distribution of membrane carriers between the luminal and the abluminal plasma membrane of endothelial cells. We found that Na+K+-ATPase and the A-system amino-acid transport system are located predominantly on the abluminal surface of brain capillary endothelial cells. This distribution of transport carriers is consistent with the low permeability of potassium and small neutral amino acids in the blood-to-brain direction. It suggests, however, that both solutes can be actively transported across brain capillaries from the brain interstitial fluid to the blood. In tissue culture, the endothelial cells form continuous tight junctions with their neighbors. This results in a cellular layer impermeable to protein tracers. When exposed to hyperosmolar solutions, in an attempt to mimic the conditions that open the blood-brain barrier in vivo, we found a reversible separation of the tight junctions between contiguous endothelial cells. No indication of activation of pinocytosis was observed. In vitro systems provide a novel approach for studying the function of the blood-brain barrier and allow for observations not possible with intact animals.

Hypopituitarism induced by traumatic brain injury in the transition phase.

PubMed

Aimaretti, G; Ambrosio, M R; Di Somma, C; Gasperi, M; Cannavò, S; Scaroni, C; De Marinis, L; Baldelli, R; Bona, G; Giordano, G; Ghigo, E

2005-12-01

Traumatic brain injury (TBI) has been associated with hypopituitarism in general and GH deficiency (GHD) in particular; the consequences of this on growth and development are likely to be critical in children and adolescents in the so-called "transition phase". In order to verify the consequences of TBI on pituitary function in the transition phase, we studied a population of adolescents and young adults 3 and 12 months after brain injury [no. = 23, 9 females, 14 males; age: 16-25 yr; body mass index (BMI): 21.9 +/- 0.6 kg/m2]. At 3 months, hypopituitarism was present in 34.6%. Total, multiple and isolated deficits were present in 8.6, 4.3 and 21.7%, respectively. Diabetes insipidus (DI) was present in 8.6% patients and mild hyperprolactinemia in 4.3%. At 12 months, hypopituitarism was present in 30.3%. Total, multiple and isolated deficits were present in 8.6, 4.3 and 17.4%, respectively. DI was present in 4.3% of patients and mild hyperprolactinemia in 4.3%. Total hypopituitarism was always confirmed at retesting. Multiple and isolated hypopituitarism were confirmed in 0/1 and 2/5, respectively. Two/23 patients showed isolated hypopituitarism at 12 months only; 1 patient with isolated at 3 months showed multiple hypopituitarism at retesting. GHD and secondary hypogonadism were the most common acquired pituitary deficits. These results show the high risk of TBI-induced hypopituitarism also in the transition age. Thus it is recommended that pediatric endocrinologists follow-up pituitary function of children and adolescents after brain injuries.

Isolation and purification of monosialotetrahexosylgangliosides from pig brain by extraction and liquid chromatography.

PubMed

Bian, Liujiao; Yang, Jianting; Sun, Yu

2015-10-01

Monosialotetrahexosylganglioside (GM1), one of glycosphingolipids containing sialic acid, plays particularly important role in fighting against paralysis, dementia and other diseases caused by brain and nerve damage. In this work, a simple and highly efficient method with high yield was developed for isolation and purification of GM1 from pig brain. The method consisted of an extraction by chloroform-methanol-water and a two-step chromatographic separation by DEAE-Sepharose Fast Flow anion-exchange medium and Sephacryl S-100 HR size-exclusion medium. The purified GM1 was proved to be homogeneous and had a purity of >98.0% by high-performance anion-exchange and size-exclusion chromatography. The molecular weight was 30.0 kDa by high-performance size-exclusion chromatography and 1546.9 Da by electrospray ionization mass spectrometry. The chromogenic reaction by resorcinol-hydrochloric acid solution indicated that the purified GM1 showed a specific chromogenic reaction of sialic acid. Through this isolation and purification program, ~1.0 mg of pure GM1 could be captured from 500 g wet pig brain tissue and the yield of GM1 was around 0.022%, which was higher than the yields by other methods. The method may provide an alternative for isolation and purification of GM1 in other biological tissues. Copyright © 2015 John Wiley & Sons, Ltd.

Isolated traumatic brain injury results in significant pre-hospital derangement of cardiovascular physiology.

PubMed

Gavrilovski, M; El-Zanfaly, M; Lyon, R M

2018-04-20

Major trauma can result in both life-threatening haemorrhage and traumatic brain injury (TBI). The pre-hospital management of these conditions, particularly in relation to the cardiovascular system, is very different. TBI can result in cardiovascular instability but the exact incidence remains poorly described. This study explores the incidence of cardiovascular instability in patients undergoing pre-hospital anaesthesia for suspected TBI. Retrospective case series of all pre-hospital trauma patients attended by Kent, Surrey & Sussex Air Ambulance Trust (United Kingdom) trauma team during the period 1 January 2015-31 December 2016. Patients were included if they showed clinical signs of TBI, underwent pre-hospital anaesthesia and hospital computed tomography scanning subsequently confirmed an isolated TBI. Out of 121 patients with confirmed isolated TBI, 68 were cardiovascularly stable throughout the pre-anaesthesia phase, whilst 53 (44%) showed signs of instability (HR > 100bpm and/or SBP < 100 mmHg pre-anaesthesia). Hypotension (SBP < 100) with or without tachycardia was present in 14 (12%) patients. 10 (8%) patients with isolated TBI received pre-hospital blood product transfusion. Increased awareness that traumatic brain injury can cause significant derangement to heart rate and blood pressure, even in the absence of major haemorrhage, would allow the pre-hospital clinician to treat cardiovascular instability with the most appropriate means, such as crystalloid and vasopressors, to limit secondary brain injury. Copyright © 2018. Published by Elsevier Ltd.

Aquaporin-4 polymorphisms and brain/body weight ratio in sudden infant death syndrome (SIDS).

PubMed

Studer, Jacqueline; Bartsch, Christine; Haas, Cordula

2014-07-01

Failure in the regulation of homeostatic water balance in the brain is associated with severe cerebral edema and increased brain weights and may also play an important role in the pathogenesis of sudden infant death syndrome (SIDS). We genotyped three single-nucleotide polymorphisms in the aquaporin-4 water channel-encoding gene (AQP4), which were previously shown to be associated with (i) SIDS in Norwegian infants (rs2075575), (ii) severe brain edema (rs9951307), and (iii) increased brain water permeability (rs3906956). We also determined whether the brain/body weight ratio is increased in SIDS infants compared with sex- and age-matched controls. Genotyping of the three AQP4 single-nucleotide polymorphisms was performed in 160 Caucasian SIDS infants and 181 healthy Swiss adults using a single-base extension method. Brain and body weights were measured during autopsy in 157 SIDS and 59 non-SIDS infants. No differences were detected in the allelic frequencies of the three AQP4 single-nucleotide polymorphisms between SIDS and adult controls. The brain/body weight ratio was similarly distributed in SIDS and non-SIDS infants. Variations in the AQP4 gene seem of limited significance as predisposing factors in Caucasian SIDS infants. Increased brain weights may only become evident in conjunction with environmental or other genetic risk factors.

Curcumin micelles improve mitochondrial function in neuronal PC12 cells and brains of NMRI mice - Impact on bioavailability.

PubMed

Hagl, Stephanie; Kocher, Alexa; Schiborr, Christina; Kolesova, Natalie; Frank, Jan; Eckert, Gunter P

2015-10-01

Curcumin, a polyphenolic compound abundant in the rhizome of Curcuma longa, has been reported to have various beneficial biological and pharmacological activities. Recent research revealed that curcumin might be valuable in the prevention and therapy of numerous disorders including neurodegenerative diseases like Alzheimer's disease. Due to its low absorption and quick elimination from the body, curcumin bioavailability is rather low which poses major problems for the use of curcumin as a therapeutic agent. There are several approaches to ameliorate curcumin bioavailability after oral administration, amongst them simultaneous administration with secondary plant compounds, micronization and micellation. We examined bioavailability in vivo in NMRI mice and the effects of native curcumin and a newly developed curcumin micelles formulation on mitochondrial function in vitro in PC12 cells and ex vivo in isolated mouse brain mitochondria. We found that curcumin micelles improved bioavailability of native curcumin around 10- to 40-fold in plasma and brain of mice. Incubation with native curcumin and curcumin micelles prevented isolated mouse brain mitochondria from swelling, indicating less mitochondrial permeability transition pore (mPTP) opening and prevention of injury. Curcumin micelles proved to be more efficient in preventing mitochondrial swelling in isolated mouse brain mitochondria and protecting PC12 cells from nitrosative stress than native curcumin. Due to their improved effectivity, curcumin micelles might be a suitable formulation for the prevention of mitochondrial dysfunction in brain aging and neurodegeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory.

PubMed

Kim, Kamin; Ekstrom, Arne D; Tandon, Nitin

2016-10-01

Electrical stimulation of the brain is a unique tool to perturb endogenous neural signals, allowing us to evaluate the necessity of given neural processes to cognitive processing. An important issue, gaining increasing interest in the literature, is whether and how stimulation can be employed to selectively improve or disrupt declarative memory processes. Here, we provide a comprehensive review of both invasive and non-invasive stimulation studies aimed at modulating memory performance. The majority of past studies suggest that invasive stimulation of the hippocampus impairs memory performance; similarly, most non-invasive studies show that disrupting frontal or parietal regions also impairs memory performance, suggesting that these regions also play necessary roles in declarative memory. On the other hand, a handful of both invasive and non-invasive studies have also suggested modest improvements in memory performance following stimulation. These studies typically target brain regions connected to the hippocampus or other memory "hubs," which may affect endogenous activity in connected areas like the hippocampus, suggesting that to augment declarative memory, altering the broader endogenous memory network activity is critical. Together, studies reporting memory improvements/impairments are consistent with the idea that a network of distinct brain "hubs" may be crucial for successful memory encoding and retrieval rather than a single primary hub such as the hippocampus. Thus, it is important to consider neurostimulation from the network perspective, rather than from a purely localizationalist viewpoint. We conclude by proposing a novel approach to neurostimulation for declarative memory modulation that aims to facilitate interactions between multiple brain "nodes" underlying memory rather than considering individual brain regions in isolation. Copyright © 2016. Published by Elsevier Inc.

Acquired Brain Injury Club at a Community College: Opportunities for Support, Involvement, and Leadership

ERIC Educational Resources Information Center

Chinn, Nancy Resendes

2009-01-01

College students with acquired brain injuries face unique challenges. The likelihood of individuals with acquired brain injury experiencing isolation, lack of social support, and diminished self-esteem, along with cognitive impairments, is well documented in the literature. This article presents an overview of a community college's club for…

Single Cell Immuno-Laser Microdissection Coupled to Label-Free Proteomics to Reveal the Proteotypes of Human Brain Cells After Ischemia.

PubMed

García-Berrocoso, Teresa; Llombart, Víctor; Colàs-Campàs, Laura; Hainard, Alexandre; Licker, Virginie; Penalba, Anna; Ramiro, Laura; Simats, Alba; Bustamante, Alejandro; Martínez-Saez, Elena; Canals, Francesc; Sanchez, Jean-Charles; Montaner, Joan

2018-01-01

Cerebral ischemia entails rapid tissue damage in the affected brain area causing devastating neurological dysfunction. How each component of the neurovascular unit contributes or responds to the ischemic insult in the context of the human brain has not been solved yet. Thus, the analysis of the proteome is a straightforward approach to unraveling these cell proteotypes. In this study, post-mortem brain slices from ischemic stroke patients were obtained corresponding to infarcted (IC) and contralateral (CL) areas. By means of laser microdissection, neurons and blood brain barrier structures (BBB) were isolated and analyzed using label-free quantification. MS data are available via ProteomeXchange with identifier PXD003519. Ninety proteins were identified only in neurons, 260 proteins only in the BBB and 261 proteins in both cell types. Bioinformatics analyses revealed that repair processes, mainly related to synaptic plasticity, are outlined in microdissected neurons, with nonexclusive important functions found in the BBB. A total of 30 proteins showing p < 0.05 and fold-change> 2 between IC and CL areas were considered meaningful in this study: 13 in neurons, 14 in the BBB and 3 in both cell types. Twelve of these proteins were selected as candidates and analyzed by immunohistofluorescence in independent brains. The MS findings were completely verified for neuronal SAHH2 and SRSF1 whereas the presence in both cell types of GABT and EAA2 was only validated in neurons. In addition, SAHH2 showed its potential as a prognostic biomarker of neurological improvement when analyzed early in the plasma of ischemic stroke patients. Therefore, the quantitative proteomes of neurons and the BBB (or proteotypes) after human brain ischemia presented here contribute to increasing the knowledge regarding the molecular mechanisms of ischemic stroke pathology and highlight new proteins that might represent putative biomarkers of brain ischemia or therapeutic targets. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain

PubMed Central

Lee, Won Hee; Sonntag, William E.; Mitschelen, Matthew; Yan, Han; Lee, Yong Woo

2010-01-01

Purpose Pro-inflammatory environments in the brain have been implicated in the onset and progression of neurological disorders. In the present study, we investigate the hypothesis that brain irradiation induces regionally specific alterations in cytokine gene and protein expression. Materials and methods Four month old F344 × BN rats received either whole brain irradiation with a single dose of 10 Gy γ-rays or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA and protein expression levels of pro-inflammatory mediators were analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. To elucidate the molecular mechanisms of irradiation-induced brain inflammation, effects of irradiation on the DNA-binding activity of pro-inflammatory transcription factors were also examined. Results A significant and marked up-regulation of mRNA and protein expression of pro-inflammatory mediators, including tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1), was observed in hippocampal and cortical regions isolated from irradiated brain. Cytokine expression was regionally specific since TNF-α levels were significantly elevated in cortex compared to hippocampus (57% greater) and IL-1β levels were elevated in hippocampus compared to cortical samples (126% greater). Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. A series of electrophoretic mobility shift assays (EMSA) demonstrated that irradiation significantly increased activation of activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and cAMP response element-binding protein (CREB). Conclusion The present study demonstrated that whole brain irradiation induces regionally specific pro-inflammatory environments through activation of AP-1, NF-κB, and CREB and overexpression of TNF-α, IL-1β, and MCP-1 in rat brain and may contribute to unique pathways for the radiation-induced impairments in tissue function. PMID:20148699

Modulatory effects of perforin gene dosage on pathogen-associated blood-brain barrier (BBB) disruption.

PubMed

Willenbring, Robin C; Jin, Fang; Hinton, David J; Hansen, Mike; Choi, Doo-Sup; Pavelko, Kevin D; Johnson, Aaron J

2016-08-31

CD8 T cell-mediated blood-brain barrier (BBB) disruption is dependent on the effector molecule perforin. Human perforin has extensive single nucleotide variants (SNVs), the significance of which is not fully understood. These SNVs can result in reduced, but not ablated, perforin activity or expression. However, complete loss of perforin expression or activity results in the lethal disease familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). In this study, we address the hypothesis that a single perforin allele can alter the severity of BBB disruption in vivo using a well-established model of CNS vascular permeability in C57Bl/6 mice. The results of this study provide insight into the significance of perforin SNVs in the human population. We isolated the effect a single perforin allele has on CNS vascular permeability through the use of perforin-heterozygous (perforin+/-) C57BL/6 mice in the peptide-induced fatal syndrome (PIFS) model of immune-mediated BBB disruption. Seven days following Theiler's murine encephalomyelitis virus (TMEV) CNS infection, neuroinflammation and TMEV viral control were assessed through flow cytometric analysis and quantitative real-time PCR of the viral genome, respectively. Following immune-mediated BBB disruption, gadolinium-enhanced T1-weighted MRI, with 3D volumetric analysis, and confocal microscopy were used to define CNS vascular permeability. Finally, the open field behavior test was used to assess locomotor activity of mice following immune-mediated BBB disruption. Perforin-null mice had negligible CNS vascular permeability. Perforin-WT mice have extensive CNS vascular permeability. Interestingly, perforin-heterozygous mice had an intermediate level of CNS vascular permeability as measured by both gadolinium-enhanced T1-weighted MRI and fibrinogen leakage in the brain parenchyma. Differences in BBB disruption were not a result of increased CNS immune infiltrate. Additionally, TMEV was controlled in a perforin dose-dependent manner. Furthermore, a single perforin allele is sufficient to induce locomotor deficit during immune-mediated BBB disruption. Perforin modulates BBB disruption in a dose-dependent manner. This study demonstrates a potentially advantageous role for decreased perforin expression in reducing BBB disruption. This study also provides insight into the effect SNVs in a single perforin allele could have on functional deficit in neurological disease.

Adaptive evolution of simian immunodeficiency viruses isolated from two conventional progressor macaques with neuroaids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foley, Brian T; Korber, Bette T

2008-01-01

Simian immunodeficiency virus infection of macaques may result in neuroAIDS, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. This is the first report of two conventional progressors (H631 and H636) with encephalitis in rhesus macaques inoculated with a derivative of SIVsmES43-3. Phylogenetic analyses of viruses isolated from the cerebral spinal fluid (CSF) and plasma from both animals demonstrated tissue compartmentalization. Additionally, virus from the central nervous system (CNS) was able to infect primary macaque monocyte-derived macrophages more efficiently than virus from plasma. Conversely, virus isolated from plasma was able to replicatemore » better in peripheral blood mononuclear cells than virus from CNS. We speculate that these viruses were under different selective pressures in their separate compartments. Furthermore, these viruses appear to have undergone adaptive evolution to preferentially replicate in their respective cell targets. Analysis of the number of potential N-linked glycosylation sites (PNGS) in gp160 showed that there was a statistically significant loss of PNGS in viruses isolated from CNS in both macaques compared to SIVsmE543-3. Moreover, virus isolated from the brain in H631, had statistically significant loss of PNGS compared to virus isolated from CSF and plasma of the same animal. It is possible that the brain isolate may have adapted to decrease the number of PNGS given that humoral immune selection pressure is less likely to be encountered in the brain. These viruses provide a relevant model to study the adaptations required for SIV to induce encephalitis.« less

Whole-brain diffusion tensor imaging in correlation to visual-evoked potentials in multiple sclerosis: a tract-based spatial statistics analysis.

PubMed

Lobsien, D; Ettrich, B; Sotiriou, K; Classen, J; Then Bergh, F; Hoffmann, K-T

2014-01-01

Functional correlates of microstructural damage of the brain affected by MS are incompletely understood. The purpose of this study was to evaluate correlations of visual-evoked potentials with microstructural brain changes as determined by DTI in patients with demyelinating central nervous disease. Sixty-one patients with clinically isolated syndrome or MS were prospectively recruited. The mean P100 visual-evoked potential latencies of the right and left eyes of each patient were calculated and used for the analysis. For DTI acquisition, a single-shot echo-planar imaging pulse sequence with 80 diffusion directions was performed at 3T. Fractional anisotropy, radial diffusivity, and axial diffusivity were calculated and correlated with mean P100 visual-evoked potentials by tract-based spatial statistics. Significant negative correlations between mean P100 visual-evoked potentials and fractional anisotropy and significant positive correlations between mean P100 visual-evoked potentials and radial diffusivity were found widespread over the whole brain. The highest significance was found in the optic radiation, frontoparietal white matter, and corpus callosum. Significant positive correlations between mean P100 visual-evoked potentials and axial diffusivity were less widespread, notably sparing the optic radiation. Microstructural changes of the whole brain correlated significantly with mean P100 visual-evoked potentials. The distribution of the correlations showed clear differences among axial diffusivity, fractional anisotropy, and radial diffusivity, notably in the optic radiation. This finding suggests a stronger correlation of mean P100 visual-evoked potentials to demyelination than to axonal damage. © 2014 by American Journal of Neuroradiology.

Isolation of a single rice chromosome by optical micromanipulation

NASA Astrophysics Data System (ADS)

Wang, Haowei; Liu, Xiaohui; Li, Yinmei; Han, Bin; Lou, Liren; Wang, Kangjun

2004-01-01

A new method based on optical tweezers technology is reported for the isolation of a single chromosome. A rice cell suspended in liquid was first fragmented by laser pulses (optical scalpel). Then a single released chromosome from the cell was manipulated and pulled away from other cells and oddments by optical tweezers without any direct mechanical contact. Finally the isolated single chromosome was extracted individually into a glass capillary nearby. After molecular cloning of the isolated chromosome, we obtained some specific DNA segments from the single chromosome. All these segments can be used for rice genomic sequencing. Different methods of extracting a single chromosome are compared. The advantages of optical micromanipulation method are summarized.

Multifunctional and Context-Dependent Control of Vocal Acoustics by Individual Muscles

PubMed Central

Srivastava, Kyle H.; Elemans, Coen P.H.

2015-01-01

The relationship between muscle activity and behavioral output determines how the brain controls and modifies complex skills. In vocal control, ensembles of muscles are used to precisely tune single acoustic parameters such as fundamental frequency and sound amplitude. If individual vocal muscles were dedicated to the control of single parameters, then the brain could control each parameter independently by modulating the appropriate muscle or muscles. Alternatively, if each muscle influenced multiple parameters, a more complex control strategy would be required to selectively modulate a single parameter. Additionally, it is unknown whether the function of single muscles is fixed or varies across different vocal gestures. A fixed relationship would allow the brain to use the same changes in muscle activation to, for example, increase the fundamental frequency of different vocal gestures, whereas a context-dependent scheme would require the brain to calculate different motor modifications in each case. We tested the hypothesis that single muscles control multiple acoustic parameters and that the function of single muscles varies across gestures using three complementary approaches. First, we recorded electromyographic data from vocal muscles in singing Bengalese finches. Second, we electrically perturbed the activity of single muscles during song. Third, we developed an ex vivo technique to analyze the biomechanical and acoustic consequences of single-muscle perturbations. We found that single muscles drive changes in multiple parameters and that the function of single muscles differs across vocal gestures, suggesting that the brain uses a complex, gesture-dependent control scheme to regulate vocal output. PMID:26490859

Single-Cell Isolation of Circulating Tumor Cells from Whole Blood by Lateral Magnetophoretic Microseparation and Microfluidic Dispensing.

PubMed

Kim, Jinho; Cho, Hyungseok; Han, Song-I; Han, Ki-Ho

2016-05-03

This paper introduces a single-cell isolation technology for circulating tumor cells (CTCs) using a microfluidic device (the "SIM-Chip"). The SIM-Chip comprises a lateral magnetophoretic microseparator and a microdispenser as a two-step cascade platform. First, CTCs were enriched from whole blood by the lateral magnetophoretic microseparator based on immunomagnetic nanobeads. Next, the enriched CTCs were electrically identified by single-cell impedance cytometer and isolated as single cells using the microshooter. Using 200 μL of whole blood spiked with 50 MCF7 breast cancer cells, the analysis demonstrated that the single-cell isolation efficiency of the SIM-Chip was 82.4%, and the purity of the isolated MCF7 cells with respect to WBCs was 92.45%. The data also showed that the WBC depletion rate of the SIM-Chip was 2.5 × 10(5) (5.4-log). The recovery rates were around 99.78% for spiked MCF7 cells ranging in number from 10 to 90. The isolated single MCF7 cells were intact and could be used for subsequent downstream genetic assays, such as RT-PCR. Single-cell culture evaluation of the proliferation of MCF7 cells isolated by the SIM-Chip showed that 84.1% of cells at least doubled in 5 days. Consequently, the SIM-Chip could be used for single-cell isolation of rare target cells from whole blood with high purity and recovery without cell damage.

[Therapeutic strategies targeting brain tumor stem cells].

PubMed

Toda, Masahiro

2009-07-01

Progress in stem cell research reveals cancer stem cells to be present in a variety of malignant tumors. Since they exhibit resistance to anticancer drugs and radiotherapy, analysis of their properties has been rapidly carried forward as an important target for the treatment of intractable malignancies, including brain tumors. In fact, brain cancer stem cells (BCSCs) have been isolated from brain tumor tissue and brain tumor cell lines by using neural stem cell culture methods and isolation methods for side population (SP) cells, which have high drug-efflux capacity. Although the analysis of the properties of BCSCs is the most important to developing methods in treating BCSCs, the absence of BCSC purification methods should be remedied by taking it up as an important research task in the immediate future. Thus far, there are no effective treatment methods for BCSCs, and several treatment methods have been proposed based on the cell biology characteristics of BCSCs. In this article, I outline potential treatment methods damaging treatment-resistant BCSCs, including immunotherapy which is currently a topic of our research.

Drop-on-Demand Single Cell Isolation and Total RNA Analysis

PubMed Central

Moon, Sangjun; Kim, Yun-Gon; Dong, Lingsheng; Lombardi, Michael; Haeggstrom, Edward; Jensen, Roderick V.; Hsiao, Li-Li; Demirci, Utkan

2011-01-01

Technologies that rapidly isolate viable single cells from heterogeneous solutions have significantly contributed to the field of medical genomics. Challenges remain both to enable efficient extraction, isolation and patterning of single cells from heterogeneous solutions as well as to keep them alive during the process due to a limited degree of control over single cell manipulation. Here, we present a microdroplet based method to isolate and pattern single cells from heterogeneous cell suspensions (10% target cell mixture), preserve viability of the extracted cells (97.0±0.8%), and obtain genomic information from isolated cells compared to the non-patterned controls. The cell encapsulation process is both experimentally and theoretically analyzed. Using the isolated cells, we identified 11 stem cell markers among 1000 genes and compare to the controls. This automated platform enabling high-throughput cell manipulation for subsequent genomic analysis employs fewer handling steps compared to existing methods. PMID:21412416

Stability of an ERP-based measure of brain network activation (BNA) in athletes: A new electrophysiological assessment tool for concussion.

PubMed

Eckner, James T; Rettmann, Ashley; Narisetty, Naveen; Greer, Jacob; Moore, Brandon; Brimacombe, Susan; He, Xuming; Broglio, Steven P

2016-01-01

To determine test-re-test reliabilities of novel Evoked Response Potential (ERP)-based Brain Network Activation (BNA) scores in healthy athletes. Observational, repeated-measures study. Forty-two healthy male and female high school and collegiate athletes completed auditory oddball and go/no-go ERP assessments at baseline, 1 week, 6 weeks and 1 year. The BNA algorithm was applied to the ERP data, considering electrode location, frequency band, peak latency and normalized amplitude to generate seven unique BNA scores for each testing session. Mean BNA scores, intra-class correlation coefficient (ICC) values and reliable change (RC) values were calculated for each of the seven BNA networks. BNA scores ranged from 46.3 ± 34.9 to 69.9 ± 22.8, ICC values ranged from 0.46-0.65 and 95% RC values ranged from 38.3-68.1 across the seven networks. The wide range of BNA scores observed in this population of healthy athletes suggests that a single BNA score or set of BNA scores from a single after-injury test session may be difficult to interpret in isolation without knowledge of the athlete's own baseline BNA score(s) and/or the results of serial tests performed at additional time points. The stability of each BNA network should be considered when interpreting test-re-test BNA score changes.

Design and use of a folded four-ring double-tuned birdcage coil for rat brain sodium imaging at 9.4 T

NASA Astrophysics Data System (ADS)

Ha, YongHyun; Choi, Chang-Hoon; Worthoff, Wieland A.; Shymanskaya, Aliaksandra; Schöneck, Michael; Willuweit, Antje; Felder, Jörg; Shah, N. Jon

2018-01-01

A folded four-ring quadrature birdcage coil was designed and constructed with a double-tune configuration of an outer high-pass coil for 1H (400 MHz) and inner low-pass coil for 23Na (105.72 MHz at 9.4 T). The coil was evaluated on the bench and in the scanner, comparing its performance with that of single-tuned coils and a large four-ring coil. All coils were tuned and matched and the isolation between two quadrature ports was found to be better than -13.7 dB for 1H and -27 dB for 23Na. Signal-to-noise ratios (SNRs) were calculated and 23Na flip angle maps were acquired. 23Na SNR of the folded four-ring reached ∼93% of that obtained with the single-tuned coil. A set of in vivo1H and 23Na axial images to cover the whole rat brain were obtained. The performance of the folded four-ring coil and its benefit for 23Na imaging experiments have been demonstrated. This proposed four-ring coil could avoid length restrictions, e.g. the shoulders, by folding the outer rings vertically. This facilitates the construction of double-tuned four-ring birdcage coils just to fit the head, leading to higher filling factors and better SNR.

The direct relationship between inhibitory currents and local field potentials.

PubMed

Trevelyan, Andrew J

2009-12-02

The frequency profiles of various extracellular field oscillations are known to reflect functional brain states, yet we lack detailed explanations of how these brain oscillations arise. Of particular clinical relevance are the high-frequency oscillations (HFOs) associated with interictal events and the onset of seizures. These time periods are also when pyramidal firing appears to be vetoed by high-frequency volleys of inhibitory synaptic currents, thereby providing an inhibitory restraint that opposes epileptiform spread (Trevelyan et al., 2006, 2007). The pattern and timing of this inhibitory volley is suggestive of a causal relationship between the restraint and HFOs. I show that at these times, isolated inhibitory currents from single pyramidal cells have a similarity to the extracellular signal that significantly exceeds chance. The ability to extrapolate from discrete currents in single cells to the extracellular signal arises because these inhibitory currents are synchronized in local populations of pyramidal cells. The visibility of these inhibitory currents in the field recordings is greatest when local pyramidal activity is suppressed: the correlation between the inhibitory currents and the field signal becomes worse when local activity increases, suggestive of a switch from one source of HFO to another as the restraint starts to fail. This association suggests that a significant component of HFOs reflects the last act of defiance in the face of an advancing ictal event.

Nitric oxide augments single Ca(2+) channel currents via cGMP-dependent protein kinase in Kenyon cells isolated from the mushroom body of the cricket brain.

PubMed

Kosakai, Kumiko; Tsujiuchi, Yuuki; Yoshino, Masami

2015-07-01

Behavioral and pharmacological studies in insects have suggested that the nitric oxide (NO)/cyclic GMP (cGMP) signaling pathway is involved in the formation of long-term memory (LTM) associated with olfactory learning. However, the target molecules of NO and the downstream signaling pathway are still not known. In this study, we investigated the action of NO on single voltage-dependent Ca(2+) channels in the intrinsic neurons known as Kenyon cells within the mushroom body of the cricket brain, using the cell-attached configuration of the patch-clamp technique. Application of the NO donor S-nitrosoglutathione (GSNO) increased the open probability (NPO) of single Ca(2+) channel currents. This GSNO-induced increase was blocked by ODQ, a soluble guanylate cyclase (sGC) inhibitor, suggesting that the NO generated by GSNO acts via sGC to raise cGMP levels. The membrane-permeable cGMP analog 8-Bro-cGMP also increased the NPO of single Ca(2+) channel currents. Pretreatment of cells with KT5823, a protein kinase G blocker, abolished the excitatory effect of GSNO. These results suggest that NO augments the activity of single Ca(2+) channels via the cGMP/PKG signaling pathway. To gain insight into the physiological role of NO, we examined the effect of GSNO on action potentials of Kenyon cells under current-clamp conditions. Application of GSNO increased the frequency of action potentials elicited by depolarizing current injections, indicating that NO acts as a modulator resulting in a stimulatory signal in Kenyon cells. We discuss the increased Ca(2+) influx through these Ca(2+) channels via the NO/cGMP signaling cascade in relation to the formation of olfactory LTM. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Simple and Reproducible Method to Prepare Membrane Samples from Freshly Isolated Rat Brain Microvessels.

PubMed

Brzica, Hrvoje; Abdullahi, Wazir; Reilly, Bianca G; Ronaldson, Patrick T

2018-05-07

The blood-brain barrier (BBB) is a dynamic barrier tissue that responds to various pathophysiological and pharmacological stimuli. Such changes resulting from these stimuli can greatly modulate drug delivery to the brain and, by extension, cause considerable challenges in the treatment of central nervous system (CNS) diseases. Many BBB changes that affect pharmacotherapy, involve proteins that are localized and expressed at the level of endothelial cells. Indeed, such knowledge on BBB physiology in health and disease has sparked considerable interest in the study of these membrane proteins. From a basic science research standpoint, this implies a requirement for a simple but robust and reproducible method for isolation of microvessels from brain tissue harvested from experimental animals. In order to prepare membrane samples from freshly isolated microvessels, it is essential that sample preparations be enriched in endothelial cells but limited in the presence of other cell types of the neurovascular unit (i.e., astrocytes, microglia, neurons, pericytes). An added benefit is the ability to prepare samples from individual animals in order to capture the true variability of protein expression in an experimental population. In this manuscript, details regarding a method that is utilized for isolation of rat brain microvessels and preparation of membrane samples are provided. Microvessel enrichment, from samples derived, is achieved by using four centrifugation steps where dextran is included in the sample buffer. This protocol can easily be adapted by other laboratories for their own specific applications. Samples generated from this protocol have been shown to yield robust experimental data from protein analysis experiments that can greatly aid the understanding of BBB responses to physiological, pathophysiological, and pharmacological stimuli.

Differential susceptibility of mitochondrial complex II to inhibition by oxaloacetate in brain and heart.

PubMed

Stepanova, Anna; Shurubor, Yevgeniya; Valsecchi, Federica; Manfredi, Giovanni; Galkin, Alexander

2016-09-01

Mitochondrial Complex II is a key mitochondrial enzyme connecting the tricarboxylic acid (TCA) cycle and the electron transport chain. Studies of complex II are clinically important since new roles for this enzyme have recently emerged in cell signalling, cancer biology, immune response and neurodegeneration. Oxaloacetate (OAA) is an intermediate of the TCA cycle and at the same time is an inhibitor of complex II with high affinity (Kd~10(-8)M). Whether or not OAA inhibition of complex II is a physiologically relevant process is a significant, but still controversial topic. We found that complex II from mouse heart and brain tissue has similar affinity to OAA and that only a fraction of the enzyme in isolated mitochondrial membranes (30.2±6.0% and 56.4±5.6% in the heart and brain, respectively) is in the free, active form. Since OAA could bind to complex II during isolation, we established a novel approach to deplete OAA in the homogenates at the early stages of isolation. In heart, this treatment significantly increased the fraction of free enzyme, indicating that OAA binds to complex II during isolation. In brain the OAA-depleting system did not significantly change the amount of free enzyme, indicating that a large fraction of complex II is already in the OAA-bound inactive form. Furthermore, short-term ischemia resulted in a dramatic decline of OAA in tissues, but it did not change the amount of free complex II. Our data show that in brain OAA is an endogenous effector of complex II, potentially capable of modulating the activity of the enzyme. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

A Method for Isolation of Extracellular Vesicles and Characterization of Exosomes from Brain Extracellular Space.

PubMed

Pérez-González, Rocío; Gauthier, Sebastien A; Kumar, Asok; Saito, Mitsuo; Saito, Mariko; Levy, Efrat

2017-01-01

Extracellular vesicles (EV), including exosomes, secreted vesicles of endocytic origin, and microvesicles derived from the plasma membrane, have been widely isolated and characterized from conditioned culture media and bodily fluids. The difficulty in isolating EV from tissues, however, has hindered their study in vivo. Here, we describe a novel method designed to isolate EV and characterize exosomes from the extracellular space of brain tissues. The purification of EV is achieved by gentle dissociation of the tissue to free the brain extracellular space, followed by sequential low-speed centrifugations, filtration, and ultracentrifugations. To further purify EV from other extracellular components, they are separated on a sucrose step gradient. Characterization of the sucrose step gradient fractions by electron microscopy demonstrates that this method yields pure EV preparations free of large vesicles, subcellular organelles, or debris. The level of EV secretion and content are determined by assays for acetylcholinesterase activity and total protein estimation, and exosomal identification and protein content are analyzed by Western blot and immuno-electron microscopy. Additionally, we present here a method to delipidate EV in order to improve the resolution of downstream electrophoretic analysis of EV proteins.

First isolate of Toxoplasma gondii from arctic fox (Vulpes lagopus) from Svalbard.

PubMed

Prestrud, Kristin Wear; Dubey, J P; Asbakk, Kjetil; Fuglei, Eva; Su, C

2008-02-14

Cats are considered essential for the maintenance of Toxoplasma gondii in nature. However, T. gondii infection has been reported in arctic fox (Vulpes lagopus) from the Svalbard high arctic archipelago where felids are virtually absent. To identify the potential source of T. gondii, we attempted to isolate and genetically characterize the parasite from arctic foxes in Svalbard. Eleven foxes were trapped live in Grumant (78 degrees 11'N, 15 degrees 09'E), Svalbard, in September 2005 and 2006. One of the foxes was found to be seropositive to T. gondii by the modified agglutination test (MAT). The fox was euthanized and its heart and brain were bioassayed in mice for the isolation of T. gondii. All 10 mice inoculated with brain tissue and one of the five inoculated with heart developed MAT antibodies, and tissue cysts were found in the brains of seropositive mice. Two cats fed tissues from infected mice shed T. gondii oocysts. Genotyping using 10 PCR-RFLP markers and DNA sequencing of gene loci BSR4, GRA6, UPRT1 and UPRT2 determined the isolate to be Type II strain, the predominant T. gondii lineage in the world.

Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues.

PubMed Central

Prody, C A; Zevin-Sonkin, D; Gnatt, A; Goldberg, O; Soreq, H

1987-01-01

To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase (BtChoEase; EC 3.1.1.8) and Torpedo electric organ "true" acetylcholinesterase (AcChoEase; EC 3.1.1.7). Using these probes, we isolated several cDNA clones from lambda gt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. In RNA blots of poly(A)+ RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These findings demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species. Images PMID:3035536

Evidence against impaired brain microtubule protein polymerization at high glucose concentrations or during diabetes mellitus.

PubMed

Eaker, E Y; Angelastro, J M; Purich, D L; Sninsky, C A

1991-06-01

Previous studies suggest that brain microtubule protein exposed to high glucose levels or isolated from diabetic rats can become glucosylated and that this impairs GTP-induced microtubule polymerization. We set out to extend that investigation to define the mechanistic basis for inhibition of microtubule assembly during diabetes or on incubation at high glucose levels. Rat and bovine brain microtubule protein was purified by cycles of polymerization/depolymerization. When microtubules were incubated for 1 h in either buffer or buffer containing glucose (up to 165 mM), there was no difference in polymerization, a finding contrary to the earlier study. Other rats were injected with vehicle or streptozotocin (90 mg/kg) to induce diabetes as evidenced by serum glucose in excess of 300 mg%, and at 4 weeks, brain microtubule protein was isolated by the polymerization cycling method. Again, there was no difference in the amount or purity of isolated microtubule protein between control or diabetic rats. We also observed no increase in microtubule glucosylation, and GTP-induced polymerization in vitro was indistinguishable for protein derived from brains of normal rats and rats with diabetes as measured by turbidity or electron microscopy. Our results suggest that in vitro incubation with glucose or in vivo elevation of glucose during diabetes fails to impair microtubule polymerization, pointing to other mechanisms for the neuropathy associated with diabetes.

Determination of regional brain temperature using proton magnetic resonance spectroscopy to assess brain-body temperature differences in healthy human subjects.

PubMed

Childs, Charmaine; Hiltunen, Yrjö; Vidyasagar, Rishma; Kauppinen, Risto A

2007-01-01

Proton magnetic resonance spectroscopy ((1)H MRS) was used to determine brain temperature in healthy volunteers. Partially water-suppressed (1)H MRS data sets were acquired at 3T from four different gray matter (GM)/white matter (WM) volumes. Brain temperatures were determined from the chemical-shift difference between the CH(3) of N-acetyl aspartate (NAA) at 2.01 ppm and water. Brain temperatures in (1)H MRS voxels of 2 x 2 x 2 cm(3) showed no substantial heterogeneity. The volume-averaged temperature from single-voxel spectroscopy was compared with body temperatures obtained from the oral cavity, tympanum, and temporal artery regions. The mean brain parenchyma temperature was 0.5 degrees C cooler than readings obtained from three extra-brain sites (P < 0.01). (1)H MRS imaging (MRSI) data were acquired from a slice encompassing the single-voxel volumes to assess the ability of spectroscopic imaging to determine regional brain temperature within the imaging slice. Brain temperature away from the center of the brain determined by MRSI differed from that obtained by single-voxel MRS in the same brain region, possibly due to a poor line width (LW) in MRSI. The data are discussed in the light of proposed brain-body temperature gradients and the use of (1)H MRSI to monitor brain temperature in pathologies, such as brain trauma.

I know I've seen you before: Distinguishing recent-single-exposure-based familiarity from pre-existing familiarity

PubMed Central

Gimbel, Sarah I.; Brewer, James B.; Maril, Anat

2018-01-01

This study examines how individuals differentiate recent-single-exposure-based familiarity from pre-existing familiarity. If these are two distinct cognitive processes, are they supported by the same neural bases? This study examines how recent-single-exposure-based familiarity and multiple-previous-exposure-based familiarity are supported and represented in the brain using functional MRI. In a novel approach, we first behaviorally show that subjects can divide retrieval of items in pre-existing memory into judgments of recollection and familiarity. Then, using functional magnetic resonance imaging, we examine the differences in blood oxygen level dependent activity and regional connectivity during judgments of recent-single-exposure-based and pre-existing familiarity. Judgments of these two types of familiarity showed distinct regions of activation in a whole-brain analysis, in medial temporal lobe (MTL) substructures, and in MTL substructure functional-correlations with other brain regions. Specifically, within the MTL, perirhinal cortex showed increased activation during recent-single-exposure-based familiarity while parahippocampal cortex showed increased activation during judgments of pre-existing familiarity. We find that recent-single-exposure-based and pre-existing familiarity are represented as distinct neural processes in the brain; this is supported by differing patterns of brain activation and regional correlations. This spatially distinct regional brain involvement suggests that the two separate experiences of familiarity, recent-exposure-based familiarity and pre-existing familiarity, may be cognitively distinct. PMID:28073651

Anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose isolated from leaves of Mangifera indica.

PubMed

Viswanatha, G L; Mohan, C G; Shylaja, H; Yuvaraj, H C; Sunil, V

2013-07-01

The present study was aimed to evaluate the anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) isolated from methanolic leaf extracts of Mangifera indica in mice. Anticonvulsant activity of PGG was evaluated against pentylenetetrazole (PTZ)-induced and maximal electroshock (MES)-induced convulsions in mice. Additionally, locomotor activity and GABA levels in the brain were estimated to explore the possible CNS-depressant activity and mechanism behind the anticonvulsant activity, respectively. In these studies, PGG (2.5, 5, and 10 mg/kg, intraperitoneal (i.p.)) showed significant and dose-dependent inhibition of PTZ and MES-induced convulsions. Furthermore, PGG administration showed significant decrease in the locomotor activity as an indication of its CNS-depressant property; also, PGG has significantly increased the GABA levels in the cerebellum and whole brain other than the cerebellum. In conclusion, PGG isolated from M. indica showed potent anticonvulsant activity, and possible mechanism may be due to enhanced GABA levels in the brain.

Proteomic analysis of synaptoneurosomes highlights the relevant role of local translation in the hippocampus.

PubMed

Benito, Itziar; Casañas, Juan José; Montesinos, María Luz

2018-06-19

Several proteomic analyses have been performed on synaptic fractions isolated from cortex or even total brain, resulting in preparations with a high synaptic heterogeneity and complexity. Synaptoneurosomes (SNs) are subcellular membranous elements that contain sealed pre- and post-synaptic components. They are obtained by subcellular fractionation of brain homogenates and serve as a suitable model to study many aspects of the synapse physiology. Here we report the proteomic content of SNs isolated from hippocampus of adult mice, a brain region involved in memory that presents lower synaptic heterogeneity than cortex. Interestingly, in addition to pre- and post-synaptic proteins, we found that proteins involved in RNA binding and translation were overrepresented in our preparation. These results validate the protocol we previously reported for SNs isolation, and, as reported by other authors, highlight the relevance of local synaptic translation for hippocampal physiology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Isolation of Neospora caninum from dairy zero grazing cattle in Israel.

PubMed

Fish, L; Mazuz, M; Molad, T; Savitsky, I; Shkap, V

2007-11-10

First Israeli Neospora caninum isolates were obtained from brain tissues of aborted fetuses (NcIs491 and NcIs580) from dairy farms endemic for neosporosis and maintaining cattle on zero grazing. Tissues from different parts of the fetus brains were used to infect Vero cells. Tachyzoites of N. caninum were first observed in cultures from days 30 and 32 after infection. To confirm the identity of the isolated parasites, DNA extracts from brains and cultures were tested by PCR with specific primers based on the Nc5 gene. Specific fragments were amplified by PCR from infected cultures of both fetuses on day 25. Susceptible seronegative gerbils (Meriones tristrami) were inoculated intraperitoneally with 10(3) to 10(5) tenfold dilutions of subculture tachyzoites. The inoculated gerbils developed specific antibodies to N. caninum, with end-point serum dilution of 1:4096 in the IFA assay, whereas no neurological signs or deaths were seen during 4 months of observation.

Isolation and Characterization of Ischemia-Derived Astrocytes (IDAs) with Ability to Transactivate Quiescent Astrocytes

PubMed Central

Villarreal, Alejandro; Rosciszewski, Gerardo; Murta, Veronica; Cadena, Vanesa; Usach, Vanina; Dodes-Traian, Martin M.; Setton-Avruj, Patricia; Barbeito, Luis H.; Ramos, Alberto J.

2016-01-01

Reactive gliosis involving activation and proliferation of astrocytes and microglia, is a widespread but largely complex and graded glial response to brain injury. Astroglial population has a previously underestimated high heterogeneity with cells differing in their morphology, gene expression profile, and response to injury. Here, we identified a subset of reactive astrocytes isolated from brain focal ischemic lesions that show several atypical characteristics. Ischemia-derived astrocytes (IDAs) were isolated from early ischemic penumbra and core. IDA did not originate from myeloid precursors, but rather from pre-existing local progenitors. Isolated IDA markedly differ from primary astrocytes, as they proliferate in vitro with high cell division rate, show increased migratory ability, have reduced replicative senescence and grow in the presence of macrophages within the limits imposed by the glial scar. Remarkably, IDA produce a conditioned medium that strongly induced activation on quiescent primary astrocytes and potentiated the neuronal death triggered by oxygen-glucose deprivation. When re-implanted into normal rat brains, eGFP-IDA migrated around the injection site and induced focal reactive gliosis. Inhibition of gamma secretases or culture on quiescent primary astrocytes monolayers facilitated IDA differentiation to astrocytes. We propose that IDA represent an undifferentiated, pro-inflammatory, highly replicative and migratory astroglial subtype emerging from the ischemic microenvironment that may contribute to the expansion of reactive gliosis. Main Points: Ischemia-derived astrocytes (IDA) were isolated from brain ischemic tissue IDA show reduced replicative senescence, increased cell division and spontaneous migration IDA potentiate death of oxygen-glucose deprived cortical neurons IDA propagate reactive gliosis on quiescent astrocytes in vitro and in vivo Inhibition of gamma secretases facilitates IDA differentiation to astrocytes PMID:27313509

Efficient recovery of proteins from multiple source samples after TRIzol(®) or TRIzol(®)LS RNA extraction and long-term storage.

PubMed

Simões, André E S; Pereira, Diane M; Amaral, Joana D; Nunes, Ana F; Gomes, Sofia E; Rodrigues, Pedro M; Lo, Adrian C; D'Hooge, Rudi; Steer, Clifford J; Thibodeau, Stephen N; Borralho, Pedro M; Rodrigues, Cecília M P

2013-03-15

Simultaneous isolation of nucleic acids and proteins from a single biological sample facilitates meaningful data interpretation and reduces time, cost and sampling errors. This is particularly relevant for rare human and animal specimens, often scarce, and/or irreplaceable. TRIzol(®) and TRIzol(®)LS are suitable for simultaneous isolation of RNA, DNA and proteins from the same biological sample. These reagents are widely used for RNA and/or DNA isolation, while reports on their use for protein extraction are limited, attributable to technical difficulties in protein solubilisation. TRIzol(®)LS was used for RNA isolation from 284 human colon cancer samples, including normal colon mucosa, tubulovillous adenomas, and colon carcinomas with proficient and deficient mismatch repair system. TRIzol(®) was used for RNA isolation from human colon cancer cells, from brains of transgenic Alzheimer's disease mice model, and from cultured mouse cortical neurons. Following RNA extraction, the TRIzol(®)-chloroform fractions from human colon cancer samples and from mouse hippocampus and frontal cortex were stored for 2 years and 3 months, respectively, at -80°C until used for protein isolation.Simple modifications to the TRIzol(®) manufacturer's protocol, including Urea:SDS solubilization and sonication, allowed improved protein recovery yield compared to the TRIzol(®) manufacturer's protocol. Following SDS-PAGE and Ponceau and Coomassie staining, recovered proteins displayed wide molecular weight range and staining pattern comparable to those obtainable with commonly used protein extraction protocols. We also show that nuclear and cytosolic proteins can be easily extracted and detected by immunoblotting, and that posttranslational modifications, such as protein phosphorylation, are detectable in proteins recovered from TRIzol(®)-chloroform fractions stored for up to 2 years at -80°C. We provide a novel approach to improve protein recovery from samples processed for nucleic acid extraction with TRIzol(®) and TRIzol(®)LS compared to the manufacturer`s protocol, allowing downstream immunoblotting and evaluation of steady-state relative protein expression levels. The method was validated in large sets of samples from multiple sources, including human colon cancer and brains of transgenic Alzheimer's disease mice model, stored in TRIzol(®)-chloroform for up to two years. Collectively, we provide a faster and cheaper alternative to the TRIzol(®) manufacturer`s protein extraction protocol, illustrating the high relevance, and wide applicability, of the present protein isolation method for the immunoblot evaluation of steady-state relative protein expression levels in samples from multiple sources, and following prolonged storage.

Brain and Cognitive-Behavioural Development after Asphyxia at Term Birth

ERIC Educational Resources Information Center

de Haan, Michelle; Wyatt, John S.; Roth, Simon; Vargha-Khadem, Faraneh; Gadian, David; Mishkin, Mortimer

2006-01-01

Perinatal asphyxia occurs in approximately 1-6 per 1000 live full-term births. Different patterns of brain damage can result, though the relation of these patterns to long-term cognitive-behavioural outcome remains under investigation. The hippocampus is one brain region that can be damaged (typically not in isolation), and this site of damage has…

Brain Research, Learning and Emotions: Implications for Education Research, Policy and Practice

ERIC Educational Resources Information Center

Hinton, Christina; Miyamoto, Koji; Della-Chiesa, Bruno

2008-01-01

Recent advancements in neuroscience heighten its relevance to education. Newly developed imaging technologies enable scientists to peer into the working brain for the first time, providing powerful insights into how we learn. Research reveals that the brain is not a stable and isolated entity, but a dynamic system that is keenly responsive to…

Peripubertal viral-like challenge and social isolation mediate overlapping but distinct effects on behaviour and brain interferon regulatory factor 7 expression in the adult Wistar rat.

PubMed

Lukasz, Bartlomiej; O'Sullivan, Niamh C; Loscher, Jennifer S; Pickering, Mark; Regan, Ciaran M; Murphy, Keith J

2013-01-01

A range of adverse, early life environmental influences such as viral infection and social deprivation are thought to increase risk of psychiatric illness later in life. Here, we used peripheral administration of the viral infection mimic polyriboinosinic-polyribocytidylic acid (polyI:C) to compare the consequences of peripubertal infection and isolation rearing. Isolation rearing induced deficits in sensorimotor gating and recognition memory while no changes in social interaction or spatial learning were observed. PolyI:C injection during the peripubertal period markedly increased expression of interferon-stimulated genes (Ifit2, Prkr, Mx2 and Irf7) in the hippocampal dentate gyrus demonstrating that peripheral administration of the viral mimic in the adolescent animal does have direct effects in the brain. Peripubertal infection mimicry induced a similar but later emerging behavioural deficit in prepulse inhibition implying the existence of a peripubertal window of opportunity for viral-mediated cytokine increases to impact brain development and function. PolyI:C treatment also impaired novel object recognition but did not alter spatial reference memory or social interaction. Combining the polyI:C challenge with social isolation did not exacerbate the behavioural deficits seen with isolation rearing alone. Using Irf7 as a marker, peripubertal viral infection mimicry, isolation rearing and a combination of both were all seen to produce a long-lasting molecular imprint on the interferon-associated signalling pathway in the principal neuron population of the hippocampal dentate gyrus. The data suggest that the sensitivity of brain structure and function to disruption by viral infection extends into the peripubertal period. Moreover, augmented interferon signalling in hippocampus may represent a common molecular imprint of environmental insults associated with neuropsychiatric illnesses like schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

Recombinant EPF/chaperonin 10 promotes the survival of O4-positive pro-oligodendrocytes prepared from neonatal rat brain.

PubMed

McCombe, P A

2008-12-01

Chaperonin 10 (cpn 10) is a small heat-shock protein that is usually intracellular. Early pregnancy factor (EPF), a biologically active protein that was first described in the serum of pregnant mammals, is homologous to cpn 10. EPF/cpn 10 has been reported to have effects on immunomodulation and cell survival and to inhibit activation of toll-like receptors by lipopolysaccharide. We found that recombinant EPF/cpn 10 was able to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, which is a disease causing inflammation and demyelination of the brain and spinal cord. This beneficial effect could be due to anti-inflammatory and/or cell survival properties of EPF/cpn 10. We aimed to assess the effects of cpn 10 on cells of the oligodendrocyte lineage because oligodendrocytes are the brain cells that produce myelin and that are depleted in multiple sclerosis. Two forms of recombinant EPF/cpn 10 were prepared in the pGEX expression system and in the baculovirus expression system. Purified O4(+) pro-oligodendrocytes were prepared from the brains of day-old Wistar rats and isolated by cell sorting with flow cytometry. Single cells were dispensed into micro-well plates and tested for survival in the presence of a range of concentrations of the two forms of cpn 10. We also studied the effects of bFGF, PDGF, IGF-1 and insulin as controls. With cpn 10 present, there was enhanced survival of O4(+) cells.

Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort.

PubMed

Dufouil, Carole; Dubois, Bruno; Vellas, Bruno; Pasquier, Florence; Blanc, Frédéric; Hugon, Jacques; Hanon, Olivier; Dartigues, Jean-François; Harston, Sandrine; Gabelle, Audrey; Ceccaldi, Mathieu; Beauchet, Olivier; Krolak-Salmon, Pierre; David, Renaud; Rouaud, Olivier; Godefroy, Olivier; Belin, Catherine; Rouch, Isabelle; Auguste, Nicolas; Wallon, David; Benetos, Athanase; Pariente, Jérémie; Paccalin, Marc; Moreaud, Olivier; Hommet, Caroline; Sellal, François; Boutoleau-Bretonniére, Claire; Jalenques, Isabelle; Gentric, Armelle; Vandel, Pierre; Azouani, Chabha; Fillon, Ludovic; Fischer, Clara; Savarieau, Helen; Operto, Gregory; Bertin, Hugo; Chupin, Marie; Bouteloup, Vincent; Habert, Marie-Odile; Mangin, Jean-François; Chêne, Geneviève

2017-08-29

The natural history and disease mechanisms of Alzheimer's disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements. In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1.5 SD below age, sex and education-level norms) while not demented (Clinical Dementia Rating [CDR] <1). Baseline data collection included neurological and physical examinations as well as extensive neuropsychological testing. To be included in the MEMENTO cohort, participants had to agree to undergo both brain magnetic resonance imaging (MRI) and blood sampling. Cerebral 18 F-fluorodeoxyglucose positon emission tomography and lumbar puncture were optional. Automated analyses of cerebral MRI included assessments of volumes of whole-brain, hippocampal and white matter lesions. The 2323 participants, recruited from April 2011 to June 2014, were aged 71 years, on average (SD 8.7), and 62% were women. CDR was 0 in 40% of participants, and 30% carried at least one apolipoprotein E ε4 allele. We observed that more than half (52%) of participants had amnestic mild cognitive impairment (17% single-domain aMCI), 32% had non-amnestic mild cognitive impairment (16.9% single-domain naMCI) and 16% had isolated SCCs. Multivariable analyses of neuroimaging markers associations with cognitive categories showed that participants with aMCI had worse levels of imaging biomarkers than the others, whereas participants with naMCI had markers at intermediate levels between SCC and aMCI. The burden of white matter lesions tended to be larger in participants with aMCI. Independently of CDR, all neuroimaging and neuropsychological markers worsened with age, whereas differences were not consistent according to sex. MEMENTO is a large cohort with extensive clinical, neuropsychological and neuroimaging data and represents a platform for studying the natural history of ADRD in a large group of participants with different subtypes of MCI (amnestic or not amnestic) or isolated SCCs. Clinicaltrials.gov, NCT01926249 . Registered on 16 August 2013.

