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Sample records for early brain tropism

  1. Affinity (tropism) of caprine arthritis encephalitis virus for brain cells ...

    African Journals Online (AJOL)

    Affinity (tropism) of caprine arthritis encephalitis virus for brain cells. ... chain reaction (RTPCR) and transmission electron microscopy (TEM techniques). ... CAE virus infection of goat brain cells to that of HIV infection in humans thus suggesting ...

  2. Murine Models for Trypanosoma brucei gambiense disease progression--from silent to chronic infections and early brain tropism.

    Directory of Open Access Journals (Sweden)

    Christiane Giroud

    Full Text Available Human African trypanosomiasis (HAT caused by Trypanosoma brucei gambiense remains highly prevalent in west and central Africa and is lethal if left untreated. The major problem is that the disease often evolves toward chronic or asymptomatic forms with low and fluctuating parasitaemia producing apparently aparasitaemic serological suspects who remain untreated because of the toxicity of the chemotherapy. Whether the different types of infections are due to host or parasite factors has been difficult to address, since T. b. gambiense isolated from patients is often not infectious in rodents thus limiting the variety of isolates.T. b. gambiense parasites were outgrown directly from the cerebrospinal fluid of infected patients by in vitro culture and analyzed for their molecular polymorphisms. Experimental murine infections showed that these isolates could be clustered into three groups with different characteristics regarding their in vivo infection properties, immune response and capacity for brain invasion. The first isolate induced a classical chronic infection with a fluctuating blood parasitaemia, an invasion of the central nervous system (CNS, a trypanosome specific-antibody response and death of the animals within 6-8 months. The second group induced a sub-chronic infection resulting in a single wave of parasitaemia after infection, followed by a low parasitaemia with no parasites detected by microscope observations of blood but detected by PCR, and the presence of a specific antibody response. The third isolate induced a silent infection characterised by the absence of microscopically detectable parasites throughout, but infection was detectable by PCR during the whole course of infection. Additionally, specific antibodies were barely detectable when mice were infected with a low number of this group of parasites. In both sub-chronic and chronic infections, most of the mice survived more than one year without major clinical symptoms

  3. Affinity (tropism) of caprine arthritis encephalitis virus for brain cells.

    Science.gov (United States)

    Adebayo, I A; Olaleye, O D; Awoniyi, T A M

    2010-12-01

    One of the constraints in unraveling the mysteries blurring the advancement of research in the quest to totally put HIV problems under control is getting the appropriate animal model that would truly simulate human cases. This problem is more apparent in studies involving the central nervous system. Consequently, a viable animal model to generate information for the production of drugs and vaccines for the prevention and or control of lentiviral induced dementia in affected host animals is pertinent and vital. In this study, explant cultures prepared from the brain of new-born goat-kid were infected with CaprineArthritis Encephalitis (CAE) virus- a retrovirus affecting goats. The specific brain cell types infected by the (CAE) virus were determined using reverse-transcription polymerase chain reaction (RT-PCR) and transmission electron microscopy (TEM techniques). TEM showed that in 85 - 90% cases, microglia were the cells specifically infected by the virus. Amplification of the genomic sequence of the envelope and the gag genes by RT-PCR confirmed the presence of CAEV proviral DNA in the brain cells of affected animals. No productive infection of the astrocytes was observed. The results of this study showed a lot of similarities in the tropism of CAE virus infection of goat brain cells to that of HIV infection in humans thus suggesting the potential usefulness of the caprine model for the study of HIV neuropathology. The goat model system as a non-primate model therefore could be more adaptable as a simple animal model than primate models with their complexity of anthropological, environmental and safety problems.

  4. Surface chemistry governs cellular tropism of nanoparticles in the brain

    Science.gov (United States)

    Song, Eric; Gaudin, Alice; King, Amanda R.; Seo, Young-Eun; Suh, Hee-Won; Deng, Yang; Cui, Jiajia; Tietjen, Gregory T.; Huttner, Anita; Saltzman, W. Mark

    2017-05-01

    Nanoparticles are of long-standing interest for the treatment of neurological diseases such as glioblastoma. Most past work focused on methods to introduce nanoparticles into the brain, suggesting that reaching the brain interstitium will be sufficient to ensure therapeutic efficacy. However, optimized nanoparticle design for drug delivery to the central nervous system is limited by our understanding of their cellular deposition in the brain. Here, we investigated the cellular fate of poly(lactic acid) nanoparticles presenting different surface chemistries, after administration by convection-enhanced delivery. We demonstrate that nanoparticles with `stealth' properties mostly avoid internalization by all cell types, but internalization can be enhanced by functionalization with bio-adhesive end-groups. We also show that association rates measured in cultured cells predict the extent of internalization of nanoparticles in cell populations. Finally, evaluating therapeutic efficacy in an orthotopic model of glioblastoma highlights the need to balance significant uptake without inducing adverse toxicity.

  5. Tropism mechanism of stem cells targeting injured brain tissues by stromal cell-derived factor-1

    Institute of Scientific and Technical Information of China (English)

    ZHANG Sai; LIU Xiao-zhi; LIU Zhen-lin; SHANG Chong-zhi; HU Qun-liang

    2009-01-01

    Objective: To explore the role and function of stromal cell-derived factor- 1 (SDF- 1) in stem cells migrating into injured brain area.Methods: Rat-derived nerve stem cells (NSCs) were isolated and cultured routinely. Transwell system was used to observe the migration ability of NSCs into injured nerve cells. Immunocytochemistry was used to explore the expression of chemotactic factor receptor-4 (CXCR-4) in NSCs. In vivo, we applied immunofluorescence technique to observe the migration of NSCs into injured brain area. Immunofluorescence technique and Western blotting were used to test expression level of SDF- 1. After AMD3100 (a special chemical blocker) blocking CXCR-4, the migration ability of NSCs was tested in vivo and in vitro, respectively.Results: NSCs displayed specific tropism for injured nerve cells or traumatic brain area in vivo and in vitro. The expression level of SDF-1 in traumatic brain area increased remarkably and the expression level of CXCR-4 in the NSCs increased simultaneously. After AMD3100 blocking the expression of CXCR-4, the migration ability of NSCs decreased significantly both in vivo and in vitro.Conclusions: SDF-1 may play a key role in stem cells migrating into injured brain area through specially combining with CXCR-4.

  6. Structure of HIV-1 quasi-species as early indicator for switches of co-receptor tropism

    Directory of Open Access Journals (Sweden)

    Hoffmann Daniel

    2010-11-01