A single acute hepatotoxic dose of CCl4 causes oxidative stress in the rat brain.

PubMed

Ritesh, K R; Suganya, A; Dileepkumar, H V; Rajashekar, Y; Shivanandappa, T

2015-01-01

Carbon tetrachloride (CCl 4 ), a hepatotoxic agent is widely used to study the toxic mechanisms in experimental animals. We have investigated whether oxidative stress is induced in the brain at a single hepatotoxic dosage (1 ml/kg bw) of CCl 4 . Increased lipid peroxidation (LPO), protein carbonyls (PC) content and glutathione (GSH) depletion were observed in the brain regions of rats treated with CCl 4 which was higher than that of liver. A drastic reduction in the activity of glutathione- S -transferase (GST) was seen in the brain regions which was higher than that of liver. Similarly, activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), NADH- and NADPH-dehydrogenase were reduced in the brain regions similar to that of liver. Higher induction of oxidative stress in the brain compared to that of liver implies vulnerability of the brain for CCl 4 neurotoxicity. Our study shows that a single hepatotoxic dose of CCl 4 is equally neurotoxic to rats.

Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats

PubMed Central

Neth, Katharina; Lucio, Marianna; Walker, Alesia; Zorn, Julia; Schmitt-Kopplin, Philippe; Michalke, Bernhard

2015-01-01

Exposure to high concentrations of Manganese (Mn) is known to potentially induce an accumulation in the brain, leading to a Parkinson related disease, called manganism. Versatile mechanisms of Mn-induced brain injury are discussed, with inactivation of mitochondrial defense against oxidative stress being a major one. So far, studies indicate that the main Mn-species entering the brain are low molecular mass (LMM) compounds such as Mn-citrate. Applying a single low dose MnCl2 injection in rats, we observed alterations in Mn-species pattern within the brain by analysis of aqueous brain extracts by size-exclusion chromatography—inductively coupled plasma mass spectrometry (SEC-ICP-MS). Additionally, electrospray ionization—ion cyclotron resonance-Fourier transform-mass spectrometry (ESI-ICR/FT-MS) measurement of methanolic brain extracts revealed a comprehensive analysis of changes in brain metabolisms after the single MnCl2 injection. Major alterations were observed for amino acid, fatty acid, glutathione, glucose and purine/pyrimidine metabolism. The power of this metabolomic approach is the broad and detailed overview of affected brain metabolisms. We also correlated results from the metallomic investigations (Mn concentrations and Mn-species in brain) with the findings from metabolomics. This strategy might help to unravel the role of different Mn-species during Mn-induced alterations in brain metabolism. PMID:26383269

The Brain Tourniquet: Physiological Isolation of Brain Regions Damaged by Traumatic Head Injury

DTIC Science & Technology

2008-06-19

brain slices were treated after injury with either a nootropic agent ( aniracetam , cyclothiazide, IDRA 21, or 1-BCP) or the antiepileptic drug...tourniquet approach. Four well-known nootropic agents were evaluated: aniracetam , a pyrrolidione analog that slows non-NMDA (AMPA/kainate) receptor...to improve cognition in rats [Stdubli et al., 1994], and has more potent effects than aniracetam in rat brain slices [Arai et al., 1994]. In

Val66Met Polymorphism of BDNF Alters Prodomain Structure to Induce Neuronal Growth Cone Retraction

PubMed Central

Anastasia, Agustin; Deinhardt, Katrin; Chao, Moses V.; Will, Nathan E.; Irmady, Krithi; Lee, Francis S.; Hempstead, Barbara L.; Bracken, Clay

2013-01-01

A common single-nucleotide polymorphism in the human brain-derived neurotrophic factor (BDNF) gene results in a Val66Met substitution in the BDNF prodomain region. This single-nucleotide polymorphism is associated with alterations in memory and with enhanced risk to develop depression and anxiety disorders in humans. Here we show that the isolated BDNF prodomain is detected in the hippocampus and that it can be secreted from neurons in an activity-dependent manner. Using nuclear magnetic resonance spectroscopy and circular dichroism we find that the prodomain is intrinsically disordered, and the Val66Met substitution induces structural changes. Surprisingly, application of Met66 (but not Val66) BDNF prodomain induces acute growth cone retraction and a decrease in Rac activity in hippocampal neurons. Expression of p75NTR and differential engagement of the Met66 prodomain to the SorCS2 receptor are required for this effect. These results identify the Met66 prodomain as a new active ligand which modulates neuronal morphology. PMID:24048383

Brain cDNA clone for human cholinesterase

DOE Office of Scientific and Technical Information (OSTI.GOV)

McTiernan, C.; Adkins, S.; Chatonnet, A.

1987-10-01

A cDNA library from human basal ganglia was screened with oligonucleotide probes corresponding to portions of the amino acid sequence of human serum cholinesterase. Five overlapping clones, representing 2.4 kilobases, were isolated. The sequenced cDNA contained 207 base pairs of coding sequence 5' to the amino terminus of the mature protein in which there were four ATG translation start sites in the same reading frame as the protein. Only the ATG coding for Met-(-28) lay within a favorable consensus sequence for functional initiators. There were 1722 base pairs of coding sequence corresponding to the protein found circulating in human serum.more » The amino acid sequence deduced from the cDNA exactly matched the 574 amino acid sequence of human serum cholinesterase, as previously determined by Edman degradation. Therefore, our clones represented cholinesterase rather than acetylcholinesterase. It was concluded that the amino acid sequences of cholinesterase from two different tissues, human brain and human serum, were identical. Hybridization of genomic DNA blots suggested that a single gene, or very few genes coded for cholinesterase.« less

Acute hydrocephalus caused by intraspinal neurocysticercosis: case report

PubMed Central

2014-01-01

Background Intraspinal neurocysticercosis is an uncommon manifestation that may present as an isolated lesion. Furthermore, acute hydrocephalus caused by isolated intraspinal neurocysticercosis without concomitant cerebral involvement is extremely rare. Case presentation A 64-year-old man presented with a history of severe headache, an unsteady gait, and occasional urinary incontinence. Magnetic resonance imaging of the thoraco-lumbar spine revealed multiple, cystic, contrast-enhancing intraspinal lesions. A computed tomographic scan of the brain showed marked ventricular dilatation but no intraparenchymal lesions or intraventricular cysticercal lesions. This case of acute hydrocephalus was found to be caused by isolated intraspinal neurocysticercosis and was treated by ventriculoperitoneal shunt placement and surgical removal of the intraspinal lesions (which were histologically confirmed as neurocysticercosis), followed by administration of dexamethasone and albendazole. Conclusion Isolated spinal neurocysticercosis should be considered in the differential diagnosis of acute hydrocephalus when no explanation is found in the brain, particularly in geographical regions endemic for cysticercosis. PMID:24383427

Radiation dose reduction using a neck detection algorithm for single spiral brain and cervical spine CT acquisition in the trauma setting.

PubMed

Ardley, Nicholas D; Lau, Ken K; Buchan, Kevin

2013-12-01

Cervical spine injuries occur in 4-8 % of adults with head trauma. Dual acquisition technique has been traditionally used for the CT scanning of brain and cervical spine. The purpose of this study was to determine the efficacy of radiation dose reduction by using a single acquisition technique that incorporated both anatomical regions with a dedicated neck detection algorithm. Thirty trauma patients for brain and cervical spine CT were included and were scanned with the single acquisition technique. The radiation doses from the single CT acquisition technique with the neck detection algorithm, which allowed appropriate independent dose administration relevant to brain and cervical spine regions, were recorded. Comparison was made both to the doses calculated from the simulation of the traditional dual acquisitions with matching parameters, and to the doses of retrospective dual acquisition legacy technique with the same sample size. The mean simulated dose for the traditional dual acquisition technique was 3.99 mSv, comparable to the average dose of 4.2 mSv from 30 previous patients who had CT of brain and cervical spine as dual acquisitions. The mean dose from the single acquisition technique was 3.35 mSv, resulting in a 16 % overall dose reduction. The images from the single acquisition technique were of excellent diagnostic quality. The new single acquisition CT technique incorporating the neck detection algorithm for brain and cervical spine significantly reduces the overall radiation dose by eliminating the unavoidable overlapping range between 2 anatomical regions which occurs with the traditional dual acquisition technique.

New Severity Indices for Quantifying Single-suture Metopic Craniosynostosis

PubMed Central

Ruiz-Correa, Salvador; Starr, Jacqueline R.; Lin, H. Jill; Kapp-Simon, Kathleen A.; Sze, Raymond W.; Ellenbogen, Richard G.; Speltz, Matthew L.; Cunningham, Michael L.

2012-01-01

OBJECTIVE To describe novel severity indices with which to quantify severity of trigonocephaly malformation in children diagnosed with isolated metopic synostosis. METHODS Computed tomographic scans of the cranium were obtained from 38 infants diagnosed with isolated metopic synostosis and 53 age-matched control patients. Volumetric reformations of the cranium were used to trace two-dimensional planes defined by the cranium-base plane and well-defined brain landmarks. For each patient, novel trigonocephaly severity indices (TSI) were computed from outline cranium shapes on each of these planes. The metopic severity index based on measurements of interlandmark distances was also computed and a receiver operating characteristic analysis used to compare the accuracy of classification based on TSIs versus that based on the metopic severity index. RESULTS The proposed TSIs are a sensitive measure of trigonocephaly malformation that can provide a classification accuracy of 96% with a specificity of 95%, in contrast with 82% of the metopic severity index at the same specificity level. CONCLUSIONS We completed exploratory analysis of outline-based severity measurements computed from computed tomographic image planes of the cranium. These TSIs enable quantitative analysis of cranium features in isolated metopic synostosis that may not be accurately detected by analytic tools derived from a sparse set of traditional interlandmark and semilandmark distances. PMID:18797362

N-isopropyl-(/sup 123/I)p-iodoamphetamine: single-pass brain uptake and washout; binding to brain synaptosomes; and localization in dog and monkey brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winchell, H.S.; Horst, W.D.; Braun, L.

1980-10-01

The kinetics of N-isopropyl-p-(/sup 123/I)iodoamphetamine in rat brains were determined by serial measurements of brain uptake index (BUI) after intracarotid injection; also studied were its effects on amine uptake and release in rat's brain cortical synaptosomes; and its in vivo distribution in the dog and monkey. No specific localization in brain nuclei of the dog was seen, but there was progressive accumulation in the eyes. Rapid initial brain uptake in the ketamine-sedated monkey was noted, and further slow brain uptake occurred during the next 20 min but without retinal localization. High levels of brain activity were maintained for several hours.more » The quantitative initial single-pass clearance of the agent in the brain suggests its use in evaluation of regional brain perfusion. Its interaction with brain amine-binding sites suggests its possible application in studies of cerebral amine metabolism.« less

Outcomes of surgery followed by local brain radiotherapy compared with surgery followed by whole brain radiotherapy for single brain metastasis.

PubMed

Igaki, Hiroshi; Harada, Ken; Umezawa, Rei; Miyakita, Yasuji; Ohno, Makoto; Takahashi, Masamichi; Sumi, Minako; Inaba, Koji; Murakami, Naoya; Ito, Yoshinori; Narita, Yoshitaka; Itami, Jun

2017-07-31

To determine the clinical efficacy of surgery followed by local brain radiotherapy (LBRT) for patients with a single brain metastasis, by comparing the results with those of postoperative whole brain radiotherapy (WBRT). We performed a retrospective analysis to compare the survival rate, recurrence-free rates, and causes of death for single brain metastasis patients who underwent surgery followed by LBRT or WBRT in the 2010-2015 period. After their surgery, 22 and 32 patients were treated by LBRT and WBRT, respectively. The median survival times for these LBRT and WBRT groups were 18.3 months and 19.2 months, respectively (p = 0.356). The local recurrence-free rates were 81.2% at 1 year and 81.2% at 2 years after LBRT, and 63.8% at 1 year and 58.9% at 2 years after WBRT (p = 0.589). The distant brain recurrence-free rates were 42.5% at 1 year and 25.5% at 2 years after LBRT, and 69.8% at 1 year and 52.4% at 2 years after WBRT (p = 0.044). Distant brain recurrences were observed significantly more frequently in the LBRT group, but the rates of salvage treatment application and survival were not significantly different between the LBRT and WBRT groups. The probability of neurologic death was not significantly higher in the LBRT group compared with the WBRT group. Surgery followed by LBRT for single brain metastasis is not inferior to postoperative WBRT, because survival and the necessity of salvage treatment after LBRT were equivalent to those after WBRT.

Heparanase Mechanisms in Melanoma Brain Metastasis

DTIC Science & Technology

2015-10-01

and ultimately affecting the modulation of BMM. 4 2. KEYWORDS: Brain-metastatic melanoma (BMM), Heparanase (HPSE), Exosomes , proteomic profiling...levels of exosomes , microvescicles that were found to be significantly implicated in the metastatic cancer events, notably to brain (6). Exosomes ...microenvironment. Thus, exosomes isolated from our melanoma/BMM cell models were interrogated for HPSE, MicroRNAs, and for protein expression contents by

Plasma brain-derived neurotrophic factor in women after bariatric surgery: a pilot study.

PubMed

Merhi, Zaher O; Minkoff, Howard; Lambert-Messerlian, Geralyn M; Macura, Jerzy; Feldman, Joseph; Seifer, David B

2009-04-01

Eighteen morbidly obese women had plasma brain-derived neurotrophic factor (BDNF) measured before bariatric surgery and 3 months postoperatively. We analyzed plasma BDNF levels in all the participants then subdivided according to menopausal status and type of surgery. Brain-derived neurotrophic factor decreased significantly in all the participants and in the premenopausal group when looked at in isolation.

Expression and function of orphan nuclear receptor TLX in adult neural stem cells.

PubMed

Shi, Yanhong; Chichung Lie, D; Taupin, Philippe; Nakashima, Kinichi; Ray, Jasodhara; Yu, Ruth T; Gage, Fred H; Evans, Ronald M

2004-01-01

The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

I know I've seen you before: Distinguishing recent-single-exposure-based familiarity from pre-existing familiarity.

PubMed

Gimbel, Sarah I; Brewer, James B; Maril, Anat

2017-03-01

This study examines how individuals differentiate recent-single-exposure-based familiarity from pre-existing familiarity. If these are two distinct cognitive processes, are they supported by the same neural bases? This study examines how recent-single-exposure-based familiarity and multiple-previous-exposure-based familiarity are supported and represented in the brain using functional MRI. In a novel approach, we first behaviorally show that subjects can divide retrieval of items in pre-existing memory into judgments of recollection and familiarity. Then, using functional magnetic resonance imaging, we examine the differences in blood oxygen level dependent activity and regional connectivity during judgments of recent-single-exposure-based and pre-existing familiarity. Judgments of these two types of familiarity showed distinct regions of activation in a whole-brain analysis, in medial temporal lobe (MTL) substructures, and in MTL substructure functional-correlations with other brain regions. Specifically, within the MTL, perirhinal cortex showed increased activation during recent-single-exposure-based familiarity while parahippocampal cortex showed increased activation during judgments of pre-existing familiarity. We find that recent-single-exposure-based and pre-existing familiarity are represented as distinct neural processes in the brain; this is supported by differing patterns of brain activation and regional correlations. This spatially distinct regional brain involvement suggests that the two separate experiences of familiarity, recent-exposure-based familiarity and pre-existing familiarity, may be cognitively distinct. Copyright © 2017 Elsevier B.V. All rights reserved.

Edwardsiella tarda and Aeromonas hydrophila isolated from diseased Southern flounder (Paralichthys lethostigma) are virulent to channel catfish and Nile tilapia

USDA-ARS?s Scientific Manuscript database

The aim of this study is to identify bacterial pathogens isolated from diseased Southern flounder and determine their virulence to channel catfish and Nile tilapia. Twenty five Gram-negative bacteria isolates were recovered from five tissues (skin lesions, brain, liver, intestine, and posterior kidn...

Social Isolation Co-opts Fear and Aggression Circuits.

PubMed

Rodriguez-Romaguera, Jose; Stuber, Garret D

2018-05-17

Social isolation is a stressful condition that often leads to maladaptive behaviors. In this issue of Cell, Zelikowsky et al. find that chronic social isolation stress triggers an increase in neuronal tachykinin signaling across distinct brain regions that mediate fear and aggression, elucidating the neural basis of these maladaptive responses. Copyright © 2018. Published by Elsevier Inc.

Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution.

PubMed

Chiang, Ann-Shyn; Lin, Chih-Yung; Chuang, Chao-Chun; Chang, Hsiu-Ming; Hsieh, Chang-Huain; Yeh, Chang-Wei; Shih, Chi-Tin; Wu, Jian-Jheng; Wang, Guo-Tzau; Chen, Yung-Chang; Wu, Cheng-Chi; Chen, Guan-Yu; Ching, Yu-Tai; Lee, Ping-Chang; Lin, Chih-Yang; Lin, Hui-Hao; Wu, Chia-Chou; Hsu, Hao-Wei; Huang, Yun-Ann; Chen, Jing-Yi; Chiang, Hsin-Jung; Lu, Chun-Fang; Ni, Ru-Fen; Yeh, Chao-Yuan; Hwang, Jenn-Kang

2011-01-11

Animal behavior is governed by the activity of interconnected brain circuits. Comprehensive brain wiring maps are thus needed in order to formulate hypotheses about information flow and also to guide genetic manipulations aimed at understanding how genes and circuits orchestrate complex behaviors. To assemble this map, we deconstructed the adult Drosophila brain into approximately 16,000 single neurons and reconstructed them into a common standardized framework to produce a virtual fly brain. We have constructed a mesoscopic map and found that it consists of 41 local processing units (LPUs), six hubs, and 58 tracts covering the whole Drosophila brain. Despite individual local variation, the architecture of the Drosophila brain shows invariance for both the aggregation of local neurons (LNs) within specific LPUs and for the connectivity of projection neurons (PNs) between the same set of LPUs. An open-access image database, named FlyCircuit, has been constructed for online data archiving, mining, analysis, and three-dimensional visualization of all single neurons, brain-wide LPUs, their wiring diagrams, and neural tracts. We found that the Drosophila brain is assembled from families of multiple LPUs and their interconnections. This provides an essential first step in the analysis of information processing within and between neurons in a complete brain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of growth hormone deficiency on brain structure, motor function and cognition.

PubMed

Webb, Emma A; O'Reilly, Michelle A; Clayden, Jonathan D; Seunarine, Kiran K; Chong, Wui K; Dale, Naomi; Salt, Alison; Clark, Chris A; Dattani, Mehul T

2012-01-01

The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone <6.7 µg/l) and idiopathic short stature (peak growth hormone >10 µg/l) underwent cognitive assessment, diffusion tensor imaging and volumetric magnetic resonance imaging prior to commencing growth hormone treatment. Total brain, corpus callosal, hippocampal, thalamic and basal ganglia volumes were determined using Freesurfer. Fractional anisotropy (a marker of white matter structural integrity) images were aligned and tract-based spatial statistics performed. Fifteen children (mean 8.8 years of age) with isolated growth hormone deficiency [peak growth hormone <6.7 µg/l (mean 3.5 µg/l)] and 14 controls (mean 8.4 years of age) with idiopathic short stature [peak growth hormone >10 µg/l (mean 15 µg/l) and normal growth rate] were recruited. Compared with controls, children with isolated growth hormone deficiency had lower Full-Scale IQ (P < 0.01), Verbal Comprehension Index (P < 0.01), Processing Speed Index (P < 0.05) and Movement-Assessment Battery for Children (P < 0.008) scores. Verbal Comprehension Index scores correlated significantly with insulin-like growth factor-1 (P < 0.03) and insulin-like growth factor binding protein-3 (P < 0.02) standard deviation scores in isolated growth hormone deficiency. The splenium of the corpus callosum, left globus pallidum, thalamus and hippocampus (P < 0.01) were significantly smaller; and corticospinal tract (bilaterally; P < 0.045, P < 0.05) and corpus callosum (P < 0.05) fractional anisotropy were significantly lower in the isolated growth hormone deficiency group. Basal ganglia volumes and bilateral corticospinal tract fractional anisotropy correlated significantly with Movement-Assessment Battery for Children scores, and corpus callosum fractional anisotropy with Full-Scale IQ and Processing Speed Index. In patients with isolated growth hormone deficiency, white matter abnormalities in the corpus callosum and corticospinal tract, and reduced thalamic and globus pallidum volumes relate to deficits in cognitive function and motor performance. Follow-up studies that investigate the course of the structural and cognitive deficits on growth hormone treatment are now required to confirm that growth hormone deficiency impacts significantly on brain structure, cognitive function and motor performance.

Gene Expression in Single Cells Isolated from the CWR-R1 Prostate Cancer Cell Line and Human Prostate Tissue Based on the Side Population Phenotype.

PubMed

Gangavarapu, Kalyan J; Miller, Austin; Huss, Wendy J

2016-09-01

Defining biological signals at the single cell level can identify cancer initiating driver mutations. Techniques to isolate single cells such as microfluidics sorting and magnetic capturing systems have limitations such as: high cost, labor intense, and the requirement of a large number of cells. Therefore, the goal of our current study is to identify a cost and labor effective, reliable, and reproducible technique that allows single cell isolation for analysis to promote regular laboratory use, including standard reverse transcription PCR (RT-PCR). In the current study, we utilized single prostate cells isolated from the CWR-R1 prostate cancer cell line and human prostate clinical specimens, based on the ATP binding cassette (ABC) transporter efflux of dye cycle violet (DCV), side population assay. Expression of four genes: ABCG2; Aldehyde dehydrogenase1A1 (ALDH1A1); androgen receptor (AR); and embryonic stem cell marker, Oct-4, were determined. Results from the current study in the CWR-R1 cell line showed ABCG2 and ALDH1A1 gene expression in 67% of single side population cells and in 17% or 100% of non-side population cells respectively. Studies using single cells isolated from clinical specimens showed that the Oct-4 gene is detected in only 22% of single side population cells and in 78% of single non-side population cells. Whereas, AR gene expression is in 100% single side population and non-side population cells isolated from the same human prostate clinical specimen. These studies show that performing RT-PCR on single cells isolated by FACS can be successfully conducted to determine gene expression in single cells from cell lines and enzymatically digested tissue. While these studies provide a simple yes/no expression readout, the more sensitive quantitative RT-PCR would be able to provide even more information if necessary.

Gene Expression in Single Cells Isolated from the CWR-R1 Prostate Cancer Cell Line and Human Prostate Tissue Based on the Side Population Phenotype

PubMed Central

Gangavarapu, Kalyan J; Miller, Austin; Huss, Wendy J

2016-01-01

Defining biological signals at the single cell level can identify cancer initiating driver mutations. Techniques to isolate single cells such as microfluidics sorting and magnetic capturing systems have limitations such as: high cost, labor intense, and the requirement of a large number of cells. Therefore, the goal of our current study is to identify a cost and labor effective, reliable, and reproducible technique that allows single cell isolation for analysis to promote regular laboratory use, including standard reverse transcription PCR (RT-PCR). In the current study, we utilized single prostate cells isolated from the CWR-R1 prostate cancer cell line and human prostate clinical specimens, based on the ATP binding cassette (ABC) transporter efflux of dye cycle violet (DCV), side population assay. Expression of four genes: ABCG2; Aldehyde dehydrogenase1A1 (ALDH1A1); androgen receptor (AR); and embryonic stem cell marker, Oct-4, were determined. Results from the current study in the CWR-R1 cell line showed ABCG2 and ALDH1A1 gene expression in 67% of single side population cells and in 17% or 100% of non-side population cells respectively. Studies using single cells isolated from clinical specimens showed that the Oct-4 gene is detected in only 22% of single side population cells and in 78% of single non-side population cells. Whereas, AR gene expression is in 100% single side population and non-side population cells isolated from the same human prostate clinical specimen. These studies show that performing RT-PCR on single cells isolated by FACS can be successfully conducted to determine gene expression in single cells from cell lines and enzymatically digested tissue. While these studies provide a simple yes/no expression readout, the more sensitive quantitative RT-PCR would be able to provide even more information if necessary. PMID:27785389

Ammonia-induced mitochondrial dysfunction and energy metabolism disturbances in isolated brain and liver mitochondria, and the effect of taurine administration: relevance to hepatic encephalopathy treatment

PubMed Central

Niknahad, Hossein; Jamshidzadeh, Akram; Zarei, Mahdi; Ommati, Mohammad Mehdi

2017-01-01

Introduction Ammonia-induced oxidative stress, mitochondrial dysfunction, and energy crisis are known as some the major mechanisms of brain injury in hepatic encephalopathy (HE). Hyperammonemia also affects the liver and hepatocytes. Therefore, targeting mitochondria seems to be a therapeutic point of intervention in the treatment of HE. Taurine is an abundant amino acid in the human body. Several biological functions including the mitochondrial protective properties are attributed to this amino acid. The aim of this study is to evaluate the effect of taurine administration on ammonia-induced mitochondrial dysfunction. Material and methods Isolated mice liver and brain mitochondria were exposed to different concentrations of ammonia (1, 5, 10, and 20 mM) and taurine (1, 5, and 10 mM), and several mitochondrial indices were assessed. Results It was found that ammonia inhibited mitochondrial dehydrogenases activity caused collapse of mitochondrial membrane potential (MMP), induced mitochondrial swelling (MPP), and increased reactive oxygen species (ROS) in isolated liver and brain mitochondria. Furthermore, a significant amount of lipid peroxidation (LPO), along with glutathione (GSH) and ATP depletion, was detected in ammonia exposed mitochondria. Taurine administration (5 and 10 mM) mitigated ammonia-induced mitochondrial dysfunction. Conclusions The current investigation demonstrates that taurine is instrumental in preserving brain and liver mitochondrial function in a hyperammonemic environment. The data suggest taurine as a potential protective agent with a therapeutic capability against hepatic encephalopathy and hyperammonemia. PMID:29062904

Exploring the mechanical behavior of single intermediate filaments.

PubMed

Kreplak, L; Bär, H; Leterrier, J F; Herrmann, H; Aebi, U

2005-12-02

Intermediate filaments (IFs) are structural elements of eukaryotic cells with distinct mechanical properties. Tissue integrity is severely impaired, in particular in skin and muscle, when IFs are either absent or malfunctioning due to mutations. Our knowledge on the mechanical properties of IFs is mainly based on tensile testing of macroscopic fibers and on the rheology of IF networks. At the single filament level, the only piece of data available is a measure of the persistence length of vimentin IFs. Here, we have employed an atomic force microscopy (AFM) based protocol to directly probe the mechanical properties of single cytoplasmic IFs when adsorbed to a solid support in physiological buffer environment. Three IF types were studied in vitro: recombinant murine desmin, recombinant human keratin K5/K14 and neurofilaments isolated from rat brains, which are composed of the neurofilament triplet proteins NF-L, NF-M and NF-H. Depending on the experimental conditions, the AFM tip was used to laterally displace or to stretch single IFs on the support they had been adsorbed to. Upon applying force, IFs were stretched on average 2.6-fold. The maximum stretching that we encountered was 3.6-fold. A large reduction of the apparent filament diameter was observed concomitantly. The observed mechanical properties therefore suggest that IFs may indeed function as mechanical shock absorbers in vivo.

Silicon Dioxide Thin Film Mediated Single Cell Nucleic Acid Isolation

PubMed Central

Bogdanov, Evgeny; Dominova, Irina; Shusharina, Natalia; Botman, Stepan; Kasymov, Vitaliy; Patrushev, Maksim

2013-01-01

A limited amount of DNA extracted from single cells, and the development of single cell diagnostics make it necessary to create a new highly effective method for the single cells nucleic acids isolation. In this paper, we propose the DNA isolation method from biomaterials with limited DNA quantity in sample, and from samples with degradable DNA based on the use of solid-phase adsorbent silicon dioxide nanofilm deposited on the inner surface of PCR tube. PMID:23874571

PET and Single-Photon Emission Computed Tomography in Brain Concussion.

PubMed

Raji, Cyrus A; Henderson, Theodore A

2018-02-01

This article offers an overview of the application of PET and single photon emission computed tomography brain imaging to concussion, a type of mild traumatic brain injury and traumatic brain injury, in general. The article reviews the application of these neuronuclear imaging modalities in cross-sectional and longitudinal studies. Additionally, this article frames the current literature with an overview of the basic physics and radiation exposure risks of each modality. Copyright © 2017 Elsevier Inc. All rights reserved.

Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis

PubMed Central

Lees, John A.; Kremer, Philip H. C.; Manso, Ana S.; Croucher, Nicholas J.; Ferwerda, Bart; Serón, Mercedes Valls; Oggioni, Marco R.; Parkhill, Julian; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik

2017-01-01

Recent studies have provided evidence for rapid pathogen genome diversification, some of which could potentially affect the course of disease. We have previously described such variation seen between isolates infecting the blood and cerebrospinal fluid (CSF) of a single patient during a case of bacterial meningitis. Here, we performed whole-genome sequencing of paired isolates from the blood and CSF of 869 meningitis patients to determine whether such variation frequently occurs between these two niches in cases of bacterial meningitis. Using a combination of reference-free variant calling approaches, we show that no genetic adaptation occurs in either invaded niche during bacterial meningitis for two major pathogen species, Streptococcus pneumoniae and Neisseria meningitidis. This study therefore shows that the bacteria capable of causing meningitis are already able to do this upon entering the blood, and no further sequence change is necessary to cross the blood–brain barrier. Our findings place the focus back on bacterial evolution between nasopharyngeal carriage and invasion, or diversity of the host, as likely mechanisms for determining invasiveness. PMID:28348877

Isolation, morphological identification and in vitro antibacterial activity of endophytic bacteria isolated from Azadirachta indica (neem) leaves

PubMed Central

Singh, Ankit Kumar; Sharma, Rajesh Kumar; Sharma, Varsha; Singh, Tanmay; Kumar, Rajesh; Kumari, Dimple

2017-01-01

Aim: The objective of this study was to isolate endophytic bacteria from Azadirachta indica (neem) leaves, their identification and investigate their antibacterial activity against three Gram-positive bacteria, Staphylococcus aureus, Streptococcus pyogenes and Bacillus cereus and Gram-negative bacteria Escherichia coli, Salmonella Typhimurium and Klebsiella pneumoniae. Materials and Methods: Fresh leaves of A. indica (neem) was procured from the Department of Botany, JNKVV, Jabalpur. Five samples were taken, and each sample was divided into five subsamples and separated for further isolation of endophytic bacteria. For sterilization leaves were treated with double distilled water, 0.1% sodium hypochlorite, 0.01% bavistin, 0.05% and 70% ethanol. Sterilized leaves of the plants were embedded in Kings B (KB) petri plates and incubated at 37°C for 24 h. Characterization of the bacteria was done according to its morphology and by Gram-staining. After that, a single colony was transferred into brain heart infusion (BHI) broth and incubated at 37°C for 24 h. The antibacterial effect was studied by the disk diffusion method with known antibiotic ciprofloxacin (Ci) as standard. Results: A total of 25 bacterial isolates from A. indica (neem) were obtained and identified morphologically. Most of the samples on KB media depicted irregular shape, flat elevation, undulated, rough, opaque, and white in color. Most of the samples on blood agar showed irregular, raise elevation, undulated, smooth, opaque and all the isolates were nonhemolytic and nonchromogenic. The growth of endophytic bacteria in BHI broth were all isolates showed turbidity. The microscopic examination revealed that maximum isolates were Gram-positive and rod shaped. Good antibacterial activity was observed against S. aureus, Streptococcus pyogenes, E. coli, Salmonella Typhimurium, and K. pneumoniae. Conclusions: Endophytic bacteria are present in leaves of A. indica (neem) and it possesses antibacterial activity against few Gram-positive and Gram-negative bacteria. PMID:28620254

Construction of Microdrive Arrays for Chronic Neural Recordings in Awake Behaving Mice

PubMed Central

Chang, Eric H.; Frattini, Stephen A.; Robbiati, Sergio; Huerta, Patricio T.

2013-01-01

State-of-the-art electrophysiological recordings from the brains of freely behaving animals allow researchers to simultaneously examine local field potentials (LFPs) from populations of neurons and action potentials from individual cells, as the animal engages in experimentally relevant tasks. Chronically implanted microdrives allow for brain recordings to last over periods of several weeks. Miniaturized drives and lightweight components allow for these long-term recordings to occur in small mammals, such as mice. By using tetrodes, which consist of tightly braided bundles of four electrodes in which each wire has a diameter of 12.5 μm, it is possible to isolate physiologically active neurons in superficial brain regions such as the cerebral cortex, dorsal hippocampus, and subiculum, as well as deeper regions such as the striatum and the amygdala. Moreover, this technique insures stable, high-fidelity neural recordings as the animal is challenged with a variety of behavioral tasks. This manuscript describes several techniques that have been optimized to record from the mouse brain. First, we show how to fabricate tetrodes, load them into driveable tubes, and gold-plate their tips in order to reduce their impedance from MΩ to KΩ range. Second, we show how to construct a custom microdrive assembly for carrying and moving the tetrodes vertically, with the use of inexpensive materials. Third, we show the steps for assembling a commercially available microdrive (Neuralynx VersaDrive) that is designed to carry independently movable tetrodes. Finally, we present representative results of local field potentials and single-unit signals obtained in the dorsal subiculum of mice. These techniques can be easily modified to accommodate different types of electrode arrays and recording schemes in the mouse brain. PMID:23851569

Complete genome assemblies for two single-chromosome Vibrio cholerae isolates, strains 1154-74 (serogroup O49) and 10432-62 (serogroup O27)

DOE PAGES

Johnson, Shannon Lyn; Khiani, A.; Bishop-Lilly, K. A.; ...

2015-05-14

We report the completed genome sequences for two non-O1/non-O139 Vibrio cholerae isolates. Each isolate has only a single chromosome, as opposed to the normal paradigm of two chromosomes found in all other V. cholerae isolates.

Complete genome assemblies for two single-chromosome Vibrio cholerae isolates, strains 1154-74 (serogroup O49) and 10432-62 (serogroup O27)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Shannon Lyn; Khiani, A.; Bishop-Lilly, K. A.

We report the completed genome sequences for two non-O1/non-O139 Vibrio cholerae isolates. Each isolate has only a single chromosome, as opposed to the normal paradigm of two chromosomes found in all other V. cholerae isolates.

Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria.

PubMed

Ahadpour, Morteza; Eskandari, Mohammad Reza; Mashayekhi, Vida; Haj Mohammad Ebrahim Tehrani, Kamaleddin; Jafarian, Iman; Naserzadeh, Parvaneh; Hosseini, Mir-Jamal

2016-01-01

Isoniazid (INH or isonicotinic hydrazide) is used for the treatment and prophylaxis of tuberculosis. Liver and brain are two important target organs in INH toxicity. However, the exact mechanisms behind the INH hepatotoxicity or neurotoxicity have not yet been completely understood. Considering the mitochondria as one of the possible molecular targets for INH toxicity, the aim of this study was to evaluate the mechanisms of INH mitochondrial toxicity on isolated mitochondria. Mitochondria were isolated by differential ultracentrifugation from male Sprague-Dawley rats and incubated with different concentrations of INH (25-2000 μM) for the investigation of mitochondrial parameters. The results indicated that INH could interact with mitochondrial respiratory chain and inhibit its activity. Our results showed an elevation in mitochondrial reactive oxygen species (ROS) formation, lipid peroxidation and mitochondrial membrane potential collapse after exposure of isolated liver mitochondria in INH. However, different results were obtained in brain mitochondria. Noteworthy, significant glutathione oxidation, adenosine triphosphate (ATP) depletion and lipid peroxidation were observed in higher concentration of INH, as compared to liver mitochondria. In conclusion, our results suggest that INH may initiate its toxicity in liver mitochondria through interaction with electron transfer chain, lipid peroxidation, mitochondrial membrane potential decline and cytochrome c expulsion which ultimately lead to cell death signaling.

Thick corpus callosum in the second trimester can be transient and is of uncertain significance.

PubMed

Shinar, S; Har-Toov, J; Lerman-Sagie, T; Malinger, G

2016-10-01

Depiction of a thick corpus callosum (CC) in utero is rare, and is generally associated with severe brain anomalies. Our aim was to describe a group of fetuses diagnosed during second-trimester ultrasound examination as having an apparently isolated thick CC, which normalized subsequently in the cases followed to term. Among 59 fetuses referred to the Ob-Gyn Ultrasound Division of Lis Maternity Hospital with suspected callosal anomalies between January 2013 and June 2014, we identified nine cases with an apparently isolated thick CC for inclusion in this retrospective cohort study. Length and body thickness of the CC were compared with previously published nomograms. Fetuses with a suspected isolated thick CC were identified and followed until delivery or termination of pregnancy (TOP). Evaluation consisted of chromosomal analysis, at least one magnetic resonance imaging (MRI) examination and repeat ultrasound examinations. Postnatal evaluation included brain ultrasound examination, MRI when indicated and neurodevelopmental assessment through validated pediatric questionnaires. The nine fetuses were diagnosed with an apparently isolated thick CC at a mean gestational age of 23 + 5 (range, 21-29) weeks. Eight exhibited a CC body thickness ≥ 2SD above the mean for gestational age and one exhibited only a thickened genu. Six also exhibited a relatively short CC. Two patients opted for TOP but declined autopsy. In five of the seven remaining fetuses, the CC thickness normalized during follow-up. In the remaining two, the increased CC thickness was a variant of the cingulate sulcus. The CC length remained ≤ 2SD in five of the six fetuses with a short CC. Fetal MRI was performed and confirmed the diagnosis in six fetuses. The karyotype was normal in all fetuses. Short-term neurodevelopmental outcome was reported as normal in all six children with complete follow-up. Although the number of fetuses in our study is relatively small, it seems that an apparently isolated thick CC is not necessarily associated with poor prognosis. In such cases, a definitive diagnosis should not be reached based on a single measurement and repeat follow-up examinations during the third trimester are recommended. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Single-voxel and multi-voxel spectroscopy yield comparable results in the normal juvenile canine brain when using 3 Tesla magnetic resonance imaging.

PubMed

Lee, Alison M; Beasley, Michaela J; Barrett, Emerald D; James, Judy R; Gambino, Jennifer M

2018-06-10

Conventional magnetic resonance imaging (MRI) characteristics of canine brain diseases are often nonspecific. Single- and multi-voxel spectroscopy techniques allow quantification of chemical biomarkers for tissues of interest and may help to improve diagnostic specificity. However, published information is currently lacking for the in vivo performance of these two techniques in dogs. The aim of this prospective, methods comparison study was to compare the performance of single- and multi-voxel spectroscopy in the brains of eight healthy, juvenile dogs using 3 Tesla MRI. Ipsilateral regions of single- and multi-voxel spectroscopy were performed in symmetric regions of interest of each brain in the parietal (n = 3), thalamic (n = 2), and piriform lobes (n = 3). In vivo single-voxel spectroscopy and multi-voxel spectroscopy metabolite ratios from the same size and multi-voxel spectroscopy ratios from different sized regions of interest were compared. No significant difference was seen between single-voxel spectroscopy and multi-voxel spectroscopy metabolite ratios for any lobe when regions of interest were similar in size and shape. Significant lobar single-voxel spectroscopy and multi-voxel spectroscopy differences were seen between the parietal lobe and thalamus (P = 0.047) for the choline to N-acetyl aspartase ratios when large multi-voxel spectroscopy regions of interest were compared to very small multi-voxel spectroscopy regions of interest within the same lobe; and for the N-acetyl aspartase to creatine ratios in all lobes when single-voxel spectroscopy was compared to combined (pooled) multi-voxel spectroscopy datasets. Findings from this preliminary study indicated that single- and multi-voxel spectroscopy techniques using 3T MRI yield comparable results for similar sized regions of interest in the normal canine brain. Findings also supported using the contralateral side as an internal control for dogs with brain lesions. © 2018 American College of Veterinary Radiology.

The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study

PubMed Central

Fair, Damien A.; Choi, Alexander H.; Dosenbach, Yannic B.L.; Coalson, Rebecca S.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

2009-01-01

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we use an event-related design, which allowed us to isolate trial related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single-subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. PMID:19819000

The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study.

PubMed

Fair, Damien A; Choi, Alexander H; Dosenbach, Yannic B L; Coalson, Rebecca S; Miezin, Francis M; Petersen, Steven E; Schlaggar, Bradley L

2010-08-01

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon is accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we used an event-related design, which allowed us to isolate trial-related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial-related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. 2009 Elsevier Inc. All rights reserved.

The Complete Remission of Acquired Immunodeficiency Syndrome-associated Isolated Central Nervous System Lymphomatoid Granulomatosis: A Case Report and Review of the Literature.

PubMed

Kano, Yasuhiro; Kodaira, Minori; Ushiki, Atsuhito; Kosaka, Makoto; Yamada, Mitsunori; Shingu, Kunihiko; Nishihara, Hiroshi; Hanaoka, Masayuki; Sekijima, Yoshiki

2017-09-15

A 49-year-old man presented with gradually progressive aphasia one month after being diagnosed with acquired immunodeficiency syndrome (AIDS). Brain magnetic resonance imaging showed multiple brain lesions with punctate and linear enhancement. A polymerase chain reaction detected Epstein-Barr virus (EBV) in the patient's cerebrospinal fluid. A diagnosis of isolated central nervous system lymphomatoid granulomatosis (CNS-LYG) was made based on the brain biopsy findings. The complete remission of CNS-LYG was achieved by anti-retroviral therapy (ART) alone. In the present case, the development of AIDS-associated CNS-LYG was considered to have been initiated by the reactivation of EBV in the CNS under immunosuppressive conditions. The patient's condition improved with the reconstitution of the patient's immune system.

Epidemiology of Mild Traumatic Brain Injury with Intracranial Hemorrhage: Focusing Predictive Models for Neurosurgical Intervention.

PubMed

Orlando, Alessandro; Levy, A Stewart; Carrick, Matthew M; Tanner, Allen; Mains, Charles W; Bar-Or, David

2017-11-01

To outline differences in neurosurgical intervention (NI) rates between intracranial hemorrhage (ICH) types in mild traumatic brain injuries and help identify which ICH types are most likely to benefit from creation of predictive models for NI. A multicenter retrospective study of adult patients spanning 3 years at 4 U.S. trauma centers was performed. Patients were included if they presented with mild traumatic brain injury (Glasgow Coma Scale score 13-15) with head CT scan positive for ICH. Patients were excluded for skull fractures, "unspecified hemorrhage," or coagulopathy. Primary outcome was NI. Stepwise multivariable logistic regression models were built to analyze the independent association between ICH variables and outcome measures. The study comprised 1876 patients. NI rate was 6.7%. There was a significant difference in rate of NI by ICH type. Subdural hematomas had the highest rate of NI (15.5%) and accounted for 78% of all NIs. Isolated subarachnoid hemorrhages had the lowest, nonzero, NI rate (0.19%). Logistic regression models identified ICH type as the most influential independent variable when examining NI. A model predicting NI for isolated subarachnoid hemorrhages would require 26,928 patients, but a model predicting NI for isolated subdural hematomas would require only 328 patients. This study highlighted disparate NI rates among ICH types in patients with mild traumatic brain injury and identified mild, isolated subdural hematomas as most appropriate for construction of predictive NI models. Increased health care efficiency will be driven by accurate understanding of risk, which can come only from accurate predictive models. Copyright © 2017 Elsevier Inc. All rights reserved.

High-throughput dual-colour precision imaging for brain-wide connectome with cytoarchitectonic landmarks at the cellular level

PubMed Central

Gong, Hui; Xu, Dongli; Yuan, Jing; Li, Xiangning; Guo, Congdi; Peng, Jie; Li, Yuxin; Schwarz, Lindsay A.; Li, Anan; Hu, Bihe; Xiong, Benyi; Sun, Qingtao; Zhang, Yalun; Liu, Jiepeng; Zhong, Qiuyuan; Xu, Tonghui; Zeng, Shaoqun; Luo, Qingming

2016-01-01

The precise annotation and accurate identification of neural structures are prerequisites for studying mammalian brain function. The orientation of neurons and neural circuits is usually determined by mapping brain images to coarse axial-sampling planar reference atlases. However, individual differences at the cellular level likely lead to position errors and an inability to orient neural projections at single-cell resolution. Here, we present a high-throughput precision imaging method that can acquire a co-localized brain-wide data set of both fluorescent-labelled neurons and counterstained cell bodies at a voxel size of 0.32 × 0.32 × 2.0 μm in 3 days for a single mouse brain. We acquire mouse whole-brain imaging data sets of multiple types of neurons and projections with anatomical annotation at single-neuron resolution. The results show that the simultaneous acquisition of labelled neural structures and cytoarchitecture reference in the same brain greatly facilitates precise tracing of long-range projections and accurate locating of nuclei. PMID:27374071

Persistency and flexibility of complex brain networks underlie dual-task interference.

PubMed

Alavash, Mohsen; Hilgetag, Claus C; Thiel, Christiane M; Gießing, Carsten

2015-09-01

Previous studies on multitasking suggest that performance decline during concurrent task processing arises from interfering brain modules. Here, we used graph-theoretical network analysis to define functional brain modules and relate the modular organization of complex brain networks to behavioral dual-task costs. Based on resting-state and task fMRI we explored two organizational aspects potentially associated with behavioral interference when human subjects performed a visuospatial and speech task simultaneously: the topological overlap between persistent single-task modules, and the flexibility of single-task modules in adaptation to the dual-task condition. Participants showed a significant decline in visuospatial accuracy in the dual-task compared with single visuospatial task. Global analysis of topological similarity between modules revealed that the overlap between single-task modules significantly correlated with the decline in visuospatial accuracy. Subjects with larger overlap between single-task modules showed higher behavioral interference. Furthermore, lower flexible reconfiguration of single-task modules in adaptation to the dual-task condition significantly correlated with larger decline in visuospatial accuracy. Subjects with lower modular flexibility showed higher behavioral interference. At the regional level, higher overlap between single-task modules and less modular flexibility in the somatomotor cortex positively correlated with the decline in visuospatial accuracy. Additionally, higher modular flexibility in cingulate and frontal control areas and lower flexibility in right-lateralized nodes comprising the middle occipital and superior temporal gyri supported dual-tasking. Our results suggest that persistency and flexibility of brain modules are important determinants of dual-task costs. We conclude that efficient dual-tasking benefits from a specific balance between flexibility and rigidity of functional brain modules. © 2015 Wiley Periodicals, Inc.

Causes of failure of pallidal deep brain stimulation in cases with pre-operative diagnosis of isolated dystonia.

PubMed

Pauls, K Amande M; Krauss, Joachim K; Kämpfer, Constanze E; Kühn, Andrea A; Schrader, Christoph; Südmeyer, Martin; Allert, Niels; Benecke, Rainer; Blahak, Christian; Boller, Jana K; Fink, Gereon R; Fogel, Wolfgang; Liebig, Thomas; El Majdoub, Faycal; Mahlknecht, Philipp; Kessler, Josef; Mueller, Joerg; Voges, Juergen; Wittstock, Matthias; Wolters, Alexander; Maarouf, Mohammad; Moro, Elena; Volkmann, Jens; Bhatia, Kailash P; Timmermann, Lars

2017-10-01

Pallidal deep brain stimulation (GPi-DBS) is an effective therapy for isolated dystonia, but 10-20% of patients show improvement below 25-30%. We here investigated causes of insufficient response to GPi-DBS in isolated dystonia in a cross-sectional study. Patients with isolated dystonia at time of surgery, and <30% improvement on the Burke-Fahn-Marsden dystonia-rating-scale (BFMDRS) after ≥6 months of continuous GPi-DBS were videotaped ON and OFF stimulation, and history, preoperative videos, brain MRI, medical records, stimulation settings, stimulation system integrity, lead location, and genetic information were obtained and reviewed by an expert panel. 22 patients from 11 centres were included (8 men, 14 women; 9 generalized, 9 segmental, 3 focal, 1 bibrachial dystonia; mean (range): age 48.7 (25-72) years, disease duration 22.0 (2-40) years, DBS duration 45.5 (6-131) months). Mean BFMDRS-score was 31.7 (4-93) preoperatively and 32.3 (5-101) postoperatively. Half of the patients (n = 11) had poor lead positioning alone or in combination with other problems (combined with: other disease n = 6, functional dystonia n = 1, other problems n = 2). Other problems were disease other than isolated inherited or idiopathic dystonia (n = 5), fixed deformities (n = 2), functional dystonia (n = 3), and other causes (n = 1). Excluding patients with poor lead location from further analysis, non-isolated dystonia accounted for 45.5%, functional dystonia for 27.3%, and fixed deformities for 18.2%. In patients with true isolated dystonia, lead location was the most frequent problem. After exclusion of lead placement and stimulation programming issues, non-isolated dystonia, functional dystonia and fixed deformities account for the majority of GPi-DBS failures in dystonia. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Identification, localisation and functional implication of 26RFa orthologue peptide in the brain of zebra finch (Taeniopygia guttata).

PubMed

Tobari, Y; Iijima, N; Tsunekawa, K; Osugi, T; Haraguchi, S; Ubuka, T; Ukena, K; Okanoya, K; Tsutsui, K; Ozawa, H

2011-09-01

Several neuropeptides with the C-terminal Arg-Phe-NH(2) (RFa) sequence have been identified in the hypothalamus of a variety of vertebrates. The present study was conducted to isolate novel RFa peptides from the zebra finch brain. Peptides were isolated by immunoaffinity purification using an antibody that recognises avian RFa peptides. The isolated peptide consisted of 25 amino acids with RFa at its C-terminus. The sequence was SGTLGNLAEEINGYNRRKGGFTFRFa. Alignment of the peptide with vertebrate 26RFa has revealed that the identified peptide is the zebra finch 26RFa. We also cloned the precursor cDNA encoding this peptide. Synteny analysis of the gene showed a high conservation of this gene among vertebrates. In addition, we cloned the cDNA encoding a putative 26RFa receptor, G protein-coupled receptor 103 (GPR103) in the zebra finch brain. GPR103 cDNA encoded a 432 amino acid protein that has seven transmembrane domains. In situ hybridisation analysis in the brain showed that the expression of 26RFa mRNA is confined to the anterior-medial hypothalamic area, ventromedial nucleus of the hypothalamus and the lateral hypothalamic area, the brain regions that are involved in the regulation of feeding behaviour, whereas GPR103 mRNA is distributed throughout the brain in addition to the hypothalamic nuclei. When administered centrally in free-feeding male zebra finches, 26RFa increased food intake 24 h after injection without body mass change. Diencephalic GPR103 mRNA expression was up-regulated by fasting for 10 h. Our data suggest that the hypothalamic 26RFa-its receptor system plays an important role in the central control of food intake and energy homeostasis in the zebra finch. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

Regulation of respiration in brain mitochondria and synaptosomes: restrictions of ADP diffusion in situ, roles of tubulin, and mitochondrial creatine kinase.

PubMed

Monge, Claire; Beraud, Nathalie; Kuznetsov, Andrey V; Rostovtseva, Tatiana; Sackett, Dan; Schlattner, Uwe; Vendelin, Marko; Saks, Valdur A

2008-11-01

The role of ubiquitous mitochondrial creatine kinase (uMtCK) reaction in regulation of mitochondrial respiration was studied in purified preparations of rat brain synaptosomes and mitochondria. In permeabilized synaptosomes, apparent Km for exogenous ADP, Km (ADP), in regulation of respiration in situ was rather high (110 +/- 11 microM) in comparison with isolated brain mitochondria (9 +/- 1 microM). This apparent Km for ADP observed in isolated mitochondria in vitro dramatically increased to 169 +/- 52 microM after their incubation with 1 muM of dimeric tubulin showing that in rat brain, particularly in synaptosomes, mitochondrial outer membrane permeability for ADP, and ATP may be restricted by tubulin binding to voltage dependent anion channel (VDAC). On the other hand, in synaptosomes apparent Km (ADP) decreased to 25 +/- 1 microM in the presence of 20 mM creatine. To fully understand this effect of creatine on kinetics of respiration regulation, complete kinetic analysis of uMtCK reaction in isolated brain mitochondria was carried out. This showed that oxidative phosphorylation specifically altered only the dissociation constants for MgATP, by decreasing that from ternary complex MtCK.Cr.MgATP (K (a)) from 0.13 +/- 0.02 to 0.018 +/- 0.007 mM and that from binary complex MtCK.MgATP (K (ia)) from 1.1 +/- 0.29 mM to 0.17 +/- 0.07 mM. Apparent decrease of dissociation constants for MgATP reflects effective cycling of ATP and ADP between uMtCK and adenine nucleotide translocase (ANT). These results emphasize important role and various pathophysiological implications of the phosphocreatine-creatine kinase system in energy transfer in brain cells, including synaptosomes.

Extracts and constituents of Leontopodium alpinum enhance cholinergic transmission: Brain ACh increasing and memory improving properties

PubMed Central

Hornick, Ariane; Schwaiger, Stefan; Rollinger, Judith M.; Vo, Nguyen Phung; Prast, Helmut; Stuppner, Hermann

2012-01-01

Leontopodium alpinum (‘Edelweiss’) was phytochemically investigated for constituents that might enhance cholinergic neurotransmission. The potency to increase synaptic availability of acetylcholine (ACh) in rat brain served as key property for the bioguided isolation of cholinergically active compounds using different chromatographic techniques. The dichlormethane (DCM) extract of the root, fractions and isolated constituents were injected i.c.v. and the effect on brain ACh was detected via the push–pull technique. The DCM extract enhanced extracellular ACh concentration in rat brain and inhibited acetylcholinesterase (AChE) in vitro. The extracellular level of brain ACh was significantly increased by the isolated sesquiterpenes, isocomene and 14-acetoxyisocomene, while silphiperfolene acetate and silphinene caused a small increasing tendency. Only silphiperfolene acetate showed in vitro AChE inhibitory activity, thus suggesting the other sesquiterpenes to stimulate cholinergic transmission by an alternative mechanism of action. Isocomene was further investigated with behavioural tasks in mice. It restored object recognition in scopolamine-impaired mice and showed nootropic effects in the T-maze alternation task in normal and scopolamine-treated mice. Additionally, this sesquiterpene reduced locomotor activity of untreated mice in the open field task, while the activity induced by scopolamine was abolished. The enhancement of synaptic availability of ACh, the promotion of alternation, and the amelioration of scopolamine-induced deficit are in accordance with a substance that amplifies cholinergic transmission. Whether the mechanism of action is inhibition of AChE or another pro-cholinergic property remains to be elucidated. Taken together, isocomene and related constituents of L. alpinum deserve further interest as potential antidementia agents in brain diseases associated with cholinergic deficits. PMID:18541221

Single-shot ADC imaging for fMRI.

PubMed

Song, Allen W; Guo, Hua; Truong, Trong-Kha

2007-02-01

It has been suggested that apparent diffusion coefficient (ADC) contrast can be sensitive to cerebral blood flow (CBF) changes during brain activation. However, current ADC imaging techniques have an inherently low temporal resolution due to the requirement of multiple acquisitions with different b-factors, as well as potential confounds from cross talk between the deoxyhemoglobin-induced background gradients and the externally applied diffusion-weighting gradients. In this report a new method is proposed and implemented that addresses these two limitations. Specifically, a single-shot pulse sequence that sequentially acquires one gradient-echo (GRE) and two diffusion-weighted spin-echo (SE) images was developed. In addition, the diffusion-weighting gradient waveform was numerically optimized to null the cross terms with the deoxyhemoglobin-induced background gradients to fully isolate the effect of diffusion weighting from that of oxygenation-level changes. The experimental results show that this new single-shot method can acquire ADC maps with sufficient signal-to-noise ratio (SNR), and establish its practical utility in functional MRI (fMRI) to complement the blood oxygenation level-dependent (BOLD) technique and provide differential sensitivity for different vasculatures to better localize neural activity originating from the small vessels. Copyright (c) 2007 Wiley-Liss, Inc.

Sequence polymorphism in an insect RNA virus field population: A snapshot from a single point in space and time reveals stochastic differences among and within individual hosts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stenger, Drake C., E-mail: drake.stenger@ars.usda.

Population structure of Homalodisca coagulata Virus-1 (HoCV-1) among and within field-collected insects sampled from a single point in space and time was examined. Polymorphism in complete consensus sequences among single-insect isolates was dominated by synonymous substitutions. The mutant spectrum of the C2 helicase region within each single-insect isolate was unique and dominated by nonsynonymous singletons. Bootstrapping was used to correct the within-isolate nonsynonymous:synonymous arithmetic ratio (N:S) for RT-PCR error, yielding an N:S value ~one log-unit greater than that of consensus sequences. Probability of all possible single-base substitutions for the C2 region predicted N:S values within 95% confidence limits of themore » corrected within-isolate N:S when the only constraint imposed was viral polymerase error bias for transitions over transversions. These results indicate that bottlenecks coupled with strong negative/purifying selection drive consensus sequences toward neutral sequence space, and that most polymorphism within single-insect isolates is composed of newly-minted mutations sampled prior to selection. -- Highlights: •Sampling protocol minimized differential selection/history among isolates. •Polymorphism among consensus sequences dominated by negative/purifying selection. •Within-isolate N:S ratio corrected for RT-PCR error by bootstrapping. •Within-isolate mutant spectrum dominated by new mutations yet to undergo selection.« less

Surveillance imaging in children with malignant CNS tumors: low yield of spine MRI.

PubMed

Perreault, Sébastien; Lober, Robert M; Carret, Anne-Sophie; Zhang, Guohua; Hershon, Linda; Décarie, Jean-Claude; Vogel, Hannes; Yeom, Kristen W; Fisher, Paul G; Partap, Sonia

2014-02-01

Magnetic resonance imaging (MRI) is routinely obtained in patients with central nervous system (CNS) tumors, but few studies have been conducted to evaluate this practice. We assessed the benefits of surveillance MRI and more specifically spine MRI in a contemporary cohort. We evaluated MRI results of children diagnosed with CNS tumors from January 2000 to December 2011. Children with at least one surveillance MRI following the diagnosis of medulloblastoma (MB), atypical teratoid rhabdoid tumor (ATRT), pineoblastoma (PB), supratentorial primitive neuroectodermal tumor, supratentorial high-grade glioma (World Health Organization grade III-IV), CNS germ cell tumors or ependymoma were included. A total of 2,707 brain and 1,280 spine MRI scans were obtained in 258 patients. 97% of all relapses occurred in the brain and 3% were isolated to the spine. Relapse was identified in 226 (8%) brain and 48 (4%) spine MRI scans. The overall rate of detecting isolated spinal relapse was 9/1,000 and 7/1,000 for MB patients. MRI performed for PB showed the highest rate for detecting isolated spinal recurrence with 49/1,000. No initial isolated spinal relapse was identified in patients with glioma, supratentorial primitive neuroectodermal tumor and ATRT. Isolated spinal recurrences are infrequent in children with malignant CNS tumors and the yield of spine MRI is very low. Tailoring surveillance spine MRI to patients with higher spinal relapse risk such as PB, MB with metastatic disease and within 3 years of diagnosis could improve allocation of resources without compromising patient care.

DNA methylation of the GC box in the promoter region mediates isolation rearing-induced suppression of srd5a1 transcription in the prefrontal cortex.

PubMed

Araki, Ryota; Nishida, Shoji; Hiraki, Yosuke; Matsumoto, Kinzo; Yabe, Takeshi

2015-10-08

The levels of allopregnanolone (ALLO), a neurosteroid, in brain and serum are related to severity of depression and anxiety. Steroid 5α-reductase type I is the rate-limiting enzyme in ALLO biosynthesis and plays an important role in control of the ALLO level in mammalian brain. In this study, we examined an epigenetic mechanism for transcriptional regulation of srd5a1, which codes for steroid 5α-reductase type I, using isolation-reared mice. The mRNA level of srd5a1 was decreased in the prefrontal cortex (PFC) in isolation-reared mice. Rearing in social isolation increased methylation of cytosines at -82 and -12 bp downstream of the transcription start site, which are located in a GC box element in the promoter region of srd5a1. Binding of Sp1, a ubiquitous transcription factor, to the GC box was decreased in the promoter region of srd5a1 in the PFC in isolation-reared mice. Site-specific methylation at cytosine -12 of a srd5a1 promoter-luciferase reporter construct, but not that of cytosine -82, downregulated the promoter activity of srd5a1. These findings suggest that transcription of srd5a1 in brain is regulated by environmental factor-induced cytosine methylation in the promoter region. This finding could contribute to development of antidepressant and anxiolytic agents. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Stable long-term chronic brain mapping at the single-neuron level.

PubMed

Fu, Tian-Ming; Hong, Guosong; Zhou, Tao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

2016-10-01

Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

Effect of Growth Hormone Deficiency on Brain Structure, Motor Function and Cognition

ERIC Educational Resources Information Center

Webb, Emma A.; O'Reilly, Michelle A.; Clayden, Jonathan D.; Seunarine, Kiran K.; Chong, Wui K.; Dale, Naomi; Salt, Alison; Clark, Chris A.; Dattani, Mehul T.

2012-01-01

The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone less than 6.7 [micro]g/l) and idiopathic short stature (peak growth hormone greater than 10 [micro]g/l)…

Early-Life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats.

PubMed

Soga, Tomoko; Teo, Chuin Hau; Cham, Kai Lin; Idris, Marshita Mohd; Parhar, Ishwar S

2015-01-01

Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH) neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinizing hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic-GnIH neuronal system using enhanced green fluorescent protein (EGFP)-tagged GnIH transgenic rats. Socially isolated rats were observed for anxious and depressive behaviors. Using immunohistochemistry, we examined c-Fos protein expression in EGFP-GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group housing. We also inspected serotonergic fiber juxtapositions in EGFP-GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviors. The total number of EGFP-GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fiber juxtapositions on EGFP-GnIH neurons were also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early-life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure.

Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing.

PubMed

Renthal, William

2018-01-01

Background Migraine is a debilitating disorder characterized by severe headaches and associated neurological symptoms. A key challenge to understanding migraine has been the cellular complexity of the human brain and the multiple cell types implicated in its pathophysiology. The present study leverages recent advances in single-cell transcriptomics to localize the specific human brain cell types in which putative migraine susceptibility genes are expressed. Methods The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2,039 individual human brain cells across two published single-cell RNA sequencing datasets. Enrichment of migraine-associated genes was determined for each brain cell type. Results Analysis of single-brain cell RNA sequencing data from five major subtypes of cells in the human cortex (neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells) indicates that over 40% of known migraine-associated genes are enriched in the expression profiles of a specific brain cell type. Further analysis of neuronal migraine-associated genes demonstrated that approximately 70% were significantly enriched in inhibitory neurons and 30% in excitatory neurons. Conclusions This study takes the next step in understanding the human brain cell types in which putative migraine susceptibility genes are expressed. Both familial and common migraine may arise from dysfunction of discrete cell types within the neurovascular unit, and localization of the affected cell type(s) in an individual patient may provide insight into to their susceptibility to migraine.

Isolation and biological and molecular characterization of Neospora caninum (NC-SP1) from a naturally infected adult asymptomatic cattle (Bos taurus) in the state of São Paulo, Brazil.

PubMed

Oliveira, Solange; Soares, Rodrigo Martins; Aizawa, Juliana; Soares, Herbert Sousa; Chiebao, Daniela Pontes; Ortega-Mora, Luis Miguel; Regidor-Cerrillo, Javier; Silva, Natália Quadros Bressa; Gennari, Solange Maria; Pena, Hilda Fátima Jesus

2017-05-01

The biological and genetic diversity of Neospora caninum is very limited because of availability of only a few viable isolates worldwide. This study describes the isolation and biological and molecular characterization of a new viable isolate of N. caninum (NC-SP1), from a cattle in Brazil. Approximately 400 g of brain from a naturally infected adult male cattle from an abattoir was fed to a 2-month-old dog. Neospora-like oocysts were observed on day 7 post-inoculation (PI) and the duration of oocyst shedding was 14 days. The DNA obtained from oocysts was characterized molecularly and the final sequence was 99% identical to homologous sequences of N. caninum available in GenBank®. For bioassay, gerbils (Meriones unguiculatus) were orally inoculated with 10 100 and 1000 oocysts; all gerbils remained clinically normal but developed N. caninum antibodies 14 days PI. Cell culture isolation was successful using the brain homogenate from one of the gerbils and tachyzoites were observed 24 days PI. Microsatellite genotyping revealed a unique genetic profile for this new reference isolate.

Rapid and reversible impairments of short- and long-term social recognition memory are caused by acute isolation of adult rats via distinct mechanisms.

PubMed

Shahar-Gold, Hadar; Gur, Rotem; Wagner, Shlomo

2013-01-01

Mammalian social organizations require the ability to recognize and remember individual conspecifics. This social recognition memory (SRM) can be examined in rodents using their innate tendency to investigate novel conspecifics more persistently than familiar ones. Here we used the SRM paradigm to examine the influence of housing conditions on the social memory of adult rats. We found that acute social isolation caused within few days a significant impairment in acquisition of short-term SRM of male and female rats. Moreover, SRM consolidation into long-term memory was blocked following only one day of social isolation. Both impairments were reversible, but with different time courses. Furthermore, only the impairment in SRM consolidation was reversed by systemic administration of arginine-vasopressin (AVP). In contrast to SRM, object recognition memory was not affected by social isolation. We conclude that acute social isolation rapidly induces reversible changes in the brain neuronal and molecular mechanisms underlying SRM, which hamper its acquisition and completely block its consolidation. These changes occur via distinct, AVP sensitive and insensitive mechanisms. Thus, acute social isolation of rats swiftly causes changes in their brain and interferes with their normal social behavior.

A survey of human brain transcriptome diversity at the single cell level.

PubMed

Darmanis, Spyros; Sloan, Steven A; Zhang, Ye; Enge, Martin; Caneda, Christine; Shuer, Lawrence M; Hayden Gephart, Melanie G; Barres, Ben A; Quake, Stephen R

2015-06-09

The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.

A non-aggressive, highly efficient, enzymatic method for dissociation of human brain-tumors and brain-tissues to viable single-cells.

PubMed

Volovitz, Ilan; Shapira, Netanel; Ezer, Haim; Gafni, Aviv; Lustgarten, Merav; Alter, Tal; Ben-Horin, Idan; Barzilai, Ori; Shahar, Tal; Kanner, Andrew; Fried, Itzhak; Veshchev, Igor; Grossman, Rachel; Ram, Zvi

2016-06-01

Conducting research on the molecular biology, immunology, and physiology of brain tumors (BTs) and primary brain tissues requires the use of viably dissociated single cells. Inadequate methods for tissue dissociation generate considerable loss in the quantity of single cells produced and in the produced cells' viability. Improper dissociation may also demote the quality of data attained in functional and molecular assays due to the presence of large quantities cellular debris containing immune-activatory danger associated molecular patterns, and due to the increased quantities of degraded proteins and RNA. Over 40 resected BTs and non-tumorous brain tissue samples were dissociated into single cells by mechanical dissociation or by mechanical and enzymatic dissociation. The quality of dissociation was compared for all frequently used dissociation enzymes (collagenase, DNase, hyaluronidase, papain, dispase) and for neutral protease (NP) from Clostridium histolyticum. Single-cell-dissociated cell mixtures were evaluated for cellular viability and for the cell-mixture dissociation quality. Dissociation quality was graded by the quantity of subcellular debris, non-dissociated cell clumps, and DNA released from dead cells. Of all enzymes or enzyme combinations examined, NP (an enzyme previously not evaluated on brain tissues) produced dissociated cell mixtures with the highest mean cellular viability: 93 % in gliomas, 85 % in brain metastases, and 89 % in non-tumorous brain tissue. NP also produced cell mixtures with significantly less cellular debris than other enzymes tested. Dissociation using NP was non-aggressive over time-no changes in cell viability or dissociation quality were found when comparing 2-h dissociation at 37 °C to overnight dissociation at ambient temperature. The use of NP allows for the most effective dissociation of viable single cells from human BTs or brain tissue. Its non-aggressive dissociative capacity may enable ambient-temperature shipping of tumor pieces in multi-center clinical trials, meanwhile being dissociated. As clinical grade NP is commercially available it can be easily integrated into cell-therapy clinical trials in neuro-oncology. The high quality viable cells produced may enable investigators to conduct more consistent research by avoiding the experimental artifacts associated with the presence dead cells or cellular debris.

Brain Peptides and Psychopharmacology

ERIC Educational Resources Information Center

Arehart-Treichel, Joan

1976-01-01

Proteins isolated from the brain and used as drugs can improve and apparently even transfer mental states and behavior. Much of the pioneering work and recent research with humans and animals is reviewed and crucial questions that are being posed about the psychologically active peptides are related. (BT)

Identification of substance P precursor forms in human brain tissue.

PubMed Central

Nyberg, F; le Grevés, P; Terenius, L

1985-01-01

Substance P prohormones were identified in the caudate nucleus, hypothalamus, and substantia nigra of human brain. A polypeptide fraction of acidic brain extracts was fractionated on Sephadex G-50. The lyophilized fractions were sequentially treated with trypsin and a substance P-degrading enzyme with strong preference toward the Phe7-Phe8 and Phe8-Gly9 bonds. The released substance P(1-7) fragment was isolated by ion-exchange chromatography and quantitated by a specific radioimmunoassay. Confirmation of the structure of the isolated radioimmunoassay-active fragment was achieved by electrophoresis and HPLC. By using this enzymatic/radioimmunoassay procedure, two polypeptide fractions of apparent Mr 5000 and 15,000, respectively, were identified. The latter component was the major one of the two but was estimated to account for only about 5% of total substance P radioimmunoassay activity. Because it is of the size predicted from the nucleotide sequences of cDNA for substance P prohormones in bovine brain, the Mr 15,000 component may represent the full-length prohormone. PMID:2408270

DNA isolation protocol effects on nuclear DNA analysis by microarrays, droplet digital PCR, and whole genome sequencing, and on mitochondrial DNA copy number estimation.

PubMed

Nacheva, Elizabeth; Mokretar, Katya; Soenmez, Aynur; Pittman, Alan M; Grace, Colin; Valli, Roberto; Ejaz, Ayesha; Vattathil, Selina; Maserati, Emanuela; Houlden, Henry; Taanman, Jan-Willem; Schapira, Anthony H; Proukakis, Christos

2017-01-01

Potential bias introduced during DNA isolation is inadequately explored, although it could have significant impact on downstream analysis. To investigate this in human brain, we isolated DNA from cerebellum and frontal cortex using spin columns under different conditions, and salting-out. We first analysed DNA using array CGH, which revealed a striking wave pattern suggesting primarily GC-rich cerebellar losses, even against matched frontal cortex DNA, with a similar pattern on a SNP array. The aCGH changes varied with the isolation protocol. Droplet digital PCR of two genes also showed protocol-dependent losses. Whole genome sequencing showed GC-dependent variation in coverage with spin column isolation from cerebellum. We also extracted and sequenced DNA from substantia nigra using salting-out and phenol / chloroform. The mtDNA copy number, assessed by reads mapping to the mitochondrial genome, was higher in substantia nigra when using phenol / chloroform. We thus provide evidence for significant method-dependent bias in DNA isolation from human brain, as reported in rat tissues. This may contribute to array "waves", and could affect copy number determination, particularly if mosaicism is being sought, and sequencing coverage. Variations in isolation protocol may also affect apparent mtDNA abundance.

DNA isolation protocol effects on nuclear DNA analysis by microarrays, droplet digital PCR, and whole genome sequencing, and on mitochondrial DNA copy number estimation

PubMed Central

Nacheva, Elizabeth; Mokretar, Katya; Soenmez, Aynur; Pittman, Alan M.; Grace, Colin; Valli, Roberto; Ejaz, Ayesha; Vattathil, Selina; Maserati, Emanuela; Houlden, Henry; Taanman, Jan-Willem; Schapira, Anthony H.

2017-01-01

Potential bias introduced during DNA isolation is inadequately explored, although it could have significant impact on downstream analysis. To investigate this in human brain, we isolated DNA from cerebellum and frontal cortex using spin columns under different conditions, and salting-out. We first analysed DNA using array CGH, which revealed a striking wave pattern suggesting primarily GC-rich cerebellar losses, even against matched frontal cortex DNA, with a similar pattern on a SNP array. The aCGH changes varied with the isolation protocol. Droplet digital PCR of two genes also showed protocol-dependent losses. Whole genome sequencing showed GC-dependent variation in coverage with spin column isolation from cerebellum. We also extracted and sequenced DNA from substantia nigra using salting-out and phenol / chloroform. The mtDNA copy number, assessed by reads mapping to the mitochondrial genome, was higher in substantia nigra when using phenol / chloroform. We thus provide evidence for significant method-dependent bias in DNA isolation from human brain, as reported in rat tissues. This may contribute to array “waves”, and could affect copy number determination, particularly if mosaicism is being sought, and sequencing coverage. Variations in isolation protocol may also affect apparent mtDNA abundance. PMID:28683077

Brain MRI volumetry in a single patient with mild traumatic brain injury.

PubMed

Ross, David E; Castelvecchi, Cody; Ochs, Alfred L

2013-01-01

This letter to the editor describes the case of a 42 year old man with mild traumatic brain injury and multiple neuropsychiatric symptoms which persisted for a few years after the injury. Initial CT scans and MRI scans of the brain showed no signs of atrophy. Brain volume was measured using NeuroQuant®, an FDA-approved, commercially available software method. Volumetric cross-sectional (one point in time) analysis also showed no atrophy. However, volumetric longitudinal (two points in time) analysis showed progressive atrophy in several brain regions. This case illustrated in a single patient the principle discovered in multiple previous group studies, namely that the longitudinal design is more powerful than the cross-sectional design for finding atrophy in patients with traumatic brain injury.

Design and use of a folded four-ring double-tuned birdcage coil for rat brain sodium imaging at 9.4 T.

PubMed

Ha, YongHyun; Choi, Chang-Hoon; Worthoff, Wieland A; Shymanskaya, Aliaksandra; Schöneck, Michael; Willuweit, Antje; Felder, Jörg; Shah, N Jon

2018-01-01

A folded four-ring quadrature birdcage coil was designed and constructed with a double-tune configuration of an outer high-pass coil for 1 H (400 MHz) and inner low-pass coil for 23 Na (105.72 MHz at 9.4 T). The coil was evaluated on the bench and in the scanner, comparing its performance with that of single-tuned coils and a large four-ring coil. All coils were tuned and matched and the isolation between two quadrature ports was found to be better than -13.7 dB for 1 H and -27 dB for 23 Na. Signal-to-noise ratios (SNRs) were calculated and 23 Na flip angle maps were acquired. 23 Na SNR of the folded four-ring reached ∼93% of that obtained with the single-tuned coil. A set of in vivo 1 H and 23 Na axial images to cover the whole rat brain were obtained. The performance of the folded four-ring coil and its benefit for 23 Na imaging experiments have been demonstrated. This proposed four-ring coil could avoid length restrictions, e.g. the shoulders, by folding the outer rings vertically. This facilitates the construction of double-tuned four-ring birdcage coils just to fit the head, leading to higher filling factors and better SNR. Copyright © 2017 Elsevier Inc. All rights reserved.

Columnar processing in primate pFC: evidence for executive control microcircuits.

PubMed

Opris, Ioan; Hampson, Robert E; Gerhardt, Greg A; Berger, Theodore W; Deadwyler, Sam A

2012-12-01

A common denominator for many cognitive disorders of human brain is the disruption of neural activity within pFC, whose structural basis is primarily interlaminar (columnar) microcircuits or "minicolumns." The importance of this brain region for executive decision-making has been well documented; however, because of technological constraints, the minicolumnar basis is not well understood. Here, via implementation of a unique conformal multielectrode recording array, the role of interlaminar pFC minicolumns in the executive control of task-related target selection is demonstrated in nonhuman primates performing a visuomotor DMS task. The results reveal target-specific, interlaminar correlated firing during the decision phase of the trial between multielectrode recording array-isolated minicolumnar pairs of neurons located in parallel in layers 2/3 and layer 5 of pFC. The functional significance of individual pFC minicolumns (separated by 40 μm) was shown by reduced correlated firing between cell pairs within single minicolumns on error trials with inappropriate target selection. To further demonstrate dependence on performance, a task-disrupting drug (cocaine) was administered in the middle of the session, which also reduced interlaminar firing in minicolumns that fired appropriately in the early (nondrug) portion of the session. The results provide a direct demonstration of task-specific, real-time columnar processing in pFC indicating the role of this type of microcircuit in executive control of decision-making in primate brain.

Subtle learning and memory impairment in an idiopathic rat model of Alzheimer's disease utilizing cholinergic depletions and β-amyloid.

PubMed

Deibel, S H; Weishaupt, N; Regis, A M; Hong, N S; Keeley, R J; Balog, R J; Bye, C M; Himmler, S M; Whitehead, S N; McDonald, R J

2016-09-01

Alzheimer's disease (AD) is a disease of complex etiology, involving multiple risk factors. When these risk factors are presented concomitantly, cognition and brain pathology are more severely compromised than if those risk factors were presented in isolation. Reduced cholinergic tone and elevated amyloid-beta (Aβ) load are pathological hallmarks of AD. The present study sought to investigate brain pathology and alterations in learning and memory when these two factors were presented together in rats. Rats received either sham surgeries, cholinergic depletions of the medial septum, intracerebroventricular Aβ25-35 injections, or both cholinergic depletion and Aβ25-35 injections (Aβ+ACh group). The Aβ+ACh rats were unimpaired in a striatal dependent visual discrimination task, but had impaired acquisition in the standard version of the Morris water task. However, these rats displayed normal Morris water task retention and no impairment in acquisition of a novel platform location during a single massed training session. Aβ+ACh rats did not have exacerbated brain pathology as indicated by activated astroglia, activated microglia, or accumulation of Aβ. These data suggest that cholinergic depletions and Aβ injections elicit subtle cognitive deficits when behavioural testing is conducted shortly after the presentation of these factors. These factors might have altered hippocampal synaptic plasticity and thus resemble early AD pathology. Copyright © 2016 Elsevier B.V. All rights reserved.

Utility of human embryonic kidney cell line HEK-293 for rapid isolation of fixed and street rabies viruses: comparison with Neuro-2a and BHK-21 cell lines.

PubMed

Madhusudana, Shampur Narayan; Sundaramoorthy, Subha; Ullas, Padinjaremattatthil Thankappan

2010-12-01

A confirmatory rabies diagnosis can be achieved by rapid virus isolation in cell culture using brain tissue from the suspect animal. Several cell lines have been used for this purpose and the murine neuroblastoma cell line Neuro-2a has been found to be the most sensitive. The human embryonic kidney cell line HEK-293 is known to express several neuronal proteins and is believed to be of neuronal origin. We hypothesized that this cell line could be susceptible to rabies virus, which is highly neurotropic. First we tested the sensitivity of HEK-293 cells to the laboratory strain, challenge virus standard (CVS). We then tested 120 brain samples from different animals and humans suspected to have died of rabies by fluorescent antibody test (FAT). Both FAT-positive and FAT-negative brains were tested for virus isolation using Neuro-2a, BHK-21, and HEK-293 cell lines and also by mouse inoculation. There was 100% correlation between FAT, virus isolation in Neuro-2a and HEK-293 cells, and mouse inoculation. However, the rate of virus isolation in the BHK-21 cell line was only 28% when compared to the other cell lines. The sensitivity of HEK-293 to CVS strain of virus was similar to that of Neuro-2a. We conclude that the HEK-293 cell line is as sensitive as the Neuro-2a cell line for the rapid isolation of rabies virus and may serve as an alternative cell line for rabies diagnosis and future research. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Isolation of virus from brain after immunosuppression of mice with latent herpes simplex

NASA Astrophysics Data System (ADS)

Kastrukoff, Lorne; Long, Carol; Doherty, Peter C.; Wroblewska, Zofia; Koprowski, Hilary

1981-06-01

Herpes simplex virus (HSV) is usually present in a latent form in the trigeminal ganglion of man1-3. Various stress factors may induce virus reactivation, which is manifest by a lip lesion (innervated from the trigeminal ganglion) and the production of infectious virus. The considerable experimental efforts to define the conditions that lead to the reactivation of latent HSV have concentrated on isolating virus either from the original extraneural site of virus inoculation, or from cell-free homogenates of sensory ganglia from latently infected animals4-15. Recent DNA hybridization experiments resulted in the demonstration of the presence of HSV genomes in the brain tissue of both latently infected mice, and of humans who showed no clinical symptoms of HSV (ref. 16 and N. Fraser, personal communication). This led us to consider the possibility that HSV may be present in brain tissue as the result of either reactivation of the virus in brain cells or the passage of reactivated virus from trigeminal ganglia through the brain stem to the brain. The presence of infectious HSV in brain tissue has not previously been demonstrated; yet this could be a factor in chronic, relapsing neurological diseases such as multiple sclerosis. We have now shown experimentally that mice carrying latent HSV in their trigeminal ganglia may, following massive immunosuppression, express infectious virus in the central nervous system (CNS).

Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain.

PubMed

Joshi, Gururaj; Sultana, Rukhsana; Tangpong, Jitbanjong; Cole, Marsha Paulette; St Clair, Daret K; Vore, Mary; Estus, Steven; Butterfield, D Allan

2005-11-01

Adriamycin (ADR) is a chemotherapeutic agent useful in treating various cancers. ADR is a quinone-containing anthracycline chemotherapeutic and is known to produce reactive oxygen species (ROS) in heart. Application of this drug can have serious side effects in various tissues, including brain, apart from the known cardiotoxic side effects, which limit the successful use of this drug in treatment of cancer. Neurons treated with ADR demonstrate significant protein oxidation and lipid peroxidation. Patients under treatment with this drug often complain of forgetfulness, lack of concentration, dizziness (collectively called somnolence or sometimes called chemobrain). In this study, we tested the hypothesis that ADR induces oxidative stress in brain. Accordingly, we examined the in vivo levels of brain protein oxidation and lipid peroxidation induced by i.p. injection of ADR. We also measured levels of the multidrug resistance-associated protein (MRP1) in brain isolated from ADR- or saline-injected mice. MRP1 mediates ATP-dependent export of cytotoxic organic anions, glutathione S-conjugates and sulphates. The current results demonstrated a significant increase in levels of protein oxidation and lipid peroxidation and increased expression of MRP1 in brain isolated from mice, 72 h post i.p injection of ADR. These results are discussed with reference to potential use of this redox cycling chemotheraputic agent in the treatement of cancer and its chemobrain side effect in brain.

Control of Multilayer Networks

PubMed Central

Menichetti, Giulia; Dall’Asta, Luca; Bianconi, Ginestra

2016-01-01

The controllability of a network is a theoretical problem of relevance in a variety of contexts ranging from financial markets to the brain. Until now, network controllability has been characterized only on isolated networks, while the vast majority of complex systems are formed by multilayer networks. Here we build a theoretical framework for the linear controllability of multilayer networks by mapping the problem into a combinatorial matching problem. We found that correlating the external signals in the different layers can significantly reduce the multiplex network robustness to node removal, as it can be seen in conjunction with a hybrid phase transition occurring in interacting Poisson networks. Moreover we observe that multilayer networks can stabilize the fully controllable multiplex network configuration that can be stable also when the full controllability of the single network is not stable. PMID:26869210

A human scFv antibody that targets and neutralizes high molecular weight pathogenic amyloid-β oligomers.

PubMed

Sebollela, Adriano; Cline, Erika N; Popova, Izolda; Luo, Kevin; Sun, Xiaoxia; Ahn, Jay; Barcelos, Milena A; Bezerra, Vanessa N; Lyra E Silva, Natalia M; Patel, Jason; Pinheiro, Nathalia R; Qin, Lei A; Kamel, Josette M; Weng, Anthea; DiNunno, Nadia; Bebenek, Adrian M; Velasco, Pauline T; Viola, Kirsten L; Lacor, Pascale N; Ferreira, Sergio T; Klein, William L

2017-07-03

Brain accumulation of soluble oligomers of the amyloid-β peptide (AβOs) is increasingly considered a key early event in the pathogenesis of Alzheimer's disease (AD). A variety of AβO species have been identified, both in vitro and in vivo, ranging from dimers to 24mers and higher order oligomers. However, there is no consensus in the literature regarding which AβO species are most germane to AD pathogenesis. Antibodies capable of specifically recognizing defined subpopulations of AβOs would be a valuable asset in the identification, isolation, and characterization of AD-relevant AβO species. Here, we report the characterization of a human single chain antibody fragment (scFv) denoted NUsc1, one of a number of scFvs we have identified that stringently distinguish AβOs from both monomeric and fibrillar Aβ. NUsc1 readily detected AβOs previously bound to dendrites in cultured hippocampal neurons. In addition, NUsc1 blocked AβO binding and reduced AβO-induced neuronal oxidative stress and tau hyperphosphorylation in cultured neurons. NUsc1 further distinguished brain extracts from AD-transgenic mice from wild type (WT) mice, and detected endogenous AβOs in fixed AD brain tissue and AD brain extracts. Biochemical analyses indicated that NUsc1 targets a subpopulation of AβOs with apparent molecular mass greater than 50 kDa. Results indicate that NUsc1 targets a particular AβO species relevant to AD pathogenesis, and suggest that NUsc1 may constitute an effective tool for AD diagnostics and therapeutics. © 2017 International Society for Neurochemistry.

Early fever after trauma: Does it matter?

PubMed

Hinson, Holly E; Rowell, Susan; Morris, Cynthia; Lin, Amber L; Schreiber, Martin A

2018-01-01

Fever is strongly associated with poor outcome after traumatic brain injury (TBI). We hypothesized that early fever is a direct result of brain injury and thus would be more common in TBI than in patients without brain injury and associated with inflammation. We prospectively enrolled patients with major trauma with and without TBI from a busy Level I trauma center intensive care unit (ICU). Patients were assigned to one of four groups based on their presenting Head Abbreviated Injury Severity Scale scores: multiple injuries: head Abbreviated Injury Scale (AIS) score greater than 2, one other region greater than 2; isolated head: head AIS score greater than 2, all other regions less than 3; isolated body: one region greater than 2, excluding head/face; minor injury: no region with AIS greater than 2. Early fever was defined as at least one recorded temperature greater than 38.3°C in the first 48 hours after admission. Outcome measures included neurologic deterioration, length of stay in the ICU, hospital mortality, discharge Glasgow Outcome Scale-Extended, and plasma levels of seven key cytokines at admission and 24 hours (exploratory). Two hundred sixty-eight patients were enrolled, including subjects with multiple injuries (n = 59), isolated head (n = 97), isolated body (n = 100), and minor trauma (n = 12). The incidence of fever was similar in all groups irrespective of injury (11-24%). In all groups, there was a significant association between the presence of early fever and death in the hospital (6-18% vs. 0-3%), as well as longer median ICU stays (3-7 days vs. 2-3 days). Fever was significantly associated with elevated IL-6 at admission (50.7 pg/dL vs. 16.9 pg/dL, p = 0.0067) and at 24 hours (83.1 pg/dL vs. 17.1 pg/dL, p = 0.0025) in the isolated head injury group. Contrary to our hypothesis, early fever was not more common in patients with brain injury, though fever was associated with longer ICU stays and death in all groups. Additionally, fever was associated with elevated IL-6 levels in isolated head injury. Prognostic and Epidemiological study, level III.

Diagnostic findings in the 1992 epornitic of neurotropic velogenic Newcastle disease in double-crested cormorants from the upper midwestern United States.

USGS Publications Warehouse

Meteyer, Carol U.; Docherty, Douglas E.; Glaser, Linda C.; Franson, J.C.; Senne, Dennis A.; Duncan, Ruth

1997-01-01

Neurotropic velogenic Newcastle disease (NVND) occurred in juvenile double-crested cormorants,Phalacrocorax auritus, simultaneously in nesting colonies in Minnesota, North Dakota, South Dakota, and Nebraska and in Lakes Michigan, Superior, Huron, and Ontario during the summer of 1992. Mortality as high as 80%-90% was estimated in some of the nesting colonies. Clinical signs observed in 4- to -6wk-old cormorants included torticollis, tremors, ataxia, curled toes, and paresis or weakness of legs, wings or both, which was sometimes unilateral. No significant mortality or unusual clinical signs were seen in adult cormorants. Necropsy of 88 cormorants yielded no consistent gross observations. Microscopic lesions in the brain and spinal cord were consistently present in all cormorants from which Newcastle disease virus (NDV) was isolated. Characteristic brain lesions provided rapid identification of new suspect sites of NVND. Lesions were also present in the heart, kidney, proventriculus, spleen, and pancreas but were less consistent or nonspecific. NDV was isolated at the National Wildlife Health Center from 27 of 93 cormorants tested. Virus was most frequently isolated from intestine or brain tissue of cormorants submitted within the first 4wk of the epornitic. Sera collected from cormorants with neurologic signs were consistently positive for NDV antibody.The NDV isolate from cormorants was characterized as NVND virus at the National Veterinary Services Laboratories Ames, Iowa. The NVND virus was also identified as the cause of neurologic disease in a North Dakota turkey flock during the summer of 1992. Although no virus was isolated from cormorants tested after the first month of submissions, brain and spinal cord lesions characteristic of NVND were observed in cormorants from affected sites for 2 mo, at which time nesting colonies dispersed and no more submissions were received. Risk to susceptible populations of both wild avian species and domestic poultry makes early recognition and confirmation of NVND in wild birds a priority.

Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

PubMed

Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

2015-05-01

Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

The Relationship of Exposure to Anesthesia on Outcomes in Children with Isolated Oral Clefts

PubMed Central

Conrad, Amy L.; Goodwin, Jon; Choi, James; Block, Robert I.; Nopoulos, Peg

2016-01-01

This study evaluated the relationship between exposure to anesthesia and previously identified differences in cognitive functioning, growth, and volumetric brain measures among a sample of children, adolescents, and young adults with isolated oral clefts (iCL/P). Data from a cross-sectional study was combined with a retrospective chart review. Data was obtained for 87 participants with iCL/P (55% male), ranging from 7.5 to 27 years old (mean = 15.78 [SD = 4.58]). Measures of interest included cognitive functioning, growth measures, and brain volumes. Number of surgeries and time under anesthesia were obtained through systematic medical record review. Potential sex and cleft type differences in exposure as well as relationships between anesthesia exposure and outcome measures were evaluated. Participants with isolated cleft lip and palate had more surgeries and were under anesthesia longer. For participants with isolated cleft lip only, more surgeries were correlated to lower verbal IQ and higher frontal lobe volume. PMID:28193114

The Complete Remission of Acquired Immunodeficiency Syndrome-associated Isolated Central Nervous System Lymphomatoid Granulomatosis: A Case Report and Review of the Literature

PubMed Central

Kano, Yasuhiro; Kodaira, Minori; Ushiki, Atsuhito; Kosaka, Makoto; Yamada, Mitsunori; Shingu, Kunihiko; Nishihara, Hiroshi; Hanaoka, Masayuki; Sekijima, Yoshiki

2017-01-01

A 49-year-old man presented with gradually progressive aphasia one month after being diagnosed with acquired immunodeficiency syndrome (AIDS). Brain magnetic resonance imaging showed multiple brain lesions with punctate and linear enhancement. A polymerase chain reaction detected Epstein-Barr virus (EBV) in the patient's cerebrospinal fluid. A diagnosis of isolated central nervous system lymphomatoid granulomatosis (CNS-LYG) was made based on the brain biopsy findings. The complete remission of CNS-LYG was achieved by anti-retroviral therapy (ART) alone. In the present case, the development of AIDS-associated CNS-LYG was considered to have been initiated by the reactivation of EBV in the CNS under immunosuppressive conditions. The patient's condition improved with the reconstitution of the patient's immune system. PMID:28824078

Next-Generation Sequencing of Coccidioides immitis Isolated during Cluster Investigation

PubMed Central

Engelthaler, David M.; Chiller, Tom; Schupp, James A.; Colvin, Joshua; Beckstrom-Sternberg, Stephen M.; Driebe, Elizabeth M.; Moses, Tracy; Tembe, Waibhav; Sinari, Shripad; Beckstrom-Sternberg, James S.; Christoforides, Alexis; Pearson, John V.; Carpten, John; Keim, Paul; Peterson, Ashley; Terashita, Dawn

2011-01-01

Next-generation sequencing enables use of whole-genome sequence typing (WGST) as a viable and discriminatory tool for genotyping and molecular epidemiologic analysis. We used WGST to confirm the linkage of a cluster of Coccidioides immitis isolates from 3 patients who received organ transplants from a single donor who later had positive test results for coccidioidomycosis. Isolates from the 3 patients were nearly genetically identical (a total of 3 single-nucleotide polymorphisms identified among them), thereby demonstrating direct descent of the 3 isolates from an original isolate. We used WGST to demonstrate the genotypic relatedness of C. immitis isolates that were also epidemiologically linked. Thus, WGST offers unique benefits to public health for investigation of clusters considered to be linked to a single source. PMID:21291593

A Child's Brain. Part II. The Human Brain: How Every Single Cell is Organized for Action.

ERIC Educational Resources Information Center

Sylwester, Robert

1982-01-01

The second in a series of three articles concerning children's brain development focuses on the organization of the brain. Aspects of the brain's vertical, neocortex, and temporal organization are discussed and references for further reading are provided. (CJ)

Developmental changes in metabolism and transport properties of capillaries isolated from rat brain.

PubMed

Betz, A L; Goldstein, G W

1981-03-01

1. Capillaries were isolated from the brains of 1- to 45-day-old rats in order to study the development of metabolic and transport aspects of the blood-brain barrier. 2. The hydroxyproline content of capillary hydrolysates increased nearly threefold between 5 and 45 days of age. This finding is consistent with histological studies showing thickening of capillary basement membrane during development. 3. The activities of L-DOPA decarboxylase and monoamine oxidase were greatest in capillaries from 10-day-old rat brain. Thus, the metabolic blood-brain barrier for amine precursors is present during early development. 4. Capillaries from all ages were able to metabolize glucose, beta-hydroxybutyrate and palmitate. The rate of glucose oxidation more than doubled between 21 and 30 days of age but subsequently decreased. In contrast, beta-hydroxybutyrate and palmitate oxidation increased throughout development. These data suggest a sparing effect by alternate fuels on glucose metabolism. 5. Capillary glucose uptake was similar at 10 and 30 days of age and activity of the ouabain-sensitive K+ pump (measured using 86Rb+) was relatively constant at all ages. In contrast, Na+-dependent neutral amino acid transport was not present until after 21 days of age. Since this transport system may be responsible for the active efflux of neutral amino acids from brain to blood, it is likely that this process does not occur at the immature blood-brain barrier. 6. We conclude that various aspects of brain capillary functions show distinct developmental patterns which may be related to changes in blood-brain barrier permeability during development.

Parsing the Behavioral and Brain Mechanisms of Third-Party Punishment

PubMed Central

Bonnie, Richard J.; Hoffman, Morris B.; Shen, Francis X.; Simons, Kenneth W.

2016-01-01

The evolved capacity for third-party punishment is considered crucial to the emergence and maintenance of elaborate human social organization and is central to the modern provision of fairness and justice within society. Although it is well established that the mental state of the offender and the severity of the harm he caused are the two primary predictors of punishment decisions, the precise cognitive and brain mechanisms by which these distinct components are evaluated and integrated into a punishment decision are poorly understood. Using fMRI, here we implement a novel experimental design to functionally dissociate the mechanisms underlying evaluation, integration, and decision that were conflated in previous studies of third-party punishment. Behaviorally, the punishment decision is primarily defined by a superadditive interaction between harm and mental state, with subjects weighing the interaction factor more than the single factors of harm and mental state. On a neural level, evaluation of harms engaged brain areas associated with affective and somatosensory processing, whereas mental state evaluation primarily recruited circuitry involved in mentalization. Harm and mental state evaluations are integrated in medial prefrontal and posterior cingulate structures, with the amygdala acting as a pivotal hub of the interaction between harm and mental state. This integrated information is used by the right dorsolateral prefrontal cortex at the time of the decision to assign an appropriate punishment through a distributed coding system. Together, these findings provide a blueprint of the brain mechanisms by which neutral third parties render punishment decisions. SIGNIFICANCE STATEMENT Punishment undergirds large-scale cooperation and helps dispense criminal justice. Yet it is currently unknown precisely how people assess the mental states of offenders, evaluate the harms they caused, and integrate those two components into a single punishment decision. Using a new design, we isolated these three processes, identifying the distinct brain systems and activities that enable each. Additional findings suggest that the amygdala plays a crucial role in mediating the interaction of mental state and harm information, whereas the dorsolateral prefrontal cortex plays a crucial, final-stage role, both in integrating mental state and harm information and in selecting a suitable punishment amount. These findings deepen our understanding of how punishment decisions are made, which may someday help to improve them. PMID:27605616

Parsing the Behavioral and Brain Mechanisms of Third-Party Punishment.

PubMed

Ginther, Matthew R; Bonnie, Richard J; Hoffman, Morris B; Shen, Francis X; Simons, Kenneth W; Jones, Owen D; Marois, René

2016-09-07

The evolved capacity for third-party punishment is considered crucial to the emergence and maintenance of elaborate human social organization and is central to the modern provision of fairness and justice within society. Although it is well established that the mental state of the offender and the severity of the harm he caused are the two primary predictors of punishment decisions, the precise cognitive and brain mechanisms by which these distinct components are evaluated and integrated into a punishment decision are poorly understood. Using fMRI, here we implement a novel experimental design to functionally dissociate the mechanisms underlying evaluation, integration, and decision that were conflated in previous studies of third-party punishment. Behaviorally, the punishment decision is primarily defined by a superadditive interaction between harm and mental state, with subjects weighing the interaction factor more than the single factors of harm and mental state. On a neural level, evaluation of harms engaged brain areas associated with affective and somatosensory processing, whereas mental state evaluation primarily recruited circuitry involved in mentalization. Harm and mental state evaluations are integrated in medial prefrontal and posterior cingulate structures, with the amygdala acting as a pivotal hub of the interaction between harm and mental state. This integrated information is used by the right dorsolateral prefrontal cortex at the time of the decision to assign an appropriate punishment through a distributed coding system. Together, these findings provide a blueprint of the brain mechanisms by which neutral third parties render punishment decisions. Punishment undergirds large-scale cooperation and helps dispense criminal justice. Yet it is currently unknown precisely how people assess the mental states of offenders, evaluate the harms they caused, and integrate those two components into a single punishment decision. Using a new design, we isolated these three processes, identifying the distinct brain systems and activities that enable each. Additional findings suggest that the amygdala plays a crucial role in mediating the interaction of mental state and harm information, whereas the dorsolateral prefrontal cortex plays a crucial, final-stage role, both in integrating mental state and harm information and in selecting a suitable punishment amount. These findings deepen our understanding of how punishment decisions are made, which may someday help to improve them. Copyright © 2016 Ginther et al.

Disease-Associated Prion Protein in Neural and Lymphoid Tissues of Mink (Mustela vison) Inoculated with Transmissible Mink Encephalopathy

PubMed Central

Schneider, D. A.; Harrington, R. D.; Zhuang, D.; Yan, H.; Truscott, T. C.; Dassanayake, R. P.; O'Rourke, K. I.

2012-01-01

Summary Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrPd). The distribution of PrPd within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrPTME and of which only the HY strain is associated with accumulation of PrPTME in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrPTME in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrPTME was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrPTME was detected readily in the brain and retropharyngeal lymph node during preclinical infection with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrPTME in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrPTME accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrPTME in the lymphoid tissues of mink but not in hamsters. Thus mink are a relevant animal model for further study of this unique strain, which ultimately may have been introduced through consumption of a TSE of ruminant origin. PMID:22595634

Genotyping of Toxoplasma gondii isolates with 15 microsatellite markers in a single multiplex PCR assay.

PubMed

Ajzenberg, Daniel; Collinet, Frédéric; Mercier, Aurélien; Vignoles, Philippe; Dardé, Marie-Laure

2010-12-01

We developed an easy-to-use method for genotyping Toxoplasma gondii isolates in a single multiplex PCR assay with 15 microsatellite markers. This method was validated by testing 26 reference isolates that had been characterized with other sets of markers.

Human homologues of the bacterial heat-shock protein DnaJ are preferentially expressed in neurons.

PubMed Central

Cheetham, M E; Brion, J P; Anderton, B H

1992-01-01

The bacterial heat-shock protein DnaJ has been implicated in protein folding and protein complex dissociation. The DnaJ protein interacts with the prokaryotic analogue of Hsp70, DnaK, and accelerates the rate of ATP hydrolysis by DnaK. Several yeast homologues of DnaJ, with different proposed subcellular localizations and functions, have recently been isolated and are the only eukaryotic forms of DnaJ so far described. We have isolated cDNAs corresponding to two alternatively spliced transcripts of a novel human gene, HSJ1, which show sequence similarity to the bacterial DnaJ protein and the yeast homologues. The cDNA clones were isolated from a human brain-frontal-cortex expression library screened with a polyclonal antiserum raised to paired-helical-filament (PHF) proteins isolated from extracts of the brains of patients suffering from Alzheimer's disease. The similarity between the predicted human protein sequences and the bacterial and yeast proteins is highest at the N-termini, this region also shows a limited similarity to viral T-antigens and is a possible common motif involved in the interaction with DnaK/Hsp70. Northern-blot analysis has shown that human brain contains higher levels of mRNA for the DnaJ homologue than other tissues examined, and hybridization studies with riboprobes in situ show a restricted pattern of expression of the mRNA within the brain, with neuronal layers giving the strongest signal. These findings suggest that the DnaJ-DnaK (Hsp70) interaction is general to eukaryotes and, indeed, to higher organisms. Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:1599432

Oxidative metabolism and Ca2+ handling in isolated brain mitochondria and striatal neurons from R6/2 mice, a model of Huntington's disease.

PubMed

Hamilton, James; Pellman, Jessica J; Brustovetsky, Tatiana; Harris, Robert A; Brustovetsky, Nickolay

2016-07-01

Alterations in oxidative metabolism and defects in mitochondrial Ca 2+ handling have been implicated in the pathology of Huntington's disease (HD), but existing data are contradictory. We investigated the effect of human mHtt fragments on oxidative metabolism and Ca 2+ handling in isolated brain mitochondria and cultured striatal neurons from the R6/2 mouse model of HD. Non-synaptic and synaptic mitochondria isolated from the brains of R6/2 mice had similar respiratory rates and Ca 2+ uptake capacity compared with mitochondria from wild-type (WT) mice. Respiratory activity of cultured striatal neurons measured with Seahorse XF24 flux analyzer revealed unaltered cellular respiration in neurons derived from R6/2 mice compared with neurons from WT animals. Consistent with the lack of respiratory dysfunction, ATP content of cultured striatal neurons from R6/2 and WT mice was similar. Mitochondrial Ca 2+ accumulation was also evaluated in cultured striatal neurons from R6/2 and WT animals. Our data obtained with striatal neurons derived from R6/2 and WT mice show that both glutamate-induced increases in cytosolic Ca 2+ and subsequent carbonilcyanide p-triflouromethoxyphenylhydrazone-induced increases in cytosolic Ca 2+ were similar between WT and R6/2, suggesting that mitochondria in neurons derived from both types of animals accumulated comparable amounts of Ca 2+ Overall, our data argue against respiratory deficiency and impaired Ca 2+ handling induced by human mHtt fragments in both isolated brain mitochondria and cultured striatal neurons from transgenic R6/2 mice. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The diagnosis of organic brain syndrome.

PubMed

Berger, D M

1977-03-01

Because it stems from a variety of causes and interacting factors, organic brain syndrome is a difficult condition to diagnose. Several factors make it distinguishable from functional disorders, schizophrenia or hysteria. The syndrome cannot be considered in isolation from the patient's personality, however, since this will affect his coping with the disorder.

The Gully in the "Brain Glitch" Theory

ERIC Educational Resources Information Center

Willis, Judy

2007-01-01

Learning to read is a complex process that requires multiple areas of the brain to operate together through intricate networks of neurons. The author of this article, a neurologist and middle school teacher, takes exception to interpretations of neuroimaging research that treat reading as an isolated, independent cognitive process. She…

Early-Life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats

PubMed Central

Soga, Tomoko; Teo, Chuin Hau; Cham, Kai Lin; Idris, Marshita Mohd; Parhar, Ishwar S.

2015-01-01

Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH) neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinizing hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic–GnIH neuronal system using enhanced green fluorescent protein (EGFP)-tagged GnIH transgenic rats. Socially isolated rats were observed for anxious and depressive behaviors. Using immunohistochemistry, we examined c-Fos protein expression in EGFP–GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group housing. We also inspected serotonergic fiber juxtapositions in EGFP–GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviors. The total number of EGFP–GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fiber juxtapositions on EGFP–GnIH neurons were also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early-life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure. PMID:26617573

Analysis of a Viral Agent Isolated from Multiple Sclerosis Brain Tissue: Characterization as a Parainfluenzavirus Type 1

PubMed Central

Lewandowski, L. J.; Lief, F. S.; Verini, M. A.; Pienkowski, M. M.; ter Meulen, V.; Koprowski, H.

1974-01-01

A virus originally isolated from cell cultures obtained by lysolecithin-induced fusion of human multiple sclerosis brain cells with CV-1 cells has been analyzed for its antigenic, RNA, and polypeptide compositions, and for selective biological properties. Our findings establish that this isolate, designated 6/94 virus, contains a 50S RNA genome and is, as yet, indistinguishable from Sendai virus in its antigenic and total polypeptide compositions. Despite these similarities, the 6/94 and Sendai viruses differ in certain phenotypic properties. 6/94 virus is markedly less cytocidal for chick fibroblasts, especially at 37 C and, after β-propiolactone inactivation, it possesses a greater capacity for cell fusion and a lower toxicity than does comparably treated Sendai virus. In addition, 6/94 virus shows greater hemolytic activity. Images PMID:4363249

Distinct cognitive mechanisms involved in the processing of single objects and object ensembles

PubMed Central

Cant, Jonathan S.; Sun, Sol Z.; Xu, Yaoda

2015-01-01

Behavioral research has demonstrated that the shape and texture of single objects can be processed independently. Similarly, neuroimaging results have shown that an object's shape and texture are processed in distinct brain regions with shape in the lateral occipital area and texture in parahippocampal cortex. Meanwhile, objects are not always seen in isolation and are often grouped together as an ensemble. We recently showed that the processing of ensembles also involves parahippocampal cortex and that the shape and texture of ensemble elements are processed together within this region. These neural data suggest that the independence seen between shape and texture in single-object perception would not be observed in object-ensemble perception. Here we tested this prediction by examining whether observers could attend to the shape of ensemble elements while ignoring changes in an unattended texture feature and vice versa. Across six behavioral experiments, we replicated previous findings of independence between shape and texture in single-object perception. In contrast, we observed that changes in an unattended ensemble feature negatively impacted the processing of an attended ensemble feature only when ensemble features were attended globally. When they were attended locally, thereby making ensemble processing similar to single-object processing, interference was abolished. Overall, these findings confirm previous neuroimaging results and suggest that distinct cognitive mechanisms may be involved in single-object and object-ensemble perception. Additionally, they show that the scope of visual attention plays a critical role in determining which type of object processing (ensemble or single object) is engaged by the visual system. PMID:26360156

Preliminary pilot fMRI study of neuropostural optimization with a noninvasive asymmetric radioelectric brain stimulation protocol in functional dysmetria

PubMed Central

Mura, Marco; Castagna, Alessandro; Fontani, Vania; Rinaldi, Salvatore

2012-01-01

Purpose This study assessed changes in functional dysmetria (FD) and in brain activation observable by functional magnetic resonance imaging (fMRI) during a leg flexion-extension motor task following brain stimulation with a single radioelectric asymmetric conveyer (REAC) pulse, according to the precisely defined neuropostural optimization (NPO) protocol. Population and methods Ten healthy volunteers were assessed using fMRI conducted during a simple motor task before and immediately after delivery of a single REAC-NPO pulse. The motor task consisted of a flexion-extension movement of the legs with the knees bent. FD signs and brain activation patterns were compared before and after REAC-NPO. Results A single 250-millisecond REAC-NPO treatment alleviated FD, as evidenced by patellar asymmetry during a sit-up motion, and modulated activity patterns in the brain, particularly in the cerebellum, during the performance of the motor task. Conclusion Activity in brain areas involved in motor control and coordination, including the cerebellum, is altered by administration of a REAC-NPO treatment and this effect is accompanied by an alleviation of FD. PMID:22536071

Structure of pleiotrophin- and hepatocyte growth factor-binding sulfated hexasaccharide determined by biochemical and computational approaches.

PubMed

Li, Fuchuan; Nandini, Chilkunda D; Hattori, Tomohide; Bao, Xingfeng; Murayama, Daisuke; Nakamura, Toshikazu; Fukushima, Nobuhiro; Sugahara, Kazuyuki

2010-09-03

Endogenous pleiotrophin and hepatocyte growth factor (HGF) mediate the neurite outgrowth-promoting activity of chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chains isolated from embryonic pig brain. CS/DS hybrid chains isolated from shark skin have a different disaccharide composition, but also display these activities. In this study, pleiotrophin- and HGF-binding domains in shark skin CS/DS were investigated. A high affinity CS/DS fraction was isolated using a pleiotrophin-immobilized column. It showed marked neurite outgrowth-promoting activity and strong inhibitory activity against the binding of pleiotrophin to immobilized CS/DS chains from embryonic pig brain. The inhibitory activity was abolished by chondroitinase ABC or B, and partially reduced by chondroitinase AC-I. A pentasulfated hexasaccharide with a novel structure was isolated from the chondroitinase AC-I digest using pleiotrophin affinity and anion exchange chromatographies. It displayed a potent inhibitory effect on the binding of HGF to immobilized shark skin CS/DS chains, suggesting that the pleiotrophin- and HGF-binding domains at least partially overlap in the CS/DS chains involved in the neuritogenic activity. Computational chemistry using molecular modeling and calculations of the electrostatic potential of the hexasaccharide and two pleiotrophin-binding octasaccharides previously isolated from CS/DS hybrid chains of embryonic pig brain identified an electronegative zone potentially involved in the molecular recognition of the oligosaccharides by pleiotrophin. Homology modeling of pleiotrophin based on a related midkine protein structure predicted the binding pocket of pleiotrophin for the oligosaccharides and provided new insights into the molecular mechanism of the interactions between the oligosaccharides and pleiotrophin.

Development of a facile droplet-based single-cell isolation platform for cultivation and genomic analysis in microorganisms.

PubMed

Zhang, Qiang; Wang, Tingting; Zhou, Qian; Zhang, Peng; Gong, Yanhai; Gou, Honglei; Xu, Jian; Ma, Bo

2017-01-23

Wider application of single-cell analysis has been limited by the lack of an easy-to-use and low-cost strategy for single-cell isolation that can be directly coupled to single-cell sequencing and single-cell cultivation, especially for small-size microbes. Herein, a facile droplet microfluidic platform was developed to dispense individual microbial cells into conventional standard containers for downstream analysis. Functional parts for cell encapsulation, droplet inspection and sorting, as well as a chip-to-tube capillary interface were integrated on one single chip with simple architecture, and control of the droplet sorting was achieved by a low-cost solenoid microvalve. Using microalgal and yeast cells as models, single-cell isolation success rate of over 90% and single-cell cultivation success rate of 80% were demonstrated. We further showed that the individual cells isolated can be used in high-quality DNA and RNA analyses at both gene-specific and whole-genome levels (i.e. real-time quantitative PCR and genome sequencing). The simplicity and reliability of the method should improve accessibility of single-cell analysis and facilitate its wider application in microbiology researches.

Development of a facile droplet-based single-cell isolation platform for cultivation and genomic analysis in microorganisms

PubMed Central

Zhang, Qiang; Wang, Tingting; Zhou, Qian; Zhang, Peng; Gong, Yanhai; Gou, Honglei; Xu, Jian; Ma, Bo

2017-01-01

Wider application of single-cell analysis has been limited by the lack of an easy-to-use and low-cost strategy for single-cell isolation that can be directly coupled to single-cell sequencing and single-cell cultivation, especially for small-size microbes. Herein, a facile droplet microfluidic platform was developed to dispense individual microbial cells into conventional standard containers for downstream analysis. Functional parts for cell encapsulation, droplet inspection and sorting, as well as a chip-to-tube capillary interface were integrated on one single chip with simple architecture, and control of the droplet sorting was achieved by a low-cost solenoid microvalve. Using microalgal and yeast cells as models, single-cell isolation success rate of over 90% and single-cell cultivation success rate of 80% were demonstrated. We further showed that the individual cells isolated can be used in high-quality DNA and RNA analyses at both gene-specific and whole-genome levels (i.e. real-time quantitative PCR and genome sequencing). The simplicity and reliability of the method should improve accessibility of single-cell analysis and facilitate its wider application in microbiology researches. PMID:28112223

Genotyping of Toxoplasma gondii Isolates with 15 Microsatellite Markers in a Single Multiplex PCR Assay ▿

PubMed Central

Ajzenberg, Daniel; Collinet, Frédéric; Mercier, Aurélien; Vignoles, Philippe; Dardé, Marie-Laure

2010-01-01

We developed an easy-to-use method for genotyping Toxoplasma gondii isolates in a single multiplex PCR assay with 15 microsatellite markers. This method was validated by testing 26 reference isolates that had been characterized with other sets of markers. PMID:20881166

Effect of Contamination with Perennial Permafrost Microorganisms on the Outcome of Closed Brain Neurotrauma.

PubMed

Malchevskii, V A; Subbotin, A M; Nemkov, A G; Petrov, S A

2016-07-01

We studied the effect of contamination with Bacillus genus microorganisms isolated from perennial permafrost samples on the outcome of closed brain neurotrauma in Wistar rats. It was found that contamination with different Bacillus strains produced different effects on the mortality of experimental animals with closed neurotrauma. The complex of metabolites from strain Ch2/9 - Bacillus spp. (pumilus) produced a protective effect in experimental closed brain neurotrauma.

Toxoplasma gondii: isolation, biological and molecular characterisation of samples from free-range Gallus gallus domesticus from countryside Southeast Brazil.

PubMed

Ferreira, Tamiris Cristine Ribeiro; Buery, Julyana Cerqueira; Moreira, Narcisa Imaculada Brant; Santos, Claudiney Biral; Costa, Júlia Gatti Ladeia; Pinto, Lorena Velozo; Baraviera, Ramon Castro de Araújo; Vitor, Ricardo Wagner Almeida; Fux, Blima

2018-05-24

Toxoplasma gondii presents a high prevalence worldwide, infecting several animals. Felines are considered the definitive hosts and among the intermediate hosts we highlight mammals and birds. The man can become infected by ingesting tissue cysts present in birds and mammals. Biological and molecular aspects of T. gondii allows a better understanding of the epidemiology of toxoplasmosis. This work is a serologic screening of 58 chickens grown (Gallus gallus domesticus) for human consumption in Espírito Santo State, by means of indirect haemagglutination assay (IHA). Thirteen chickens tested positive for anti-T. gondii antibodies. The heart and brain of five positive chickens were harvested, treated with pepsin and inoculated separately, in two Swiss mice, intraperitoneally. Tachyzoites were observed in the peritoneum of all the animals, between seven and 10 days after the inoculum. Ten isolates were obtained and biologically characterised in BALB/c mice inoculated with 101 to 104 tachyzoites. All isolates were classified as virulent or intermediately virulent. Isolates were genotyped by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, revealing three different genotypes. None of the isolates exhibited the clonal type I, II or III genotype. No genotypic differences were observed between the isolates from the brain or heart from the same bird.

Genome sequences of thirty Escherichia coli O157:H7 isolates recovered from a single dairy farm and its associated off-site heifer raising facility

USDA-ARS?s Scientific Manuscript database

Cattle are the primary reservoir of Escherichia coli O157:H7, the most frequently isolated serotype of enterohemorrhagic E. coli infections among humans in North America. To evaluate the diversity of E. coli O157:H7 isolates within a single dairy herd the genomes of 30 isolates collected over a 7-ye...

Evaluation of Brain Pharmacokinetic and Neuropharmacodynamic Attributes of an Antiepileptic Drug, Lacosamide, in Hepatic and Renal Impairment: Preclinical Evidence.

PubMed

Kumar, Baldeep; Modi, Manish; Saikia, Biman; Medhi, Bikash

2017-07-19

The knowledge of pharmacokinetic and pharmacodynamic properties of antiepileptic drugs is helpful in optimizing drug therapy for epilepsy. This study was designed to evaluate the pharmacokinetic and pharmacodynamic properties of lacosamide in experimentally induced hepatic and renal impairment in seizure animals. Hepatic or renal impairment was induced by injection of carbon tetrachloride or diclofenac sodium, respectively. After induction, the animals were administered a single dose of lacosamide. At different time points, maximal electroshock (MES) seizure recordings were made followed by isolation of plasma and brain samples for drug quantification and pharmacodynamic measurements. Our results showed a significant increase in the area under the curve of lacosamide in hepatic and renal impairment groups. Reduced clearance of lacosamide was observed in animals with renal impairment. Along with pharmacokinetic alterations, the changes in pharmacodynamic effects of lacosamide were also observed in all the groups. Lacosamide showed a significant protection against MES-induced seizures, oxidative stress, and neuroinflammatory cytokines. These findings revealed that experimentally induced hepatic or renal impairment could alter the pharmacokinetic as well as pharmacodynamic properties of lacosamide. Hence, these conditions may affect the safety and efficacy of lacosamide.

Cognitive impairment and memory loss associated with histoplasmosis: a case study.

PubMed

Loughan, Ashlee R; Perna, Robert; Hertza, Jeremy

2014-01-01

Histoplasmosis is a rare disease caused by inhalation of the fungus Histoplasma capsulatum. It can spread via cerebral circulation to the central nervous system as a manifestation of a disseminated infection; particularly in patients with immune suppression, which can result in isolated ring-enhancing lesions and inflammation in the brain. Of the reported disseminated histoplasmosis cases (approximately 1 in 2000 per year), only 5-20% have evidence of central nervous system involvement. This paper reviews a single case study of a 57-year-old female diagnosed with disseminated CNS histoplasmosis. Patient's complaints included reduced short-term memory, word-finding problems, and difficulty organizing, making decisions, getting lost while driving, recalling names, retaining information while reading, and slowed processing speed. There was also a history of mild depression and anxiety. Direct testing revealed deficits in multiple cognitive domains including complex attention, processing speed, semantic fluency, visual scanning, motor speed, set-shifting, naming, nonverbal memory, and verbal memory. Neuropsychological deficits suggest cortical and subcortical brain dysfunction, including anterior, temporal, and mesial-temporal regions. This case illustrates the need for neuropsychologists to understand histoplasmosis, the related pathophysiology, and the neuropsychological impact; particularly with the potential for delayed progression.

Heterothallic Type of Mating System for Cordyceps cardinalis

PubMed Central

Sung, Gi-Ho; Shrestha, Bhushan; Han, Sang-Kuk; Kim, Soo-Young

2010-01-01

Cordyceps cardinalis successfully produced its fruiting bodies from multi-ascospore isolates. However, subcultures of multi-ascospore isolates could not produce fruiting bodies after few generations. Fruiting body production also differed from sector to sector of the same isolate. Single ascospore isolates were then co-inoculated in combinations of two to observe the fruiting characteristics. Combinations of certain isolates produced perithecial stromata formation, whereas other combinations did not produce any fruiting bodies. These results show that C. cardinalis is a heterothallic fungus, requiring two isolates of opposite mating types for fruiting body production. It was also shown that single ascospore isolates are hermaphrodites. PMID:23956667

Development of the self-learning machine for creating models of microprocessor of single-phase earth fault protection devices in networks with isolated neutral voltage above 1000 V

NASA Astrophysics Data System (ADS)

Utegulov, B. B.; Utegulov, A. B.; Meiramova, S.

2018-02-01

The paper proposes the development of a self-learning machine for creating models of microprocessor-based single-phase ground fault protection devices in networks with an isolated neutral voltage higher than 1000 V. Development of a self-learning machine for creating models of microprocessor-based single-phase earth fault protection devices in networks with an isolated neutral voltage higher than 1000 V. allows to effectively implement mathematical models of automatic change of protection settings. Single-phase earth fault protection devices.

Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus

PubMed Central

Zawaski, Janice A.; Sahnoune, Iman

2016-01-01

Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT. PMID:27242931

Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus.

PubMed

Rodgers, Shaefali P; Zawaski, Janice A; Sahnoune, Iman; Leasure, J Leigh; Gaber, M Waleed

2016-01-01

Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT.

T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

PubMed

van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

2018-05-01

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4-) expressed the highest very late antigen-4 levels and selectively accumulated in natalizumab-treated patients who remained free of clinical relapses. This was not found in patients who experienced relapses during natalizumab treatment. The enhanced potential of Th17.1 cells to infiltrate the central nervous system was supported by their predominance in cerebrospinal fluid of early multiple sclerosis patients and their preferential transmigration across human brain endothelial layers. These findings reveal a dominant contribution of Th1-like Th17 subpopulations, in particular Th17.1 cells, to clinical disease activity and provide a strong rationale for more specific and earlier use of T cell-targeted therapy in multiple sclerosis.

Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease

NASA Astrophysics Data System (ADS)

Baker, Christopher A.; Manuelidis, Laura

2003-01-01

Previous studies in Creutzfeldt-Jakob disease (CJD) have shown that myeloid cells in the periphery as well as derivative microglial cells in the brain are infectious. Microglia can show an activated phenotype before prion protein (PrP) pathology is detectable in brain, and isolated infectious microglia contain very little PrP. To find whether a set of inflammatory genes are significantly induced or suppressed with infection, we analyzed RNA from isolated microglia with relevant cDNA arrays, and identified 30 transcripts not previously examined in any transmissible spongiform encephalopathy. This CJD expression profile contrasted with that of uninfected microglia exposed to prototypic inflammatory stimuli such as lipopolysaccharide and IFN-, as well as PrP amyloid. These findings underscore inflammatory pathways evoked by the infectious agent in brain. Transcript profiles unique for CJD microglia and other myeloid cells provide opportunities for more sensitive preclinical diagnoses of infectious and noninfectious neurodegenerative diseases.

Memory recall in arousing situations - an emotional von Restorff effect?

PubMed

Wiswede, Daniel; Rüsseler, Jascha; Hasselbach, Simone; Münte, Thomas F

2006-07-24

Previous research has demonstrated a relationship between memory recall and P300 amplitude in list learning tasks, but the variables mediating this P300-recall relationship are not well understood. In the present study, subjects were required to recall items from lists consisting of 12 words, which were presented in front of pictures taken from the IAPS collection. One word per list is made distinct either by font color or by a highly arousing background IAPS picture. This isolation procedure was first used by von Restorff. Brain potentials were recorded during list presentation. Recall performance was enhanced for color but not for emotional isolates. Event-related brain potentials (ERP) showed a more positive P300-component for recalled non-isolated words and color-isolated words, compared to the respective non-remembered words, but not for words isolated by arousing background. Our findings indicate that it is crucial to take emotional mediator variables into account, when using the P300 to predict later recall. Highly arousing environments might force the cognitive system to interrupt rehearsal processes in working memory, which might benefit transfer into other, more stable memory systems. The impact of attention-capturing properties of arousing background stimuli is also discussed.

Mycoplasmas: Brain invaders?

PubMed

Rosales, Rubén S; Puleio, Roberto; Loria, Guido R; Catania, Salvatore; Nicholas, Robin A J

2017-08-01

Mycoplasmas of humans and animals are usually associated with respiratory, autoimmune, genital and joint diseases. Human mycoplasmas have also been known to affect the brain. Severe central nervous system (CNS) diseases, such as encephalitis, have been linked to Mycoplasma pneumoniae and ureaplasma infections. Less well known is the sheep and goat pathogen, Mycoplasma agalactiae, which has been found in large quantities in the brain where it may be responsible for non-purulent encephalitis as well as ataxia in young animals. Experimental intra-mammary infections of sheep with this mycoplasma have resulted in histopathological changes in the CNS. The cattle pathogen, M. bovis, has been reported occasionally in the brains of calves and adult cattle showing a range of histopathological lesions including abscesses and fibrinous meningitis. Two avian pathogens, M. gallisepticum and M. synoviae have been isolated from the brains of poultry showing meningeal vasculitis and encephalitis. There have been no reported detections of two other avian pathogens, M. meleagridis or M. iowae in the CNS. Over the last few decades, mycoplasmas have been isolated from the brains of sea mammals dying in large numbers in the North Sea although it was concluded that their role may be secondary to underlying viral disease. Finally, evidence has been advanced that certain Spiroplasma species may have a role in the development of the transmissible spongiform encephalopathies (TSE). Invasion of the brain by mycoplasmas may be as a result of direct entry following damage to the inner ear as seen with M. bovis or across the blood brain barrier by mechanisms as yet uncertain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Group A Rotavirus Associated with Encephalitis in Red Fox.

PubMed

Busi, Chiara; Martella, Vito; Papetti, Alice; Sabelli, Cristiano; Lelli, Davide; Alborali, G Loris; Gibelli, Lucia; Gelmetti, Daniela; Lavazza, Antonio; Cordioli, Paolo; Boniotti, M Beatrice

2017-09-01

In 2011, a group A rotavirus was isolated from the brain of a fox with encephalitis and neurologic signs, detected by rabies surveillance in Italy. Intracerebral inoculation of fox brain homogenates into mice was fatal. Genome sequencing revealed a heterologous rotavirus of avian origin, which could provide a model for investigating rotavirus neurovirulence.

The Diagnosis of Organic Brain Syndrome

PubMed Central

Berger, David M.

1977-01-01

Because it stems from a variety of causes and interacting factors, organic brain syndrome is a difficult condition to diagnose. Several factors make it distinguishable from functional disorders, schizophrenia or hysteria. The syndrome cannot be considered in isolation from the patient's personality, however, since this will affect his coping with the disorder. PMID:21304779

Expressive Electronic Journal Writing: Freedom of Communication for Survivors of Acquired Brain Injury

ERIC Educational Resources Information Center

Fraas, Michael; Balz, Magdalen A.

2008-01-01

In addition to the impaired ability to effectively communicate, adults with acquired brain injury (ABI) also experience high incidences of depression, social isolation, and decreased quality of life. Expressive writing programs have been shown to be effective in alleviating these concomitant impairments in other populations including incarcerated…

Pregnancy and Birth-Related Brain Disorders.

ERIC Educational Resources Information Center

Fink, Leslie

1986-01-01

Although it once seemed simple to say that a single event such as birth trauma or asphyxia caused brain disorders like cerebral palsy, mental retardation, and epilepsy, a recent study showed that it is nearly impossible to pinpoint a single cause and its effects. Recommendations for further research are made. (BB)

Freeze-Drying as Sample Preparation for Micellar Electrokinetic Capillary Chromatography – Electrochemical Separations of Neurochemicals in Drosophila Brains

PubMed Central

Berglund, E. Carina; Kuklinski, Nicholas J.; Karagündüz, Ekin; Ucar, Kubra; Hanrieder, Jörg; Ewing, Andrew G.

2013-01-01

Micellar electrokinetic capillary chromatography with electrochemical detection has been used to quantify biogenic amines in freeze-dried Drosophila melanogaster brains. Freeze drying samples offers a way to preserve the biological sample while making dissection of these tiny samples easier and faster. Fly samples were extracted in cold acetone and dried in a rotary evaporator. Extraction and drying times were optimized in order to avoid contamination by red-pigment from the fly eyes and still have intact brain structures. Single freeze-dried fly-brain samples were found to produce representative electropherograms as a single hand-dissected brain sample. Utilizing the faster dissection time that freeze drying affords, the number of brains in a fixed homogenate volume can be increased to concentrate the sample. Thus, concentrated brain samples containing five or fifteen preserved brains were analyzed for their neurotransmitter content, and five analytes; dopamine N-acetyloctopamine, Nacetylserotonin, N-acetyltyramine, N-acetyldopamine were found to correspond well with previously reported values. PMID:23387977

Laser Capture Microdissection Assessment of Virus Compartmentalization in the Central Nervous Systems of Macaques Infected with Neurovirulent Simian Immunodeficiency Virus

PubMed Central

Matsuda, Kenta; Brown, Charles R.; Foley, Brian; Goeken, Robert; Whitted, Sonya; Dang, Que; Wu, Fan; Plishka, Ronald; Buckler-White, Alicia

2013-01-01

Nonhuman primate-simian immunodeficiency virus (SIV) models are powerful tools for studying the pathogenesis of human immunodeficiency virus type 1 (HIV-1) in the brain. Our laboratory recently isolated a neuropathogenic viral swarm, SIVsmH804E, a derivative of SIVsmE543-3, which was the result of sequential intravenous passages of viruses isolated from the brains of rhesus macaques with SIV encephalitis. Animals infected with SIVsmH804E or its precursor (SIVsmH783Br) developed SIV meningitis and/or encephalitis at high frequencies. Since we observed macaques with a combination of meningitis and encephalitis, as well as animals in which meningitis or encephalitis was the dominant component, we hypothesized that distinct mechanisms could be driving the two pathological states. Therefore, we assessed viral populations in the meninges and the brain parenchyma by laser capture microdissection. Viral RNAs were isolated from representative areas of the meninges, brain parenchyma, terminal plasma, and cerebrospinal fluid (CSF) and from the inoculum, and the SIV envelope fragment was amplified by PCR. Phylogenetic analysis of envelope sequences from the conventional progressors revealed compartmentalization of viral populations between the meninges and the parenchyma. In one of these animals, viral populations in meninges were closely related to those from CSF and shared signature truncations in the cytoplasmic domain of gp41, consistent with a common origin. Apart from magnetic resonance imaging (MRI) and positron-emission tomography (PET) imaging, CSF is the most accessible assess to the central nervous system for HIV-1-infected patients. However, our results suggest that the virus in the CSF may not always be representative of viral populations in the brain and that caution should be applied in extrapolating between the properties of viruses in these two compartments. PMID:23720733

A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research.

PubMed

Kouzani, Abbas Z; Abulseoud, Osama A; Tye, Susannah J; Hosain, M D Kamal; Berk, Michael

2013-01-01

Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented.

Analysis of the time-varying energy of brain responses to an oddball paradigm using short-term smoothed Wigner-Ville distribution.

PubMed

Tağluk, M E; Cakmak, E D; Karakaş, S

2005-04-30

Cognitive brain responses to external stimuli, as measured by event related potentials (ERPs), have been analyzed from a variety of perspectives to investigate brain dynamics. Here, the brain responses of healthy subjects to auditory oddball paradigms, standard and deviant stimuli, recorded on an Fz electrode site were studied using a short-term version of the smoothed Wigner-Ville distribution (STSW) method. A smoothing kernel was designed to preserve the auto energy of the signal with maximum time and frequency resolutions. Analysis was conducted mainly on the time-frequency distributions (TFDs) of sweeps recorded during successive trials including the TFD of averaged single sweeps as the evoked time-frequency (ETF) brain response and the average of TFDs of single sweeps as the time-frequency (TF) brain response. Also the power entropy and the phase angles of the signal at frequency f and time t locked to the stimulus onset were studied across single trials as the TF power-locked and the TF phase-locked brain responses, respectively. TFDs represented in this way demonstrated the ERP spectro-temporal characteristics from multiple perspectives. The time-varying energy of the individual components manifested interesting TF structures in the form of amplitude modulated (AM) and frequency modulated (FM) energy bursts. The TF power-locked and phase-locked brain responses provoked ERP energies in a manner modulated by cognitive functions, an observation requiring further investigation. These results may lead to a better understanding of integrative brain dynamics.

Huperzine A protects isolated rat brain mitochondria against beta-amyloid peptide.

PubMed

Gao, Xin; Zheng, Chun Yan; Yang, Ling; Tang, Xi Can; Zhang, Hai Yan

2009-06-01

Our previous work in cells and animals showed that mitochondria are involved in the neuroprotective effect of huperzine A (HupA). In this study, the effects of HupA on isolated rat brain mitochondria were investigated. In addition to inhibiting the Abeta(25-35) (40 microM)-induced decrease in mitochondrial respiration, adenosine 5'-triphosphate (ATP) synthesis, enzyme activity, and transmembrane potential, HupA (0.01 or 0.1 microM) effectively prevented Abeta-induced mitochondrial swelling, reactive oxygen species increase, and cytochrome c release. More interestingly, administration of HupA to isolated mitochondria promoted the rate of ATP production and blocked mitochondrial swelling caused by normal osmosis. These results indicate that HupA protects mitochondria against Abeta at least in part by preserving membrane integrity and improving energy metabolism. These direct effects on mitochondria further extend the noncholinergic functions of HupA.

Congenital transmission of Neospora caninum in white-tailed deer (Odocoileus virginianus).

PubMed

Dubey, J P; Jenkins, M C; Kwok, O C H; Ferreira, L R; Choudhary, S; Verma, S K; Villena, I; Butler, E; Carstensen, M

2013-09-23

Neosporosis is an important cause of bovine abortion worldwide. Many aspects of transmission of Neospora caninum in nature are unknown. The white-tailed deer (Odocoileus virginianus) is considered one of the most important wildlife reservoirs of N. caninum in the USA. During the hunting seasons of 2008, 2009, and 2010, brains of 155 white-tailed deer fetuses were bioassayed in mice for protozoal isolation. Viable N. caninum (NcWTDMn1, NcWTDMn2) was isolated from the brains of two fetuses by bioassays in mice, and subsequent propagation in cell culture. Dams of these two infected fetuses had antibodies to N. caninum by Neospora agglutination test at 1:100 serum dilution. DNA obtained from culture-derived N. caninum tachyzoites of the two isolates with Nc5 PCR confirmed diagnosis. Results prove congenital transmission of N. caninum in the white tailed deer for the first time. Published by Elsevier B.V.

Label-free isolation of a prostate cancer cell among blood cells and the single-cell measurement of drug accumulation using an integrated microfluidic chip.

PubMed

Khamenehfar, A; Beischlag, T V; Russell, P J; Ling, M T P; Nelson, C; Li, P C H

2015-11-01

Circulating tumor cells (CTCs) are found in the blood of patients with cancer. Although these cells are rare, they can provide useful information for chemotherapy. However, isolation of these rare cells from blood is technically challenging because they are small in numbers. An integrated microfluidic chip, dubbed CTC chip, was designed and fabricated for conducting tumor cell isolation. As CTCs usually show multidrug resistance (MDR), the effect of MDR inhibitors on chemotherapeutic drug accumulation in the isolated single tumor cell is measured. As a model of CTC isolation, human prostate cancer cells were mixed with mouse blood cells and the label-free isolation of the tumor cells was conducted based on cell size difference. The major advantages of the CTC chip are the ability for fast cell isolation, followed by multiple rounds of single-cell measurements, suggesting a potential assay for detecting the drug responses based on the liquid biopsy of cancer patients.

Isolated Brain Metastases as the First Relapse After the Curative Surgical Resection in Non-Small-Cell Lung Cancer Patients With an EGFR Mutation.

PubMed

Sadoyama, Shinko; Sekine, Akimasa; Satoh, Hiroaki; Iwasawa, Tae; Kato, Terufumi; Ikeda, Satoshi; Sata, Masafumi; Baba, Tomohisa; Tabata, Erina; Minami, Yuko; Nemoto, Kenji; Hayashihara, Kenji; Saito, Takefumi; Okudela, Koji; Ohashi, Kenichi; Tajiri, Michihiko; Ogura, Takashi

2018-01-01

The aim of this study was to clarify the incidence and disease behavior of brain metastases (BM) without extracranial disease (ie, isolated BM) as the first relapse after curative surgery in non-small-cell lung cancer (NSCLC) patients, analyzed according to epidermal growth factor receptor (EGFR) mutation status. A review of the medical charts of consecutive NSCLC patients diagnosed between 2005 and 2016 with BM as the first relapse after curative surgery was performed. Among 1191 patients evaluated for EGFR mutation status, 28 patients who met the inclusion criteria were divided into 2 groups: EGFR mutation group (16 patients) and wild type group (12 patients). At BM diagnosis, the EGFR-mutation group tended to have more commonly isolated BM compared with that in the wild type group (11 of 16 vs. 3 of 12; P = .054). In the EGFR mutation group, the patients with isolated BM showed longer overall survival than those with non-isolated BM (39.6 vs. 18.7 months; P = .038). Notably, isolated BM in the EGFR mutation group was neurologically asymptomatic in 10 of the 11 patients. With regard to upfront treatment for isolated BM in the EGFR mutation group, 10 of 11 patients were treated with only cranial radiotherapy without EGFR tyrosine kinase inhibitors, but two-thirds of the patients (7 of 11; 64%) developed extracranial disease during the study period. In curatively resected NSCLC patients with EGFR mutation, isolated BM would be correlated with better prognosis, but regarded as a precursor to systemic disease. Because isolated BM can be neurologically asymptomatic, it would be important to periodically perform cranial evaluation to detect isolated BM. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential Processing of Isolated Object and Multi-item Pop-Out Displays in LIP and PFC.

PubMed

Meyers, Ethan M; Liang, Andy; Katsuki, Fumi; Constantinidis, Christos

2017-10-11

Objects that are highly distinct from their surroundings appear to visually "pop-out." This effect is present for displays in which: (1) a single cue object is shown on a blank background, and (2) a single cue object is highly distinct from surrounding objects; it is generally assumed that these 2 display types are processed in the same way. To directly examine this, we applied a decoding analysis to neural activity recorded from the lateral intraparietal (LIP) area and the dorsolateral prefrontal cortex (dlPFC). Our analyses showed that for the single-object displays, cue location information appeared earlier in LIP than in dlPFC. However, for the display with distractors, location information was substantially delayed in both brain regions, and information first appeared in dlPFC. Additionally, we see that pattern of neural activity is similar for both types of displays and across different color transformations of the stimuli, indicating that location information is being coded in the same way regardless of display type. These results lead us to hypothesize that 2 different pathways are involved processing these 2 types of pop-out displays. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Age related rise in lactate and its correlation with lactate dehydrogenase (LDH) status in post-mitochondrial fractions isolated from different regions of brain in mice.

PubMed

Datta, Siddhartha; Chakrabarti, Nilkanta

2018-04-18

Rise in brain lactate is the hallmark of ageing. Separate studies report that ageing is associated with elevation of lactate level and alterations of lactate dehydrogenase (LDH)-A/B mRNA-expression-ratio in cerebral cortex and hippocampus. However, age related lactate rise in brain and its association with LDH status and their brain regional variations are still elusive. In the present study, level of lactate, LDH (A and B) activity and LDH-A expression were evaluated in post-mitochondrial fraction of tissues isolated from four different brain regions (cerebral cortex, hippocampus, substantia nigra and cerebellum) of young and aged mice. Lactate levels elevated in four brain regions with maximum rise in substantia nigra of aged mice. LDH-A protein expression and its activity decreased in cerebral cortex, hippocampus and substantia nigra without any changes of these parameters in cerebellum of aged mice. LDH-B activity decreased in hippocampus, substantia nigra and cerebellum whereas its activity remains unaltered in cerebral cortex of aged mice. Accordingly, the ratio of LDH-A/LDH-B-activity remains unaltered in hippocampus and substantia nigra, decreased in cerebral cortex and increased in cerebellum. Therefore, rise of lactate in three brain regions (cerebral cortex, hippocampus, substantia nigra) appeared to be not correlated with the alterations of its regulatory enzymes activities in these three brain regions, rather it supports the fact of involvement of other mechanisms, like lactate transport and/or aerobic/anaerobic metabolism as the possible cause(s) of lactate rise in these three brain regions. The increase in LDH-A/LDH-B-activity-ratio appeared to be positively correlated with elevated lactate level in cerebellum of aged mice. Overall, the present study indicates that the mechanism of rise in lactate in brain varies with brain regions where LDH status plays an important role during ageing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Augmented Renal Clearance in Traumatic Brain Injury: A Single-Center Observational Study of Atrial Natriuretic Peptide, Cardiac Output, and Creatinine Clearance.

PubMed

Udy, Andrew A; Jarrett, Paul; Lassig-Smith, Melissa; Stuart, Janine; Starr, Therese; Dunlop, Rachel; Deans, Renae; Roberts, Jason A; Senthuran, Siva; Boots, Robert; Bisht, Kavita; Bulmer, Andrew C; Lipman, Jeffrey

2017-01-01

Augmented renal clearance (ARC) is being increasingly described in neurocritical care practice. The mechanisms driving this phenomenon are largely unknown. The aim of this project was therefore to explore changes in renal function, cardiac output (CO), and atrial natriuretic peptide (ANP) concentrations in patients with isolated traumatic brain injury (TBI). This prospective observational cohort study was conducted in a tertiary-level, university-affiliated intensive care unit (ICU). Patients with normal plasma creatinine concentrations (<120 μmol/L) at admission and no history of chronic kidney disease, admitted with isolated TBI, were eligible for enrollment. Continuous CO measures were obtained using arterial pulse waveform analysis. Eight-hour urinary creatinine clearances (CL CR ) were used to quantify renal function. ANP concentrations in plasma were measured on alternate days. Data were collected from study enrollment until ICU discharge, death, or day 15, which ever came first. Eleven patients, contributing 100 ICU days of physiological data, were enrolled into the study. Most participants were young men, requiring mechanical ventilation. Median ICU length of stay was 9.6 [7.8-13.0] days. Elevated CL CR measures (>150 mL/min) were frequent and appeared to parallel changes in CO. Plasma ANP concentrations were also significantly elevated over the study period (minimum value = 243 pg/mL). These data suggest that ARC is likely to complicate the care of TBI patients with normal plasma creatinine concentrations, and may be driven by associated cardiovascular changes and/or elevated plasma ANP concentrations. However, significant additional research is required to further understand these findings.

Cell-poor septa separate representations of digits in the ventroposterior nucleus of the thalamus in monkeys and prosimian galagos.

PubMed

Qi, Hui-Xin; Gharbawie, Omar A; Wong, Peiyan; Kaas, Jon H

2011-03-01

The architectonic features of the ventroposterior nucleus (VP) were visualized in coronal brain sections from two macaque monkeys, two owl monkeys, two squirrel monkeys, and three galagos that were processed for cytochrome oxidase, Nissl bodies, or the vesicular glutamate transporter 2 (vGluT2). The traditional ventroposterior medial (VPM) and ventroposterior lateral (VPL) subnuclei were easily identified, as well as the forelimb and hindlimb compartments of VPL, as they were separated by poorly staining, cell-poor septa. Septa also separated other cell groups within VPM and VPL, specifically in the medial compartment of VPL representing the hand (hand VPL). In one squirrel monkey and one galago we demonstrated that these five groups of cells represent digits 1-5 in a mediolateral sequence by injecting tracers into the cortical representation of single digits, defined by microelectrode recordings, and relating concentrations of labeled neurons to specific cell groups in hand VPL. The results establish the existence of septa that isolate the representation of the five digits in VPL of primates and demonstrate that the isolated cell groups represent digits 1-5 in a mediolateral sequence. The present results show that the septa are especially prominent in brain sections processed for vGluT2, which is expressed in the synaptic terminals of excitatory neurons in most nuclei of the brainstem and thalamus. As vGluT2 is expressed in the synaptic terminations from dorsal columns and trigeminal brainstem nuclei, the effectiveness of vGluT2 preparations in revealing septa in VP likely reflects a lack of synapses using glutamate in the septa. Copyright © 2010 Wiley-Liss, Inc.

Purification, cDNA cloning, and regulation of lysophospholipase from rat liver.

PubMed

Sugimoto, H; Hayashi, H; Yamashita, S

1996-03-29

A lysophospholipase was purified 506-fold from rat liver supernatant. The preparation gave a single 24-kDa protein band on SDS-polyacrylamide gel electrophoresis. The enzyme hydrolyzed lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylinositol, lysophosphatidylserine, and 1-oleoyl-2-acetyl-sn-glycero-3-phosphocholine at pH 6-8. The purified enzyme was used for the preparation of antibody and peptide sequencing. A cDNA clone was isolated by screening a rat liver lambda gt11 cDNA library with the antibody, followed by the selection of further extended clones from a lambda gt10 library. The isolated cDNA was 2,362 base pairs in length and contained an open reading frame encoding 230 amino acids with a Mr of 24,708. The peptide sequences determined were found in the reading frame. When the cDNA was expressed in Escherichia coli cells as the beta-galactosidase fusion, lysophosphatidylcholine-hydrolyzing activity was markedly increased. The deduced amino acid sequence showed significant similarity to Pseudomonas fluorescence esterase A and Spirulina platensis esterase. The three sequences contained the GXSXG consensus at similar positions. The transcript was found in various tissues with the following order of abundance: spleen, heart, kidney, brain, lung, stomach, and testis = liver. In contrast, the enzyme protein was abundant in the following order: testis, liver, kidney, heart, stomach, lung, brain, and spleen. Thus the mRNA abundance disagreed with the level of the enzyme protein in liver, testis, and spleen. When HL-60 cells were induced to differentiate into granulocytes with dimethyl sulfoxide, the 24-kDa lysophospholipase protein increased significantly, but the mRNA abundance remained essentially unchanged. Thus a posttranscriptional control mechanism is present for the regulation of 24-kDa lysophospholipase.

Cell-Poor Septa Separate Representations of Digits in the Ventroposterior Nucleus of the Thalamus in Monkeys and Prosimian Galagos

PubMed Central

Qi, Hui-Xin; Gharbawie, Omar A.; Wong, Peiyan; Kaas, Jon H.

2013-01-01

The architectonic features of the ventroposterior nucleus (VP) were visualized in coronal brain sections from two macaque monkeys, two owl monkeys, two squirrel monkeys, and three galagos that were processed for cytochrome oxidase, Nissl bodies, or the vesicular glutamate transporter 2 (vGluT2). The traditional ventroposterior medial (VPM) and ventroposterior lateral (VPL) subnuclei were easily identified, as well as the forelimb and hindlimb compartments of VPL, as they were separated by poorly staining, cell-poor septa. Septa also separated other cell groups within VPM and VPL, specifically in the medial compartment of VPL representing the hand (hand VPL). In one squirrel monkey and one galago we demonstrated that these five groups of cells represent digits 1–5 in a mediolateral sequence by injecting tracers into the cortical representation of single digits, defined by microelectrode recordings, and relating concentrations of labeled neurons to specific cell groups in hand VPL. The results establish the existence of septa that isolate the representation of the five digits in VPL of primates and demonstrate that the isolated cell groups represent digits 1–5 in a mediolateral sequence. The present results show that the septa are especially prominent in brain sections processed for vGluT2, which is expressed in the synaptic terminals of excitatory neurons in most nuclei of the brainstem and thalamus. As vGluT2 is expressed in the synaptic terminations from dorsal columns and trigeminal brainstem nuclei, the effectiveness of vGluT2 preparations in revealing septa in VP likely reflects a lack of synapses using glutamate in the septa. J. Comp. Neurol. 519:738–758, 2011. PMID:21246552

The arteries of the base of the brain in the N. American mink (Mustela vison (Brisson, 1756)).

PubMed

Gościcka, D; Stankiewicz, W; Szpinda, M

1995-01-01

110 brains of the N. American mink were studied for the arteries of the base of the brain, using the anatomical method and Digital Imaging Analysis. Two arterial circles were isolated: the larger cerebral circle (CC) and the smaller medullar circle (MC). These were connected by the basal artery of the brain. We found that in CC, its left part was larger, whereas in MC, it was the right part that was larger. Also, the capacity was larger in the caudal part of MC than in its rostral part.

Early life adversities or high fat diet intake reduce cognitive function and alter BDNF signaling in adult rats: Interplay of these factors changes these effects.

PubMed

Arcego, Danusa Mar; Krolow, Rachel; Lampert, Carine; Toniazzo, Ana Paula; Berlitz, Carolina; Lazzaretti, Camilla; Schmitz, Felipe; Rodrigues, André Felipe; Wyse, Angela T S; Dalmaz, Carla

2016-05-01

Environmental factors, like early exposure to stressors or high caloric diets, can alter the early programming of central nervous system, leading to long-term effects on cognitive function, increased vulnerability to cognitive decline and development of psychopathologies later in life. The interaction between these factors and their combined effects on brain structure and function are still not completely understood. In this study, we evaluated long-term effects of social isolation in the prepubertal period, with or without chronic high fat diet access, on memory and on neurochemical markers in the prefrontal cortex of rats. We observed that early social isolation led to impairment in short-term and working memory in adulthood, and to reductions of Na(+),K(+)-ATPase activity and the immunocontent of phospho-AKT, in prefrontal cortex. Chronic exposure to a high fat diet impaired short-term memory (object recognition), and decreased BDNF levels in that same brain area. Remarkably, the association of social isolation with chronic high fat diet rescued the memory impairment on the object recognition test, as well as the changes in BDNF levels, Na(+),K(+)-ATPase activity, MAPK, AKT and phospho-AKT to levels similar to the control-chow group. In summary, these findings showed that a brief social isolation period and access to a high fat diet during a sensitive developmental period might cause memory deficits in adulthood. On the other hand, the interplay between isolation and high fat diet access caused a different brain programming, preventing some of the effects observed when these factors are separately applied. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Brief Social Isolation in the Adolescent Wistar-Kyoto Rat Model of Endogenous Depression Alters Corticosterone and Regional Monoamine Concentrations.

PubMed

Shetty, Reshma A; Sadananda, Monika

2017-05-01

The Wistar-Kyoto rat (WKY) model has been suggested as a model of adult and adolescent depression though face, predictive and construct validities of the model to depression remain equivocal. The suitability of the WKY as a diathesis model that tests the double-hit hypothesis, particularly during critical periods of brain and behavioural development remains to be established. Here, effects of post-weaning social isolation were assessed during early adolescence (~30pnd) on behavioural despair and learned helplessness in the forced swim test (FST), plasma corticosterone levels and tissue monoamine concentrations in brain areas critically involved in depression, such as prefrontal cortex, nucleus accumbens, striatum and hippocampus. Significantly increased immobility in the FST was observed in socially-isolated, adolescent WKY with a concomitant increase in corticosterone levels over and above the FST-induced stress. WKY also demonstrated a significantly increased release and utilization of dopamine, as manifested by levels of metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in nucleus accumbens, indicating that the large dopamine storage pool evident during adolescence induces greater dopamine release when stimulated. The serotonin metabolite 5-hydroxy-indoleacetic acid was also significantly increased in nucleus accumbens, indicating increased utilization of serotonin, along with norepinephrine levels which were also signficantly elevated in socially-isolated adolescent WKY. Differences in neurochemistry suggest that social or environmental stimuli during critical periods of brain and behavioural development can determine the developmental trajectories of implicated pathways.

Brain activation in teenagers with isolated spelling disorder during tasks involving spelling assessment and comparison of pseudowords. fMRI study.

PubMed

Borkowska, Aneta Rita; Francuz, Piotr; Soluch, Paweł; Wolak, Tomasz

2014-10-01

The present study aimed at defining the specific traits of brain activation in teenagers with isolated spelling disorder in comparison with good spellers. fMRI examination was performed where the subject's task involved taking a decision 1/whether the visually presented words were spelled correctly or not (the orthographic decision task), and 2/whether the two presented letters strings (pseudowords) were identical or not (the visual decision task). Half of the displays showing meaningful words with an orthographic difficulty contained pairs with both words spelled correctly, and half of them contained one misspelled word. Half of the pseudowords were identical, half of them were not. The participants of the study included 15 individuals with isolated spelling disorder and 14 good spellers, aged 13-15. The results demonstrated that the essential differences in brain activation between teenagers with isolated spelling disorder and good spellers were found in the left inferior frontal gyrus, left medial frontal gyrus and right cerebellum posterior lobe, i.e. structures important for language processes, working memory and automaticity of behaviour. Spelling disorder is not only an effect of language dysfunction, it could be a symptom of difficulties in learning and automaticity of motor and visual shapes of written words, rapid information processing as well as automating use of orthographic lexicon. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Development of the central nervous system in the larvacean Oikopleura dioica and the evolution of the chordate brain.

PubMed

Cañestro, Cristian; Bassham, Susan; Postlethwait, John

2005-09-15

In non-vertebrate chordates, central nervous system (CNS) development has been studied in only two taxa, the Cephalochordata and a single Class (Ascidiacea) of the morphologically diverse Urochordata. To understand development and molecular regionalization of the brain in a different deeply diverging chordate clade, we isolated and determined the expression patterns of orthologs of vertebrate CNS markers (otxa, otxb, otxc, pax6, pax2/5/8a, pax2/5/8b, engrailed, and hox1) in Oikopleura dioica (Subphylum Urochordata, Class Larvacea). The three Oikopleura otx genes are expressed similarly to vertebrate Otx paralogs, demonstrating that trans-homologs converged on similar evolutionary outcomes by independent neo- or subfunctionalization processes during the evolution of the two taxa. This work revealed that the Oikopleura CNS possesses homologs of the vertebrate forebrain, hindbrain, and spinal cord, but not the midbrain. Comparing larvacean gene expression patterns to published results in ascidians disclosed important developmental differences and similarities that suggest mechanisms of development likely present in their last common ancestor. In contrast to ascidians, the lack of a radical reorganization of the CNS as larvaceans become adults allows us to relate embryonic gene expression patterns to three subdivisions of the adult anterior brain. Our study of the Oikopleura brain provides new insights into chordate CNS evolution: first, the absence of midbrain is a urochordate synapomorphy and not a peculiarity of ascidians, perhaps resulting from their drastic CNS metamorphosis; second, there is no convincing evidence for a homolog of a midbrain-hindbrain boundary (MHB) organizer in urochordates; and third, the expression pattern of "MHB-genes" in the urochordate hindbrain suggests that they function in the development of specific neurons rather than in an MHB organizer.

Alcohol Dose Effects on Brain Circuits During Simulated Driving: An fMRI Study

PubMed Central

Meda, Shashwath A.; Calhoun, Vince D.; Astur, Robert S.; Turner, Beth M.; Ruopp, Kathryn; Pearlson, Godfrey D.

2009-01-01

Driving while intoxicated remains a major public health hazard. Driving is a complex task involving simultaneous recruitment of multiple cognitive functions. The investigators studied the neural substrates of driving and their response to different blood alcohol concentrations (BACs), using functional magnetic resonance imaging (fMRI) and a virtual reality driving simulator. We used independent component analysis (ICA) to isolate spatially independent and temporally correlated driving-related brain circuits in 40 healthy, adult moderate social drinkers. Each subject received three individualized, separate single-blind doses of beverage alcohol to produce BACs of 0.05% (moderate), 0.10% (high), or 0% (placebo). 3 T fMRI scanning and continuous behavioral measurement occurred during simulated driving. Brain function was assessed and compared using both ICA and a conventional general linear model (GLM) analysis. ICA results replicated and significantly extended our previous 1.5T study (Calhoun et al. [2004a]: Neuropsychopharmacology 29:2097–2017). GLM analysis revealed significant dose-related functional differences, complementing ICA data. Driving behaviors including opposite white line crossings and mean speed independently demonstrated significant dose-dependent changes. Behavior-based factors also predicted a frontal-basal-temporal circuit to be functionally impaired with alcohol dosage across baseline scaled, good versus poorly performing drivers. We report neural correlates of driving behavior and found dose-related spatio-temporal disruptions in critical driving-associated regions including the superior, middle and orbito frontal gyri, anterior cingulate, primary/supplementary motor areas, basal ganglia, and cerebellum. Overall, results suggest that alcohol (especially at high doses) causes significant impairment of both driving behavior and brain functionality related to motor planning and control, goal directedness, error monitoring, and memory. PMID:18571794

[Molecular organization of glutamate-sensitive chemoexcitatory membranes of nerve cells. Comparative analysis of glutamate-binding membrane proteins from the cerebral cortex of rats and humans].

PubMed

Dambinova, S A; Gorodinskiĭ, A I; Lekomtseva, T M; Koreshonkov, O N

1987-10-01

The kinetics of 3H-L-glutamate binding to human brain synaptic membranes revealed the existence of one type of binding sites with Kd and Vmax comparable with those for freshly isolated rat brain membranes. The fraction of glutamate-binding proteins (GBP) was shown to contain three components with Mr of 14, 60 and 280 kD whose stoichiometry is specific for human and rat brain. All fractions were found to bind the radiolabeled neurotransmitter and to dissociate into subunits with Mr of 14 kD after treatment with-potent detergents (with the exception of the 56-60 kD component). Study of association-dissociation of GBP protein subunits by high performance liquid chromatography confirmed the hypothesis on the oligomeric structure of glutamate receptors which are made up of low molecular weight glycoprotein-lipid subunits and which form ionic channels by way of repeated association. Despite the similarity of antigen determinants in the active center of glutamate receptors from human and rat brain, it was assumed that the stoichiometry of structural organization of receptor subunits isolated from different sources is different. The functional role of structural complexity of human brain glutamate receptors is discussed.

Resolving rates of mutation in the brain using single-neuron genomics

PubMed Central

Evrony, Gilad D; Lee, Eunjung; Park, Peter J; Walsh, Christopher A

2016-01-01

Whether somatic mutations contribute functional diversity to brain cells is a long-standing question. Single-neuron genomics enables direct measurement of somatic mutation rates in human brain and promises to answer this question. A recent study (Upton et al., 2015) reported high rates of somatic LINE-1 element (L1) retrotransposition in the hippocampus and cerebral cortex that would have major implications for normal brain function, and suggested that these events preferentially impact genes important for neuronal function. We identify aspects of the single-cell sequencing approach, bioinformatic analysis, and validation methods that led to thousands of artifacts being interpreted as somatic mutation events. Our reanalysis supports a mutation frequency of approximately 0.2 events per cell, which is about fifty-fold lower than reported, confirming that L1 elements mobilize in some human neurons but indicating that L1 mosaicism is not ubiquitous. Through consideration of the challenges identified, we provide a foundation and framework for designing single-cell genomics studies. DOI: http://dx.doi.org/10.7554/eLife.12966.001 PMID:26901440

Brain and Adrenal Metabolic Responses to Stress (The Role of Brain Catecholamines in Regulation of Response to Stress).

DTIC Science & Technology

1982-03-15

gland was studied in stress states with the finding that there were delayed effects of cold stress*1 on key enzymes effecting the ability to form...phosphorylation. A series of studies were conducted of the effects of various drugs on aggressive behavior. Isolation housing was shown to alter cyclic AMP...mechanisms in the brain. Social behavior was studied in relation to drugs and the effects of amphetamine in relation to paranoid behavior demonstrated using a

Intestinal and Blood-Brain Barrier Permeability of Ginkgolides and Bilobalide: In Vitro and In Vivo Approaches

USDA-ARS?s Scientific Manuscript database

In this study intestinal and blood brain barrier (BBB) transport of ginkgolides A, B, C, J and bilobalide, isolated from Ginkgo biloba (Family-Ginkgoaceae), was evaluated in Caco-2 and MDR1-MDCK cell monolayer models. Transepithelial transport was examined for 2 hours in both absorptive and secretor...

Expressive Art for the Social and Community Integration of Adolescents with Acquired Brain Injuries: A Systematic Review

ERIC Educational Resources Information Center

Goyal, Anita; Keightley, Michelle L.

2008-01-01

Adolescents with acquired brain injuries suffer from social and community withdrawal that result in isolation from their peer groups. The review highlights the evidence of effectiveness of expressive art interventions in the form of theatre for populations with difficulties in physical, emotional, cognitive, or social functioning. A systematic…

Functional and genetic diversity of mycorrhizal fungi from single plants of Caladenia formosa (Orchidaceae)

PubMed Central

Huynh, Tien T.; Thomson, Richard; Mclean, Cassandra B.; Lawrie, Ann C.

2009-01-01

Background and Aims Mycorrhizal associations are essential to the plant kingdom. The largest flowering plant family, the Orchidaceae, relies on mycorrhizal fungi for germination, growth and survival. Evidence suggests varying degrees of fungal-host specificity based on a single fungal isolate from a single plant. This paper shows for the first time the diversity of endophytes colonizing in a single plant over consecutive years and the functional significance of this diversity. Methods Stem-collars of Caladenia formosa were collected in different seasons and years. Mycorrhizal fungi isolated were tested for their efficacy to induce leafing and genetically determined using ITS-RFLP and sequencing. Results Multiple mycorrhizal fungi were repeatedly isolated from a single collar that displayed varying effectiveness in germination percentages and adult leaf length. Additional factors contributed to the isolation of effective mycorrhizal fungi; fungal collection season, year of collection and individual isolates. Surface sterilization only improved the number of isolated mycorrhizal fungi. Dual inoculation did not increase germination. All 59 mycorrhizal fungi effective in germinating seed belonged to one clearly defined ITS (internal transcribed spacer) clade and clustered close to Sebacina vermifera (79–89 % homology). Isolates resulting in the greatest germination were not necessarily those resulting in the greatest survival and growth 1 year after germination. Conclusion Single orchid plants contained multiple mycorrhizal fungal strains of one species that had diverse functional differences. These results suggest that our current knowledge of fungal–host specificity may be incomplete due to experimental and analytical limitations. It also suggests that the long-term effectiveness of a mycorrhizal fungus or fungi could only be found by germination and longer-term growth tests rather than genetically. PMID:19561011

The accumulation of brain injury leads to severe neuropathological and neurobehavioral changes after repetitive mild traumatic brain injury.

PubMed

Gao, Huabin; Han, Zhaoli; Bai, Ruojing; Huang, Shan; Ge, Xintong; Chen, Fanglian; Lei, Ping

2017-02-15

Traumatic brain injury (TBI) is a major public health problem with long-term neurobehavioral sequela. The evidences have revealed that TBI is a risk factor for later development of neurodegenerative disease and both the single and repetitive brain injury can lead to the neurodegeneration. But whether the effects of accumulation play an important role in the neurodegenerative disease is still unknown. We utilized the Sprague Dawley (SD) rats to develop the animal models of repetitive mild TBI and single mild TBI in order to detect the neurobehavioral changes. The results of neurobehavioral test revealed that the repetitive mild TBI led to more severe behavioral injuries than the single TBI. There were more activated microglia cells and astrocytes in the repetitive mild TBI group than the single TBI group. In consistent with this, the levels of TNF-α and IL-6 were higher and the expression of IL-10 was lower in the repetitive mild TBI group compared with the single TBI group. The expression of amyloid precursor protein (APP) increased in the repetitive TBI group detected by ELISA and western blot. But the levels of total tau (Tau-5) and P-tau (ser202) seem no different between the two groups in most time point. In conclusion, repetitive mild TBI could lead to more severe neurobehavioral impairments and the effects of accumulation may be associated with the increased inflammation in the brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain Abscess Associated with Isolated Left Superior Vena Cava Draining into the Left Atrium in the Absence of Coronary Sinus and Atrial Septal Defect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erol, Ilknur; Cetin, I. Ilker; Alehan, Fuesun

A previously healthy 12-year-old girl presented with severe headache for 2 weeks. On physical examination, there was finger clubbing without apparent cyanosis. Neurological examination revealed only papiledema without focal neurologic signs. Cerebral magnetic resonance imaging showed the characteristic features of brain abscess in the left frontal lobe. Cardiologic workup to exclude a right-to-left shunt showed an abnormality of the systemic venous drainage: presence of isolated left superior vena cava draining into the left atrium in the absence of coronary sinus and atrial septal defect. This anomaly is rare, because only a few other cases have been reported.

Single Subject Prediction of Brain Disorders in Neuroimaging: Promises and Pitfalls

PubMed Central

Arbabshirani, Mohammad R.; Plis, Sergey; Sui, Jing; Calhoun, Vince D.

2016-01-01

Neuroimaging-based single subject prediction of brain disorders has gained increasing attention in recent years. Using a variety of neuroimaging modalities such as structural, functional and diffusion MRI, along with machine learning techniques, hundreds of studies have been carried out for accurate classification of patients with heterogeneous mental and neurodegenerative disorders such as schizophrenia and Alzheimer's disease. More than 500 studies have been published during the past quarter century on single subject prediction focused on a multiple brain disorders. In the first part of this study, we provide a survey of more than 200 reports in this field with a focus on schizophrenia, mild cognitive impairment (MCI), Alzheimer's disease (AD), depressive disorders, autism spectrum disease (ASD) and attention-deficit hyperactivity disorder (ADHD). Detailed information about those studies such as sample size, type and number of extracted features and reported accuracy are summarized and discussed. To our knowledge, this is by far the most comprehensive review of neuroimaging-based single subject prediction of brain disorders. In the second part, we present our opinion on major pitfalls of those studies from a machine learning point of view. Common biases are discussed and suggestions are provided. Moreover, emerging trends such as decentralized data sharing, multimodal brain imaging, differential diagnosis, disease subtype classification and deep learning are also discussed. Based on this survey, there are extensive evidences showing the great potential of neuroimaging data for single subject prediction of various disorders. However, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper. Emerging big data technologies and advanced data-intensive machine learning methodologies such as deep learning have coincided with an increasing need for accurate, robust and generalizable single subject prediction of brain disorders during an exciting time. In this report, we survey the past and offer some opinions regarding the road ahead. PMID:27012503

Single subject prediction of brain disorders in neuroimaging: Promises and pitfalls.

PubMed

Arbabshirani, Mohammad R; Plis, Sergey; Sui, Jing; Calhoun, Vince D

2017-01-15

Neuroimaging-based single subject prediction of brain disorders has gained increasing attention in recent years. Using a variety of neuroimaging modalities such as structural, functional and diffusion MRI, along with machine learning techniques, hundreds of studies have been carried out for accurate classification of patients with heterogeneous mental and neurodegenerative disorders such as schizophrenia and Alzheimer's disease. More than 500 studies have been published during the past quarter century on single subject prediction focused on a multiple brain disorders. In the first part of this study, we provide a survey of more than 200 reports in this field with a focus on schizophrenia, mild cognitive impairment (MCI), Alzheimer's disease (AD), depressive disorders, autism spectrum disease (ASD) and attention-deficit hyperactivity disorder (ADHD). Detailed information about those studies such as sample size, type and number of extracted features and reported accuracy are summarized and discussed. To our knowledge, this is by far the most comprehensive review of neuroimaging-based single subject prediction of brain disorders. In the second part, we present our opinion on major pitfalls of those studies from a machine learning point of view. Common biases are discussed and suggestions are provided. Moreover, emerging trends such as decentralized data sharing, multimodal brain imaging, differential diagnosis, disease subtype classification and deep learning are also discussed. Based on this survey, there is extensive evidence showing the great potential of neuroimaging data for single subject prediction of various disorders. However, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper. Emerging big data technologies and advanced data-intensive machine learning methodologies such as deep learning have coincided with an increasing need for accurate, robust and generalizable single subject prediction of brain disorders during an exciting time. In this report, we survey the past and offer some opinions regarding the road ahead. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of Surgery, Radiosurgery and Whole Brain Radiation Therapy in the Management of Patients with Metastatic Brain Tumors

PubMed Central

Ellis, Thomas L.; Neal, Matthew T.; Chan, Michael D.

2012-01-01

Brain tumors constitute the most common intracranial tumor. Management of brain metastases has become increasingly complex as patients with brain metastases are living longer and more treatment options develop. The goal of this paper is to review the role of stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), and surgery, in isolation and in combination, in the contemporary treatment of brain metastases. Surgery and SRS both offer management options that may help to optimize therapy in selected patients. WBRT is another option but can lead to late toxicity and suboptimal local control in longer term survivors. Improved prognostic indices will be critical for selecting the best therapies. Further prospective trials are necessary to continue to elucidate factors that will help triage patients to the proper brain-directed therapy for their cancer. PMID:22312545

Cell lineage analysis in human brain using endogenous retroelements

PubMed Central

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.

2015-01-01

Summary 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 sub-lineages 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. PMID:25569347

Novel active contour model based on multi-variate local Gaussian distribution for local segmentation of MR brain images

NASA Astrophysics Data System (ADS)

Zheng, Qiang; Li, Honglun; Fan, Baode; Wu, Shuanhu; Xu, Jindong

2017-12-01

Active contour model (ACM) has been one of the most widely utilized methods in magnetic resonance (MR) brain image segmentation because of its ability of capturing topology changes. However, most of the existing ACMs only consider single-slice information in MR brain image data, i.e., the information used in ACMs based segmentation method is extracted only from one slice of MR brain image, which cannot take full advantage of the adjacent slice images' information, and cannot satisfy the local segmentation of MR brain images. In this paper, a novel ACM is proposed to solve the problem discussed above, which is based on multi-variate local Gaussian distribution and combines the adjacent slice images' information in MR brain image data to satisfy segmentation. The segmentation is finally achieved through maximizing the likelihood estimation. Experiments demonstrate the advantages of the proposed ACM over the single-slice ACM in local segmentation of MR brain image series.

C-type natriuretic peptide functions as an innate neuroprotectant in neonatal hypoxic-ischemic brain injury in mouse via natriuretic peptide receptor 2.

PubMed

Ma, Qingyi; Zhang, Lubo

2018-06-01

Neonatal hypoxia-ischemia (HI) is the most common cause of brain injury in neonates, which leads to high neonatal mortality and severe neurological morbidity in later life (Vannucci, 2000; Volpe, 2001). Yet the molecular mechanisms of neuronal death and brain damage induced by neonatal HI remain largely elusive. Herein, using both in vivo and in vitro models, we determine an endogenous neuroprotectant role of c-type natriuretic peptide (CNP) in preserving neuronal survival after HI brain injury in mouse pups. Postnatal day 7 (P7) mouse pups with CNP deficiency (Nppc lbab/lbab ) exhibit increased brain infarct size and worsened long-term locomotor function after neonatal HI compared with wildtype control (Nppc +/+ ). In isolated primary cortical neurons, recombinant CNP dose-dependently protects primary neurons from oxygen-glucose deprivation (OGD) insult. This neuroprotective effect appears to be mediated through its cognate natriuretic peptide receptor 2 (NPR2), in that antagonization of NPR2, but not NPR3, exacerbates neuronal death and counteracts the protective effect of CNP on primary neurons exposed to OGD insult. Immunoblot and confocal microscopy demonstrate the abundant expression of NPR2 in neurons of the neonatal brain and in isolated primary cortical neurons as well. Moreover, similar to CNP deficiency, administration of NPR2 antagonist P19 via intracerebroventricular injection prior to HI results in exacerbated neuronal death and brain injury after HI. Altogether, the present study indicates that CNP and its cognate receptor NPR2 mainly expressed in neurons represent an innate neuroprotective mechanism in neonatal HI brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Blood-brain barrier KCa3.1 channels: evidence for a role in brain Na uptake and edema in ischemic stroke.

PubMed

Chen, Yi-Je; Wallace, Breanna K; Yuen, Natalie; Jenkins, David P; Wulff, Heike; O'Donnell, Martha E

2015-01-01

KCa3.1, a calcium-activated potassium channel, regulates ion and fluid secretion in the lung and gastrointestinal tract. It is also expressed on vascular endothelium where it participates in blood pressure regulation. However, the expression and physiological role of KCa3.1 in blood-brain barrier (BBB) endothelium has not been investigated. BBB endothelial cells transport Na(+) and Cl(-) from the blood into the brain transcellularly through the co-operation of multiple cotransporters, exchangers, pumps, and channels. In the early stages of cerebral ischemia, when the BBB is intact, edema formation occurs by processes involving increased BBB transcellular Na(+) transport. This study evaluated whether KCa3.1 is expressed on and participates in BBB ion transport. The expression of KCa3.1 on cultured cerebral microvascular endothelial cells, isolated microvessels, and brain sections was evaluated by Western blot and immunohistochemistry. Activity of KCa3.1 on cerebral microvascular endothelial cells was examined by K(+) flux assays and patch-clamp. Magnetic resonance spectroscopy and MRI were used to measure brain Na(+) uptake and edema formation in rats with focal ischemic stroke after TRAM-34 treatment. KCa3.1 current and channel protein were identified on bovine cerebral microvascular endothelial cells and freshly isolated rat microvessels. In situ KCa3.1 expression on BBB endothelium was confirmed in rat and human brain sections. TRAM-34 treatment significantly reduced Na(+) uptake, and cytotoxic edema in the ischemic brain. BBB endothelial cells exhibit KCa3.1 protein and activity and pharmacological blockade of KCa3.1 seems to provide an effective therapeutic approach for reducing cerebral edema formation in the first 3 hours of ischemic stroke. © 2014 American Heart Association, Inc.

Eff ect of a single asenapine treatment on Fos expression in the brain catecholamine-synthesizing neurons: impact of a chronic mild stress preconditioning.

PubMed

Osacka, J; Horvathova, L; Majercikova, Z; Kiss, Alexander

2017-04-25

Fos protein expression in catecholamine-synthesizing neurons of the substantia nigra (SN) pars compacta (SNC, A8), pars reticulata (SNR, A9), and pars lateralis (SNL), the ventral tegmental area (VTA, A10), the locus coeruleus (LC, A6) and subcoeruleus (sLC), the ventrolateral pons (PON-A5), the nucleus of the solitary tract (NTS-A2), the area postrema (AP), and the ventrolateral medulla (VLM-A1) was quantitatively evaluated aft er a single administration of asenapine (ASE) (designated for schizophrenia treatment) in male Wistar rats preconditioned with a chronic unpredictable variable mild stress (CMS) for 21 days. Th e aim of the present study was to reveal whether a single ASE treatment may 1) activate Fos expression in the brain areas selected; 2) activate tyrosine hydroxylase (TH)-synthesizing cells displaying Fos presence; and 3) be modulated by CMS preconditioning. Control (CON), ASE, CMS, and CMS+ASE groups were used. CMS included restraint, social isolation, crowding, swimming, and cold. Th e ASE and CMS+ASE groups received a single dose of ASE (0.3 mg/kg, s.c.) and CON and CMS saline (300 μl/rat, s.c.). The animals were sacrificed 90 min aft er the treatments. Fos protein and TH-labeled immunoreactive perikarya were analyzed on double labeled histological sections and enumerated on captured pictures using combined light and fluorescence microscope illumination. Saline or CMS alone did not promote Fos expression in any of the structures investigated. ASE alone or in combination with CMS elicited Fos expression in two parts of the SN (SNC, SNR) and the VTA. Aside from some cells in the central gray tegmental nuclei adjacent to LC, where a small number of Fos profiles occurred, none or negligible Fos occurrence was detected in the other structures investigated including the LC and sLC, PON-A5, NTS-A2, AP, and VLM-A1. CMS preconditioning did not infl uence the level of Fos induction in the SN and VTA elicited by ASE administration. Similarly, the ratio between the amount of free Fos and Fos colocalized with TH was not aff ected by stress preconditioning in the SNC, SNR, and the VTA. Th e present study provides an anatomical/functional knowledge about the nature of the acute ASE treatment on the catecholamine-synthesizing neurons activity in certain brain structures and their missing interplay with the CMS preconditioning.

Efficacy, safety and outcome of frameless image-guided robotic radiosurgery for brain metastases after whole brain radiotherapy.

PubMed

Lohkamp, Laura-Nanna; Vajkoczy, Peter; Budach, Volker; Kufeld, Markus

2018-05-01

Estimating efficacy, safety and outcome of frameless image-guided robotic radiosurgery for the treatment of recurrent brain metastases after whole brain radiotherapy (WBRT). We performed a retrospective single-center analysis including patients with recurrent brain metastases after WBRT, who have been treated with single session radiosurgery, using the CyberKnife® Radiosurgery System (CKRS) (Accuray Inc., CA) between 2011 and 2016. The primary end point was local tumor control, whereas secondary end points were distant tumor control, treatment-related toxicity and overall survival. 36 patients with 140 recurrent brain metastases underwent 46 single session CKRS treatments. Twenty one patients had multiple brain metastases (58%). The mean interval between WBRT and CKRS accounted for 2 years (range 0.2-7 years). The median number of treated metastases per treatment session was five (range 1-12) with a tumor volume of 1.26 ccm (mean) and a median tumor dose of 18 Gy prescribed to the 70% isodose line. Two patients experienced local tumor recurrence within the 1st year after treatment and 13 patients (36%) developed novel brain metastases. Nine of these patients underwent additional one to three CKRS treatments. Eight patients (22.2%) showed treatment-related radiation reactions on MRI, three with clinical symptoms. Median overall survival was 19 months after CKRS. The actuarial 1-year local control rate was 94.2%. CKRS has proven to be locally effective and safe due to high local tumor control rates and low toxicity. Thus CKRS offers a reliable salvage treatment option for recurrent brain metastases after WBRT.

Development of vibration isolation platform for low amplitude vibration

NASA Astrophysics Data System (ADS)

Lee, Dae-Oen; Park, Geeyong; Han, Jae-Hung

2014-03-01

The performance of high precision payloads on board a satellite is extremely sensitive to vibration. Although vibration environment of a satellite on orbit is very gentle compared to the launch environment, even a low amplitude vibration disturbances generated by reaction wheel assembly, cryocoolers, etc may cause serious problems in performing tasks such as capturing high resolution images. The most commonly taken approach to protect sensitive payloads from performance degrading vibration is application of vibration isolator. In this paper, development of vibration isolation platform for low amplitude vibration is discussed. Firstly, single axis vibration isolator is developed by adapting three parameter model using bellows and viscous fluid. The isolation performance of the developed single axis isolator is evaluated by measuring force transmissibility. The measured transmissibility shows that both the low Q-factor (about 2) and the high roll-off rate (about -40 dB/dec) are achieved with the developed isolator. Then, six single axis isolators are combined to form Stewart platform in cubic configuration to provide multi-axis vibration isolation. The isolation performance of the developed multi-axis isolator is evaluated using a simple prototype reaction wheel model in which wheel imbalance is the major source of vibration. The transmitted force without vibration isolator is measured and compared with the transmitted force with vibration isolator. More than 20 dB reduction of the X and Y direction (radial direction of flywheel) disturbance is observed for rotating wheel speed of 100 Hz and higher.

Progressive solitary sclerosis: Gradual motor impairment from a single CNS demyelinating lesion.

PubMed

Keegan, B Mark; Kaufmann, Timothy J; Weinshenker, Brian G; Kantarci, Orhun H; Schmalstieg, William F; Paz Soldan, M Mateo; Flanagan, Eoin P

2016-10-18

To report patients with progressive motor impairment resulting from an isolated CNS demyelinating lesion in cerebral, brainstem, or spinal cord white matter that we call progressive solitary sclerosis. Thirty patients were identified with (1) progressive motor impairment for over 1 year with a single radiologically identified CNS demyelinating lesion along corticospinal tracts, (2) absence of other demyelinating CNS lesions, and (3) no history of relapses affecting other CNS pathways. Twenty-five were followed prospectively in our multiple sclerosis (MS) clinic and 5 were identified retrospectively from our progressive MS database. Patients were excluded if an alternative etiology for progressive motor impairment was found. Multiple brain and spinal cord MRI were reviewed by a neuroradiologist blinded to the clinical details. The patients' median age was 48.5 years (range 23-71) and 15 (50%) were women. The median follow-up from symptom onset was 100 months (range 15-343 months). All had insidiously progressive upper motor neuron weakness attributable to the solitary demyelinating lesion found on MRI. Clinical presentations were hemiparesis/monoparesis (n = 24), quadriparesis (n = 5), and paraparesis (n = 1). Solitary MRI lesions involved cervical spinal cord (n = 18), cervico-medullary/brainstem region (n = 6), thoracic spinal cord (n = 4), and subcortical white matter (n = 2). CSF abnormalities consistent with MS were found in 13 of 26 (50%). Demyelinating disease was confirmed pathologically in 2 (biopsy, 1; autopsy, 1). Progressive solitary sclerosis results from an isolated CNS demyelinating lesion. Future revisions to MS diagnostic criteria could incorporate this presentation of demyelinating disease. © 2016 American Academy of Neurology.

Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes.

PubMed

Di Filippo, M; Anderson, V M; Altmann, D R; Swanton, J K; Plant, G T; Thompson, A J; Miller, D H

2010-02-01

Conventional MRI lesion measures modestly predict long term disability in some clinically isolated syndrome (CIS) studies. Brain atrophy suggests neuroaxonal loss in multiple sclerosis (MS) with the potential to reflect disease progression to a greater extent than lesion measures. To investigate whether brain atrophy and lesion load, during the first year in patients presenting with CIS, independently predict clinical outcome (development of MS and disability at 6 years). 99 patients presenting with CIS were included in the study. T1 gadolinium enhanced and T2 weighted brain MRI was acquired at baseline and approximately 1 year later. Percentage brain atrophy rate between baseline and follow-up scans was analysed using SIENA. Mean annual brain atrophy rates were -0.38% for all patients, -0.50% in patients who had developed MS at 6 years and -0.26% in those who had not. Brain atrophy rate (p = 0.005) and baseline T2 lesion load (p<0.001) were independent predictors of clinically definite MS. While brain atrophy rate was a predictor of Expanded Disability Status Scale (EDSS) score in a univariate analysis, only 1 year T2 lesion load change (p = 0.007) and baseline gadolinium enhancing lesion number (p = 0.03) were independent predictors of EDSS score at the 6 year follow-up. T1 lesion load was the only MRI parameter which predicted Multiple Sclerosis Functional Composite score at the 6 year follow-up. The findings confirm that brain atrophy occurs during the earliest phases of MS and suggest that 1 year longitudinal measures of MRI change, if considered together with baseline MRI variables, might help to predict clinical status 6 years after the first demyelinating event in CIS patients, better than measurements such as lesion or brain volumes on baseline MRI alone.

Single Sustained Inflation followed by Ventilation Leads to Rapid Cardiorespiratory Recovery but Causes Cerebral Vascular Leakage in Asphyxiated Near-Term Lambs

PubMed Central

Sobotka, Kristina S.; Hooper, Stuart B.; Crossley, Kelly J.; Ong, Tracey; Schmölzer, Georg M.; Barton, Samantha K.; McDougall, Annie R. A.; Miller, Suzie L.; Tolcos, Mary; Klingenberg, Claus; Polglase, Graeme R.

2016-01-01

Background A sustained inflation (SI) rapidly restores cardiac function in asphyxic, bradycardic newborns but its effects on cerebral haemodynamics and brain injury are unknown. We determined the effect of different SI strategies on carotid blood flow (CaBF) and cerebral vascular integrity in asphyxiated near-term lambs. Methods Lambs were instrumented and delivered at 139 ± 2 d gestation and asphyxia was induced by delaying ventilation onset. Lambs were randomised to receive 5 consecutive 3 s SI (multiple SI; n = 6), a single 30 s SI (single SI; n = 6) or conventional ventilation (no SI; n = 6). Ventilation continued for 30 min in all lambs while CaBF and respiratory function parameters were recorded. Brains were assessed for gross histopathology and vascular leakage. Results CaBF increased more rapidly and to a greater extent during a single SI (p = 0.01), which then decreased below both other groups by 10 min, due to a higher cerebral oxygen delivery (p = 0.01). Blood brain barrier disruption was increased in single SI lambs as indicated by increased numbers of blood vessel profiles with plasma protein extravasation (p = 0.001) in the cerebral cortex. There were no differences in CaBF or cerebral oxygen delivery between the multiple SI and no SI lambs. Conclusions Ventilation with an initial single 30 s SI improves circulatory recovery, but is associated with greater disruption of blood brain barrier function, which may exacerbate brain injury suffered by asphyxiated newborns. This injury may occur as a direct result of the initial SI or to the higher tidal volumes delivered during subsequent ventilation. PMID:26765258

Management of brain metastasis in a patient with advanced epithelial ovarian carcinoma by gamma-knife radiosurgery.

PubMed

Nikolaoul, Marinos; Stamenković, Srdjan; Stergiou, Christos; Skarleas, Christos; Torrens, Michael

2015-01-01

Brain metastases from epithelial ovarian cancer (EOC) are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS). A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI) scan during the work-up. The decision to perform GKRS was due to a surgical inaccessibility of intracranial lesion. Twelve weeks after the procedure, the MRI scan showed reduction in the diameter of brain metastasis and surrounding edema and the patient returned to good mental and motor performance.The patient survived for 22 months following treatment and died from a progressive intra-abdominal disease. Prognosis of ovarian cancer patients with brain metastases is generally poor regardless of treatment. Our case shows that GKRS as primary treatment modality for the control of ovarian cancer metastases to the brain was effective and can be considered as a treatment of choice if international selection criteria are followed.

Particle swarm optimization and its application in MEG source localization using single time sliced data

NASA Astrophysics Data System (ADS)

Lin, Juan; Liu, Chenglian; Guo, Yongning

2014-10-01

The estimation of neural active sources from the magnetoencephalography (MEG) data is a very critical issue for both clinical neurology and brain functions research. A widely accepted source-modeling technique for MEG involves calculating a set of equivalent current dipoles (ECDs). Depth in the brain is one of difficulties in MEG source localization. Particle swarm optimization(PSO) is widely used to solve various optimization problems. In this paper we discuss its ability and robustness to find the global optimum in different depths of the brain when using single equivalent current dipole (sECD) model and single time sliced data. The results show that PSO is an effective global optimization to MEG source localization when given one dipole in different depths.

Characterization of Sri Lanka rabies virus isolates using nucleotide sequence analysis of nucleoprotein gene.

PubMed

Arai, Y T; Takahashi, H; Kameoka, Y; Shiino, T; Wimalaratne, O; Lodmell, D L

2001-01-01

Thirty-four suspected rabid brain samples from 2 humans, 24 dogs, 4 cats, 2 mongooses, I jackal and I water buffalo were collected in 1995-1996 in Sri Lanka. Total RNA was extracted directly from brain suspensions and examined using a one-step reverse transcription-polymerase chain reaction (RT-PCR) for the rabies virus nucleoprotein (N) gene. Twenty-eight samples were found positive for the virus N gene by RT-PCR and also for the virus antigens by fluorescent antibody (FA) test. Rabies virus isolates obtained from different animal species in different regions of Sri Lanka were genetically homogenous. Sequences of 203 nucleotides (nt)-long RT-PCR products obtained from 16 of 27 samples were found identical. Sequences of 1350 nt of N genes of 14 RT-PCR products were determined. The Sri Lanka isolates under study formed a specific cluster that included also an earlier isolate from India but did not include the known isolates from China, Thailand, Malaysia, Israel, Iran, Oman, Saudi Arabia, Russia, Nepal, Philippines, Japan and from several other countries. These results suggest that one type of rabies virus is circulating among human, dog, cat, mongoose, jackal and water buffalo living near Colombo City and in other five remote regions in Sri Lanka.

Memory recall in arousing situations – an emotional von Restorff effect?

PubMed Central

Wiswede, Daniel; Rüsseler, Jascha; Hasselbach, Simone; Münte, Thomas F

2006-01-01

Background Previous research has demonstrated a relationship between memory recall and P300 amplitude in list learning tasks, but the variables mediating this P300-recall relationship are not well understood. In the present study, subjects were required to recall items from lists consisting of 12 words, which were presented in front of pictures taken from the IAPS collection. One word per list is made distinct either by font color or by a highly arousing background IAPS picture. This isolation procedure was first used by von Restorff. Brain potentials were recorded during list presentation. Results Recall performance was enhanced for color but not for emotional isolates. Event-related brain potentials (ERP) showed a more positive P300-component for recalled non-isolated words and color-isolated words, compared to the respective non-remembered words, but not for words isolated by arousing background. Conclusion Our findings indicate that it is crucial to take emotional mediator variables into account, when using the P300 to predict later recall. Highly arousing environments might force the cognitive system to interrupt rehearsal processes in working memory, which might benefit transfer into other, more stable memory systems. The impact of attention-capturing properties of arousing background stimuli is also discussed. PMID:16863589

Cloning of Plasmodium falciparum by single-cell sorting

PubMed Central

Miao, Jun; Li, Xiaolian; Cui, Liwang

2010-01-01

Malaria parasite cloning is traditionally carried out mainly by using the limiting dilution method, which is laborious, imprecise, and unable to distinguish multiply-infected RBCs. In this study, we used a parasite engineered to express green fluorescent protein (GFP) to evaluate a single-cell sorting method for rapidly cloning Plasmodium falciparum. By dividing a two dimensional scattergram from a cell sorter into 17 gates, we determined the parameters for isolating singly-infected erythrocytes and sorted them into individual cultures. Pre-gating of the engineered parasites for GFP allowed the isolation of almost 100% GFP-positive clones. Compared with the limiting dilution method, the number of parasite clones obtained by single-cell sorting was much higher. Molecular analyses showed that parasite isolates obtained by single-cell sorting were highly homogenous. This highly efficient single-cell sorting method should prove very useful for cloning both P. falciparum laboratory populations from genetic manipulation experiments and clinical samples. PMID:20435038

Single-cell isolation using a DVD optical pickup

PubMed Central

Kasukurti, A.; Potcoava, M.; Desai, S.A.; Eggleton, C.; Marr, D. W. M.

2011-01-01

A low-cost single-cell isolation system incorporating a digital versatile disc burner (DVD RW) optical pickup has been developed. We show that these readily available modules have the required laser power and focusing optics to provide a steady Gaussian beam capable of optically trapping micron-sized colloids and red blood cells. Utility of the pickup is demonstrated through the non-destructive isolation of such particles in a laminar-flow based microfluidic device that captures and translates single microscale objects across streamlines into designated channel exits. In this, the integrated objective lens focusing coils are used to steer the optical trap across the channel, resulting in the isolation of colloids and red blood cells using a very inexpensive off-the-shelf optical component. PMID:21643294

Zebrafish: a model animal for analyzing the impact of environmental pollutants on muscle and brain mitochondrial bioenergetics.

PubMed

Bourdineaud, Jean-Paul; Rossignol, R; Brèthes, D

2013-01-01

Mercury, anthropogenic release of uranium (U), and nanoparticles constitute hazardous environmental pollutants able to accumulate along the aquatic food chain with severe risk for animal and human health. The impact of such pollutants on living organisms has been up to now approached by classical toxicology in which huge doses of toxic compounds, environmentally irrelevant, are displayed through routes that never occur in the lifespan of organisms (for instance injecting a bolus of mercury to an animal although the main route is through prey and fish eating). We wanted to address the effect of such pollutants on the muscle and brain mitochondrial bioenergetics under realistic conditions, at unprecedented low doses, using an aquatic model animal, the zebrafish Danio rerio. We developed an original method to measure brain mitochondrial respiration: a single brain was put in 1.5 mL conical tube containing a respiratory buffer. Brains were gently homogenized by 13 strokes with a conical plastic pestle, and the homogenates were immediately used for respiration measurements. Skinned muscle fibers were prepared by saponin permeabilization. Zebrafish were contaminated with food containing 13 μg of methylmercury (MeHg)/g, an environmentally relevant dose. In permeabilized muscle fibers, we observed a strong inhibition of both state 3 mitochondrial respiration and cytochrome c oxidase activity after 49 days of MeHg exposure. We measured a dramatic decrease in the rate of ATP release by skinned muscle fibers. Contrarily to muscles, brain mitochondrial respiration was not modified by MeHg exposure although brain accumulated twice as much MeHg than muscles. When zebrafish were exposed to 30 μg/L of waterborne U, the basal mitochondrial respiratory control ratio was decreased in muscles after 28 days of exposure. This was due to an increase of the inner mitochondrial membrane permeability. The impact of a daily ration of food containing gold nanoparticles of two sizes (12 and 50 nm) was investigated at a very low dose for 60 days (40 ng gold/fish/day). Mitochondrial dysfunctions appeared in brain and muscle for both tested sizes. In conclusion, at low environmental doses, dietary or waterborne heavy metals impinged on zebrafish tissue mitochondrial respiration. Due to its incredible simplicity avoiding tedious and time-consuming mitochondria isolation, our one-pot method allowing brain respiratory analysis should give colleagues the incentive to use zebrafish brain as a model in bioenergetics. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Unlocking the Secrets of the Brain, Part II: A Continuing Look at Techniques for Exploring the Brain.

ERIC Educational Resources Information Center

Powledge, Tabitha M.

1997-01-01

Describes techniques for delving into the brain including positron emission tomography (PET), single photon emission computed tomography (SPECT), electroencephalogram (EEG), magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), and low-tech indirect studies. (JRH)

Performance and brain electrical activity during prolonged confinement.

PubMed

Lorenz, B; Lorenz, J; Manzey, D

1996-01-01

A subset of the AGARD-STRES battery including memory search, unstable tracking, and a combination of both tasks (dual-task), was applied repeatedly to the four chamber crew members before, during, and after the 60-day isolation period of EXEMSI. Five ground control group members served as a control group. A subjective state questionnaire was also included. The results were subjected to a quantitative single-subject analysis. Electroencephalograms (EEG) were recorded to permit correlation of changes in task performance with changes in the physiological state. Evaluation of the EEG focused on spectral parameters of spontaneous EEG waves. No physiological data were collected from the control group. Significant decrements in tracking ability were observed in the chamber crew. The time course of these effects followed a triphasic pattern with initial deterioration, intermediate recovery to pre-isolation baseline scores after the first half of the isolation period, and a second deterioration towards the end. None of the control group subjects displayed such an effect. Memory search (speed and accuracy) was only occasionally impaired during isolation, but the control group displayed a similar pattern of changes. It is suggested that a state of decreased alertness causes tracking deterioration, which leads to a reduced efficiency of sustained cue utilization. The assumption of low alertness was further substantiated by higher fatigue ratings by the chamber crew compared to those of the control group. Analysis of the continuous EEG recordings revealed that only two subjects produced reliable alpha wave activity (8-12 Hz) over Pz and, to a much smaller extent, Fz-theta wave activity (5-7 Hz) during task performance. In both subjects Pz-alpha power decreased consistently under task conditions involving single-task and dual-task tracking. Fz-theta activity was increased more by single-task and dual-task memory search than by single-task tracking. The alpha attenuation appears to be associated with an increasing demand on perceptual cue utilization required by the tracking performance. In one subject marked attenuation of alpha power occurred during the first half of the confinement period, where he also scored the highest fatigue ratings. A striking increase in fronto-central theta activity was observed in the same subject after six weeks of isolation. The change was associated with an efficient rather than a degraded task performance, and a high rating of the item "concentrated" and a low rating of the item "fatigued." This finding supports the hypothesis that the activation state associated with increased fronto-central theta activity accompanies efficient performance of demanding mental tasks. The usefulness of standardized laboratory tasks as monitoring instruments is demonstrated by the direct comparability with results of studies obtained from other relevant research applications using the same tasks. The feasibility of a self-administered integrated psychophysiological assessment of the individual state was illustrated by the nearly complete collection of data. The large number of individual data collected over the entire period permitted application of quantitative single-subject analysis, allowing reliable determination of changes in the individual state in the course of time. It thus appears that this assessment technique can be adapted for in-flight monitoring of astronauts during prolonged spaceflights. Parallel EEG recording can provide relevant supplementary information for diagnosing the individual activation state associated with task performance. The existence of large individual differences in the generation of task-sensitive EEG rhythms forms an important issue for further studies.

Warnings and caveats in brain controllability.

PubMed

Tu, Chengyi; Rocha, Rodrigo P; Corbetta, Maurizio; Zampieri, Sandro; Zorzi, Marco; Suweis, S

2018-08-01

A recent article by Gu et al. (Nat. Commun. 6, 2015) proposed to characterize brain networks, quantified using anatomical diffusion imaging, in terms of their "controllability", drawing on concepts and methods of control theory. They reported that brain activity is controllable from a single node, and that the topology of brain networks provides an explanation for the types of control roles that different regions play in the brain. In this work, we first briefly review the framework of control theory applied to complex networks. We then show contrasting results on brain controllability through the analysis of five different datasets and numerical simulations. We find that brain networks are not controllable (in a statistical significant way) by one single region. Additionally, we show that random null models, with no biological resemblance to brain network architecture, produce the same type of relationship observed by Gu et al. between the average/modal controllability and weighted degree. Finally, we find that resting state networks defined with fMRI cannot be attributed specific control roles. In summary, our study highlights some warning and caveats in the brain controllability framework. Copyright © 2018 Elsevier Inc. All rights reserved.

Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single-Isocenter Volumetric Modulated Arc Therapy.

PubMed

Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J; Wen, Ning

2016-09-30

Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly.

Brevibacterium casei as a cause of brain abscess in an immunocompetent patient.

PubMed

Kumar, V Anil; Augustine, Deepthi; Panikar, Dilip; Nandakumar, Aswathy; Dinesh, Kavitha R; Karim, Shamsul; Philip, Rosamma

2011-12-01

Coryneform bacteria belonging to the genus Brevibacterium have emerged as opportunistic pathogens. Of the nine known species of Brevibacterium isolated from human clinical samples, Brevibacterium casei is the most frequently reported species from clinical specimens. We report the first case of B. casei brain abscess in an immunocompetent patient successfully treated by surgery and antimicrobial therapy.

[Efficacy of bemithyl and pyrazidol in patients with cerebroasthenia due to brain injury].

PubMed

Zarubina, I V; Narmanbetova, F N; Agadzhanian, E F; Shabanov, P D

2005-01-01

The article is dedicated to therapeutic efficacy of a combination of the antihypoxant bemithyl and the antidepressant pyrazidol in patients with asthenoneurotic and asthenovegetative syndromes after moderate isolated brain injury (BI). The combined therapy was shown to reduce long-term sequences of BI such as asthenic symptoms, stabilize both lipid peroxidation processes and serum antioxidative systems.

Detection of AIDS Virus in Macrophages in Brain Tissue from AIDS Patients with Encephalopathy

NASA Astrophysics Data System (ADS)

Koenig, Scott; Gendelman, Howard E.; Orenstein, Jan M.; Canto, Mauro C.; Pezeshkpour, Gholam H.; Yungbluth, Margaret; Janotta, Frank; Aksamit, Allen; Martin, Malcolm A.; Fauci, Anthony S.

1986-09-01

One of the common neurological complications in patients with the acquired immune deficiency syndrome (AIDS) is a subacute encephalopathy with progressive dementia. By using the techniques of cocultivation for virus isolation, in situ hybridization, immunocytochemistry, and transmission electron microscopy, the identity of an important cell type that supports replication of the AIDS retrovirus in brain tissue was determined in two affected individuals. These cells were mononucleated and multinucleated macrophages that actively synthesized viral RNA and produced progeny virions in the brains of the patients. Infected brain macrophages may serve as a reservoir for virus and as a vehicle for viral dissemination in the infected host.

Composite technique for regional neurochemical studies: measurement of energy and neurotransmitter metabolites in single tissue sample.

PubMed

Djuricic, B M; Ueki, Y; Spatz, M

1985-06-01

A combined method is described for the determination of various metabolites from a single tissue sample of the brain. It comprises a quick inactivation of cerebral enzymes by microwave irradiation, easy separation of the desired brain regions, and perchloric acid extraction of tissue substances, which are assayed either by specific enzymatic techniques or by HPLC with electrochemical detection. The obtained values of most energy and neurotransmitter metabolites in the brain are in agreement with those reported using other methods. However, this technique, in contrast to the brain freezing in vitro or freeze-blowing, provides a more efficient procedure for rapid arrest of cerebral metabolism even in the deep brain structures and is therefore suitable for detection of early changes particularly those occurring in experimental pathological conditions such as ischemia.

Biochemical properties of Na+/K(+)-ATPase in axonal growth cone particles isolated from fetal rat brain.

PubMed

Mercado, R; Hernández, J

1994-08-01

Axonal growth cones (AGC) isolated from fetal rat brain have an important specific activity of N+/K(+)-ATPase. Kinetic assays of the enzyme in AGC showed that Km values for ATP or K+ are similar to those reported for the adult brain enzyme. For Na+ the affinity (Km) was lower. Vmax for the three substrates was several times lower in AGC as compared to the adult value. We also observed two apparent inhibition constants of Na+/K(+)-ATPase by ouabain, one of low affinity, possibly corresponding to the alpha 1 isoform and another of high affinity which is different to that described for the alpha 2 isoform of the enzyme. These results support an important role for the sodium pump in the maintainance of volume and cationic balance in neuronal differentiating structures. The functional differences observed also suggest that the enzymatic complex of Na+/K(+)-ATPase in AGC is in a transitional state towards the adult configuration.

Modelling of Cerebral Tuberculosis: Hope for Continuous Research in Solving the Enigma of the Bottom Billion’s Disease

PubMed Central

Hernández Pando, Rogelio

2011-01-01

Cerebral tuberculosis is a severe type of extrapulmonary disease that is highly predominant in children. It is thought that meningeal tuberculosis, the most common form of cerebral tuberculosis, begins with respiratory infection followed by early haematogenous dissemination to extrapulmonary sites involving the brain. Host genetic susceptibility factors and specific mycobacteria substrains could be involved in the development of this serious form of tuberculosis. In this editorial the different animal models of cerebral tuberculosis are commented, highlighting a recently described murine model in which BALB/c mice were infected by the intratracheal route with clinical isolates, which exhibited rapid dissemination and brain infection. These strains were isolated from the cerebrospinal fluid of patients with meningeal tuberculosis; they showed specific genotype and induced a peculiar immune response in the infected brain. This model could be a useful tool to study host and bacilli factors involved in the pathogenesis of the most severe form of tuberculosis. PMID:22135568

Embracing covariation in brain evolution: Large brains, extended development, and flexible primate social systems

PubMed Central

Charvet, Christine J.; Finlay, Barbara L.

2012-01-01

Brain size, body size, developmental length, life span, costs of raising offspring, behavioral complexity, and social structures are correlated in mammals due to intrinsic life-history requirements. Dissecting variation and direction of causation in this web of relationships often draw attention away from the factors that correlate with basic life parameters. We consider the “social brain hypothesis,” which postulates that overall brain and the isocortex are selectively enlarged to confer social abilities in primates, as an example of this enterprise and pitfalls. We consider patterns of brain scaling, modularity, flexibility of brain organization, the “leverage,” and direction of selection on proposed dimensions. We conclude that the evidence supporting selective changes in isocortex or brain size for the isolated ability to manage social relationships is poor. Strong covariation in size and developmental duration coupled with flexible brains allow organisms to adapt in variable social and ecological environments across the life span and in evolution. PMID:22230623

Lipid extraction from isolated single nerve cells

NASA Technical Reports Server (NTRS)

Krasnov, I. V.

1977-01-01

A method of extracting lipids from single neurons isolated from lyophilized tissue is described. The method permits the simultaneous extraction of lipids from 30-40 nerve cells and for each cell provides equal conditions of solvent removal at the conclusion of extraction.

Single Spore Isolation as a Simple and Efficient Technique to obtain fungal pure culture

NASA Astrophysics Data System (ADS)

Noman, E.; Al-Gheethi, AA; Rahman, N. K.; Talip, B.; Mohamed, R.; H, N.; Kadir, O. A.

2018-04-01

The successful identification of fungi by phenotypic methods or molecular technique depends mainly on the using an advanced technique for purifying the isolates. The most efficient is the single spore technique due to the simple requirements and the efficiency in preventing the contamination by yeast, mites or bacteria. The method described in the present work is depends on the using of a light microscope to transfer one spore into a new culture medium. The present work describes a simple and efficient procedure for single spore isolation to purify of fungi recovered from the clinical wastes.

Label-free isolation and deposition of single bacterial cells from heterogeneous samples for clonal culturing

NASA Astrophysics Data System (ADS)

Riba, J.; Gleichmann, T.; Zimmermann, S.; Zengerle, R.; Koltay, P.

2016-09-01

The isolation and analysis of single prokaryotic cells down to 1 μm and less in size poses a special challenge and requires micro-engineered devices to handle volumes in the picoliter to nanoliter range. Here, an advanced Single-Cell Printer (SCP) was applied for automated and label-free isolation and deposition of bacterial cells encapsulated in 35 pl droplets by inkjet-like printing. To achieve this, dispenser chips to generate micro droplets have been fabricated with nozzles 20 μm in size. Further, the magnification of the optical system used for cell detection was increased. Redesign of the optical path allows for collision-free addressing of any flat substrate since no compartment protrudes below the nozzle of the dispenser chip anymore. The improved system allows for deterministic isolation of individual bacterial cells. A single-cell printing efficiency of 93% was obtained as shown by printing fluorescent labeled E. coli. A 96-well plate filled with growth medium is inoculated with single bacteria cells on average within about 8 min. Finally, individual bacterial cells from a heterogeneous sample of E. coli and E. faecalis were isolated for clonal culturing directly on agar plates in user-defined array geometry.

Characteristics of breast cancer patients with central nervous system metastases: a single-center experience.

PubMed

Harputluoglu, Hakan; Dizdar, Omer; Aksoy, Sercan; Kilickap, Saadettin; Dede, Didem S; Ozisik, Yavuz; Guler, Nilufer; Barista, Ibrahim; Gullu, Ibrahim; Hayran, Mutlu; Selek, Ugur; Cengiz, Mustafa; Zorlu, Faruk; Tekuzman, Gulten; Altundag, Kadri

2008-05-01

The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis.

Reconfigurable visible nanophotonic switch for optogenetic applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Mohanty, Aseema; Li, Qian; Tadayon, Mohammad Amin; Bhatt, Gaurang R.; Cardenas, Jaime; Miller, Steven A.; Kepecs, Adam; Lipson, Michal

2017-02-01

High spatiotemporal resolution deep-brain optical excitation for optogenetics would enable activation of specific neural populations and in-depth study of neural circuits. Conventionally, a single fiber is used to flood light into a large area of the brain with limited resolution. The scalability of silicon photonics could enable neural excitation over large areas with single-cell resolution similar to electrical probes. However, active control of these optical circuits has yet to be demonstrated for optogenetics. Here we demonstrate the first active integrated optical switch for neural excitation at 473 nm, enabling control of multiple beams for deep-brain neural stimulation. Using a silicon nitride waveguide platform, we develop a cascaded Mach-Zehnder interferometer (MZI) network located outside the brain to direct light to 8 different grating emitters located at the tip of the neural probe. We use integrated platinum microheaters to induce a local thermo-optic phase shift in the MZI to control the switch output. We measure an ON/OFF extinction ratio of >8dB for a single switch and a switching speed of 20 microseconds. We characterize the optical output of the switch by imaging its excitation of fluorescent dye. Finally, we demonstrate in vivo single-neuron optical activation from different grating emitters using a fully packaged device inserted into a mouse brain. Directly activated neurons showed robust spike firing activities with low first-spike latency and small jitter. Active switching on a nanophotonic platform is necessary for eventually controlling highly-multiplexed reconfigurable optical circuits, enabling high-resolution optical stimulation in deep-brain regions.

Tembusu-like flavivirus (Perak virus) as the cause of neurological disease outbreaks in young Pekin ducks.

PubMed

Homonnay, Zalán Gábor; Kovács, Edit Walkóné; Bányai, Krisztián; Albert, Mihály; Fehér, Enikő; Mató, Tamás; Tatár-Kis, Tímea; Palya, Vilmos

2014-01-01

A neurological disease of young Pekin ducks characterized by ataxia, lameness, and paralysis was observed at several duck farms in Malaysia in 2012. Gross pathological lesions were absent or inconsistent in most of the cases, but severe and consistent microscopic lesions were found in the brain and spinal cord, characterized by non-purulent panencephalomyelitis. Several virus isolates were obtained in embryonated duck eggs and in cell cultures (Vero and DF-1) inoculated with the brain homogenates of affected ducks. After exclusion of other viruses, the isolates were identified as a flavivirus by flavivirus-specific reverse transcription-polymerase chain reaction (RT-PCR) assays. Inoculation of 2-week-old Pekin ducks with a flavivirus isolate by the subcutaneous or intramuscular route resulted in typical clinical signs and histological lesions in the brain and spinal cord. The inoculated virus was detected by RT-PCR from organ samples of ducks with clinical signs and histological lesions. With a few days delay, the disease was also observed among co-mingled contact control birds. Phylogenetic analysis of NS5 and E gene sequences proved that the isolates were representatives of a novel phylogenetic group within clade XI (Ntaya virus group) of the Flavivirus genus. This Malaysian Duck Tembusu Virus (DTMUV), named Perak virus, has moderate genomic RNA sequence similarity to a related DTMUV identified in China. In our experiment the Malaysian strain of DTMUV could be transmitted in the absence of mosquito vectors. These findings may have implications for the control and prevention of this emerging group of flaviviruses.

Brain Connectivity as a DNA Sequencing Problem

NASA Astrophysics Data System (ADS)

Zador, Anthony

The mammalian cortex consists of millions or billions of neurons, each connected to thousands of other neurons. Traditional methods for determining the brain connectivity rely on microscopy to visualize neuronal connections, but such methods are slow, labor-intensive and often lack single neuron resolution. We have recently developed a new method, MAPseq, to recast the determination of brain wiring into a form that can exploit the tremendous recent advances in high-throughput DNA sequencing. DNA sequencing technology has outpaced even Moore's law, so that the cost of sequencing the human genome has dropped from a billion dollars in 2001 to below a thousand dollars today. MAPseq works by introducing random sequences of DNA-``barcodes''-to tag neurons uniquely. With MAPseq, we can determine the connectivity of over 50K single neurons in a single mouse cortex in about a week, an unprecedented throughput, ushering in the era of ``big data'' for brain wiring. We are now developing analytical tools and algorithms to make sense of these novel data sets.

A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development.

PubMed

Yao, Zizhen; Mich, John K; Ku, Sherman; Menon, Vilas; Krostag, Anne-Rachel; Martinez, Refugio A; Furchtgott, Leon; Mulholland, Heather; Bort, Susan; Fuqua, Margaret A; Gregor, Ben W; Hodge, Rebecca D; Jayabalu, Anu; May, Ryan C; Melton, Samuel; Nelson, Angelique M; Ngo, N Kiet; Shapovalova, Nadiya V; Shehata, Soraya I; Smith, Michael W; Tait, Leah J; Thompson, Carol L; Thomsen, Elliot R; Ye, Chaoyang; Glass, Ian A; Kaykas, Ajamete; Yao, Shuyuan; Phillips, John W; Grimley, Joshua S; Levi, Boaz P; Wang, Yanling; Ramanathan, Sharad

2017-01-05

During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course. Comparisons with primary mouse and human gene expression data demonstrated rostral and caudal progenitor and neuronal identities from early brain development. Bayesian analyses inferred a unified cell-type lineage tree that bifurcates between cortical and mid/hindbrain cell types. Two methods of clonal analyses confirmed these findings and further revealed the importance of Wnt/β-catenin signaling in controlling this lineage decision. Together, these findings provide a rich transcriptome-based lineage map for studying human brain development and modeling developmental disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Exploring the brain on multiple scales with correlative two-photon and light sheet microscopy

NASA Astrophysics Data System (ADS)

Silvestri, Ludovico; Allegra Mascaro, Anna Letizia; Costantini, Irene; Sacconi, Leonardo; Pavone, Francesco S.

2014-02-01

One of the unique features of the brain is that its activity cannot be framed in a single spatio-temporal scale, but rather spans many orders of magnitude both in space and time. A single imaging technique can reveal only a small part of this complex machinery. To obtain a more comprehensive view of brain functionality, complementary approaches should be combined into a correlative framework. Here, we describe a method to integrate data from in vivo two-photon fluorescence imaging and ex vivo light sheet microscopy, taking advantage of blood vessels as reference chart. We show how the apical dendritic arbor of a single cortical pyramidal neuron imaged in living thy1-GFP-M mice can be found in the large-scale brain reconstruction obtained with light sheet microscopy. Starting from the apical portion, the whole pyramidal neuron can then be segmented. The correlative approach presented here allows contextualizing within a three-dimensional anatomic framework the neurons whose dynamics have been observed with high detail in vivo.

Serological comparison of selected isolates of Aeromonas salmonicida ssp. Salmonicida

USGS Publications Warehouse

Hahnel, G.B.; Gould, R.W.; Boatman, E.S.

1983-01-01

Eight isolates of Acronionus salmonicida ssp. salmonicida were collected during furunculosis epizootics in North American Pacific coast states and provinces. Both virulent and avirulent forms of each isolate, confirmed by challenge and electron microscopy, were examined. Serological comparisons by cross-absorption agglutination tests revealed no serological differences between isolates. Using the double diffusion precipitin test, a single band was observed when antigen from a sonicated virulent strain was reacted with antiserum against a sonicated, virulent strain absorbed with homologous, avirulent strain. The presence of the single band was eliminated by excess sonication.

Single-Fraction Versus Multifraction (3 × 9 Gy) Stereotactic Radiosurgery for Large (>2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it; IRCCS Neuromed, Pozzilli; Scaringi, Claudia

Purpose: To investigate the local control and radiation-induced brain necrosis in patients with brain metastases >2 cm in size who received single-fraction or multifraction stereotactic radiosurgery (SRS); factors associated with clinical outcomes and the development of brain radionecrosis were assessed. Methods and Materials: Two hundred eighty-nine consecutive patients with brain metastases >2.0 cm who received SRS as primary treatment at Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy, were analyzed. Cumulative incidence analysis was used to compare local control and radiation-induced brain necrosis between groups from the time of SRS. To achieve a balanced distribution of baseline covariates between treatment groups, amore » propensity score analysis was used. Results: The 1-year cumulative local control rates were 77% in the single-fraction SRS (SF-SRS) group and 91% in the multifraction SRS (MF-SRS) group (P=.01). Recurrences occurred in 25 and 11 patients who received SF-SRS or MF-SRS (P=.03), respectively. Thirty-one patients (20%) undergoing SF-SRS and 11 (8%) subjected to MF-SRS experienced brain radionecrosis (P=.004); the 1-year cumulative incidence rate of radionecrosis was 18% and 9% (P=.01), respectively. Significant differences between the 2 groups in terms of local control and risk of radionecrosis were maintained after propensity score adjustment. Conclusions: Multifraction SRS at a dose of 27 Gy in 3 daily fractions seems to be an effective treatment modality for large brain metastases, associated with better local control and a reduced risk of radiation-induced radionecrosis as compared with SF-SRS.« less

Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors.

PubMed

Delgado-Goñi, T; Martín-Sitjar, J; Simões, R V; Acosta, M; Lope-Piedrafita, S; Arús, C

2013-02-01

Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n=3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n=3) and MRSI (n=9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5-fold higher than in control mouse brain (p<0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 ± 0.58 and 4.57 ± 1.15 h, respectively. MRSI maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T(1) contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact blood-brain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors 'invisible' to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response. Copyright © 2012 John Wiley & Sons, Ltd.

512-Channel and 13-Region Simultaneous Recordings Coupled with Optogenetic Manipulation in Freely Behaving Mice

PubMed Central

Xie, Kun; Fox, Grace E.; Liu, Jun; Tsien, Joe Z.

2016-01-01

The development of technologies capable of recording both single-unit activity and local field potentials (LFPs) over a wide range of brain circuits in freely behaving animals is the key to constructing brain activity maps. Although mice are the most popular mammalian genetic model, in vivo neural recording has been traditionally limited to smaller channel count and fewer brain structures because of the mouse’s small size and thin skull. Here, we describe a 512-channel tetrode system that allows us to record simultaneously over a dozen cortical and subcortical structures in behaving mice. This new technique offers two major advantages – namely, the ultra-low cost and the do-it-yourself flexibility for targeting any combination of many brain areas. We show the successful recordings of both single units and LFPs from 13 distinct neural circuits of the mouse brain, including subregions of the anterior cingulate cortices, retrosplenial cortices, somatosensory cortices, secondary auditory cortex, hippocampal CA1, dentate gyrus, subiculum, lateral entorhinal cortex, perirhinal cortex, and prelimbic cortex. This 512-channel system can also be combined with Cre-lox neurogenetics and optogenetics to further examine interactions between genes, cell types, and circuit dynamics across a wide range of brain structures. Finally, we demonstrate that complex stimuli – such as an earthquake and fear-inducing foot-shock – trigger firing changes in all of the 13 brain regions recorded, supporting the notion that neural code is highly distributed. In addition, we show that localized optogenetic manipulation in any given brain region could disrupt network oscillations and caused changes in single-unit firing patterns in a brain-wide manner, thereby raising the cautionary note of the interpretation of optogenetically manipulated behaviors. PMID:27378865

Volume estimation of brain abnormalities in MRI data

NASA Astrophysics Data System (ADS)

Suprijadi, Pratama, S. H.; Haryanto, F.

2014-02-01

The abnormality of brain tissue always becomes a crucial issue in medical field. This medical condition can be recognized through segmentation of certain region from medical images obtained from MRI dataset. Image processing is one of computational methods which very helpful to analyze the MRI data. In this study, combination of segmentation and rendering image were used to isolate tumor and stroke. Two methods of thresholding were employed to segment the abnormality occurrence, followed by filtering to reduce non-abnormality area. Each MRI image is labeled and then used for volume estimations of tumor and stroke-attacked area. The algorithms are shown to be successful in isolating tumor and stroke in MRI images, based on thresholding parameter and stated detection accuracy.

[Electron microscopic study of the An-750 strain of Powassan virus isolated in the Soviet Union].

PubMed

Sobolev, S G; Shestopalova, N M; Linev, M B; Rubin, S G

1978-01-01

Electron microscopic examinations of brains of white mice inoculated with the An 750 strain isolated for the first time from adult mosquitoes and with the prototype LB strain of Powassan virus were carried out. The method of combination of light and electron microscopy used in the study permitted to compare ultrastructural changes in one cell with the results of light microscopy. Sizes of virions and their localizations in the brain cells were determined. Virus particles were found in large and small neurons as well as in glial elements. Subcellular changes in neurons associated with virus multiplication are described. The causes of differences in sizes of virions measured in ultrathin sections are discussed.

Isolated, relative aproverbia without focal lesion.

PubMed

Brown, Cora; Smith-Benjamin, Sarah; Patira, Riddhi; Altschuler, Eric L

2016-06-01

We have seen a patient with a profound, isolated, and quite selective deficit in proverb interpretation-aproverbia. The patient presented to us after an anoxic brain injury with aproverbia. Interestingly, the aproverbia appeared to be premorbid to the presenting event. Furthermore, the patient had no brain lesion that has been associated or even proposed as a cause of deficit in proverb or metaphor interpretation. The patient did have acute bilateral hippocampi lesions and associated severe anterograde amnesia, but he retained good retrograde memory with which he is able to give good, logical but concrete explanations for proverbs. This case highlights the need, importance, and interest in further neuropsychologic, imaging and functional studies of proverb and interpretation in patients and normal subjects populations.

Molecular vibrations in metal-single-molecule-metal junctions

NASA Astrophysics Data System (ADS)

Yokota, Kazumichi; Taniguchi, Masateru; Kawai, Tomoji

2010-03-01

Molecular vibrations in a metal-single-molecule-metal junction were studied based on density functional theory using a single benzenedithiolate molecule connected between gold clusters. We found that the difference in vibrational energy between an isolated benzenedithiol and the single-molecule junction is less than 3% in the energy range above 540 cm -1, where sulfur atoms contribute little to molecular vibrations. The finding implies that we can predict the peak energy in the inelastic electron tunneling spectrum of the single-molecule junction in the high energy range by vibrational analyses of isolated molecules.

A prokaryotic viral sequence is expressed and conserved in mammalian brain.

PubMed

Yeh, Yang-Hui; Gunasekharan, Vignesh; Manuelidis, Laura

2017-07-03

A natural and permanent transfer of prokaryotic viral sequences to mammals has not been reported by others. Circular "SPHINX" DNAs <5 kb were previously isolated from nuclease-protected cytoplasmic particles in rodent neuronal cell lines and brain. Two of these DNAs were sequenced after Φ29 polymerase amplification, and they revealed significant but imperfect homology to segments of commensal Acinetobacter phage viruses. These findings were surprising because the brain is isolated from environmental microorganisms. The 1.76-kb DNA sequence (SPHINX 1.8), with an iteron before its ORF, was evaluated here for its expression in neural cells and brain. A rabbit affinity purified antibody generated against a peptide without homology to mammalian sequences labeled a nonglycosylated ∼41-kDa protein (spx1) on Western blots, and the signal was efficiently blocked by the competing peptide. Spx1 was resistant to limited proteinase K digestion, but was unrelated to the expression of host prion protein or its pathologic amyloid form. Remarkably, spx1 concentrated in selected brain synapses, such as those on anterior motor horn neurons that integrate many complex neural inputs. SPHINX 1.8 appears to be involved in tissue-specific differentiation, including essential functions that preserve its propagation during mammalian evolution, possibly via maternal inheritance. The data here indicate that mammals can share and exchange a larger world of prokaryotic viruses than previously envisioned.

A radioimmunoassay for ependymins beta and gamma: two goldfish brain proteins involved in behavioral plasticity.

PubMed

Schmidt, R; Shashoua, V E

1981-04-01

A radioimmunoassay (RIA) using 125I-labeled antigen was developed for the quantitative determination of two goldfish brain proteins (ependymins beta and gamma). The proteins were isolated from the cerebrospinal fluid (CSF) and cells of the ependymal zone surrounding goldfish brain ventricles. The turnover rates of beta and gamma were previously shown to be specifically enhanced after the animals successfully acquired a new pattern of swimming behavior. Femtomole quantities of ependymin beta were measurable by the RIA. In applications of the assay, beta and gamma ependymins were found to have common immunological properties, since 125I-beta-antigen bound to antibody could be displaced by unlabeled ependymin gamma as well as ependymin beta but not by a variety of other proteins including several purified glycoproteins isolated from goldfish brain. The ependymins were shown to constitute 14% of the total protein content of the brain extracellular fluid and also to be present as a minor component of the serum proteins (0.3%). Ependymins beta and gamma have an immunological reactivity in these fractions that can be increased by a factor of 30 on heating. The data suggest that the antigenicity of the molecules is highly masked, and that it may require some unraveling of the quaternary structure of the proteins before maximal interaction with the antisera becomes possible.

Heterogeneity of the calcium-induced permeability transition in isolated non-synaptic brain mitochondria.

PubMed

Kristián, Tibor; Weatherby, Tina M; Bates, Timothy E; Fiskum, Gary

2002-12-01

Calcium overload of neural cell mitochondria plays a key role in excitotoxic and ischemic brain injury. This study tested the hypothesis that brain mitochondria consist of subpopulations with differential sensitivity to calcium-induced inner membrane permeability transition, and that this sensitivity is greatly reduced by physiological levels of adenine nucleotides. Isolated non-synaptosomal rat brain mitochondria were incubated in a potassium-based medium in the absence or presence of ATP or ADP. Measurements were made of medium and intramitochondrial free calcium, light scattering, mitochondrial ultrastructure, and the elemental composition of electron-opaque deposits within mitochondria treated with calcium. In the absence of adenine nucleotides, calcium induced a partial decrease in light scattering, accompanied by three distinct ultrastructural morphologies, including large-amplitude swelling, matrix vacuolization and a normal appearance. In the presence of ATP or ADP the mitochondrial calcium uptake capacity was greatly enhanced and calcium induced an increase rather than a decrease in mitochondrial light scattering. Approximately 10% of the mitochondria appeared damaged and the rest contained electron-dense precipitates that contained calcium, as determined by electron-energy loss spectroscopy. These results indicate that brain mitochondria are heterogeneous in their response to calcium. In the absence of adenine nucleotides, approximately 20% of the mitochondrial population exhibit morphological alterations consistent with activation of the permeability transition, but less than 10% exhibit evidence of osmotic swelling and membrane disruption in the presence of ATP or ADP.

Comparison of HIV-1 pol and env sequences of blood, CSF, brain and spleen isolates collected ante-mortem and post-mortem.

PubMed

Caragounis, E-C; Gisslén, M; Lindh, M; Nordborg, C; Westergren, S; Hagberg, L; Svennerholm, B

2008-02-01

HIV-1 infects the central nervous system (CNS) early in the course of infection. However, it is not known to what extent the virus evolves independently within the CNS and whether the HIV-RNA in cerebrospinal fluid (CSF) reflects the viral population replicating within the brain parenchyma or the systemic infection. The aim of this study was to investigate HIV-1 evolution in the CNS and the origin of HIV-1 in CSF. Longitudinally derived paired blood and CSF samples and post-mortem samples from CSF, brain and spleen were collected over a period of up to 63 months from three HIV-1 infected men receiving antiretroviral treatment and presenting with symptoms of AIDS dementia complex (ADC). Phylogenetic analyses of HIV-1 V3, reverse transcriptase (RT) and protease sequences from patient isolates suggest compartmentalization with distinct viral strains in blood, CSF and brain. We found a different pattern of RT and accessory protease mutations in the systemic infection compared to the CNS. We conclude that HIV-1 may to some extent evolve independently in the CNS and the viral population in CSF mainly reflects the infection in the brain parenchyma in patients with ADC. This is of importance in understanding HIV pathogenesis and can have implications on treatment of HIV-1 patients.

Selective impairment of facial recognition due to a haematoma restricted to the right fusiform and lateral occipital region

PubMed Central

Wada, Y; Yamamoto, T

2001-01-01

A 67 year old right handed Japanese man developed prosopagnosia caused by a haemorrhage. His only deficit was the inability to perceive and discriminate unfamiliar faces, and to recognise familiar faces. He did not show deficits in visual or visuospatial perception of non-facial stimuli, alexia, visual agnosia, or topographical disorientation. Brain MRI showed a haematoma limited to the right fusiform and the lateral occipital region. Single photon emission computed tomography confirmed that there was no decreased blood flow in the opposite left cerebral hemisphere. The present case indicates that a well placed small right fusiform gyrus and the adjacent area can cause isolated impairment of facial recognition. As far as we know, there has been no published case that has demonstrated this exact lesion site, which was indicated by recent functional MRI studies as the most critical area in facial recognition.

 PMID:11459906

Neural signal registration and analysis of axons grown in microchannels

NASA Astrophysics Data System (ADS)

Pigareva, Y.; Malishev, E.; Gladkov, A.; Kolpakov, V.; Bukatin, A.; Mukhina, I.; Kazantsev, V.; Pimashkin, A.

2016-08-01

Registration of neuronal bioelectrical signals remains one of the main physical tools to study fundamental mechanisms of signal processing in the brain. Neurons generate spiking patterns which propagate through complex map of neural network connectivity. Extracellular recording of isolated axons grown in microchannels provides amplification of the signal for detailed study of spike propagation. In this study we used neuronal hippocampal cultures grown in microfluidic devices combined with microelectrode arrays to investigate a changes of electrical activity during neural network development. We found that after 5 days in vitro after culture plating the spiking activity appears first in microchannels and on the next 2-3 days appears on the electrodes of overall neural network. We conclude that such approach provides a convenient method to study neural signal processing and functional structure development on a single cell and network level of the neuronal culture.

Polymorphisms in the microglial marker molecule CX3CR1 affect the blood volume of the human brain.

PubMed

Sakai, Mai; Takeuchi, Hikaru; Yu, Zhiqian; Kikuchi, Yoshie; Ono, Chiaki; Takahashi, Yuta; Ito, Fumiaki; Matsuoka, Hiroo; Tanabe, Osamu; Yasuda, Jun; Taki, Yasuyuki; Kawashima, Ryuta; Tomita, Hiroaki

2018-06-01

CX3CR1, a G-protein-coupled receptor, is involved in various inflammatory processes. Two non-synonymous single nucleotide polymorphisms, V249I (rs3732379) and T280M (rs3732378), are located in the sixth and seventh transmembrane domains of the CX3CR1 protein, respectively. Previous studies have indicated significant associations between T280M and leukocyte functional characteristics, including adhesion, signaling, and chemotaxis, while the function of V249I is unclear. In the brain, microglia are the only proven and widely accepted CX3CR1-expressing cells. This study aimed to specify whether there were specific brain regions on which these two single nucleotide polymorphisms exert their biological impacts through their functional effects on microglia. Associations between the single nucleotide polymorphisms and brain characteristics, including gray and white matter volumes, white matter integrity, resting arterial blood volume, and cerebral blood flow, were evaluated among 1300 healthy Japanese individuals. The major allele carriers (V249 and T280) were significantly associated with an increased total arterial blood volume of the whole brain, especially around the bilateral precuneus, left posterior cingulate cortex, and left posterior parietal cortex. There were no significant associations between the genotypes and other brain structural indicators. This finding suggests that the CX3CR1 variants may affect arterial structures in the brain, possibly via interactions between microglia and brain microvascular endothelial cells. © 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

Single-ring ablation compared with standard circumferential pulmonary vein isolation using remote magnetic catheter navigation.

PubMed

Sohns, Christian; Bergau, Leonard; Seegers, Joachim; Lüthje, Lars; Vollmann, Dirk; Zabel, Markus

2014-10-01

In ablation of atrial fibrillation, the single-ring method aims for isolation of the posterior wall of the left atrium (LA) including the pulmonary veins (PVs) but avoiding posterior LA lesions. The aim of this randomized prospective study was to evaluate safety and efficacy of remote magnetic navigation (RMN)-guided single-ring ablation strategy as compared to standard RMN-guided circumferential PV ablation (PVA). Eighty consecutive patients undergoing PVA were enrolled prospectively and randomized equally into two study groups. RMN using the Stereotaxis system and open-irrigated 3.5-mm ablation catheters were used with a 3D mapping system in all procedures. Forty patients underwent RMN-guided single-ring ablation, and 40 patients received RMN-guided circumferential PVA. In the circumferential group, 3.3 ± 1.1 PVs were successfully isolated at the end of the procedure as compared to 3.1 ± 1.3 in the single-ring (box) group (p=0.38). All patients in the box group required additional posterior lesions in order to achieve electrical isolation of the PVs. Single-ring ablation was associated with longer procedure duration (p=0.01) and ablation time (p=0.001). After a single procedure, the proportion of patients free of any atrial tachycardia (AT)/atrial fibrillation (AF) episode at 12-month follow-up was 57 % in the box group and 58 % in the circ group. Using RMN, only minor complications have been observed. RMN-guided single-ring PVA provides comparable acute and long-term success rates as compared to RMN-guided circumferential PVA but requires additional posterior lesions to achieve PV isolation and increased procedure and ablation time. Procedural complication rates are low when using RMN.

[The establishment of the immortalized mouse brain microvascular pericytes model and its preliminary application in screening of cerebrovascular toxicants].

PubMed

Zhao, H P; Gao, Y F; Xia, D; Zhao, Z Q; Wu, S; Wang, X H; Liu, H X; Xiao, C; Xing, X M; He, Y

2018-05-06

Objective: To establish the immortalized mouse brain microvascular pericytes model and to apply to the cerebrovascular toxicants screening study. Methods: Brain pericytes were isolated from 3 weeks of mice by tissue digestion. Immortalized pericyte cell line was constructed by infecting with LT retrovirus. Monoclone was selected to purify the immortalized pericyte cell line. The pericyte characteristics and purity were explored by immunocytochemistry. Cell proliferation was measured by using the Pomega MTS cell Proliferation Colorimetric Assay Kit. Pericytes were treated with 0, 160, 320, 640, 1 280, 2 560 μmol/L lead acetate, 0, 5, 10, 20, 40, 80 μmol/L cadmium chloride and 0, 5, 10, 20, 40, 80 μmol/L sodium arsenite in 24 hours. Cell toxicity of each group was determined by MTS assay, median lethal dose (LD(50)) was calculated in linear regression. Results: Mouse brain pericytes were successfully isolated by tissue separation and enzyme digestion method. After immortalized by LT retroviruses, monoclone was selected and expanded to establish pericyte cell line. The brain pericytes exhibited typical long spindle morphology and positive staining for α-SMA and Vimentin. The proliferation of brain pericytes cell lines was very slowly, and the doubling time was about 48 hours. The proliferation of immortalized brain pericytes cell lines was very quickly, and the doubling time was about 24 hours. After lead acetate, cadmium chloride and sodium arsenite treatment for 24 hours respectively, gradual declines in cell viability were observed. The LD(50) of lead acetate was 2 025.0 μmol/L, the LD(50) of cadmium chloride was 36.6 μmol/L, and the LD(50) of sodium arsenite was 33.2 μmol/L. Conclusion: The immortalized mouse brain microvascular pericyte model is established successfully by infecting with LT retrovirus, and can be applied to screen cerebrovascular toxicants. The toxicity of these toxicants to immortalized mouse brain microvascular pericyte is in sequence: sodium arsenite,cadmium chloride, lead acetate.

Listening to humans walking together activates the social brain circuitry.

PubMed

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.

Single unit approaches to human vision and memory.

PubMed

Kreiman, Gabriel

2007-08-01

Research on the visual system focuses on using electrophysiology, pharmacology and other invasive tools in animal models. Non-invasive tools such as scalp electroencephalography and imaging allow examining humans but show a much lower spatial and/or temporal resolution. Under special clinical conditions, it is possible to monitor single-unit activity in humans when invasive procedures are required due to particular pathological conditions including epilepsy and Parkinson's disease. We review our knowledge about the visual system and visual memories in the human brain at the single neuron level. The properties of the human brain seem to be broadly compatible with the knowledge derived from animal models. The possibility of examining high-resolution brain activity in conscious human subjects allows investigators to ask novel questions that are challenging to address in animal models.

Nursing benefits of using an automated injection system for ictal brain single photon emission computed tomography.

PubMed

Vonhofen, Geraldine; Evangelista, Tonya; Lordeon, Patricia

2012-04-01

The traditional method of administering radioactive isotopes to pediatric patients undergoing ictal brain single photon emission computed tomography testing has been by manual injections. This method presents certain challenges for nursing, including time requirements and safety risks. This quality improvement project discusses the implementation of an automated injection system for isotope administration and its impact on staffing, safety, and nursing satisfaction. It was conducted in an epilepsy monitoring unit at a large urban pediatric facility. Results of this project showed a decrease in the number of nurses exposed to radiation and improved nursing satisfaction with the use of the automated injection system. In addition, there was a decrease in the number of nursing hours required during ictal brain single photon emission computed tomography testing.

Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine-to-glutamate ratio and myo-inositol concentration in the mouse frontal cortex.

PubMed

Corcoba, Alberto; Gruetter, Rolf; Do, Kim Q; Duarte, João M N

2017-09-01

Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cysteine ligase modulatory subunit (Gclm) was exposed to social isolation stress from weaning to post-natal day 65. Using magnetic resonance methods at high-field (14.1 T), we analysed the neurochemical profile in the frontal cortex, brain size and ventricular volume of adult animals. Glutathione deficit was accompanied by elevated concentrations of N-acetylaspartate, alanine, and glutamine, as well as the ratio of glutamine-to-glutamate (Gln/Glu), and by a reduction in levels of myo-inositol and choline-containing compounds in the frontal cortex of -/- animals with respect to wild-type littermates. Although there was no significant interaction between social isolation stress and glutathione deficiency, mice reared in isolation displayed lower myo-inositol concentration (-8.4%, p < 0.05) and larger Gln/Glu (+7.6%, p < 0.05), relative to those in group housing. Furthermore, glutathione deficiency caused a reduction in whole brain volume and enlargement of ventricles, but social isolation had no effect on these parameters. We conclude that social isolation caused neurochemical alterations that may add to those associated to impaired glutathione synthesis. © 2017 International Society for Neurochemistry.

The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles.

PubMed

Barrett, C E; Arambula, S E; Young, L J

2015-07-21

Genes and social experiences interact to create variation in social behavior and vulnerability to develop disorders of the social domain. Socially monogamous prairie voles display remarkable diversity in neuropeptide receptor systems and social behavior. Here, we examine the interaction of early-life adversity and brain oxytocin receptor (OTR) density on adult social attachment in female prairie voles. First, pups were isolated for 3 h per day, or unmanipulated, from postnatal day 1-14. Adult subjects were tested on the partner preference (PP) test to assess social attachment and OTR density in the brain was quantified. Neonatal social isolation impaired female PP formation, without affecting OTR density. Accumbal OTR density was, however, positively correlated with the percent of time spent huddling with the partner in neonatally isolated females. Females with high accumbal OTR binding were resilient to neonatal isolation. These results are consistent with the hypothesis that parental nurturing shapes neural systems underlying social relationships by enhancing striatal OTR signaling. Thus, we next determined whether early touch, mimicking parental licking and grooming, stimulates hypothalamic OT neuron activity. Tactile stimulation induced immediate-early gene activity in OT neurons in neonates. Finally, we investigated whether pharmacologically potentiating OT release using a melanocortin 3/4 agonist, melanotan-II (10 mg kg(-1) subcutaneously), would mitigate the social isolation-induced impairments in attachment behavior. Neonatal melanotan-II administration buffered against the effects of early isolation on partner preference formation. Thus, variation in accumbal OTR density and early OT release induced by parental nurturing may moderate susceptibility to early adverse experiences, including neglect.

Cell-cell interactions of isolated and cultured oligodendrocytes: formation of linear occluding junctions and expression of peculiar intramembrane particles.

PubMed

Massa, P T; Szuchet, S; Mugnaini, E

1984-12-01

Oligodendrocytes were isolated from lamb brain. Freshly isolated cells and cultured cells, either 1- to 4-day-old unattached or 1- to 5-week-old attached, were examined by thin section and freeze-fracture electron microscopy. Freeze-fracture of freshly isolated oligodendrocytes showed globular and elongated intramembrane particles similar to those previously described in oligodendrocytes in situ. Enrichment of these particles was seen at sites of inter-oligodendrocyte contact. Numerous gap junctions and scattered linear tight junctional arrays were apparent. Gap junctions were connected to blebs of astrocytic plasma membrane sheared off during isolation, whereas tight junctions were facing extracellular space or blebs of oligodendrocytic plasma membrane. Thin sections of cultured, unattached oligodendrocytes showed rounded cell bodies touching one another at points without forming specialized cell junctions. Cells plated on polylysine-coated aclar dishes attached, emanated numerous, pleomorphic processes, and expressed galactocerebroside and myelin basic protein, characteristic markers for oligodendrocytes. Thin sections showed typical oligodendrocyte ultrastructure but also intermediate filaments not present in unattached cultures. Freeze-fracture showed intramembrane particles similar to but more numerous, and with a different fracture face repartition, than those seen in oligodendrocytes, freshly isolated or in situ. Gap junctions were small and rare. Apposed oligodendrocyte plasma membrane formed linear tight junctions which became more numerous with time in culture. Thus, cultured oligodendrocytes isolated from ovine brains develop and maintain features characteristic of mature oligodendrocytes in situ and can be used to explore formation and maintenance of tight junctions and possibly other classes of cell-cell interactions important in the process of myelination.

High Incidence of Pathogenic Streptococcus agalactiae ST485 Strain in Pregnant/Puerperal Women and Isolation of Hyper-Virulent Human CC67 Strain

PubMed Central

Li, Liping; Wang, Rui; Huang, Yan; Huang, Ting; Luo, Fuguang; Huang, Weiyi; Yang, Xiuying; Lei, Aiying; Chen, Ming; Gan, Xi

2018-01-01

Group B streptococcus (GBS) is the major pathogen causing diseases in neonates, pregnant/puerperal women, cows and fish. Recent studies have shown that GBS may be infectious across hosts and some fish GBS strain might originate from human. The purpose of this study is to investigate the genetic relationship of CC103 strains that recently emerged in cows and humans, and explore the pathogenicity of clinical GBS isolates from human to tilapia. Ninety-two pathogenic GBS isolates were identified from 19 patients with different diseases and their evolution and pathogenicity to tilapia were analyzed. The multilocus sequence typing revealed that clonal complex (CC) 103 strain was isolated from 21.74% (20/92) of patients and ST485 strain was from 14.13% (13/92) patients with multiple diseases including neonates. Genomic evolution analysis showed that both bovine and human CC103 strains alternately form independent evolutionary branches. Three CC67 isolates carried gbs2018-C gene and formed one evolutionary branch with ST61 and ST67 strains that specifically infect dairy cows. Studies of interspecies transmission to tilapia found that 21/92 (22.83%) isolates including all ST23 isolates were highly pathogenic to tilapia and demonstrated that streptococci could break through the blood-brain barrier into brain tissue. In conclusions, CC103 strains are highly prevalent among pathogenic GBS from humans and have evolved into the highly pathogenic ST485 strains specifically infecting humans. The CC67 strains isolated from cows are able to infect humans through evolutionary events of acquiring CC17-specific type C gbs2018 gene and others. Human-derived ST23 pathogenic GBS strains are highly pathogenic to tilapia. PMID:29467722

Isolation of viable Toxoplasma gondii from guinea fowl (Numida meleagris) and rabbits from Brazil

USDA-ARS?s Scientific Manuscript database

Toxoplasma gondii was isolated from a feral guinea fowl (Numida meleagris) and domestic rabbits from Brazil for the first time. Serum and brains from 10 guinea fowl and 21 rabbits from Brazil were examined for T. gondii infection. Antibodies to T. gondii were found in 2 of 10 fowl and 2 of 21 rabbit...

"Relating through sameness": a qualitative study of friendship and social isolation in chronic traumatic brain injury.

PubMed

Salas, Christian E; Casassus, Martin; Rowlands, Leanne; Pimm, Steve; Flanagan, Desmond A J

2016-11-01

Social isolation has been described as a common problem among traumatic brain injury (TBI) survivors during the chronic phase. Due to physical, cognitive and behavioural changes, survivors become less socially active and experience a marked decrease in the number of friends. The goal of this investigation is to explore TBI survivors' subjective account of the challenges encountered in sustaining friendships, as well as gaining insight into their particular understanding of such difficulties. Using a thematic analysis approach, 11 survivors of TBI were interviewed in relation to their experience of social isolation and friendship during the chronic stage. Four main themes emerged from the interviews: (1) The impact of long-term cognitive and behavioural problems on relationships; (2) Loss of old friends; (3) Difficulties making new friends, and (4) Relating to other survivors in order to fight social isolation (sameness). Clinical implications of these findings, as well as their relevance in the design of long-term rehabilitation programmes, are discussed. Particular emphasis is placed on the need to acknowledge the value of relating to other survivors, as a way of resisting cultural discourses about disability, and as a source of self-cohesion in the process of identity re-construction.

Phenotypic variation in a significant spore character in Kudoa (Myxosporea: Multivalvulida) species infecting brain tissue.

PubMed

Burger, Mieke A A; Adlard, Robert D

2010-10-01

Some Kudoa species display variations in the number of polar capsules in spores within an individual pseudocyst. Nonetheless, there is usually a dominant morphotype which forms a significant element of diagnosis. In 2007, a Kudoa isolate from whiting (spores with 5 (dominant) or 6 (minor) polar capsules) was characterized by Burger et al. (2007) as being 100% identical in SSU rDNA to Kudoa yasunagai (spores with 7 polar capsules) from a halibut, despite its obvious morphological differences. The authors hypothesized that either SSU rDNA had reached its level of resolution or that the genetic identity revealed conspecificity. To further investigate these hypotheses, SSU and LSU rDNA sequence data were coupled with principal components, correlation, and regression analyses of morphometric data from different kudoid isolates that infect brain tissue to determine the relationships between spore morphotypes and different kudoid isolates. The trends in morphometrics between the spores of particular isolates were so similar that it was concluded that the molecular results did indicate conspecificity rather than SSU reaching its level of resolution. This phenotypic influence on a significant diagnostic character within the Kudoidae has a major impact on the diagnosis of this, and potentially other, pathogenic species.

Rapid eye movement sleep behaviour disorder symptomatic of a brain stem cavernoma.

PubMed

Felix, Sandra; Thobois, Stephane; Peter-Derex, Laure

2016-04-01

A 75-year-old man complained of excessive daytime sleepiness (EDS), difficulty falling asleep and nocturnal agitation during sleep. Restless legs syndrome (RLS) was diagnosed and treated. Because of persistent EDS, snoring and nycturia, a nocturnal polysomnography (PSG) was performed. PSG showed high sleep fragmentation related to a moderate to severe obstructive sleep apnea syndrome. Continuous positive airway pressure treatment (CPAP) was proposed. Because of the persistence of abnormal nocturnal behaviours, characterized by screaming, punching and falling out of bed, a video-PSG with CPAP treatment was performed. The recording showed typical chin electromyography (EMG) activity increase associated with violent movements during rapid eye movement (REM) sleep, suggesting REM sleep behaviour disorders (RBD). Clinical neurological examination found no parkinsonian syndrome, no dysautonomic sign and no neurological focal sign. Dopamine transporter imaging [123I-FP-CIT single photon emission computed tomography (SPECT)] did not find any presynaptic dopaminergic pathways degeneration. Brain magnetic resonance imaging showed a vascular lesion suggestive of cavernoma located in the pons. The present case illustrates the complexity of sleep disturbance diagnosis with a possible entanglement of aetiologies responsible for nocturnal agitation, and confirms that an isolated pons cavernoma should be considered among the rare causes of RBD. © 2016 European Sleep Research Society.

MYELIN IN THE CENTRAL NERVOUS SYSTEM AS OBSERVED IN EXPERIMENTALLY INDUCED EDEMA IN THE RAT

PubMed Central

Hirano, Asao; Zimmerman, H. M.; Levine, Seymour

1966-01-01

The compact arrangement of cells in the normal white matter of the brain makes an analysis of cellular architecture difficult. To overcome this difficulty, cerebral edema was induced in rats by means of the unilateral intracerebral implantation of silver nitrate. Within 48 hr, the brains were fixed by perfusion with glutaraldehyde followed by immersion in Dalton's chrome-osmium. Sections of the callosal radiations were studied in the electron microscope. The untreated hemisphere appeared entirely unaltered, whereas in the edematous hemisphere the edema fluid separated individual cell processes and small groups of them. The myelin sheaths and their relationships to the axons appeared essentially unaltered. In this material, analysis of cellular architecture was relatively easy, and the widely held theory of spiral wrapping could be confirmed. In addition, several other aspects of the myelin and myelin-forming cell relationships became apparent in the edematous tissue. Most of these were later confirmed by extensive and careful study of the nonedematous tissue. These included the presence of occasional isolated cytoplasmic areas in myelin and the presence of two complete sheaths around a single axon. Other observations, such as the appearance of mitochondria and dense bodies within the outer loop and the separation of myelin lamellae, are apparently limited to the edematous tissue. PMID:5971641

Mesh electronics: a new paradigm for tissue-like brain probes.

PubMed

Hong, Guosong; Yang, Xiao; Zhou, Tao; Lieber, Charles M

2018-06-01

Existing implantable neurotechnologies for understanding the brain and treating neurological diseases have intrinsic properties that have limited their capability to achieve chronically-stable brain interfaces with single-neuron spatiotemporal resolution. These limitations reflect what has been dichotomy between the structure and mechanical properties of living brain tissue and non-living neural probes. To bridge the gap between neural and electronic networks, we have introduced the new concept of mesh electronics probes designed with structural and mechanical properties such that the implant begins to 'look and behave' like neural tissue. Syringe-implanted mesh electronics have led to the realization of probes that are neuro-attractive and free of the chronic immune response, as well as capable of stable long-term mapping and modulation of brain activity at the single-neuron level. This review provides a historical overview of a 10-year development of mesh electronics by highlighting the tissue-like design, syringe-assisted delivery, seamless neural tissue integration, and single-neuron level chronic recording stability of mesh electronics. We also offer insights on unique near-term opportunities and future directions for neuroscience and neurology that now are available or expected for mesh electronics neurotechnologies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Long-term neural and physiological phenotyping of a single human

PubMed Central

Poldrack, Russell A.; Laumann, Timothy O.; Koyejo, Oluwasanmi; Gregory, Brenda; Hover, Ashleigh; Chen, Mei-Yen; Gorgolewski, Krzysztof J.; Luci, Jeffrey; Joo, Sung Jun; Boyd, Ryan L.; Hunicke-Smith, Scott; Simpson, Zack Booth; Caven, Thomas; Sochat, Vanessa; Shine, James M.; Gordon, Evan; Snyder, Abraham Z.; Adeyemo, Babatunde; Petersen, Steven E.; Glahn, David C.; Reese Mckay, D.; Curran, Joanne E.; Göring, Harald H. H.; Carless, Melanie A.; Blangero, John; Dougherty, Robert; Leemans, Alexander; Handwerker, Daniel A.; Frick, Laurie; Marcotte, Edward M.; Mumford, Jeanette A.

2015-01-01

Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders. PMID:26648521

Single photon emission computed tomography and positron emission tomography imaging of multi-drug resistant P-glycoprotein--monitoring a transport activity important in cancer, blood-brain barrier function and Alzheimer's disease.

PubMed

Piwnica-Worms, David; Kesarwala, Aparna H; Pichler, Andrea; Prior, Julie L; Sharma, Vijay

2006-11-01

Overexpression of multi-drug resistant P-glycoprotein (Pgp) remains an important barrier to successful chemotherapy in cancer patients and impacts the pharmacokinetics of many important drugs. Pgp is also expressed on the luminal surface of brain capillary endothelial cells wherein Pgp functionally comprises a major component of the blood-brain barrier by limiting central nervous system penetration of various therapeutic agents. In addition, Pgp in brain capillary endothelial cells removes amyloid-beta from the brain. Several single photon emission computed tomography and positron emission tomography radiopharmaceutical have been shown to be transported by Pgp, thereby enabling the noninvasive interrogation of Pgp-mediated transport activity in vivo. Therefore, molecular imaging of Pgp activity may enable noninvasive dynamic monitoring of multi-drug resistance in cancer, guide therapeutic choices in cancer chemotherapy, and identify transporter deficiencies of the blood-brain barrier in Alzheimer's disease.

The Theory of Localist Representation and of a Purely Abstract Cognitive System: The Evidence from Cortical Columns, Category Cells, and Multisensory Neurons.

PubMed

Roy, Asim

2017-01-01

The debate about representation in the brain and the nature of the cognitive system has been going on for decades now. This paper examines the neurophysiological evidence, primarily from single cell recordings, to get a better perspective on both the issues. After an initial review of some basic concepts, the paper reviews the data from single cell recordings - in cortical columns and of category-selective and multisensory neurons. In neuroscience, columns in the neocortex (cortical columns) are understood to be a basic functional/computational unit. The paper reviews the fundamental discoveries about the columnar organization and finds that it reveals a massively parallel search mechanism. This columnar organization could be the most extensive neurophysiological evidence for the widespread use of localist representation in the brain. The paper also reviews studies of category-selective cells. The evidence for category-selective cells reveals that localist representation is also used to encode complex abstract concepts at the highest levels of processing in the brain. A third major issue is the nature of the cognitive system in the brain and whether there is a form that is purely abstract and encoded by single cells. To provide evidence for a single-cell based purely abstract cognitive system, the paper reviews some of the findings related to multisensory cells. It appears that there is widespread usage of multisensory cells in the brain in the same areas where sensory processing takes place. Plus there is evidence for abstract modality invariant cells at higher levels of cortical processing. Overall, that reveals the existence of a purely abstract cognitive system in the brain. The paper also argues that since there is no evidence for dense distributed representation and since sparse representation is actually used to encode memories, there is actually no evidence for distributed representation in the brain. Overall, it appears that, at an abstract level, the brain is a massively parallel, distributed computing system that is symbolic. The paper also explains how grounded cognition and other theories of the brain are fully compatible with localist representation and a purely abstract cognitive system.

The Theory of Localist Representation and of a Purely Abstract Cognitive System: The Evidence from Cortical Columns, Category Cells, and Multisensory Neurons

PubMed Central

Roy, Asim

2017-01-01

The debate about representation in the brain and the nature of the cognitive system has been going on for decades now. This paper examines the neurophysiological evidence, primarily from single cell recordings, to get a better perspective on both the issues. After an initial review of some basic concepts, the paper reviews the data from single cell recordings – in cortical columns and of category-selective and multisensory neurons. In neuroscience, columns in the neocortex (cortical columns) are understood to be a basic functional/computational unit. The paper reviews the fundamental discoveries about the columnar organization and finds that it reveals a massively parallel search mechanism. This columnar organization could be the most extensive neurophysiological evidence for the widespread use of localist representation in the brain. The paper also reviews studies of category-selective cells. The evidence for category-selective cells reveals that localist representation is also used to encode complex abstract concepts at the highest levels of processing in the brain. A third major issue is the nature of the cognitive system in the brain and whether there is a form that is purely abstract and encoded by single cells. To provide evidence for a single-cell based purely abstract cognitive system, the paper reviews some of the findings related to multisensory cells. It appears that there is widespread usage of multisensory cells in the brain in the same areas where sensory processing takes place. Plus there is evidence for abstract modality invariant cells at higher levels of cortical processing. Overall, that reveals the existence of a purely abstract cognitive system in the brain. The paper also argues that since there is no evidence for dense distributed representation and since sparse representation is actually used to encode memories, there is actually no evidence for distributed representation in the brain. Overall, it appears that, at an abstract level, the brain is a massively parallel, distributed computing system that is symbolic. The paper also explains how grounded cognition and other theories of the brain are fully compatible with localist representation and a purely abstract cognitive system. PMID:28261127

Defect Effects on TiO2 Nanosheets: Stabilizing Single Atomic Site Au and Promoting Catalytic Properties.

PubMed

Wan, Jiawei; Chen, Wenxing; Jia, Chuanyi; Zheng, Lirong; Dong, Juncai; Zheng, Xusheng; Wang, Yu; Yan, Wensheng; Chen, Chen; Peng, Qing; Wang, Dingsheng; Li, Yadong

2018-03-01

Isolated single atomic site catalysts have attracted great interest due to their remarkable catalytic properties. Because of their high surface energy, single atoms are highly mobile and tend to form aggregate during synthetic and catalytic processes. Therefore, it is a significant challenge to fabricate isolated single atomic site catalysts with good stability. Herein, a gentle method to stabilize single atomic site metal by constructing defects on the surface of supports is presented. As a proof of concept, single atomic site Au supported on defective TiO 2 nanosheets is prepared and it is discovered that (1) the surface defects on TiO 2 nanosheets can effectively stabilize Au single atomic sites through forming the Ti-Au-Ti structure; and (2) the Ti-Au-Ti structure can also promote the catalytic properties through reducing the energy barrier and relieving the competitive adsorption on isolated Au atomic sites. It is believed that this work paves a way to design stable and active single atomic site catalysts on oxide supports. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The prostaglandin E2 E-prostanoid 4 receptor exerts anti-inflammatory effects in brain innate immunity.

PubMed

Shi, Ju; Johansson, Jenny; Woodling, Nathaniel S; Wang, Qian; Montine, Thomas J; Andreasson, Katrin

2010-06-15

Peripheral inflammation leads to immune responses in brain characterized by microglial activation, elaboration of proinflammatory cytokines and reactive oxygen species, and secondary neuronal injury. The inducible cyclooxygenase (COX), COX-2, mediates a significant component of this response in brain via downstream proinflammatory PG signaling. In this study, we investigated the function of the PGE2 E-prostanoid (EP) 4 receptor in the CNS innate immune response to the bacterial endotoxin LPS. We report that PGE2 EP4 signaling mediates an anti-inflammatory effect in brain by blocking LPS-induced proinflammatory gene expression in mice. This was associated in cultured murine microglial cells with decreased Akt and I-kappaB kinase phosphorylation and decreased nuclear translocation of p65 and p50 NF-kappaB subunits. In vivo, conditional deletion of EP4 in macrophages and microglia increased lipid peroxidation and proinflammatory gene expression in brain and in isolated adult microglia following peripheral LPS administration. Conversely, EP4 selective agonist decreased LPS-induced proinflammatory gene expression in hippocampus and in isolated adult microglia. In plasma, EP4 agonist significantly reduced levels of proinflammatory cytokines and chemokines, indicating that peripheral EP4 activation protects the brain from systemic inflammation. The innate immune response is an important component of disease progression in a number of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In addition, recent studies demonstrated adverse vascular effects with chronic administration of COX-2 inhibitors, indicating that specific PG signaling pathways may be protective in vascular function. This study supports an analogous and beneficial effect of PGE2 EP4 receptor signaling in suppressing brain inflammation.

Human blood-brain barrier insulin-like growth factor receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duffy, K.R.; Pardridge, W.M.; Rosenfeld, R.G.

1988-02-01

Insulin-like growth factor (IGF)-1 and IGF-2, may be important regulatory molecules in the CNS. Possible origins of IGFs in brain include either de novo synthesis or transport of circulating IGFs from blood into brain via receptor mediated transcytosis mechanisms at the brain capillary endothelial wall, ie, the blood-brain barrier (BBB). In the present studies, isolated human brain capillaries are used as an in vitro model system of the human BBB and the characteristics of IGF-1 or IGF-2 binding to this preparation were assessed. The total binding of IGF-2 at 37 degrees C exceeded 130% per mg protein and was threefoldmore » greater than the total binding for IGF-1. However, at 37 degrees C nonsaturable binding equaled total binding, suggesting that endocytosis is rate limiting at physiologic temperatures. Binding studies performed at 4 degrees C slowed endocytosis to a greater extent than membrane binding, and specific binding of either IGF-1 or IGF-2 was detectable. Scatchard plots for either peptide were linear and the molar dissociation constant of IGF-1 and IGF-2 binding was 2.1 +/- 0.4 and 1.1 +/- 0.1 nmol/L, respectively. Superphysiologic concentrations of porcine insulin inhibited the binding of both IGF-1 (ED50 = 2 micrograms/mL) and IGF-2 (ED50 = 0.5 microgram/mL). Affinity cross linking of /sup 125/I-IGF-1, /sup 125/I-IGF-2, and /sup 125/I-insulin to isolated human brain capillaries was performed using disuccinimidylsuberate (DSS). These studies revealed a 141 kd binding site for both IGF-1 and IGF-2, and a 133 kd binding site for insulin.« less

Characterization of cell proliferation throughout the brain of the African cichlid fish Astatotilapia burtoni and its regulation by social status.

PubMed

Maruska, Karen P; Carpenter, Russ E; Fernald, Russell D

2012-10-15

New cells are added in the brains of all adult vertebrates, but fishes have some of the greatest potential for neurogenesis and gliogenesis among all taxa, partly due to their indeterminate growth. Little is known, however, about how social interactions influence cell proliferation in the brain of these fishes that comprise the largest group of vertebrates. We used 5-bromo-2'-deoxyuridine (BrdU) to identify and localize proliferation zones in the telencephalon, diencephalon, mesencephalon, and rhombencephalon that were primarily associated with ventricular surfaces in the brain of the African cichlid fish Astatotilapia burtoni. Cell migration was evident in some regions by 1 day post injection, and many newborn cells coexpressed the neuronal marker HuC/D at 30 days, suggesting they had differentiated into neurons. To test the hypothesis that social status and perception of an opportunity to rise in rank influenced cell proliferation, we compared numbers of BrdU-labeled cells in multiple brain nuclei among fish of different social status. Socially suppressed subordinate males had the lowest numbers of proliferating cells in all brain regions examined, but males that were given an opportunity to rise in status had higher cell proliferation rates within 1 day, suggesting rapid upregulation of brain mitotic activity associated with this social transition. Furthermore, socially isolated dominant males had similar numbers of BrdU-labeled cells compared with dominant males that were housed in a socially rich environment, suggesting that isolation has little effect on proliferation and that reduced proliferation in subordinates is a result of the social subordination. These results suggest that A. burtoni will be a useful model to analyze the mechanisms of socially induced neurogenesis in vertebrates. Copyright © 2012 Wiley Periodicals, Inc.

Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury.

PubMed

Andrews, Allison M; Lutton, Evan M; Merkel, Steven F; Razmpour, Roshanak; Ramirez, Servio H

2016-01-01

It is well established that the endothelium responds to mechanical forces induced by changes in shear stress and strain. However, our understanding of vascular remodeling following traumatic brain injury (TBI) remains incomplete. Recently published studies have revealed that lung and umbilical endothelial cells produce extracellular microvesicles (eMVs), such as microparticles, in response to changes in mechanical forces (blood flow and mechanical injury). Yet, to date, no studies have shown whether brain endothelial cells produce eMVs following TBI. The brain endothelium is highly specialized and forms the blood-brain barrier (BBB), which regulates diffusion and transport of solutes into the brain. This specialization is largely due to the presence of tight junction proteins (TJPs) between neighboring endothelial cells. Following TBI, a breakdown in tight junction complexes at the BBB leads to increased permeability, which greatly contributes to the secondary phase of injury. We have therefore tested the hypothesis that brain endothelium responds to mechanical injury, by producing eMVs that contain brain endothelial proteins, specifically TJPs. In our study, primary human adult brain microvascular endothelial cells (BMVEC) were subjected to rapid mechanical injury to simulate the abrupt endothelial disruption that can occur in the primary injury phase of TBI. eMVs were isolated from the media following injury at 2, 6, 24, and 48 h. Western blot analysis of eMVs demonstrated a time-dependent increase in TJP occludin, PECAM-1 and ICAM-1 following mechanical injury. In addition, activation of ARF6, a small GTPase linked to extracellular vesicle production, was increased after injury. To confirm these results in vivo, mice were subjected to sham surgery or TBI and blood plasma was collected 24 h post-injury. Isolation and analysis of eMVs from blood plasma using cryo-EM and flow cytometry revealed elevated levels of vesicles containing occludin following brain trauma. These results indicate that following TBI, the cerebral endothelium undergoes vascular remodeling through shedding of eMVs containing TJPs and endothelial markers. The detection of this shedding potentially allows for a novel methodology for real-time monitoring of cerebral vascular health (remodeling), BBB status and neuroinflammation following a TBI event.

Early impact of social isolation and breast tumor progression in mice.

PubMed

Madden, Kelley S; Szpunar, Mercedes J; Brown, Edward B

2013-03-01

Evidence from cancer patients and animal models of cancer indicates that exposure to psychosocial stress can promote tumor growth and metastasis, but the pathways underlying stress-induced cancer pathogenesis are not fully understood. Social isolation has been shown to promote tumor progression. We examined the impact of social isolation on breast cancer pathogenesis in adult female severe combined immunodeficiency (SCID) mice using the human breast cancer cell line, MDA-MB-231, a high β-adrenergic receptor (AR) expressing line. When group-adapted mice were transferred into single housing (social isolation) one week prior to MB-231 tumor cell injection into a mammary fat pad (orthotopic), no alterations in tumor growth or metastasis were detected compared to group-housed mice. When social isolation was delayed until tumors were palpable, tumor growth was transiently increased in singly-housed mice. To determine if sympathetic nervous system activation was associated with increased tumor growth, spleen and tumor norepinephrine (NE) was measured after social isolation, in conjunction with tumor-promoting macrophage populations. Three days after transfer to single housing, spleen weight was transiently increased in tumor-bearing and non-tumor-bearing mice in conjunction with reduced splenic NE concentration and elevated CD11b+Gr-1+ macrophages. At day 10 after social isolation, no changes in spleen CD11b+ populations or NE were detected in singly-housed mice. In the tumors, social isolation increased CD11b+Gr-1+, CD11b+Gr-1-, and F4/80+ macrophage populations, with no change in tumor NE. The results indicate that a psychological stressor, social isolation, elicits dynamic but transient effects on macrophage populations that may facilitate tumor growth. The transiency of the changes in peripheral NE suggest that homeostatic mechanisms may mitigate the impact of social isolation over time. Studies are underway to define the neuroendocrine mechanisms underlying the tumor-promoting effects of social isolation, and to determine the contributions of increased tumor macrophages to tumor pathogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.

Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons.

PubMed

Nikolaev, Yury A; Dosen, Peter J; Laver, Derek R; van Helden, Dirk F; Hamill, Owen P

2015-05-22

The mammalian brain is a mechanosensitive organ that responds to different mechanical forces ranging from intrinsic forces implicated in brain morphogenesis to extrinsic forces that can cause concussion and traumatic brain injury. However, little is known of the mechanosensors that transduce these forces. In this study we use cell-attached patch recording to measure single mechanically-gated (MG) channel currents and their affects on spike activity in identified neurons in neonatal mouse brain slices. We demonstrate that both neocortical and hippocampal pyramidal neurons express stretch-activated MG cation channels that are activated by suctions of ~25mm Hg, have a single channel conductance for inward current of 50-70pS and show weak selectivity for alkali metal cations (i.e., Na(+)

Build-a-Brain Project: Students Design and Model the Brain of an Imaginary Animal

ERIC Educational Resources Information Center

Demetrikopoulos, Melissa K.; Pecore, John; Rose, Jordan D.; Fobbs, Archibald J., Jr.; Johnson, John I.; Carruth, Laura L.

2006-01-01

The brain is a truly fascinating structure! It controls the body and allows everyone to think, learn, speak, move, feel, remember, and experience emotions. Although the brain is a single organ, it is very complex and has several regions, each having a specific function. These functionally diverse regions work together to allow for coordination of…

New design concept of monopole antenna array for UHF 7T MRI.

PubMed

Hong, Suk-Min; Park, Joshua Haekyun; Woo, Myung-Kyun; Kim, Young-Bo; Cho, Zang-Hee

2014-05-01

We have developed and evaluated a monopole antenna array that can increase sensitivity at the center of the brain for 7T MRI applications. We have developed a monopole antenna array that has half the length of a conventional dipole antenna with eight channels for brain imaging with a 7T MRI. The eight-channel monopole antenna array and conventional eight-channel transceiver surface coil array were evaluated and compared in terms of transmit properties, specific absorption ratio (SAR), and sensitivity. The sensitivity maps were generated by dividing the SNR map by the flip angle distribution. A single surface coil provides asymmetric sensitivity resulting in reduced sensitivity at the center of the brain. In contrast, a single monopole antenna provides higher sensitivity at the center of the brain. Moreover, the monopole antenna array provides uniform sensitivity over the entire brain, and the sensitivity gain was 1.5 times higher at the center of the brain compared with the surface coil array. The monopole antenna array is a promising candidate for MRI applications, especially for brain imaging in a 7T MRI because it provides increased sensitivity at the center of the brain. Copyright © 2013 Wiley Periodicals, Inc.

Isolated brain stem edema in a pediatric patient with head trauma: a case report.

PubMed

Basarslan, K; Basarslan, F; Karakus, A; Yilmaz, C

2015-01-01

Brain stem is the most vital part of our body and is a transitional region of the brain that connects the cerebrum with the spinal cord. Though, being small in size, it is full of indispensible functions such as the breathing, heart beat. Injury to the brain stem has similar effects as a brain injury, but it is more fatal. Use of the Glasgow Coma Score as a prognostic indicator of outcome in patients with head injuries is widely accepted in clinical practice. Traumatic brain stem edema in children is rare, but is associated with poor outcome. The question is that whether it is being aware of computerized tomography appearance of the posterior fossa when initial evaluating pediatric patients with head trauma at emergency clinics. Normal and edematous brain stem without an additional pathology are slightly different and not distinguished easily. On the other hand, brain stem edema should be promptly identified and appropriately treated in a short time.

Magnetic microfluidic system for isolation of single cells

NASA Astrophysics Data System (ADS)

Mitterboeck, Richard; Kokkinis, Georgios; Berris, Theocharis; Keplinger, Franz; Giouroudi, Ioanna

2015-06-01

This paper presents the design and realization of a compact, portable and cost effective microfluidic system for isolation and detection of rare circulating tumor cells (CTCs) in suspension. The innovative aspect of the proposed isolation method is that it utilizes superparamagnetic particles (SMPs) to label CTCs and then isolate those using microtraps with integrated current carrying microconductors. The magnetically labeled and trapped CTCs can then be detected by integrated magnetic microsensors e.g. giant magnetoresistive (GMR) or giant magnetoimpedance (GMI) sensors. The channel and trap dimensions are optimized to protect the cells from shear stress and achieve high trapping efficiency. These intact single CTCs can then be used for additional analysis, testing and patient specific drug screening. Being able to analyze the CTCs metastasis-driving capabilities on the single cell level is considered of great importance for developing patient specific therapies. Experiments showed that it is possible to capture single labeled cells in multiple microtraps and hold them there without permanent electric current and magnetic field.

77 FR 38632 - Findings of Research Misconduct

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-28

... counts of nigrostriatal neurons in brains of several mice and rats by copying a single data file from a... Used Herbicide, Atrazine: Altered Function and Loss of Neurons in Brain Monamine Systems.'' Environ... 2004 and 2006; Falsifying a bar graph representing brain proteasomal activity, by selectively altering...

Why Autism Must Be Taken Apart

ERIC Educational Resources Information Center

Waterhouse, Lynn; Gillberg, Christopher

2014-01-01

Although accumulated evidence has demonstrated that autism is found with many varied brain dysfunctions, researchers have tried to find a single brain dysfunction that would provide neurobiological validity for autism. However, unitary models of autism brain dysfunction have not adequately addressed conflicting evidence, and efforts to find a…

Distributed Attention Is Implemented through Theta-Rhythmic Gamma Modulation.

PubMed

Landau, Ayelet Nina; Schreyer, Helene Marianne; van Pelt, Stan; Fries, Pascal

2015-08-31

When subjects monitor a single location, visual target detection depends on the pre-target phase of an ∼8 Hz brain rhythm. When multiple locations are monitored, performance decrements suggest a division of the 8 Hz rhythm over the number of locations, indicating that different locations are sequentially sampled. Indeed, when subjects monitor two locations, performance benefits alternate at a 4 Hz rhythm. These performance alternations were revealed after a reset of attention to one location. Although resets are common and important events for attention, it is unknown whether, in the absence of resets, ongoing attention samples stimuli in alternation. Here, we examined whether spatially specific attentional sampling can be revealed by ongoing pre-target brain rhythms. Visually induced gamma-band activity plays a role in spatial attention. Therefore, we hypothesized that performance on two simultaneously monitored stimuli can be predicted by a 4 Hz modulation of gamma-band activity. Brain rhythms were assessed with magnetoencephalography (MEG) while subjects monitored bilateral grating stimuli for a unilateral target event. The corresponding contralateral gamma-band responses were subtracted from each other to isolate spatially selective, target-related fluctuations. The resulting lateralized gamma-band activity (LGA) showed opposite pre-target 4 Hz phases for detected versus missed targets. The 4 Hz phase of pre-target LGA accounted for a 14.5% modulation in performance. These findings suggest that spatial attention is a theta-rhythmic sampling process that is continuously ongoing, with each sampling cycle being implemented through gamma-band synchrony. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mcm3 replicative helicase mutation impairs neuroblast proliferation and memory in Drosophila.

PubMed

Blumröder, R; Glunz, A; Dunkelberger, B S; Serway, C N; Berger, C; Mentzel, B; de Belle, J S; Raabe, T

2016-09-01

In the developing Drosophila brain, a small number of neural progenitor cells (neuroblasts) generate in a co-ordinated manner a high variety of neuronal cells by integration of temporal, spatial and cell-intrinsic information. In this study, we performed the molecular and phenotypic characterization of a structural brain mutant called small mushroom bodies (smu), which was isolated in a screen for mutants with altered brain structure. Focusing on the mushroom body neuroblast lineages we show that failure of neuroblasts to generate the normal number of mushroom body neurons (Kenyon cells) is the major cause of the smu phenotype. In particular, the premature loss of mushroom body neuroblasts caused a pronounced effect on the number of late-born Kenyon cells. Neuroblasts showed no obvious defects in processes controlling asymmetric cell division, but generated less ganglion mother cells. Cloning of smu uncovered a single amino acid substitution in an evolutionarily conserved protein interaction domain of the Minichromosome maintenance 3 (Mcm3) protein. Mcm3 is part of the multimeric Cdc45/Mcm/GINS (CMG) complex, which functions as a helicase during DNA replication. We propose that at least in the case of mushroom body neuroblasts, timely replication is not only required for continuous proliferation but also for their survival. The absence of Kenyon cells in smu reduced learning and early phases of conditioned olfactory memory. Corresponding to the absence of late-born Kenyon cells projecting to α'/β' and α/β lobes, smu is profoundly defective in later phases of persistent memory. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Connectivity-based neurofeedback: Dynamic causal modeling for real-time fMRI☆

PubMed Central

Koush, Yury; Rosa, Maria Joao; Robineau, Fabien; Heinen, Klaartje; W. Rieger, Sebastian; Weiskopf, Nikolaus; Vuilleumier, Patrik; Van De Ville, Dimitri; Scharnowski, Frank

2013-01-01

Neurofeedback based on real-time fMRI is an emerging technique that can be used to train voluntary control of brain activity. Such brain training has been shown to lead to behavioral effects that are specific to the functional role of the targeted brain area. However, real-time fMRI-based neurofeedback so far was limited to mainly training localized brain activity within a region of interest. Here, we overcome this limitation by presenting near real-time dynamic causal modeling in order to provide feedback information based on connectivity between brain areas rather than activity within a single brain area. Using a visual–spatial attention paradigm, we show that participants can voluntarily control a feedback signal that is based on the Bayesian model comparison between two predefined model alternatives, i.e. the connectivity between left visual cortex and left parietal cortex vs. the connectivity between right visual cortex and right parietal cortex. Our new approach thus allows for training voluntary control over specific functional brain networks. Because most mental functions and most neurological disorders are associated with network activity rather than with activity in a single brain region, this novel approach is an important methodological innovation in order to more directly target functionally relevant brain networks. PMID:23668967

Intrahippocampal Infusion of Crotamine Isolated from Crotalus durissus terrificus Alters Plasma and Brain Biochemical Parameters †

PubMed Central

Gonçalves, Rithiele; Vargas, Liane S.; Lara, Marcus V. S.; Güllich, Angélica; Mandredini, Vanusa; Ponce-Soto, Luis; Marangoni, Sergio; Dal Belo, Cháriston A.; Mello-Carpes, Pâmela B.

2014-01-01

Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus durissus terrificus. Here we sought to investigate the inflammatory and toxicological effects induced by the intrahippocampal administration of crotamine isolated from Crotalus whole venom. Adult rats received an intrahippocampal infusion of crotamine or vehicle and were euthanized 24 h or 21 days after infusion. Plasma and brain tissue were collected for biochemical analysis. Complete blood count, creatinine, urea, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine-kinase (CK), creatine kinase-muscle B (CK-MB) and oxidative parameters (assessed by DNA damage and micronucleus frequency in leukocytes, lipid peroxidation and protein carbonyls in plasma and brain) were quantified. Unpaired and paired t-tests were used for comparisons between saline and crotamine groups, and within groups (24 h vs. 21 days), respectively. After 24 h crotamine infusion promoted an increase of urea, GOT, GPT, CK, and platelets values (p ≤ 0.01), while red blood cells, hematocrit and leukocytes values decreased (p ≤ 0.01). Additionally, 21 days after infusion crotamine group showed increased creatinine, leukocytes, TBARS (plasma and brain), carbonyl (plasma and brain) and micronucleus compared to the saline-group (p ≤ 0.01). Our findings show that crotamine infusion alter hematological parameters and cardiac markers, as well as oxidative parameters, not only in the brain, but also in the blood, indicating a systemic pro-inflammatory and toxicological activity. A further scientific attempt in terms of preserving the beneficial activity over toxicity is required. PMID:25380458

Cloning of Plasmodium falciparum by single-cell sorting.

PubMed

Miao, Jun; Li, Xiaolian; Cui, Liwang

2010-10-01

Malaria parasite cloning is traditionally carried out mainly by using the limiting dilution method, which is laborious, imprecise, and unable to distinguish multiply-infected RBCs. In this study, we used a parasite engineered to express green fluorescent protein (GFP) to evaluate a single-cell sorting method for rapidly cloning Plasmodium falciparum. By dividing a two-dimensional scattergram from a cell sorter into 17 gates, we determined the parameters for isolating singly-infected erythrocytes and sorted them into individual cultures. Pre-gating of the engineered parasites for GFP allowed the isolation of almost 100% GFP-positive clones. Compared with the limiting dilution method, the number of parasite clones obtained by single-cell sorting was much higher. Molecular analyses showed that parasite isolates obtained by single-cell sorting were highly homogenous. This highly efficient single-cell sorting method should prove very useful for cloning both P. falciparum laboratory populations from genetic manipulation experiments and clinical samples. Copyright 2010 Elsevier Inc. All rights reserved.

Differential chemokine responses in the murine brain following lyssavirus infection.

PubMed

Hicks, D J; Núñez, A; Banyard, A C; Williams, A; Ortiz-Pelaez, A; Fooks, A R; Johnson, N

2013-11-01

The hallmark of lyssavirus infection is lethal encephalomyelitis. Previous studies have reported distinct lyssavirus isolate-related differences in severity of cellular recruitment into the encephalon in a murine model of infection following peripheral inoculation with rabies virus (RABV) and European bat lyssavirus (EBLV)-1 and -2. In order to understand the role of chemokines in this process, comparative studies of the chemokine pattern, distribution and production in response to infection with these lyssaviruses were undertaken. Expression of CCL2, CCL5 and CXCL10 was observed throughout the murine brain with a distinct caudal bias in distribution, similar to both inflammatory changes and virus antigen distribution. CCL2 immunolabelling was localized to neuronal and astroglial populations. CCL5 immunolabelling was only detected in the astroglia, while CXCL10 labelling, although present in the astroglia, was more prominent in neurons. Isolate-dependent differences in the amount of chemokine immunolabelling in specific brain regions and chemokine production by neurons in vitro were observed, with a greater expression of CCL5 in vivo and CXCL10 production in vitro after EBLV infection. Additionally, strong positive associations between chemokine immunolabelling and perivascular cuffing and, to a lesser extent, virus antigen score were also observed. These differences in chemokine expression may explain the variation in severity of encephalitic changes observed in animals infected with different lyssavirus isolates. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

The effect of additional brain injury on systemic interleukin (IL)-10 and IL-13 levels in trauma patients.

PubMed

Hensler, T; Sauerland, S; Riess, P; Hess, S; Helling, H J; Andermahr, J; Bouillon, B; Neugebauer, E A

2000-10-01

Besides interleukin (IL)-10, accumulating evidence from in vitro studies has indicated a strong antiinflammatory capacity for IL-13. A prospective clinical study was undertaken to assess the influence of additional brain injury on systemic IL-10 and IL-13 levels as markers for the antiinflammatory state in trauma patients. The course of IL-10 and IL-13 plasma levels from 32 patients with an isolated severe head trauma (SHT), 50 patients with multiple injuries and additional SHT and 39 patients with multiple injuries without SHT was detected using ELISA-technique. Blood samples from 37 healthy blood donors were analysed for control. IL-10 levels were significantly elevated in all 3 injury groups within 3 h after trauma. The lowest initial release was detected in patients with an isolated SHT (Injury severity score; ISS: 18.1 +/- 5.6). No difference could be demonstrated for the IL-10 levels from multiple injured patients with (ISS: 35.3 +/- 9.6) or without additional SHT (ISS: 25.5 +/- 11.7), though there were relevant differences in the ISS. In contrast, the IL-13 plasma levels were not elevated systemically after trauma. IL-10 but not IL-13 is a detectable antiinflammatory marker in trauma patients with or without brain injury and to a minor degree in patients with an isolated SHT.

Primary Cell Culture of Live Neurosurgically Resected Aged Adult Human Brain Cells and Single Cell Transcriptomics.

PubMed

Spaethling, Jennifer M; Na, Young-Ji; Lee, Jaehee; Ulyanova, Alexandra V; Baltuch, Gordon H; Bell, Thomas J; Brem, Steven; Chen, H Isaac; Dueck, Hannah; Fisher, Stephen A; Garcia, Marcela P; Khaladkar, Mugdha; Kung, David K; Lucas, Timothy H; O'Rourke, Donald M; Stefanik, Derek; Wang, Jinhui; Wolf, John A; Bartfai, Tamas; Grady, M Sean; Sul, Jai-Yoon; Kim, Junhyong; Eberwine, James H

2017-01-17

Investigation of human CNS disease and drug effects has been hampered by the lack of a system that enables single-cell analysis of live adult patient brain cells. We developed a culturing system, based on a papain-aided procedure, for resected adult human brain tissue removed during neurosurgery. We performed single-cell transcriptomics on over 300 cells, permitting identification of oligodendrocytes, microglia, neurons, endothelial cells, and astrocytes after 3 weeks in culture. Using deep sequencing, we detected over 12,000 expressed genes, including hundreds of cell-type-enriched mRNAs, lncRNAs and pri-miRNAs. We describe cell-type- and patient-specific transcriptional hierarchies. Single-cell transcriptomics on cultured live adult patient derived cells is a prime example of the promise of personalized precision medicine. Because these cells derive from subjects ranging in age into their sixties, this system permits human aging studies previously possible only in rodent systems. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Analysis and Design of Bridgeless Switched Mode Power Supply for Computers

NASA Astrophysics Data System (ADS)

Singh, S.; Bhuvaneswari, G.; Singh, B.

2014-09-01

Switched mode power supplies (SMPSs) used in computers need multiple isolated and stiffly regulated output dc voltages with different current ratings. These isolated multiple output dc voltages are obtained by using a multi-winding high frequency transformer (HFT). A half-bridge dc-dc converter is used here for obtaining different isolated and well regulated dc voltages. In the front end, non-isolated Single Ended Primary Inductance Converters (SEPICs) are added to improve the power quality in terms of low input current harmonics and high power factor (PF). Two non-isolated SEPICs are connected in a way to completely eliminate the need of single-phase diode-bridge rectifier at the front end. Output dc voltages at both the non-isolated and isolated stages are controlled and regulated separately for power quality improvement. A voltage mode control approach is used in the non-isolated SEPIC stage for simple and effective control whereas average current control is used in the second isolated stage.

Gene expression profiles of brain endothelial cells during embryonic development at bulk and single-cell levels.

PubMed

Hupe, Mike; Li, Minerva Xueting; Kneitz, Susanne; Davydova, Daria; Yokota, Chika; Kele-Olovsson, Julianna; Hot, Belma; Stenman, Jan M; Gessler, Manfred

2017-07-11

The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribosome affinity purification and single-cell RNA sequencing. We compared the brain vascular translatome with the vascular translatomes of other organs and analyzed the vascular translatomes of the brain at different time points during embryonic development. Because canonical Wnt signaling is implicated in the formation of the blood-brain barrier, we also compared the brain endothelial translatome of wild-type mice with that of mice lacking the transcriptional cofactor β-catenin ( Ctnnb1 ). Our analysis revealed extensive molecular changes during the embryonic development of the brain endothelium. We identified genes encoding brain endothelium-specific transcription factors ( Foxf2 , Foxl2 , Foxq1 , Lef1 , Ppard , Zfp551 , and Zic3 ) that are associated with maturation of the blood-brain barrier and act downstream of the Wnt-β-catenin signaling pathway. Profiling of individual brain endothelial cells revealed substantial heterogeneity in the population. Nevertheless, the high abundance of Foxf2 , Foxq1 , Ppard , or Zic3 transcripts correlated with the increased expression of genes encoding markers of brain endothelial cell differentiation. Expression of Foxf2 and Zic3 in human umbilical vein endothelial cells induced the production of blood-brain barrier differentiation markers. This comprehensive data set may help to improve the engineering of in vitro blood-brain barrier models. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Single spore isolation and morphological characterization of local Malaysian isolates of rice blast fungus Magnoporthe grisea

NASA Astrophysics Data System (ADS)

Mishra, Ankitta; Ratnam, Wickneswari; Bhuiyan, Md Atiqur Rahman; Ponaya, Ariane; Jena, Khisord K.

2015-09-01

Rice blast is a destructive disease, caused by the fungal pathogen Magnaporthe grisea. It causes considerable damage to rice and leads to crop loss in rice growing regions worldwide. Although fungicides can be used to control rice blast, they generate additional cost in rice production and contamination of environment and food. Therefore, the use of resistant varieties is thought to be one of the most economically and environmentally efficient ways of crop protection from the disease. Six new local Malaysian isolates of M. grisea were isolated using single spore isolation method. Five isolates were from infected leaf samples collected from Kompleks Latihan MADA, Kedah and one was from Kelantan. These isolates were identified using morphological characteristics and microscopic studies and later confirmed by ITSequences. These isolates were induced to sporulate and used for greenhouse screening on two differential rice varieties: Mahsuri (susceptible) and Pongsu Seribu 2 (resistant). Among the 6 isolates, isolate number 3 was found to be the most virulent showing high sporulation while isolate number 4 was very slow growing, and the least virulent.

Single Nisoldipine-Sensitive Calcium Channels in Smooth Muscle Cells Isolated from Rabbit Mesenteric Artery

NASA Astrophysics Data System (ADS)

Worley, Jennings F.; Deitmer, Joachim W.; Nelson, Mark T.

1986-08-01

Single smooth muscle cells were enzymatically isolated from the rabbit mesenteric artery. At physiological levels of external Ca, these cells were relaxed and contracted on exposure to norepinephrine, caffeine, or high levels of potassium. The patch-clamp technique was used to measure unitary currents through single channels in the isolated cells. Single channels were selective for divalent cations and exhibited two conductance levels, 8 pS and 15 pS. Both types of channels were voltage-dependent, and channel activity occurred at potentials positive to -40 mV. The activity of both channel types was almost completely inhibited by 50 nM nisoldipine. These channels appear to be the pathways for voltage-dependent Ca influx in vascular smooth muscle and may be the targets of the clinically used dihydropyridines.

Assessing the genome level diversity of Listeria monocytogenes from contaminated ice cream and environmental samples linked to a listeriosis outbreak in the United States.

PubMed

Chen, Yi; Luo, Yan; Curry, Phillip; Timme, Ruth; Melka, David; Doyle, Matthew; Parish, Mickey; Hammack, Thomas S; Allard, Marc W; Brown, Eric W; Strain, Errol A

2017-01-01

A listeriosis outbreak in the United States implicated contaminated ice cream produced by one company, which operated 3 facilities. We performed single nucleotide polymorphism (SNP)-based whole genome sequencing (WGS) analysis on Listeria monocytogenes from food, environmental and clinical sources, identifying two clusters and a single branch, belonging to PCR serogroup IIb and genetic lineage I. WGS Cluster I, representing one outbreak strain, contained 82 food and environmental isolates from Facility I and 4 clinical isolates. These isolates differed by up to 29 SNPs, exhibited 9 pulsed-field gel electrophoresis (PFGE) profiles and multilocus sequence typing (MLST) sequence type (ST) 5 of clonal complex 5 (CC5). WGS Cluster II contained 51 food and environmental isolates from Facility II, 4 food isolates from Facility I and 5 clinical isolates. Among them the isolates from Facility II and clinical isolates formed a clade and represented another outbreak strain. Isolates in this clade differed by up to 29 SNPs, exhibited 3 PFGE profiles and ST5. The only isolate collected from Facility III belonged to singleton ST489, which was in a single branch separate from Clusters I and II, and was not associated with the outbreak. WGS analyses clustered together outbreak-associated isolates exhibiting multiple PFGE profiles, while differentiating them from epidemiologically unrelated isolates that exhibited outbreak PFGE profiles. The complete genome of a Cluster I isolate allowed the identification and analyses of putative prophages, revealing that Cluster I isolates differed by the gain or loss of three putative prophages, causing the banding pattern differences among all 3 AscI-PFGE profiles observed in Cluster I isolates. WGS data suggested that certain ice cream varieties and/or production lines might have contamination sources unique to them. The SNP-based analysis was able to distinguish CC5 as a group from non-CC5 isolates and differentiate among CC5 isolates from different outbreaks/incidents.

Assessing the genome level diversity of Listeria monocytogenes from contaminated ice cream and environmental samples linked to a listeriosis outbreak in the United States

PubMed Central

Chen, Yi; Luo, Yan; Curry, Phillip; Timme, Ruth; Melka, David; Doyle, Matthew; Parish, Mickey; Hammack, Thomas S.; Allard, Marc W.; Brown, Eric W.; Strain, Errol A.

2017-01-01

A listeriosis outbreak in the United States implicated contaminated ice cream produced by one company, which operated 3 facilities. We performed single nucleotide polymorphism (SNP)-based whole genome sequencing (WGS) analysis on Listeria monocytogenes from food, environmental and clinical sources, identifying two clusters and a single branch, belonging to PCR serogroup IIb and genetic lineage I. WGS Cluster I, representing one outbreak strain, contained 82 food and environmental isolates from Facility I and 4 clinical isolates. These isolates differed by up to 29 SNPs, exhibited 9 pulsed-field gel electrophoresis (PFGE) profiles and multilocus sequence typing (MLST) sequence type (ST) 5 of clonal complex 5 (CC5). WGS Cluster II contained 51 food and environmental isolates from Facility II, 4 food isolates from Facility I and 5 clinical isolates. Among them the isolates from Facility II and clinical isolates formed a clade and represented another outbreak strain. Isolates in this clade differed by up to 29 SNPs, exhibited 3 PFGE profiles and ST5. The only isolate collected from Facility III belonged to singleton ST489, which was in a single branch separate from Clusters I and II, and was not associated with the outbreak. WGS analyses clustered together outbreak-associated isolates exhibiting multiple PFGE profiles, while differentiating them from epidemiologically unrelated isolates that exhibited outbreak PFGE profiles. The complete genome of a Cluster I isolate allowed the identification and analyses of putative prophages, revealing that Cluster I isolates differed by the gain or loss of three putative prophages, causing the banding pattern differences among all 3 AscI-PFGE profiles observed in Cluster I isolates. WGS data suggested that certain ice cream varieties and/or production lines might have contamination sources unique to them. The SNP-based analysis was able to distinguish CC5 as a group from non-CC5 isolates and differentiate among CC5 isolates from different outbreaks/incidents. PMID:28166293

Neurologic Injury and Cerebral Blood Flow In Single Ventricles Throughout Staged Surgical Reconstruction

PubMed Central

Fogel, Mark A.; Li, Christine; Elci, Okan U.; Pawlowski, Tom; Schwab, Peter J.; Wilson, Felice; Nicolson, Susan C.; Montenegro, Lisa M.; Diaz, Laura; Spray, Thomas L.; Gaynor, J William; Fuller, Stephanie; Mascio, Christopher; Keller, Marc S.; Harris, Matthew A.; Whitehead, Kevin K.; Bethel, Jim; Vossough, Arastoo; Licht, Daniel J.

2017-01-01

Background Single ventricle patients experience a high rate of brain injury and adverse neurodevelopmental outcome, however, the incidence of brain abnormalities throughout surgical reconstruction and its relationship with cerebral blood flow, oxygen delivery and carbon dioxide reactivity remains unknown. Methods Single ventricle patients were studied with MRI scans immediately prior to bidirectional Glenn (pre-BDG), prior to Fontan and then 3–9 months after Fontan reconstruction. Results One hundred and sixty eight consecutive subjects recruited into the project underwent 235 scans: 63 pre-BDG (mean age 4.8+1.7 months), 118 BDG (2.9+1.4 years) and 54 after Fontan (2.4+1.0 years). Non-acute ischemic white matter changes on T2 weighted imaging, focal tissue loss, and ventriculomegaly were all more commonly detected in BDG and Fontans compared to pre-BDG (P<0.05). BDG patients has significantly higher CBF than Fontan patients. The odds of discovering brain injury adjusting for surgical stage as well as 2 or more co-existing lesions within a patient all decreased (63–75% and 44% respectively) with increasing amount of cerebral blood flow (P<0.05). In general, there was no association of oxygen delivery (with the exception of ventriculomegaly in the BDG group) or carbon dioxide reactivity with neurological injury. Conclusion Significant brain abnormalities are commonly present in single ventricle patients and detection of these lesions increase as children progress through staged surgical reconstruction with multiple co-existing lesions more common earlier than later. In addition, this study demonstrated that BDG patients had greater CBF than Fontan patients and that there exists an inverse association of various indices of CBF with these brain lesions, however, CO2 reactivity, oxygen delivery (with one exception) were not associated with brain lesion development. PMID:28031423

Brain Magnetic Resonance Immediately Prior To Surgery In Single Ventricles and Surgical Postponement

PubMed Central

Fogel, Mark A.; Pawlowski, Tom; Schwab, Peter J.; Nicolson, Susan C.; Montenegro, Lisa M.; Berenstein, Laura Diaz; Spray, Thomas L.; Gaynor, J William; Fuller, Stephanie; Keller, Marc S.; Harris, Matthew A.; Whitehead, Kevin K.; Vossough, Arastoo; Licht, Daniel J.

2014-01-01

Background Single ventricle patients undergoing surgical reconstruction experience a high rate of brain injury; incidental findings on pre-operative brain scans may result in safety considerations involving hemorrhage extension during cardiopulmonary bypass that result in surgical postponement. Methods Single ventricle patients were studied with brain scans immediately preoperatively as part of a National Institute of Health study and were reviewed by neuroradiology immediately prior to cardiopulmonary bypass. Results One hundred and thirty four consecutive subjects recruited into the project were studied: 33 prior to stage I (3.7±1.8 days), 34 prior to bidirectional Glenn (5.8±3.5 months) and 67 prior to Fontan (3.3±1.1 years). Six (4.5%) surgeries were postponed because of concerning imaging findings on brain MRI; 2 prior to stage I, 3 prior to bidirectional Glenn and 1 prior to Fontan. Five were due to unexpected incidental findings of acute intracranial hemorrhage and one due to diffuse cerebellar cytotoxic edema; none who proceeded to surgery had these lesions. Prematurity as well as genetic syndromes were not present in any with postponed surgery. Four of 4 prior to bidirectional Glenn/Fontan with surgical delays had hypoplastic left heart syndrome compared with 44/97 who did not (P=0.048). After observation and follow up, all eventually had successful surgeries with bypass. Conclusion Preoperative brain MRI performed in children with single ventricles disclosed injuries in 4.5% leading to surgical delay; hemorrhagic lesions were most common and raised concerns for extension during surgery. The true risk of progression and need for delay of surgery due to heparinization associated with these lesions remains uncertain. PMID:25149046

Isolated Attosecond Pulse Generation without the Need to Stabilize the Carrier-Envelope Phase of Driving Lasers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilbertson, Steve; Khan, Sabih D.; Wu Yi

2010-08-27

Single isolated attosecond pulses can be extracted from a pulse train with an ultrafast gate in the generation target. By setting the gate width sufficiently narrow with the generalized double optical gating, we demonstrate that single isolated attosecond pulses can be generated with any arbitrary carrier-envelope phase value of the driving laser. The carrier-envelope phase only affects the photon flux, not the pulse duration or contrast. Our results show that isolated attosecond pulses can be generated using carrier-envelope phase unstabilized 23 fs pulses directly from chirped pulse amplifiers.

Magnetic Actuators and Suspension for Space Vibration Control

NASA Technical Reports Server (NTRS)

Knospe, Carl R.; Allaire, Paul E.; Lewis, David W.

1993-01-01

The research on microgravity vibration isolation performed at the University of Virginia is summarized. This research on microgravity vibration isolation was focused in three areas: (1) the development of new actuators for use in microgravity isolation; (2) the design of controllers for multiple-degree-of-freedom active isolation; and (3) the construction of a single-degree-of-freedom test rig with umbilicals. Described are the design and testing of a large stroke linear actuator; the conceptual design and analysis of a redundant coarse-fine six-degree-of-freedom actuator; an investigation of the control issues of active microgravity isolation; a methodology for the design of multiple-degree-of-freedom isolation control systems using modern control theory; and the design and testing of a single-degree-of-freedom test rig with umbilicals.

Octylphenol (OP) alters the expression of members of the amyloid protein family in the hypothalamus of the snapping turtle, Chelydra serpentina serpentina.

PubMed Central

Trudeau, Vance L; Chiu, Suzanne; Kennedy, Sean W; Brooks, Ronald J

2002-01-01

The gonadal estrogen estradiol-17beta (E(2)) is important for developing and regulating hypothalamic function and many aspects of reproduction in vertebrates. Pollutants such as octylphenol (OP) that mimic the actions of estrogens are therefore candidate endocrine-disrupting chemicals. We used a differential display strategy (RNA-arbitrarily primed polymerase chain reaction) to isolate partial cDNA sequences of neurotransmitter, developmental, and disease-related genes that may be regulated by OP or E(2) in the snapping turtle Chelydra serpentina serpentina hypothalamus. Hatchling and year-old male snapping turtles were exposed to a 10 ng/mL nominal concentration of waterborne OP or E(2) for 17 days. One transcript [421 base pairs (bp)] regulated by OP and E(2) was 93% identical to human APLP-2. APLP-2 and the amyloid precursor protein (APP) regulate neuronal differentiation and are also implicated in the genesis of Alzheimer disease in humans. Northern blot analysis determined that the turtle hypothalamus contains a single APLP-2 transcript of 3.75 kb in length. Exposure to OP upregulated hypothalamic APLP-2 mRNA levels 2-fold (p < 0.05) in month-old and yearling turtles. E(2) did not affect APLP-2 mRNA levels in hatchlings but stimulated a 2-fold increase (p < 0.05) in APLP-2 mRNA levels in yearling males. The protein beta-amyloid, a selectively processed peptide derived from APP, is also involved in neuronal differentiation, and accumulation of this neurotoxic peptide causes neuronal degeneration in the brains of patients with Alzheimer disease. Therefore, we also sought to determine the effects of estrogens on the expression of beta-amyloid. Using homology cloning based on known sequences, we isolated a cDNA fragment (474 bp) from turtle brain with 88% identity to human APP. Northern blot analysis determined that a single 3.5-kb transcript was expressed in the turtle hypothalamus. Waterborne OP also increased the expression of hypothalamic APP after 35 days of exposure. Our results indicate that low levels of OP are bioactive and can alter the expression of APLP-2 and APP. Because members of the APP gene family are involved in neuronal development, we hypothesize that OP exposure may disrupt hypothalamic development in young turtles. PMID:11882478

Octylphenol (OP) alters the expression of members of the amyloid protein family in the hypothalamus of the snapping turtle, Chelydra serpentina serpentina.

PubMed

Trudeau, Vance L; Chiu, Suzanne; Kennedy, Sean W; Brooks, Ronald J

2002-03-01

The gonadal estrogen estradiol-17beta (E(2)) is important for developing and regulating hypothalamic function and many aspects of reproduction in vertebrates. Pollutants such as octylphenol (OP) that mimic the actions of estrogens are therefore candidate endocrine-disrupting chemicals. We used a differential display strategy (RNA-arbitrarily primed polymerase chain reaction) to isolate partial cDNA sequences of neurotransmitter, developmental, and disease-related genes that may be regulated by OP or E(2) in the snapping turtle Chelydra serpentina serpentina hypothalamus. Hatchling and year-old male snapping turtles were exposed to a 10 ng/mL nominal concentration of waterborne OP or E(2) for 17 days. One transcript [421 base pairs (bp)] regulated by OP and E(2) was 93% identical to human APLP-2. APLP-2 and the amyloid precursor protein (APP) regulate neuronal differentiation and are also implicated in the genesis of Alzheimer disease in humans. Northern blot analysis determined that the turtle hypothalamus contains a single APLP-2 transcript of 3.75 kb in length. Exposure to OP upregulated hypothalamic APLP-2 mRNA levels 2-fold (p < 0.05) in month-old and yearling turtles. E(2) did not affect APLP-2 mRNA levels in hatchlings but stimulated a 2-fold increase (p < 0.05) in APLP-2 mRNA levels in yearling males. The protein beta-amyloid, a selectively processed peptide derived from APP, is also involved in neuronal differentiation, and accumulation of this neurotoxic peptide causes neuronal degeneration in the brains of patients with Alzheimer disease. Therefore, we also sought to determine the effects of estrogens on the expression of beta-amyloid. Using homology cloning based on known sequences, we isolated a cDNA fragment (474 bp) from turtle brain with 88% identity to human APP. Northern blot analysis determined that a single 3.5-kb transcript was expressed in the turtle hypothalamus. Waterborne OP also increased the expression of hypothalamic APP after 35 days of exposure. Our results indicate that low levels of OP are bioactive and can alter the expression of APLP-2 and APP. Because members of the APP gene family are involved in neuronal development, we hypothesize that OP exposure may disrupt hypothalamic development in young turtles.

Flexible modulation of network connectivity related to cognition in Alzheimer's disease.

PubMed

McLaren, Donald G; Sperling, Reisa A; Atri, Alireza

2014-10-15

Functional neuroimaging tools, such as fMRI methods, may elucidate the neural correlates of clinical, behavioral, and cognitive performance. Most functional imaging studies focus on regional task-related activity or resting state connectivity rather than how changes in functional connectivity across conditions and tasks are related to cognitive and behavioral performance. To investigate the promise of characterizing context-dependent connectivity-behavior relationships, this study applies the method of generalized psychophysiological interactions (gPPI) to assess the patterns of associative-memory-related fMRI hippocampal functional connectivity in Alzheimer's disease (AD) associated with performance on memory and other cognitively demanding neuropsychological tests and clinical measures. Twenty-four subjects with mild AD dementia (ages 54-82, nine females) participated in a face-name paired-associate encoding memory study. Generalized PPI analysis was used to estimate the connectivity between the hippocampus and the whole brain during encoding. The difference in hippocampal-whole brain connectivity between encoding novel and encoding repeated face-name pairs was used in multiple-regression analyses as an independent predictor for 10 behavioral, neuropsychological and clinical tests. The analysis revealed connectivity-behavior relationships that were distributed, dynamically overlapping, and task-specific within and across intrinsic networks; hippocampal-whole brain connectivity-behavior relationships were not isolated to single networks, but spanned multiple brain networks. Importantly, these spatially distributed performance patterns were unique for each measure. In general, out-of-network behavioral associations with encoding novel greater than repeated face-name pairs hippocampal-connectivity were observed in the default-mode network, while correlations with encoding repeated greater than novel face-name pairs hippocampal-connectivity were observed in the executive control network (p<0.05, cluster corrected). Psychophysiological interactions revealed significantly more extensive and robust associations between paired-associate encoding task-dependent hippocampal-whole brain connectivity and performance on memory and behavioral/clinical measures than previously revealed by standard activity-behavior analysis. Compared to resting state and task-activation methods, gPPI analyses may be more sensitive to reveal additional complementary information regarding subtle within- and between-network relations. The patterns of robust correlations between hippocampal-whole brain connectivity and behavioral measures identified here suggest that there are 'coordinated states' in the brain; that the dynamic range of these states is related to behavior and cognition; and that these states can be observed and quantified, even in individuals with mild AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Isolation of single Chlamydia-infected cells using laser microdissection.

PubMed

Podgorny, Oleg V; Polina, Nadezhda F; Babenko, Vladislav V; Karpova, Irina Y; Kostryukova, Elena S; Govorun, Vadim M; Lazarev, Vassili N

2015-02-01

Chlamydia are obligate intracellular parasites of humans and animals that cause a wide range of acute and chronic infections. To elucidate the genetic basis of chlamydial parasitism, several approaches for making genetic modifications to Chlamydia have recently been reported. However, the lack of the available methods for the fast and effective selection of genetically modified bacteria restricts the application of genetic tools. We suggest the use of laser microdissection to isolate of single live Chlamydia-infected cells for the re-cultivation and whole-genome sequencing of single inclusion-derived Chlamydia. To visualise individual infected cells, we made use of the vital labelling of inclusions with the fluorescent Golgi-specific dye BODIPY® FL C5-ceramide. We demonstrated that single Chlamydia-infected cells isolated by laser microdissection and placed onto a host cell monolayer resulted in new cycles of infection. We also demonstrated the successful use of whole-genome sequencing to study the genomic variability of Chlamydia derived from a single inclusion. Our work provides the first evidence of the successful use of laser microdissection for the isolation of single live Chlamydia-infected cells, thus demonstrating that this method can help overcome the barriers to the fast and effective selection of Chlamydia. Copyright © 2014 Elsevier B.V. All rights reserved.

Endogenous formation and repair of oxidatively induced G[8-5 m]T intrastrand cross-link lesion

PubMed Central

Wang, Jin; Cao, Huachuan; You, Changjun; Yuan, Bifeng; Bahde, Ralf; Gupta, Sanjeev; Nishigori, Chikako; Niedernhofer, Laura J.; Brooks, Philip J.; Wang, Yinsheng

2012-01-01

Exposure to reactive oxygen species (ROS) can give rise to the formation of various DNA damage products. Among them, d(G[8-5 m]T) can be induced in isolated DNA treated with Fenton reagents and in cultured human cells exposed to γ-rays, d(G[8-5m]T) can be recognized and incised by purified Escherichia coli UvrABC nuclease. However, it remains unexplored whether d(G[8-5 m]T) accumulates in mammalian tissues and whether it is a substrate for nucleotide excision repair (NER) in vivo. Here, we found that d(G[8-5 m]T) could be detected in DNA isolated from tissues of healthy humans and animals, and elevated endogenous ROS generation enhanced the accumulation of this lesion in tissues of a rat model of Wilson’s disease. Additionally, XPA-deficient human brain and mouse liver as well as various types of tissues of ERCC1-deficient mice contained higher levels of d(G[8-5 m]T) but not ROS-induced single-nucleobase lesions than the corresponding normal controls. Together, our studies established that d(G[8-5 m]T) can be induced endogenously in mammalian tissues and constitutes a substrate for NER in vivo. PMID:22581771

Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosides.

PubMed

Chen, Feng; Eckman, Elizabeth A; Eckman, Christopher B

2006-06-01

For millennia, ginseng and some of its components have been used to treat a wide variety of medical conditions, including age-related memory impairment. Because of its purported effects and apparently low rate of side effects, ginseng remains one of the top selling natural product remedies in the United States. Given its potential role for improving age-related memory impairments and its common use in China for the treatment of Alzheimer's disease-like symptoms, we analyzed the effects of commercially available preparations of ginseng on the accumulation of the Alzheimer's amyloid beta peptide (Abeta) in a cell-based model system. In this model system, ginseng treatment resulted in a significant reduction in the levels of Abeta in the conditioned medium. We next examined the effects of several compounds isolated from ginseng and found that certain ginsenosides lowered Abeta concentration in a dose-dependent manner with ginsenoside Rg3 having an approximate IC50 of under 25 microM against Abeta42. Furthermore, we found that three of these isolated components, ginsenoside Rg1, Rg3, and RE, resulted in significant reductions in the amount of Abeta detected in the brains of animals after single oral doses of these agents. The results indicate that ginseng itself, or purified ginsenosides, may have similarly useful effects in human disease.

Assessment of six different collagenase-based methods to isolate feline pancreatic islets.

PubMed

Zini, Eric; Franchini, Marco; Guscetti, Franco; Osto, Melania; Kaufmann, Karin; Ackermann, Mathias; Lutz, Thomas A; Reusch, Claudia E

2009-12-01

Isolation of pancreatic islets is necessary to study the molecular mechanisms underlying beta-cell demise in diabetic cats. Six collagenase-based methods of isolation were compared in 10 cat pancreata, including single and double course of collagenase, followed or not by Ficoll centrifugation or accutase, and collagenase plus accutase. Morphometric analysis was performed to measure the relative area of islet and exocrine tissue. Islet specific mRNA transcripts were quantified in isolates by real-time PCR. The single and double course of collagenase digestion was successful in each cat and provided similar islet-to-exocrine tissue ratio. Quantities of insulin mRNA did not differ between the two methods. However, on histological examination either method yielded only approximately 2% of pure islets. The other methods provided disrupted islets or insufficient samples in 1-7 cats. Although pancreas digestion with single and double course of collagenase was superior, further studies are needed to improve islet isolation in cats.

Mesenchymal stem cells support neuronal fiber growth in an organotypic brain slice co-culture model.

PubMed

Sygnecka, Katja; Heider, Andreas; Scherf, Nico; Alt, Rüdiger; Franke, Heike; Heine, Claudia

2015-04-01

Mesenchymal stem cells (MSCs) have been identified as promising candidates for neuroregenerative cell therapies. However, the impact of different isolation procedures on the functional and regenerative characteristics of MSC populations has not been studied thoroughly. To quantify these differences, we directly compared classically isolated bulk bone marrow-derived MSCs (bulk BM-MSCs) to the subpopulation Sca-1(+)Lin(-)CD45(-)-derived MSCs(-) (SL45-MSCs), isolated by fluorescence-activated cell sorting from bulk BM-cell suspensions. Both populations were analyzed with respect to functional readouts, that are, frequency of fibroblast colony forming units (CFU-f), general morphology, and expression of stem cell markers. The SL45-MSC population is characterized by greater morphological homogeneity, higher CFU-f frequency, and significantly increased nestin expression compared with bulk BM-MSCs. We further quantified the potential of both cell populations to enhance neuronal fiber growth, using an ex vivo model of organotypic brain slice co-cultures of the mesocortical dopaminergic projection system. The MSC populations were cultivated underneath the slice co-cultures without direct contact using a transwell system. After cultivation, the fiber density in the border region between the two brain slices was quantified. While both populations significantly enhanced fiber outgrowth as compared with controls, purified SL45-MSCs stimulated fiber growth to a larger degree. Subsequently, we analyzed the expression of different growth factors in both cell populations. The results show a significantly higher expression of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor in the SL45-MSCs population. Altogether, we conclude that MSC preparations enriched for primary MSCs promote neuronal regeneration and axonal regrowth, more effectively than bulk BM-MSCs, an effect that may be mediated by a higher BDNF secretion.

Independent Epileptiform Discharge Patterns in the Olfactory and Limbic Areas of the In Vitro Isolated Guinea Pig Brain During 4-Aminopyridine Treatment

PubMed Central

Carriero, Giovanni; Uva, Laura; Gnatkovsky, Vadym; Avoli, Massimo; de Curtis, Marco

2016-01-01

In vitro studies performed on brain slices demonstrate that the potassium channel blocker 4-aminopyridine (4AP, 50 μM) discloses electrographic seizure activity and interictal discharges. These epileptiform patterns have been further analyzed here in a isolated whole guinea pig brain in vitro by using field potential recordings in olfactory and limbic structures. In 8 of 13 experiments runs of fast oscillatory activity (fast runs, FRs) in the piriform cortex (PC) propagated to the lateral entorhinal cortex (EC), hippocampus and occasionally to the medial EC. Early and late FRs were asynchronous in the hemispheres showed different duration [1.78 ± 0.51 and 27.95 ± 4.55 (SD) s, respectively], frequency of occurrence (1.82 ± 0.49 and 34.16 ± 6.03 s) and frequency content (20–40 vs. 40–60 Hz). Preictal spikes independent from the FRs appeared in the hippocampus/EC and developed into ictal-like discharges that did not propagate to the PC. Ictal-like activity consisted of fast activity with onset either in the hippocampus (n = 6) or in the mEC (n = 2), followed by irregular spiking and sequences of diffusely synchronous bursts. Perfusion of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid (100 μM) did not prevent FRs, increased the duration of limbic ictal-like discharges and favored their propagation to olfactory structures. The AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (50 μM) blocked ictal-like events and reduced FRs. In conclusion, 4AP-induced epileptiform activities are asynchronous and independent in olfactory and hippocampal-entorhinal regions. Epileptiform discharges in the isolated guinea pig brain show different pharmacological properties compared with rodent in vitro slices. PMID:20220076

Effects of chronic social isolation on Wistar rat behavior and brain plasticity markers.

PubMed

Djordjevic, Jelena; Djordjevic, Ana; Adzic, Miroslav; Radojcic, Marija B

2012-01-01

Chronic stress is a contributing risk factor in the development of psychiatric illnesses, including depressive disorders. The mechanisms of their psychopathology are multifaceted and include, besides others, alterations in the brain plasticity. Previously, we investigated the effects of chronic social stress in the limbic brain structures of Wistar rats (hippocampus, HIPPO, and prefrontal cortex, PFC) and found multiple characteristics that resembled alterations described in some clinical studies of depression. We extended our investigations and followed the behavior of stressed animals by the open field test (OFT) and forced swimming test (FST), and the expression and polysialylation of synaptic plasticity markers, neural cell adhesion molecule (NCAM) and L1, in the HIPPO and PFC. We also determined the adrenal gland mass and plasma corticosterone (CORT) as a terminal part of the hypothalamic-pituitary-adrenal axis activity. Our data indicated that stressed animals avoided the central zone in the OFT and displayed decreased swimming, but prolonged immobility in the FST. The animals exhibited marked hypertrophy of the adrenal gland cortex, in spite of decreased serum CORT. Simultaneously, the stressed animals exhibited an increase in NCAM mRNA expression in the HIPPO, but not in the PFC. The synaptosomal NCAM of the HIPPO was markedly polysialylated, while cortical PSA-NCAM was significantly decreased. The results showed that chronic social isolation of Wistar rats causes both anxiety-like and depression-like behavior. These alterations are parallel with molecular changes in the limbic brain, including diminished NCAM sialylation in the PFC. Together with our previous results, the current observations suggest that a chronic social isolation model may potentially be used to study molecular mechanisms that underlie depressive symptomatology. Copyright © 2012 S. Karger AG, Basel.

Pathogenicity of an H5N1 avian influenza virus isolated in Vietnam in 2012 and reliability of conjunctival samples for diagnosis of infection.

PubMed

Bui, Vuong N; Dao, Tung D; Nguyen, Tham T H; Nguyen, Lien T; Bui, Anh N; Trinh, Dai Q; Pham, Nga T; Inui, Kenjiro; Runstadler, Jonathan; Ogawa, Haruko; Nguyen, Khong V; Imai, Kunitoshi

2014-01-22

The continued spread of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 among poultry in Vietnam poses a potential threat to animals and public health. To evaluate the pathogenicity of a 2012 H5N1 HPAIV isolate and to assess the utility of conjunctival swabs for viral detection and isolation in surveillance, an experimental infection with HPAIV subtype H5N1 was carried out in domestic ducks. Ducks were infected with 10(7.2) TCID50 of A/duck/Vietnam/QB1207/2012 (H5N1), which was isolated from a moribund domestic duck. In the infected ducks, clinical signs of disease, including neurological disorder, were observed. Ducks started to die at 3 days-post-infection (dpi), and the study mortality reached 67%. Viruses were recovered from oropharyngeal and conjunctival swabs until 7 dpi and from cloacal swabs until 4 dpi. In the ducks that died or were sacrificed on 3, 5, or 6 dpi, viruses were recovered from lung, brain, heart, pancreas and intestine, among which the highest virus titers were in the lung, brain or heart. Results of virus titration were confirmed by real-time RT-PCR. Genetic and phylogenetic analysis of the HA gene revealed that the isolate belongs to clade 2.3.2.1 similarly to the H5N1 viruses isolated in Vietnam in 2012. The present study demonstrated that this recent HPAI H5N1 virus of clade 2.3.2.1 could replicate efficiently in the systemic organs, including the brain, and cause severe disease with neurological symptoms in domestic ducks. Therefore, this HPAI H5N1 virus seems to retain the neurotrophic feature and has further developed properties of shedding virus from the oropharynx and conjunctiva in addition to the cloaca, potentially posing a higher risk of virus spread through cross-contact and/or environmental transmission. Continued surveillance and diagnostic programs using conjunctival swabs in the field would further verify the apparent reliability of conjunctival samples for the detection of AIV. Copyright © 2013 Elsevier B.V. All rights reserved.

Pathogenicity of an H5N1 avian influenza virus isolated in Vietnam in 2012 and reliability of conjunctival samples for diagnosis of infection

PubMed Central

Bui, Vuong N.; Dao, Tung D.; Nguyen, Tham T. H.; Nguyen, Lien T.; Bui, Anh N.; Trinh, Dai Q.; Pham, Nga T.; Inui, Kenjiro; Runstadler, Jonathan; Ogawa, Haruko; Nguyen, Khong V.; Imai, Kunitoshi

2013-01-01

The continued spread of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 among poultry in Vietnam poses a potential threat to animals and public health. To evaluate the pathogenicity of a 2012 H5N1 HPAIV isolate and to assess the utility of conjunctival swabs for viral detection and isolation in surveillance, an experimental infection with HPAIV subtype H5N1 was carried out in domestic ducks. Ducks were infected with 107.2 TCID50 of A/duck/Vietnam/QB1207/2012 (H5N1), which was isolated from a moribund domestic duck. In the infected ducks, clinical signs of disease, including neurological disorder, were observed. Ducks started to die at 3 days-post-infection (dpi), and the study mortality reached 67%. Viruses were recovered from oropharyngeal and conjunctival swabs until 7 dpi and from cloacal swabs until 4 dpi. In the ducks that died or were sacrificed on 3, 5, or 6 dpi, viruses were recovered from lung, brain, heart, pancreas and intestine, among which the highest virus titers were in the lung, brain or heart. Results of virus titration were confirmed by real-time RT-PCR. Genetic and phylogenetic analysis of the HA gene revealed that the isolate belongs to clade 2.3.2.1 similarly to the H5N1 viruses isolated in Vietnam in 2012. The present study demonstrated that this recent HPAI H5N1 virus of clade 2.3.2.1 could replicate efficiently in the systemic organs, including the brain, and cause severe disease with neurological symptoms in domestic ducks. Therefore, this HPAI H5N1 virus seems to retain the neurotrophic feature and has further developed properties of shedding virus from the oropharynx and conjunctiva in addition to the cloaca, potentially posing a higher risk of virus spread through cross-contact and/or environmental transmission. Continued surveillance and diagnostic programs using conjuntcival swabs in the field would further verify the apparent reliability of conjunctival samples for the detection of AIV. PMID:24211664

Cell diversity and network dynamics in photosensitive human brain organoids

PubMed Central

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

2017-01-01

In vitro models of the developing brain such as 3D brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, it remains undefined what cells are generated within organoids and to what extent they recapitulate the regional complexity, cellular diversity, and circuit functionality of the brain. Here, we analyzed 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 (over 9 months) enabling unprecedented levels of maturity including the formation of dendritic spines and of spontaneously-active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photoreceptor-like cells, which may offer ways to probe the functionality of human neuronal circuits using physiological sensory stimuli. PMID:28445462

Cell diversity and network dynamics in photosensitive human brain organoids.

PubMed

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.

Further refinement of the Escherichia coli brain abscess model in rat.

PubMed

Nazzaro, J M; Pagel, M A; Neuwelt, E A

1992-09-01

The rat brain abscess model provides a substrate for the modeling of delivery of therapeutic agents to intracerebral mass lesions. We now report refinement of the Escherichia coli brain abscess model in rat. A K1 surface antigen-negative E. coli isolated from human blood culture was stereotaxically inoculated into deep brain sites. Histopathologic analyses and quantitative cultures demonstrated the consistent production of lesions. No animal in this consecutive series developed meningitis, ventriculitis or sepsis. By contrast, prior experience with E. coli abscess production resulted in 25% failure rate of abscess production or death from sepsis. This improvement in the model may be attributable to specific characteristics of the bacteria used, modification of the inoculation method or the intracerebral placement technique. The present work suggests a reliable and consistent brain abscess model, which may be further used to study brain suppuration.

Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS)

PubMed Central

Chandra, Subhash; Parker, Dylan J.; Barth, Rolf F.; Pannullo, Susan C.

2016-01-01

Glioblastoma multiforme (GBM) is one of the deadliest forms of human brain tumors. The infiltrative pattern of growth of these tumors includes the spread of individual and/or clusters of tumor cells at some distance from the main tumor mass in parts of the brain protected by an intact blood-brain-barrier. Pathophysiological studies of GBM could be greatly enhanced by analytical techniques capable of in situ single-cell resolution measurements of infiltrating tumor cells. Magnesium homeostasis is an area of active investigation in high grade gliomas. In the present study, we have used the F98 rat glioma as a model of human GBM and an elemental/isotopic imaging technique of secondary ion mass spectrometry (SIMS), a CAMECA IMS-3f ion microscope, for studying Mg distributions with single-cell resolution in freeze-dried brain tissue cryosections. Quantitative observations were made on tumor cells in the main tumor mass, contiguous brain tissue, and infiltrating tumor cells in adjacent normal brain. The brain tissue contained a significantly lower total Mg concentration of 4.70 ± 0.93 mmol/Kg wet weight (mean ± SD) in comparison to 11.64 ± 1.96 mmol/Kg wet weight in tumor cells of the main tumor mass and 10.72 ± 1.76 mmol/Kg wet weight in infiltrating tumor cells (p<0.05). The nucleus of individual tumor cells contained elevated levels of bound Mg. These observations demonstrate enhanced Mg-influx and increased binding of Mg in tumor cells and provide strong support for further investigation of GBMs for altered Mg homeostasis and activation of Mg-transporting channels as possible therapeutic targets. PMID:26703785

Anomalous single-subject based morphological cortical networks in drug-naive, first-episode major depressive disorder.

PubMed

Chen, Taolin; Kendrick, Keith M; Wang, Jinhui; Wu, Min; Li, Kaiming; Huang, Xiaoqi; Luo, Yuejia; Lui, Su; Sweeney, John A; Gong, Qiyong

2017-05-01

Major depressive disorder (MDD) has been associated with disruptions in the topological organization of brain morphological networks in group-level data. Such disruptions have not yet been identified in single-patients, which is needed to show relations with symptom severity and to evaluate their potential as biomarkers for illness. To address this issue, we conducted a cross-sectional structural brain network study of 33 treatment-naive, first-episode MDD patients and 33 age-, gender-, and education-matched healthy controls (HCs). Weighted graph-theory based network models were used to characterize the topological organization of brain networks between the two groups. Compared with HCs, MDD patients exhibited lower normalized global efficiency and higher modularity in their whole-brain morphological networks, suggesting impaired integration and increased segregation of morphological brain networks in the patients. Locally, MDD patients exhibited lower efficiency in anatomic organization for transferring information predominantly in default-mode regions including the hippocampus, parahippocampal gyrus, precuneus and superior parietal lobule, and higher efficiency in the insula, calcarine and posterior cingulate cortex, and in the cerebellum. Morphological connectivity comparisons revealed two subnetworks that exhibited higher connectivity strength in MDD mainly involving neocortex-striatum-thalamus-cerebellum and thalamo-hippocampal circuitry. MDD-related alterations correlated with symptom severity and differentiated individuals with MDD from HCs with a sensitivity of 87.9% and specificity of 81.8%. Our findings indicate that single subject grey matter morphological networks are often disrupted in clinically relevant ways in treatment-naive, first episode MDD patients. Circuit-specific changes in brain anatomic network organization suggest alterations in the efficiency of information transfer within particular brain networks in MDD. Hum Brain Mapp 38:2482-2494, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

SU-G-BRC-14: Multi-Lesion, Multi-Rx, Brain Radiosurgery with Novel Single Isocenter Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honig, N; Alani, S; Schlocker, A

Purpose: There is a strong trend to treat multiple brain metastases with radiosurgery rather than whole brain irradiation. This feasibility study investigates a novel planning technique for radio-surgical treatment of multiple brain lesions with differing dose prescriptions, a single isocenter, and dynamic conformal arcs. The novel technique will be compared to the well-established single-isocenter volumetric modulated arc therapy (VMAT) technique commonly used for treating brain lesions. Methods: Six patients with metastatic brain lesions were selected for a prospective treatment planning study to evaluate Interdigitating MLC Dynamic Conformal Arc (IMDCA) technique. Arcs were planned for simultaneous irradiation to maximize beam deliverymore » efficiency. To accommodate varying PTV dose prescriptions, selected arcs were re-irradiated in reverse. Beam weights were adjusted until all prescription constraints were met. The number of lesions ranged between 2 to 4 (mode = 3). For comparison, SRS VMAT plans were generated utilizing an established single-isocenter, 3 arc planning template. All plans were compared by means of Paddick conformity index (PCI), RTOG Conformity Index (RCI), gradient index (GI), and the normal brain volume receiving 10% (V10) of the highest prescription dose. The monitor units and delivery time were tabulated for each plan. Results: IMDCA achieved conformal plans (PCI = 0.72±0.03, RCI = 1.33±0.03) with steep dose fall-off (GI = 3.79±0.03) on average for all of the plans evaluated. The VMAT plans had slightly better conformity (PCI = 0.85 ± 0.03, RCI = 1.13 ± 0.03) than IMDCA, but overall worse GI (4.29 ± 0.06). IMDCA plans had lower V10% values, required 50% fewer MUs, and had 34% shorter beam delivery time on average compared to VMAT plans. Conclusion: IMDCA plans with varying dose prescriptions for multiple lesions, had comparable dosimetric coverage as VMAT plans, but were obtained with significantly lower integral dose, fewer monitor units, and quicker delivery time.« less

Plasmid and surface antigen markers of endemic and epidemic Legionella pneumophila strains.

PubMed Central

Brown, A; Vickers, R M; Elder, E M; Lema, M; Garrity, G M

1982-01-01

Environmental and clinical isolates of Legionella pneumophila obtained from the Pittsburgh Veterans Administration Medical Center were studied for the presence of plasmids and for unique surface antigens. The majority of environmental isolates contained a single 80-megadalton plasmid. After an epidemic of nosocomial Legionnaires disease subsided in the Spring of 1981, plasmid-bearing environmental isolates persisted in the environment. Whereas L. pneumophila could not be reisolated from most sites with plasmidless isolates. During this epidemic the attack rate was highest on wards with plasmidless isolates. All clinical isolates were plasmidless. Strains were serotyped by the indirect immunofluorescence method with serum from a single immunized rat which was used both without absorption and after absorption with various plasmid-bearing and plasmidless isolates. These studies suggested that a plasmid-associated surface antigen was present and that the most common plasmidless environmental serotype was similar to the epidemic clinical serotype. Images PMID:7119096

Brain Magnetic Resonance Imaging as First-Line Investigation for Growth Hormone Deficiency Diagnosis in Early Childhood.

PubMed

Pampanini, Valentina; Pedicelli, Stefania; Gubinelli, Jessica; Scirè, Giuseppe; Cappa, Marco; Boscherini, Brunetto; Cianfarani, Stefano

2015-01-01

The diagnosis of growth hormone (GH) deficiency (GHD) in infancy and early childhood is not straightforward. GH stimulation tests are unsafe and unreliable in infants, and normative data are lacking. This study aims to investigate whether brain magnetic resonance imaging (MRI) may replace GH stimulation tests in the diagnosis of GHD in children younger than 4 years. We examined a retrospective cohort, with longitudinal follow-up, of 68 children consecutively diagnosed with GHD before the age of 4 years. The prevalence of hypothalamic-pituitary (HP) alterations at MRI and the associations with age and either isolated GHD (IGHD) or multiple pituitary hormone deficiency (MPHD) were assessed. The prevalences of IGHD and MPHD were 54.4 and 45.6%, respectively. In the first group, brain MRI showed abnormalities in 83.8%: isolated pituitary hypoplasia in 48.7% and complex defects in 35.1%. In patients with MPHD, MRI showed complex alterations in 100%. All children younger than 24 months showed HP MRI abnormalities, regardless of the diagnosis. Complex defects were found in 94% of patients younger than 12 months and in 75% of patients between 13 and 24 months. Our data suggest that brain MRI may represent the first-line investigation for diagnosing GHD in infancy and early childhood. © 2015 S. Karger AG, Basel.

Routine cervical spine immobilisation is unnecessary in patients with isolated cerebral gunshot wounds: A South African experience.

PubMed

Kong, Victor Y; Weale, Ross D; Sartorius, Benn; Bruce, John L; Laing, Grant L; Clarke, Damian L

2018-04-25

Routine immobilisation of the cervical spine in trauma has been a long established practice. Very little is known in regard to its appropriateness in the specific setting of isolated traumatic brain injury secondary to gunshot wounds (GSWs). A retrospective study was conducted over a 5 year period (January 2010 to December 2014) at the Pietermaritzburg Metropolitan Trauma Service, Pietermaritzburg, South Africa in order to determine the actual incidence of concomitant cervical spine injury (CSI) in the setting of isolated cerebral GSWs. During the 5 year study period, 102 patients were included. Ninety-two per cent (94/102) were male and the mean age was 29 years. Ninety-eight per cent of the injuries were secondary to low velocity GSWs. Twenty-seven (26%) patients had cervical collar placed by the Emergency Medical Service. The remaining 75 patients had their cervical collar placed in the resuscitation room. Fifty-five (54%) patients had a Glasgow Coma Scale (GCS) of 15 and underwent plain radiography, all of which were normal. Clearance of cervical spine based on normal radiography combined with clinical assessment was achieved in all 55 (100%) patients. The remaining 47 patients whose GCS was <15 all underwent a computed tomography (CT) scan of their cervical spine and brain. All 47 CT scans of the cervical spine were normal and there was no detectable bone or soft tissue injury noted. Patients who sustain an isolated low velocity cerebral GSW are highly unlikely to have concomitant CSI. Routine cervical spine immobilisation is unnecessary, and efforts should be directed at management strategies aiming to prevent secondary brain injury. Further studies are required to address the issue in the setting of high velocity GSWs. © 2018 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Nobiletin attenuates neurotoxic mitochondrial calcium overload through K+ influx and ΔΨm across mitochondrial inner membrane.

PubMed

Lee, Ji Hyung; Amarsanaa, Khulan; Wu, Jinji; Jeon, Sang-Chan; Cui, Yanji; Jung, Sung-Cherl; Park, Deok-Bae; Kim, Se-Jae; Han, Sang-Heon; Kim, Hyun-Wook; Rhyu, Im Joo; Eun, Su-Yong

2018-05-01

Mitochondrial calcium overload is a crucial event in determining the fate of neuronal cell survival and death, implicated in pathogenesis of neurodegenerative diseases. One of the driving forces of calcium influx into mitochondria is mitochondria membrane potential (ΔΨ m ). Therefore, pharmacological manipulation of ΔΨ m can be a promising strategy to prevent neuronal cell death against brain insults. Based on these issues, we investigated here whether nobiletin, a Citrus polymethoxylated flavone, prevents neurotoxic neuronal calcium overload and cell death via regulating basal ΔΨ m against neuronal insult in primary cortical neurons and pure brain mitochondria isolated from rat cortices. Results demonstrated that nobiletin treatment significantly increased cell viability against glutamate toxicity (100 µM, 20 min) in primary cortical neurons. Real-time imaging-based fluorometry data reveal that nobiletin evokes partial mitochondrial depolarization in these neurons. Nobiletin markedly attenuated mitochondrial calcium overload and reactive oxygen species (ROS) generation in glutamate (100 µM)-stimulated cortical neurons and isolated pure mitochondria exposed to high concentration of Ca 2+ (5 µM). Nobiletin-induced partial mitochondrial depolarization in intact neurons was confirmed in isolated brain mitochondria using a fluorescence microplate reader. Nobiletin effects on basal ΔΨ m were completely abolished in K + -free medium on pure isolated mitochondria. Taken together, results demonstrate that K + influx into mitochondria is critically involved in partial mitochondrial depolarization-related neuroprotective effect of nobiletin. Nobiletin-induced mitochondrial K + influx is probably mediated, at least in part, by activation of mitochondrial K + channels. However, further detailed studies should be conducted to determine exact molecular targets of nobiletin in mitochondria.

Cerebellar stroke presenting with isolated dizziness: Brain MRI in 136 patients.

PubMed

Perloff, Michael D; Patel, Nimesh S; Kase, Carlos S; Oza, Anuja U; Voetsch, Barbara; Romero, Jose R

2017-11-01

To evaluate occurrence of cerebellar stroke in Emergency Department (ED) presentations of isolated dizziness (dizziness with a normal exam and negative neurological review of systems). A 5-year retrospective study of ED patients presenting with a chief complaint of "dizziness or vertigo", without other symptoms or signs in narrative history or on exam to suggest a central nervous system lesion, and work-up included a brain MRI within 48h. Patients with symptoms commonly peripheral in etiology (nystagmus, tinnitus, gait instability, etc.) were included in the study. Patient demographics, stroke risk factors, and gait assessments were recorded. One hundred and thirty-six patients, who had a brain MRI for isolated dizziness, were included. There was a low correlation of gait assessment between ED physician and Neurologist (49 patients, Spearman's correlation r 2 =0.17). Based on MRI DWI sequence, 3.7% (5/136 patients) had acute cerebellar strokes, limited to or including, the medial posterior inferior cerebellar artery vascular territory. In the 5 cerebellar stroke patients, mean age, body mass index (BMI), hemoglobin A1c, gender distribution, and prevalence of hypertension were similar to the non-cerebellar stroke patient group. Mean LDL/HDL ratio was 3.63±0.80 and smoking prevalence was 80% in the cerebellar stroke group compared to 2.43±0.79 and 22% (respectively, p values<0.01) in the non-cerebellar stroke group. Though there was preselection bias for stroke risk factors, our study suggests an important proportion of cerebellar stroke among ED patients with isolated dizziness, considering how common this complaint is. Copyright © 2017 Elsevier Inc. All rights reserved.

Isolation of Protein-Associated Circular DNA from Healthy Cattle Serum

PubMed Central

Funk, Mathis; Gunst, Karin; Lucansky, Vincent; Müller, Hermann; zur Hausen, Harald

2014-01-01

Three replication-competent single-stranded DNA molecules sharing nucleotide similarity to transmissible spongiform encephalopathy (TSE)-associated isolate Sphinx 2.36 were isolated from healthy bovine serum. PMID:25169856

Brain Metastases from Endometrial Carcinoma

PubMed Central

Piura, Ettie; Piura, Benjamin

2012-01-01

This paper will focus on knowledge related to brain metastases from endometrial carcinoma. To date, 115 cases were documented in the literature with an incidence of 0.6% among endometrial carcinoma patients. The endometrial carcinoma was usually an advanced-stage and high-grade tumor. In most patients (~90%), brain metastasis was detected after diagnosis of endometrial carcinoma with a median interval from diagnosis of endometrial carcinoma to diagnosis of brain metastases of 17 months. Brain metastasis from endometrial carcinoma was either an isolated disease limited to the brain only (~50%) or part of a disseminated disease involving also other parts of the body (~50%). Most often, brain metastasis from endometrial carcinoma affected the cerebrum (~75%) and was solitary (~60%). The median survival after diagnosis of brain metastases from endometrial carcinoma was 5 months; however, a significantly better survival was achieved with multimodal therapy including surgical resection or stereotactic radiosurgery followed by whole brain radiotherapy (WBRT) and/or chemotherapy compared to WBRT alone. It is suggested that brain imaging studies should be considered in the routine follow up of patients with endometrial carcinoma and that the search for a primary source in females with brain metastases of unknown primary should include endometrial biopsy. PMID:22523707

Ketamine changes the local resting-state functional properties of anesthetized-monkey brain.

PubMed

Rao, Jia-Sheng; Liu, Zuxiang; Zhao, Can; Wei, Rui-Han; Zhao, Wen; Tian, Peng-Yu; Zhou, Xia; Yang, Zhao-Yang; Li, Xiao-Guang

2017-11-01

Ketamine is a well-known anesthetic. 'Recreational' use of ketamine common induces psychosis-like symptoms and cognitive impairments. The acute and chronic effects of ketamine on relevant brain circuits have been studied, but the effects of single-dose ketamine administration on the local resting-state functional properties of the brain remain unknown. In this study, we aimed to assess the effects of single-dose ketamine administration on the brain local intrinsic properties. We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to examine the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in the brain before and after ketamine injection. Paired comparisons were used to detect the significantly altered regions. Results showed that the fALFF of the prefrontal cortex (p=0.046), caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020) in post-injection stage significantly increased compared with those in pre-injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that of prefrontal cortex decreased (p<0.05). These findings demonstrated that single-dose ketamine administration can change the regional intensity and synchronism of brain activity, thereby providing evidence of ketamine-induced abnormal resting-state functional properties in primates. This evidence may help further elucidate the effects of ketamine on the cerebral resting status. Copyright © 2017. Published by Elsevier Inc.

The neuroendocrinology of social isolation.

PubMed

Cacioppo, John T; Cacioppo, Stephanie; Capitanio, John P; Cole, Steven W

2015-01-03

Social isolation has been recognized as a major risk factor for morbidity and mortality in humans for more than a quarter of a century. Although the focus of research has been on objective social roles and health behavior, the brain is the key organ for forming, monitoring, maintaining, repairing, and replacing salutary connections with others. Accordingly, population-based longitudinal research indicates that perceived social isolation (loneliness) is a risk factor for morbidity and mortality independent of objective social isolation and health behavior. Human and animal investigations of neuroendocrine stress mechanisms that may be involved suggest that (a) chronic social isolation increases the activation of the hypothalamic pituitary adrenocortical axis, and (b) these effects are more dependent on the disruption of a social bond between a significant pair than objective isolation per se. The relational factors and neuroendocrine, neurobiological, and genetic mechanisms that may contribute to the association between perceived isolation and mortality are reviewed.

The Neuroendocrinology of Social Isolation

PubMed Central

Cacioppo, John T.; Cacioppo, Stephanie; Capitanio, John P.; Cole, Steven W.

2016-01-01

Social isolation has been recognized as a major risk factor for morbidity and mortality in humans for more than a quarter of a century. Although the focus of research has been on objective social roles and health behavior, the brain is the key organ for forming, monitoring, maintaining, repairing, and replacing salutary connections with others. Accordingly, population-based longitudinal research indicates that perceived social isolation (loneliness) is a risk factor for morbidity and mortality independent of objective social isolation and health behavior. Human and animal investigations of neuroendocrine stress mechanisms that may be involved suggest that (a) chronic social isolation increases the activation of the hypothalamic pituitary adrenocortical axis, and (b) these effects are more dependent on the disruption of a social bond between a significant pair than objective isolation per se. The relational factors and neuroendocrine, neurobiological, and genetic mechanisms that may contribute to the association between perceived isolation and mortality are reviewed. PMID:25148851

Self-Assembly of Gold Nanoparticles Shows Microenvironment-Mediated Dynamic Switching and Enhanced Brain Tumor Targeting

PubMed Central

Feng, Qishuai; Shen, Yajing; Fu, Yingjie; Muroski, Megan E.; Zhang, Peng; Wang, Qiaoyue; Xu, Chang; Lesniak, Maciej S.; Li, Gang; Cheng, Yu

2017-01-01

Inorganic nanoparticles with unique physical properties have been explored as nanomedicines for brain tumor treatment. However, the clinical applications of the inorganic formulations are often hindered by the biological barriers and failure to be bioeliminated. The size of the nanoparticle is an essential design parameter which plays a significant role to affect the tumor targeting and biodistribution. Here, we report a feasible approach for the assembly of gold nanoparticles into ~80 nm nanospheres as a drug delivery platform for enhanced retention in brain tumors with the ability to be dynamically switched into the single formulation for excretion. These nanoassemblies can target epidermal growth factor receptors on cancer cells and are responsive to tumor microenvironmental characteristics, including high vascular permeability and acidic and redox conditions. Anticancer drug release was controlled by a pH-responsive mechanism. Intracellular L-glutathione (GSH) triggered the complete breakdown of nanoassemblies to single gold nanoparticles. Furthermore, in vivo studies have shown that nanospheres display enhanced tumor-targeting efficiency and therapeutic effects relative to single-nanoparticle formulations. Hence, gold nanoassemblies present an effective targeting strategy for brain tumor treatment. PMID:28638474

Self-Assembly of Gold Nanoparticles Shows Microenvironment-Mediated Dynamic Switching and Enhanced Brain Tumor Targeting.

PubMed

Feng, Qishuai; Shen, Yajing; Fu, Yingjie; Muroski, Megan E; Zhang, Peng; Wang, Qiaoyue; Xu, Chang; Lesniak, Maciej S; Li, Gang; Cheng, Yu

2017-01-01

Inorganic nanoparticles with unique physical properties have been explored as nanomedicines for brain tumor treatment. However, the clinical applications of the inorganic formulations are often hindered by the biological barriers and failure to be bioeliminated. The size of the nanoparticle is an essential design parameter which plays a significant role to affect the tumor targeting and biodistribution. Here, we report a feasible approach for the assembly of gold nanoparticles into ~80 nm nanospheres as a drug delivery platform for enhanced retention in brain tumors with the ability to be dynamically switched into the single formulation for excretion. These nanoassemblies can target epidermal growth factor receptors on cancer cells and are responsive to tumor microenvironmental characteristics, including high vascular permeability and acidic and redox conditions. Anticancer drug release was controlled by a pH-responsive mechanism. Intracellular L-glutathione (GSH) triggered the complete breakdown of nanoassemblies to single gold nanoparticles. Furthermore, in vivo studies have shown that nanospheres display enhanced tumor-targeting efficiency and therapeutic effects relative to single-nanoparticle formulations. Hence, gold nanoassemblies present an effective targeting strategy for brain tumor treatment.

The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles

PubMed Central

Barrett, C E; Arambula, S E; Young, L J

2015-01-01

Genes and social experiences interact to create variation in social behavior and vulnerability to develop disorders of the social domain. Socially monogamous prairie voles display remarkable diversity in neuropeptide receptor systems and social behavior. Here, we examine the interaction of early-life adversity and brain oxytocin receptor (OTR) density on adult social attachment in female prairie voles. First, pups were isolated for 3 h per day, or unmanipulated, from postnatal day 1–14. Adult subjects were tested on the partner preference (PP) test to assess social attachment and OTR density in the brain was quantified. Neonatal social isolation impaired female PP formation, without affecting OTR density. Accumbal OTR density was, however, positively correlated with the percent of time spent huddling with the partner in neonatally isolated females. Females with high accumbal OTR binding were resilient to neonatal isolation. These results are consistent with the hypothesis that parental nurturing shapes neural systems underlying social relationships by enhancing striatal OTR signaling. Thus, we next determined whether early touch, mimicking parental licking and grooming, stimulates hypothalamic OT neuron activity. Tactile stimulation induced immediate-early gene activity in OT neurons in neonates. Finally, we investigated whether pharmacologically potentiating OT release using a melanocortin 3/4 agonist, melanotan-II (10 mg kg−1 subcutaneously), would mitigate the social isolation-induced impairments in attachment behavior. Neonatal melanotan-II administration buffered against the effects of early isolation on partner preference formation. Thus, variation in accumbal OTR density and early OT release induced by parental nurturing may moderate susceptibility to early adverse experiences, including neglect. PMID:26196439

Variations of pituitary function over time after brain injuries: the lesson from a prospective study.

PubMed

Giordano, Giulio; Aimaretti, Gianluca; Ghigo, Ezio

2005-01-01

Traumatic Brain Injury (TBI) and Subarachnoid Haemorrhage (SAH) are conditions at high risk to develop hypopituitarism as pointed out by many papers in scientific literature. But most of the papers were referred to retrospective evaluations, not considering the possible evolution of the pituitary function over time. Aim of our studies was to clarify whether pituitary deficiencies and normal pituitary function recorded at short term follow-up (3 months), would improve or worsen, respectively, at long term (12 months after the brain injury). In a multicenter study protocol, in patients who suffered TBI (n = 70; 50 Males, 20 Females; age 39.31 +/- 2.4 years; BMI 23.8 +/- 0.4 kg/m(2)) or SAH (n = 32; 12M, 20F; age: 51.9 +/- 2.2 year; BMI: 24.7 +/- 0.6 kg/m(2)) we tested 3 and 12 months after the pathological events the pituitary function. In TBI patients, the 3 month evaluation had shown some degree of hypopituitarism in 32.8% and the 12 months retesting demonstrated some degree of hypopituitarism in 22.7%. Total hypopituitarism was always confirmed at 12 months while Multiple and Isolated deficits recorded at 3 months was confirmed in nearly 25% only of the patients. On the other hand, in 5.5% of TBI with normal pituitary function at 3 months Isolated deficits were recorded at 12 months testing. Moreover, in 13.3% of TBI with Isolated deficit at 3 months Multiple hypopituitarism was demonstrated at 12 months retesting. In SAH patients, the 3 months evaluation had shown some degree of hypopituitarism in 46.8% and the 12 month retesting demonstrated some degree of hypopituitarism in 37.5%. No multiple hypopituitarism recorded at 3 months was confirmed at 12 months, but 2 patients with isolated deficits at 3 months showed multiple hypopituitarism at 12 month retesting. At 12 as well as at 3 months, both in TBI and SAH patients, the most common deficit was severe GHD (>20%) followed by secondary hypogonadism and then hypoadrenalism and hypothyroidism. In all, in patients who experienced TBI or SAH the risk to develop hypopituitarism is very high; early diagnosis of total hypopituitarism is always confirmed at the long term follow-up; however pituitary function in brain injured patients may improve over time, because, isolated and even multiple pituitary insufficiencies recorded at short term can be transient; on the other hand normal pituitary function recorder at short term may, become impaired 12 months after the injury. Thus, brain injured patients must undergo neuroendocrine follow-up over time in order to monitoring pituitary function and eventually providing appropriate placement.

The Circadian Clock of the Ant Camponotus floridanus Is Localized in Dorsal and Lateral Neurons of the Brain.

PubMed

Kay, Janina; Menegazzi, Pamela; Mildner, Stephanie; Roces, Flavio; Helfrich-Förster, Charlotte

2018-06-01

The circadian clock of social insects has become a focal point of interest for research, as social insects show complex forms of timed behavior and organization within their colonies. These behaviors include brood care, nest maintenance, foraging, swarming, defense, and many other tasks, of which several require social synchronization and accurate timing. Ants of the genus Camponotus have been shown to display a variety of daily timed behaviors such as the emergence of males from the nest, foraging, and relocation of brood. Nevertheless, circadian rhythms of isolated individuals have been studied in few ant species, and the circadian clock network in the brain that governs such behaviors remains completely uncharacterized. Here we show that isolated minor workers of Camponotus floridanus exhibit temperature overcompensated free-running locomotor activity rhythms under constant darkness. Under light-dark cycles, most animals are active during day and night, with a slight preference for the night. On the neurobiological level, we show that distinct cell groups in the lateral and dorsal brain of minor workers of C. floridanus are immunostained with an antibody against the clock protein Period (PER) and a lateral group additionally with an antibody against the neuropeptide pigment-dispersing factor (PDF). PER abundance oscillates in a daily manner, and PDF-positive neurites invade most parts of the brain, suggesting that the PER/PDF-positive neurons are bona fide clock neurons that transfer rhythmic signals into the relevant brain areas controlling rhythmic behavior.

Liquid chromatographic determination of minocycline in brain-to-plasma distribution studies in the rat.

PubMed

Colovic, Milena; Caccia, Silvio

2003-07-05

An isocratic reversed-phase high-performance liquid chromatographic procedure was developed for the determination of minocycline in rat plasma and brain and applied to brain-to-blood (plasma) distribution studies. The procedure is based on isolation of the compound and the internal standard (either demeclocycline or tetracycline may be used) from plasma and brain constituents using the Oasis HLB cartridge, with satisfactory recovery and specificity, and separation on a Symmetry Shield RP8 (15 cm x 4.6 mm, 3.5 microm) column coupled with a UV detector set at 350 nm. The assay was linear over a wide range, with a lower limit of quantification of 50 ng ml(-1) or g(-1), using 0.2 ml of plasma and about 200 mg of brain tissue. Precision and accuracy were acceptable. In the rat minocycline crossed the blood-brain barrier slowly, achieving mean brain concentrations between 30 and 40% of the equivalent systemic exposure, regardless of the dose and route of administration.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2014-09-01

810. 22. Plow EB, Carey JR, Nudo RJ, Pascual-Leone A (2009) Invasive cortical stimulation to promote recovery of function after stroke: A critical...stimulation of the motor cortex enhances pro- genitor cell migration in the adult rat brain. Exp Brain Res 231(2):165–177. 28. Edwardson MA, Lucas TH, Carey ...The screws and rod were further secured with dental acrylic (all animals). In both the ADS and OLS groups, a hybrid, 16-channel, single-shank, chronic

miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway.

PubMed

Zhang, Yu; Wei, Guangkuan; Di, Zhiyong; Zhao, Qingjie

2014-09-26

Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of active compounds from Aurantii Immatri Pericarpium attenuating brain injury in a rat model of ischemia-reperfusion.

PubMed

Yang, Eun-Ju; Lim, Sun Ha; Song, Kyung-Sik; Han, Hyung Soo; Lee, Jongwon

2013-05-01

Ischemic stroke is caused by brain injury due to prolonged ischemia by occlusion of cerebral arteries. In this study, we isolated active compounds from an ethanol extract of Aurantii Immatri Pericarpium (HY5356). We first showed by DNA fragmentation assay that HY5356 improved human hepatocellular carcinoma cells (HepG2) under hypoxic conditions by inhibiting apoptosis. When HY5356 was fractionated with dichloromethane (MC), ethyl acetate (EA) and n-butanol (BU), the MC fraction improved cell viability at the lowest concentration (100 μg/ml). Intraperitoneal injection of HY5356 (200 mg/kg) or the MC fraction (200 mg/kg) to rats prior to occlusion attenuated brain injury significantly in a rat model of ischemia-reperfusion. Adopting cell viability under hypoxic conditions as an activity screening system, we isolated nobiletin and tangeretin as active compounds. The results suggest that intake of Aurantii Immatri Pericarpium containing nobiletin and tangeretin as active compounds might be beneficial for preventing ischemic stroke. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vibrio parahaemolyticus- and V. alginolyticus-associated meningo-encephalitis in a bottlenose dolphin (Tursiops truncatus) from the Adriatic coast of Italy.

PubMed

Di Renzo, Ludovica; Di Francesco, Gabriella; Profico, Chiara; Di Francesco, Cristina E; Ferri, Nicola; Averaimo, Daniela; Di Guardo, Giovanni

2017-12-01

A case of Vibrio parahaemolyticus- and V. alginolyticus-associated meningo-encephalitis in a bottlenose dolphin (Tursiops truncatus) found stranded along the Adriatic coast of Italy in 2016 is herein reported, along with a minireview on V. parahaemolyticus and V. alginolyticus infections in aquatic mammals. Macroscopically, two abscesses were found in the dolphin's forebrain, along with an extensive, bilateral, parasitic broncho-pneumonia. Histologically, a suppurative-to-pyogranulomatous meningo-encephalitis involved the brain but not the cerebellum. Microbiological investigations yielded isolation of V. parahaemolyticus and V. alginolyticus from the aforementioned abscesses and from the brain parenchyma, respectively, with simultaneous recovery of Shewanella algae from the heart and of Photobacterium damselae from a blowhole swab. Although V. parahaemolyticus and V. alginolyticus, which are widely distributed across marine ecosystems worldwide, likely played a role in the development of the suppurative meningo-encephalitis in this dolphin, we are not aware of previous isolations of any of these two bacteria neither from cetacean brain lesions, nor from abscesses in aquatic mammals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gender differences in human single neuron responses to male emotional faces.

PubMed

Newhoff, Morgan; Treiman, David M; Smith, Kris A; Steinmetz, Peter N

2015-01-01

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and ventromedial prefrontal cortex (n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% (n = 15∕66) of neurons in men were significantly affected by facial emotion, vs. 8% (n = 6∕76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p < 0.01). These results show specific differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala.

Isolated Flinders Sensitive Line rats have decreased dopamine D2 receptor mRNA.

PubMed

Bjørnebekk, Astrid; Mathé, Aleksander A; Brené, Stefan

2007-07-02

Social isolation has profound effects on animal behavior and dopamine systems. We investigated the effect of social isolation on the dopamine receptor and neuropeptide mRNAs in the brain reward system in an animal model of depression, the Flinders Sensitive Line rats and Sprague-Dawley controls. We demonstrate that socially isolated but not group housed Flinders sensitive line rats had lower dopamine D2 receptor mRNA levels compared with Sprague-Dawley rats. Isolated and group housed Flinders Sensitive Line rats had higher levels of dopamine D1 receptor and substance P and enkephalin but not dynorphin mRNAs when compared with Sprague-Dawley rats. Our findings of decreased dopamine D2 receptor levels in socially isolated Flinders Sensitive Line rats suggest that low D2 receptor expression may play a role in pathophysiology of depression.

The Brain Dynamics of Intellectual Development: Waxing and Waning White and Gray Matter

ERIC Educational Resources Information Center

Tamnes, Christian K.; Fjell, Anders M.; Ostby, Ylva; Westlye, Lars T.; Due-Tonnessen, Paulina; Bjornerud, Atle; Walhovd, Kristine B.

2011-01-01

Distributed brain areas support intellectual abilities in adults. How structural maturation of these areas in childhood enables development of intelligence is not established. Neuroimaging can be used to monitor brain development, but studies to date have typically considered single imaging modalities. To explore the impact of structural brain…

Evaluation of electrical aversion therapy for inappropriate sexual behaviour after traumatic brain injury: a single case experimental design study

PubMed Central

ter Mors, Bert Jan; van Heugten, Caroline M; van Harten, Peter N

2012-01-01

Inappropriate sexual behaviour after acquired brain injury is a severe complication. Evidence for effective treatment is not available. Electrical aversion therapy (EAT) is a behavioural therapeutic option used in persons with intellectual disabilities, which might be suitable for brain-injured individuals for whom other therapies are not effective. The effect of EAT in brain injury has not been investigated previously. A single case experimental design was used. In an ABBA (baseline-treatment-treatment-withdrawal) design the frequency of the target behaviour (ie, inappropriate sexual behaviour) in a 40-year-old man was measured daily. A total of 551 measurements were recorded. A significant reduction of the target behaviour was seen after the first treatment phase (baseline 12.18 (2.59) vs 3.15 (3.19) mean target behaviours daily); this reduction remained stable over time. We conclude that EAT was effective in this patient with inappropriate sexual behaviour due to severe brain injury. EAT can therefore be considered in therapy resistant inappropriate sexual behaviour in brain-injured patients. PMID:22922913

Brain Activation for Language Dual-Tasking: Listening to Two People Speak at the Same Time and a Change in Network Timing

PubMed Central

Buchweitz, Augusto; Keller, Timothy A.; Meyler, Ann; Just, Marcel Adam

2011-01-01

The study used fMRI to investigate brain activation in participants who were able to listen to and successfully comprehend two people speaking at the same time (dual-tasking). The study identified brain mechanisms associated with high-level, concurrent dual-tasking, as compared to comprehending a single message. Results showed an increase in the functional connectivity among areas of the language network in the dual task. The increase in synchronization of brain activation for dual-tasking was brought about primarily by a change in the timing of left inferior frontal gyrus (LIFG) activation relative to posterior temporal activation, bringing the LIFG activation into closer correspondence with temporal activation. The results show that the change in LIFG timing was greater in participants with lower working memory capacity, and that recruitment of additional activation in the dual-task occurred only in the areas adjacent to the language network that was activated in the single task. The shift in LIFG activation may be a brain marker of how the brain adapts to high-level dual-tasking. PMID:21618666

Evaluation of electrical aversion therapy for inappropriate sexual behaviour after traumatic brain injury: a single case experimental design study.

PubMed

Ter Mors, Bert Jan; van Heugten, Caroline M; van Harten, Peter N

2012-08-24

Inappropriate sexual behaviour after acquired brain injury is a severe complication. Evidence for effective treatment is not available. Electrical aversion therapy (EAT) is a behavioural therapeutic option used in persons with intellectual disabilities, which might be suitable for brain-injured individuals for whom other therapies are not effective. The effect of EAT in brain injury has not been investigated previously. A single case experimental design was used. In an ABBA (baseline-treatment-treatment-withdrawal) design the frequency of the target behaviour (ie, inappropriate sexual behaviour) in a 40-year-old man was measured daily. A total of 551 measurements were recorded. A significant reduction of the target behaviour was seen after the first treatment phase (baseline 12.18 (2.59) vs 3.15 (3.19) mean target behaviours daily); this reduction remained stable over time. We conclude that EAT was effective in this patient with inappropriate sexual behaviour due to severe brain injury. EAT can therefore be considered in therapy resistant inappropriate sexual behaviour in brain-injured patients.

Use Case Analysis: The Ambulatory EEG in Navy Medicine for Traumatic Brain Injuries

DTIC Science & Technology

2016-12-01

best uses of the device for naval medicine. 14. SUBJECT TERMS traumatic brain injuries, electroencephalography, EEG, use case study 15. NUMBER OF...Traumatic Brain Injury NCS Non-Convulsive Seizures PD Parkinson’s Disease QEEG Quantitative EEG SPECT Single-Photon Emission Computerized Tomography...INTENTIONALLY LEFT BLANK 1 I. INTRODUCTION This study examines the diagnosis of traumatic brain injuries (TBI). Early detection and diagnosis is

Single-Cell Genomics Unravels Brain Cell-Type Complexity.

PubMed

Guillaumet-Adkins, Amy; Heyn, Holger

2017-01-01

The brain is the most complex tissue in terms of cell types that it comprises, to the extent that it is still poorly understood. Single cell genome and transcriptome profiling allow to disentangle the neuronal heterogeneity, enabling the categorization of individual neurons into groups with similar molecular signatures. Herein, we unravel the current state of knowledge in single cell neurogenomics. We describe the molecular understanding of the cellular architecture of the mammalian nervous system in health and in disease; from the discovery of unrecognized cell types to the validation of known ones, applying these state-of-the-art technologies.

Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors.

PubMed

Chung, F Z; Lentes, K U; Gocayne, J; Fitzgerald, M; Robinson, D; Kerlavage, A R; Fraser, C M; Venter, J C

1987-01-26

Two cDNA clones, lambda-CLFV-108 and lambda-CLFV-119, encoding for the beta-adrenergic receptor, have been isolated from a human brain stem cDNA library. One human genomic clone, LCV-517 (20 kb), was characterized by restriction mapping and partial sequencing. The human brain beta-receptor consists of 413 amino acids with a calculated Mr of 46480. The gene contains three potential glucocorticoid receptor-binding sites. The beta-receptor expressed in human brain was homology with rodent (88%) and avian (52%) beta-receptors and with porcine muscarinic cholinergic receptors (31%), supporting our proposal [(1984) Proc. Natl. Acad. Sci. USA 81, 272 276] that adrenergic and muscarinic cholinergic receptors are structurally related. This represents the first cloning of a neurotransmitter receptor gene from human brain.

Isolation of Microarray-Grade Total RNA, MicroRNA, and DNA from a Single PAXgene Blood RNA Tube

PubMed Central

Kruhøffer, Mogens; Dyrskjøt, Lars; Voss, Thorsten; Lindberg, Raija L.P.; Wyrich, Ralf; Thykjaer, Thomas; Orntoft, Torben F.

2007-01-01

We have developed a procedure for isolation of microRNA and genomic DNA in addition to total RNA from whole blood stabilized in PAXgene Blood RNA tubes. The procedure is based on automatic extraction on a BioRobot MDx and includes isolation of DNA from a fraction of the stabilized blood and recovery of small RNA species that are otherwise lost. The procedure presented here is suitable for large-scale experiments and is amenable to further automation. Procured total RNA and DNA was tested using Affymetrix Expression and single-nucleotide polymorphism GeneChips, respectively, and isolated microRNA was tested using spotted locked nucleic acid-based microarrays. We conclude that the yield and quality of total RNA, microRNA, and DNA from a single PAXgene blood RNA tube is sufficient for downstream microarray analysis. PMID:17690207

Elastic light single-scattering spectroscopy for detection of dysplastic tissues

NASA Astrophysics Data System (ADS)

Canpolat, Murat; Denkçeken, Tuba; Akman, Ayşe.; Alpsoy, Erkan; Tuncer, Recai; Akyüz, Mahmut; Baykara, Mehmet; Yücel, Selçuk; Başsorgun, Ibrahim; ćiftçioǧlu, M. Akif; Gökhan, Güzide Ayşe.; Gürer, ElifInanç; Peştereli, Elif; Karaveli, Šeyda

2013-11-01

Elastic light single-scattering spectroscopy (ELSSS) system has been developed and tested in diagnosis of cancerous tissues of different organs. ELSSS system consists of a miniature visible light spectrometer, a single fiber optical probe, a halogen tungsten light source and a laptop. Measurements were performed on excised brain, skin, cervix and prostate tumor specimens and surrounding normal tissues. Single fiber optical probe with a core diameter of 100 μm was used to deliver white light to and from tissue. Single optical fiber probe mostly detects singly scattered light from tissue rather than diffused light. Therefore, measured spectra are sensitive to size of scatters in tissue such as cells, nuclei, mitochondria and other organelles of cells. Usually, nuclei of tumor cells are larger than nuclei of normal cells. Therefore, spectrum of singly scattered light of tumor tissue is different than normal tissue. The spectral slopes were shown to be positive for normal brain, skin and prostate and cervix tissues and negative for the tumors of the same tissues. Signs of the spectral slopes were used as a discrimination parameter to differentiate tumor from normal tissues for the three organ tissues. Sensitivity and specificity of the system in differentiation between tumors from normal tissues were 93% and %100 for brain, 87% and 85% for skin, 93.7% and 46.1% for cervix and 98% and 100% for prostate.

Live cell isolation by laser microdissection with gravity transfer

NASA Astrophysics Data System (ADS)

Podgorny, Oleg V.

2013-05-01

Laser microdissection by pulsing ultraviolet laser allows the isolation and recultivation of live cells based on morphological features or/and fluorescent labelling from adherent cell cultures. Previous investigations described only the use of the laser microdissection and pressure catapulting (LMPC) for live cell isolation. But LMPC requires complex manipulations and some skill. Furthermore, single-cell cloning using laser microdissection has not yet been demonstrated. The first evidence of successful application of laser microdissection with gravity transfer (LMDGT) for capturing and recultivation of live cells is presented. A new strategy for LMDGT is presented because of the failure to reproduce the manufacturer's protocol. Using the new strategy, successful capturing and recultivation of circle-shaped samples from confluent monolayer of HeLa cells was demonstrated. It was found that LMDGT is easier than LMPC because it doesn't require personal participation of investigator in transferring of isolated samples to final culture dishes. Moreover, for the first time, the generation of clonal colonies from single live cells isolated by laser microdissection was demonstrated. Data obtained in this study confirm that LMDGT is a reliable and high-yield method allowing isolation and expansion of both cell clusters and single cells from adherent cell cultures.

Detection and isolation of rare cells by 2-step enrichment high-speed flow cytometry/cell sorting and single cell LEAP laser ablation

NASA Astrophysics Data System (ADS)

Zordan, M. D.; Leary, James F.

2011-02-01

The clonal isolation of rare cells, especially cancer and stem cells, in a population is important to the development of improved medical treatment. We have demonstrated that the Laser-Enabled Analysis and Processing (LEAP, Cyntellect Inc., San Diego, CA) instrument can be used to efficiently produce single cell clones by photoablative dilution. Additionally, we have also shown that cells present at low frequencies can be cloned by photoablative dilution after they are pre-enriched by flow cytometry based cell sorting. Circulating tumor cells were modeled by spiking isolated peripheral blood cells with cells from the lung carcinoma cell line A549. Flow cytometry based cell sorting was used to perform an enrichment sort of A549 cells directly into a 384 well plate. Photoablative dilution was performed with the LEAPTM instrument to remove any contaminating cells, and clonally isolate 1 side population cell per well. We were able to isolate and grow single clones of side population cells using this method at greater than 90% efficiency. We have developed a 2 step method that is able to perform the clonal isolation of rare cells based on a medically relevant functional phenotype.

Magnetic resonance spectroscopy of the human brain

NASA Astrophysics Data System (ADS)

Strózik-Kotlorz, D.

2014-01-01

I give a brief description of the magnetic resonance spectroscopy (MRS) in the human brain examinations. MRS allows a noninvasive chemical analysis of the brain using a standard high field MR system. Nowadays, the dominant form of MR brain spectroscopy is proton spectroscopy. Two main techniques of MRS, which utilize the chemical shift of metabolites in the external magnetic field, are SVS (single voxel) and CSI (single slice). The major peaks in the spectrum of a normal brain include NAA, Cr, Cho and m-Ins, which are neuronal, energetic, membrane turnover and glial markers, respectively. In disease, two pathological metabolites can be found in the brain spectra: Lac, which is end product of anaerobic glycolysis and Lip, which is a marker of membrane breakdown, occurring in necrosis. The common way to analyze clinical spectra is to determine metabolite ratios, e.g. NAA/Cr, Cho/Cr, Cho/NAA. This analysis permits a safe and noninvasive examination of the brain tissue as each disease state has its own characteristic spectroscopic image. MRS is a valuable diagnostic tool in such clinical applications as detecting brain tumors and differentiating tumors from inflammatory and infectious processes. Proton MRS is also very helpful in diagnostic of ischemic lesions, Alzheimer's disease and hepatic encephalopathy. The MRS brain spectra should always be correlated with the Magnetic Resonance Imaging (MRI) results and alone cannot make neurological diagnosis.

Derivation of Functional Human Astrocytes from Cerebral Organoids

PubMed Central

Dezonne, Rômulo Sperduto; Sartore, Rafaela Costa; Nascimento, Juliana Minardi; Saia-Cereda, Verônica M.; Romão, Luciana Ferreira; Alves-Leon, Soniza Vieira; de Souza, Jorge Marcondes; Martins-de-Souza, Daniel; Rehen, Stevens Kastrup; Gomes, Flávia Carvalho Alcantara

2017-01-01

Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells. The cellular isolation of cerebral organoids yielded cells that were morphologically and functionally like astrocytes. Immunolabelling and proteomic assays revealed that human organoid-derived astrocytes express the main astrocytic molecular markers, including glutamate transporters, specific enzymes and cytoskeletal proteins. We found that organoid-derived astrocytes strongly supported neuronal survival and neurite outgrowth and responded to ATP through transient calcium wave elevations, which are hallmarks of astrocyte physiology. Additionally, these astrocytes presented similar functional pathways to those isolated from adult human cortex by surgical procedures. This is the first study to provide proteomic and functional analyses of astrocytes isolated from human cerebral organoids. The isolation of these astrocytes holds great potential for the investigation of developmental and evolutionary features of the human brain and provides a useful approach to drug screening and neurodegenerative disease modelling. PMID:28345587

Expression of the Murine Duchenne Muscular Dystrophy Gene in Muscle and Brain

NASA Astrophysics Data System (ADS)

Chamberlain, Jeffrey S.; Pearlman, Joel A.; Muzny, Donna M.; Gibbs, Richard A.; Ranier, Joel E.; Reeves, Alice A.; Caskey, C. Thomas

1988-03-01

Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations.

Functional brain imaging and the induction of traumatic recall: a cross-correlational review between neuroimaging and hypnosis.

PubMed

Vermetten, Eric; Douglas Bremner, J

2004-07-01

The behavioral and psychophysiological alterations during recall in patients with trauma disorders often resemble phenomena that are seen in hypnosis. In studies of emotional recall as well as in neuroimaging studies of hypnotic processes similar brain structures are involved: thalamus, hippocampus, amygdala, medial prefrontal cortex, anterior cingulate cortex. This paper focuses on cross-correlations in traumatic recall and hypnotic responses and reviews correlations between the involvement of brain structures in traumatic recall and processes that are involved in hypnotic responsiveness. To further improve uniformity of results of brain imaging specifically for traumatic recall studies, attention is needed for standardization of hypnotic variables, isolation of the emotional process of interest (state),and assessment of trait-related differences.

[Concentration of glutathione (GSH), ascorbic acid (vitamin C) and substances reacting with thiobarbituric acid (TBA-rs) in single human brain metastases].

PubMed

Dudek, Henryk; Farbiszewski, Ryszard; Rydzewska, Maria; Michno, Tadeusz; Kozłowski, Andrzej

2005-01-01

The aim of the study was to estimate the concentration of glutathione (GSH), ascorbic acid (vitamin C) and thiobarbituric acid (TBA-rs) in single human brain metastases and histologically unchanged nerve tissue. The research was conducted on fragments of neoplasmatic tissue collected from 45 patients undergoing surgery in the Department of Neurosurgery, Medical University of Białystok in years 1996-2002. Concentration of GSH was evaluated using the GSH-400 method, vitamin C using the method of Kyaw and TBA-rs using the method of Salaris and Babs. It has been found that there is a decrease of concentration of GSH and vitamin C and a considerable increase (p < 0.05) of concentration of TBA-rs in investigated single brain human metastasis in correlation to the concentration of the mentioned above substances in unchanged nerve tissue.

Single-task fMRI overlap predicts concurrent multitasking interference.

PubMed

Nijboer, Menno; Borst, Jelmer; van Rijn, Hedderik; Taatgen, Niels

2014-10-15

There is no consensus regarding the origin of behavioral interference that occurs during concurrent multitasking. Some evidence points toward a multitasking locus in the brain, while other results imply that interference is the consequence of task interactions in several brain regions. To investigate this issue, we conducted a functional MRI (fMRI) study consisting of three component tasks, which were performed both separately and in combination. The results indicated that no specific multitasking area exists. Instead, different patterns of activation across conditions could be explained by assuming that the interference is a result of task interactions. Additionally, similarity in single-task activation patterns correlated with a decrease in accuracy during dual-task conditions. Taken together, these results support the view that multitasking interference is not due to a bottleneck in a single "multitasking" brain region, but is a result of interactions between concurrently running processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Inflammation and white matter degeneration persist for years after a single traumatic brain injury.

PubMed

Johnson, Victoria E; Stewart, Janice E; Begbie, Finn D; Trojanowski, John Q; Smith, Douglas H; Stewart, William

2013-01-01

A single traumatic brain injury is associated with an increased risk of dementia and, in a proportion of patients surviving a year or more from injury, the development of hallmark Alzheimer's disease-like pathologies. However, the pathological processes linking traumatic brain injury and neurodegenerative disease remain poorly understood. Growing evidence supports a role for neuroinflammation in the development of Alzheimer's disease. In contrast, little is known about the neuroinflammatory response to brain injury and, in particular, its temporal dynamics and any potential role in neurodegeneration. Cases of traumatic brain injury with survivals ranging from 10 h to 47 years post injury (n = 52) and age-matched, uninjured control subjects (n = 44) were selected from the Glasgow Traumatic Brain Injury archive. From these, sections of the corpus callosum and adjacent parasaggital cortex were examined for microglial density and morphology, and for indices of white matter pathology and integrity. With survival of ≥3 months from injury, cases with traumatic brain injury frequently displayed extensive, densely packed, reactive microglia (CR3/43- and/or CD68-immunoreactive), a pathology not seen in control subjects or acutely injured cases. Of particular note, these reactive microglia were present in 28% of cases with survival of >1 year and up to 18 years post-trauma. In cases displaying this inflammatory pathology, evidence of ongoing white matter degradation could also be observed. Moreover, there was a 25% reduction in the corpus callosum thickness with survival >1 year post-injury. These data present striking evidence of persistent inflammation and ongoing white matter degeneration for many years after just a single traumatic brain injury in humans. Future studies to determine whether inflammation occurs in response to or, conversely, promotes white matter degeneration will be important. These findings may provide parallels for studying neurodegenerative disease, with traumatic brain injury patients serving as a model for longitudinal investigations, in particular with a view to identifying potential therapeutic interventions.

The “curved lead pathway” method to enable a single lead to reach any two intracranial targets

NASA Astrophysics Data System (ADS)

Ding, Chen-Yu; Yu, Liang-Hong; Lin, Yuan-Xiang; Chen, Fan; Lin, Zhang-Ya; Kang, De-Zhi

2017-01-01

Deep brain stimulation is an effective way to treat movement disorders, and a powerful research tool for exploring brain functions. This report proposes a “curved lead pathway” method for lead implantation, such that a single lead can reach in sequence to any two intracranial targets. A new type of stereotaxic system for implanting a curved lead to the brain of human/primates was designed, the auxiliary device needed for this method to be used in rat/mouse was fabricated and verified in rat, and the Excel algorithm used for automatically calculating the necessary parameters was implemented. This “curved lead pathway” method of lead implantation may complement the current method, make lead implantation for multiple targets more convenient, and expand the experimental techniques of brain function research.

Triterpenoid saponins from Albizia lebbeck (L.) Benth and their inhibitory effect on the survival of high grade human brain tumor cells.

PubMed

Noté, Olivier Placide; Jihu, Dong; Antheaume, Cyril; Zeniou, Maria; Pegnyemb, Dieudonné Emmanuel; Guillaume, Dominique; Chneiwess, Hervé; Kilhoffer, Marie Claude; Lobstein, Annelise

2015-03-02

As part of our search of new bioactive triterpenoid saponins from Cameroonian Mimosaceae plants, phytochemical investigation of the roots of Albizia lebbeck led to the isolation of two new oleanane-type saponins, named lebbeckosides A-B (1-2). Their structures were established on the basis of extensive 1D and 2D NMR ((1)H, (13)C NMR, DEPT, COSY, TOCSY, ROESY, HSQC, and HMBC) and HRESIMS studies, and by chemical evidence. Compounds 1-2 were evaluated for their inhibitory effect on the metabolism of high grade human brain tumor cells, the human glioblastoma U-87 MG cell lines and the glioblastoma stem-like TG1 cells isolated from a patient tumor, and known to be particularly resistant to standard therapies. The isolated saponins showed significant cytotoxic activity against U-87 MG and TG1 cancer cells with IC50 values of 3.46 μM and 1.36 μM for 1, and 2.10 μM and 2.24 μM for 2, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Characteristics of long-term persisting strains of tick-borne encephalitis virus in different forms of the chronic process in animals].

PubMed

Frolova, T V; Pogodina, V V; Frolova, M P; Karmysheva, V Ia

1982-01-01

The properties of the Vasilchenko strain of tick-borne encephalitis (TBE) virus and its 3 variants isolated at various stages of persistent infection (383, 453, and 535 days) in Macaca rhesus monkeys and Syrian hamsters with different forms of the chronic TBE were studied. The process characterized by chronic focal inflammatory-degenerative changes in the brains of hamsters without the disturbance of motor functions was associated with persistence of different kinds of virus-specific antigens without virulent virus production. Brain explants of this group of hamsters yielded a virus with cytopathogenic properties but not pathogenic for mice. In a chronic disease developing without the initial acute period, a virus was recovered from hamsters which proved to be virulent for mice and to possess the hemagglutinating and high invasive activity. The most virulent strain was isolated from monkeys with continuously progressive chronic encephalitis with steady paralysis of the extremities. This isolate differed from the parental Vasilchenko strain by a high pathogenicity for hamsters by intracerebral and subcutaneous routes, and thermostability at 50 degrees C.

Brain single-photon emission computed tomography in fetal alcohol syndrome: a case report and study implications.

PubMed

Codreanu, Ion; Yang, JiGang; Zhuang, Hongming

2012-12-01

The indications of brain single-photon emission computed tomography (SPECT) in fetal alcohol syndrome are not clearly defined, even though the condition is recognized as one of the most common causes of mental retardation. This article reports a case of a 9-year-old adopted girl with developmental delay, mildly dysmorphic facial features, and behavioral and cognitive abnormalities. Extensive investigations including genetic studies and brain magnetic resonance imaging (MRI) revealed no abnormalities, and a diagnosis of fetal alcohol syndrome was considered since official diagnostic criteria were met. A brain SPECT was requested and showed severely decreased tracer activity in the thalami, basal ganglia, and temporal lobes on both sides, the overall findings being consistent with the established diagnosis of fetal alcohol syndrome. With increasing availability of functional brain imaging, the study indications and possible ethical implications in suspected prenatal alcohol exposure or even before adoption need further consideration. In this patient, SPECT was the only test to yield positive results.

Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio.

PubMed

Yang, Tianzhi; Martin, Paige; Fogarty, Brittany; Brown, Alison; Schurman, Kayla; Phipps, Roger; Yin, Viravuth P; Lockman, Paul; Bai, Shuhua

2015-06-01

The blood-brain barrier (BBB) essentially restricts therapeutic drugs from entering into the brain. This study tests the hypothesis that brain endothelial cell derived exosomes can deliver anticancer drug across the BBB for the treatment of brain cancer in a zebrafish (Danio rerio) model. Four types of exosomes were isolated from brain cell culture media and characterized by particle size, morphology, total protein, and transmembrane protein markers. Transport mechanism, cell uptake, and cytotoxicity of optimized exosome delivery system were tested. Brain distribution of exosome delivered anticancer drugs was evaluated using transgenic zebrafish TG (fli1: GFP) embryos and efficacies of optimized formations were examined in a xenotransplanted zebrafish model of brain cancer model. Four exosomes in 30-100 diameters showed different morphologies and exosomes derived from brain endothelial cells expressed more CD63 tetraspanins transmembrane proteins. Optimized exosomes increased the uptake of fluorescent marker via receptor mediated endocytosis and cytotoxicity of anticancer drugs in cancer cells. Images of the zebrafish showed exosome delivered anticancer drugs crossed the BBB and entered into the brain. In the brain cancer model, exosome delivered anticancer drugs significantly decreased fluorescent intensity of xenotransplanted cancer cells and tumor growth marker. Brain endothelial cell derived exosomes could be potentially used as a carrier for brain delivery of anticancer drug for the treatment of brain cancer.

Cerebral glucose uptake in patients with chronic mental and cognitive sequelae following a single blunt mild TBI without visible brain lesions.

PubMed

Komura, Akifumi; Kawasaki, Tomohiro; Yamada, Yuichi; Uzuyama, Shiho; Asano, Yoshitaka; Shinoda, Jun

2018-06-19

The aim of this study is to investigate glucose uptake on FDG-PET in patients with chronic mental and cognitive symptoms following a single blunt mild traumatic brain injury (TBI) and without visible brain lesions on CT/MRI. Eighty-nine consecutive patients (mean age 43.8±10.75) who had a single blunt mild TBI from a traffic accident and suffering from chronic mental and cognitive symptoms without visible brain lesions on CT/MRI were enrolled in the study. Patients underwent FDG-PET imaging, and the mean interval between the TBI and FDG-PET was 50.0 months. The Wechsler Adult Intelligence Scale version III testing was performed within one month of the FDG-PET. A control group consisting of 93 healthy adult volunteers (mean age 42.2±14.3 years) also underwent FDG-PET. The glucose uptake pattern from FDG-PET in the patient group was compared to that from normal controls using statistical parametric mapping. Glucose uptake was significantly decreased in the bilateral prefrontal area and significantly increased around the limbic system in the patient group compared to normal controls. This topographical pattern of glucose uptake is different from that reported previously in patients with diffuse axonal injury (DAI), but may be similar to that seen in patients with major depression disorder. These results suggest that the pathological mechanism causing chronic mental and cognitive symptoms in patients with a single blunt mild TBI and without visible brain lesions might be different from that due to primary axonopathy in patients with DAI.

Reconstruction of the arcuate fasciculus for surgical planning in the setting of peritumoral edema using two-tensor unscented Kalman filter tractography.

PubMed

Chen, Zhenrui; Tie, Yanmei; Olubiyi, Olutayo; Rigolo, Laura; Mehrtash, Alireza; Norton, Isaiah; Pasternak, Ofer; Rathi, Yogesh; Golby, Alexandra J; O'Donnell, Lauren J

2015-01-01

Diffusion imaging tractography is increasingly used to trace critical fiber tracts in brain tumor patients to reduce the risk of post-operative neurological deficit. However, the effects of peritumoral edema pose a challenge to conventional tractography using the standard diffusion tensor model. The aim of this study was to present a novel technique using a two-tensor unscented Kalman filter (UKF) algorithm to track the arcuate fasciculus (AF) in brain tumor patients with peritumoral edema. Ten right-handed patients with left-sided brain tumors in the vicinity of language-related cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-Tesla magnetic resonance imaging (MRI) including a diffusion-weighted dataset with 31 directions. Fiber tractography was performed using both single-tensor streamline and two-tensor UKF tractography. A two-regions-of-interest approach was applied to perform the delineation of the AF. Results from the two different tractography algorithms were compared visually and quantitatively. Using single-tensor streamline tractography, the AF appeared disrupted in four patients and contained few fibers in the remaining six patients. Two-tensor UKF tractography delineated an AF that traversed edematous brain areas in all patients. The volume of the AF was significantly larger on two-tensor UKF than on single-tensor streamline tractography (p < 0.01). Two-tensor UKF tractography provides the ability to trace a larger volume AF than single-tensor streamline tractography in the setting of peritumoral edema in brain tumor patients.

Genetic variation in Pythium myriotylum based on SNP typing and development of a PCR-RFLP detection of isolates recovered from Pythium soft rot ginger.

PubMed

Le, D P; Smith, M K; Aitken, E A B

2017-10-01

Pythium myriotylum is responsible for severe losses in both capsicum and ginger crops in Australia under different regimes. Intraspecific genomic variation within the pathogen might explain the differences in aggressiveness and pathogenicity on diverse hosts. In this study, whole genome data of four P. myriotylum isolates recovered from three hosts and one Pythium zingiberis isolate were derived and analysed for sequence diversity based on single nucleotide polymorphisms (SNPs). A higher number of true and unique SNPs occurred in P. myriotylum isolates obtained from ginger with symptoms of Pythium soft rot (PSR) in Australia compared to other P. myriotylum isolates. Overall, SNPs were discovered more in the mitochondrial genome than those in the nuclear genome. Among the SNPs, a single substitution from the cytosine (C) to the thymine (T) in the partially sequenced CoxII gene of 14 representatives of PSR P. myriotylum isolates was within a restriction site of HinP1I enzyme which was used in the PCR-RFLP for detection and identification of the isolates without sequencing. The PCR-RFLP was also sensitive to detect PSR P. myriotylum strains from artificially infected ginger without the need for isolation for pure cultures. This is the first study of intraspecific variants of Pythium myriotylum isolates recovered from different hosts and origins based on single nucleotide polymorphism (SNP) genotyping of multiple genes. The SNPs discovered provide valuable makers for detection and identification of P. myriotylum strains initially isolated from Pythium soft rot (PSR) ginger by using PCR-RFLP of the CoxII locus. The PCR-RFLP was also sensitive to detect P. myriotylum directly from PSR ginger sampled from pot trials without the need of isolation for pure cultures. © 2017 The Society for Applied Microbiology.

[Digital electroencephalography in brain death diagnostics : Technical requirements and results of a survey on the compatibility with medical guidelines of digital EEG systems from providers in Germany].

PubMed

Walter, U; Noachtar, S; Hinrichs, H

2018-02-01

The guidelines of the German Medical Association and the German Society for Clinical Neurophysiology and Functional Imaging (DGKN) require a high procedural and technical standard for electroencephalography (EEG) as an ancillary method for diagnosing the irreversible cessation of brain function (brain death). Nowadays, digital EEG systems are increasingly being applied in hospitals. So far it is unclear to what extent the digital EEG systems currently marketed in Germany meet the guidelines for diagnosing brain death. In the present article, the technical und safety-related requirements for digital EEG systems and the EEG documentation for diagnosing brain death are described in detail. On behalf of the DGKN, the authors sent out a questionnaire to all identified distributors of digital EEG systems in Germany with respect to the following technical demands: repeated recording of the calibration signals during an ongoing EEG recording, repeated recording of all electrode impedances during an ongoing EEG recording, assessability of intrasystem noise and galvanic isolation of measurement earthing from earthing conductor (floating input). For 15 of the identified 20 different digital EEG systems the specifications were provided by the distributors (among them all distributors based in Germany). All of these EEG systems are provided with a galvanic isolation (floating input). The internal noise can be tested with all systems; however, some systems do not allow repeated recording of the calibration signals and/or the electrode impedances during an ongoing EEG recording. The majority but not all of the currently available digital EEG systems offered for clinical use are eligible for use in brain death diagnostics as per German guidelines.

Size-Dependent Neurotoxicity of Aluminum Oxide Particles: a Comparison Between Nano- and Micrometer Size on the Basis of Mitochondrial Oxidative Damage.

PubMed

Mirshafa, Atefeh; Nazari, Mehdi; Jahani, Daniel; Shaki, Fatemeh

2018-06-01

Aluminum nanoparticles (AlNPs) are among the most abundantly produced nanosized particles in the market. There is limited information about the potential harmful effects of aluminum oxide due to its particle size on human health. Considering the toxic effects of Al on brain as its target tissue, in this study, the toxicity of nanoparticles, microparticles, and ionic forms of Al on rat brain and isolated mitochondria was evaluated. Sixty male Wistar rats were divided into ten groups (six rats each), in which group I was the control, and the other groups were administered different doses of Al nanoparticles, Al microparticles (AlMP), and Al ionic forms (2, 4, and 8 mg/kg, i.p.) for 28 days. After 24 h, the animals were killed, brain tissue was separated, the mitochondrial fraction was isolated, and oxidative stress markers were measured. Also, mitochondrial function was assayed by MTT test. The results showed that all forms of Al particles induced ROS formation, lipid peroxidation, protein oxidation, glutathione depletion, mitochondrial dysfunction, and gait abnormalities in a dose-dependent manner. In addition, Al particles decreased mitochondrial membrane potential. These data indicated that oxidative stress might contribute to the toxicity effects of Al. Comparison of oxidative stress markers between all forms of Al revealed that the toxic effect of AlNP on brain tissue was substantially more than that caused by AlMP and bulk form. This study showed more neurotoxicity of AlNPs compared to other forms on brain oxidative damage that probably is due to more penetration into the brain.

Defining the Phosphodiesterase Superfamily Members in Rat Brain Microvessels

PubMed Central

2011-01-01

Eleven phosphodiesterase (PDE) families are known, each having several different isoforms and splice variants. Recent evidence indicates that expression of individual PDE family members is tissue-specific. Little is known concerning detailed PDE component expression in brain microvessels where the blood-brain-barrier and the local cerebral blood flow are thought to be regulated by PDEs. The present study attempted to identify PDE family members that are expressed in brain microvessels. Adult male F344 rats were sacrificed and blocks of the cerebral cortex and infratentorial areas were dissected. Microvessels were isolated using a filtration method, and total RNA was extracted. RNA quality and quantity were determined using an Agilent bioanalyzer. The isolated cortical and infratentorial microvessel total RNA amounts were 2720 ± 750 ng (n = 2) and 250 ± 40 ng (n = 2), respectively. Microarrays with 22 000 transcripts demonstrated that there were 16 PDE transcripts in the PDE superfamily, exhibiting quantifiable density in the microvessels. An additional immunofluorescent study verified that PDE4D (cAMP-specific) and PDE5A (cGMP-specific) were colocalized with RECA-1 (an endothelial marker) in the cerebral cortex using both F344 rats and Sprague–Dawley rats (n = 3–6/strain). In addition, PDE4D and PDE5A were found to be colocalized with alpha-smooth muscle actin which delineates cerebral arteries and arterioles as well as pericytes. In conclusion, a filtration method followed by microarray analyses allows PDE components to be identified in brain microvessels, and confirmed that PDE4D and PDE5A are the primary forms expressed in rat brain microvessels. PMID:22860158

Expensive Brains: "Brainy" Rodents have Higher Metabolic Rate.

PubMed

Sobrero, Raúl; May-Collado, Laura J; Agnarsson, Ingi; Hernández, Cristián E

2011-01-01

Brains are the centers of the nervous system of animals, controlling the organ systems of the body and coordinating responses to changes in the ecological and social environment. The evolution of traits that correlate with cognitive ability, such as relative brain size is thus of broad interest. Brain mass relative to body mass (BM) varies among mammals, and diverse factors have been proposed to explain this variation. A recent study provided evidence that energetics play an important role in brain evolution (Isler and van Schaik, 2006). Using composite phylogenies and data drawn from multiple sources, these authors showed that basal metabolic rate (BMR) correlates with brain mass across mammals. However, no such relationship was found within rodents. Here we re-examined the relationship between BMR and brain mass within Rodentia using a novel species-level phylogeny. Our results are sensitive to parameter evaluation; in particular how species mass is estimated. We detect no pattern when applying an approach used by previous studies, where each species BM is represented by two different numbers, one being the individual that happened to be used for BMR estimates of that species. However, this approach may compromise the analysis. When using a single value of BM for each species, whether representing a single individual, or available species mean, our findings provide evidence that brain mass (independent of BM) and BMR are correlated. These findings are thus consistent with the hypothesis that large brains evolve when the payoff for increased brain mass is greater than the energetic cost they incur.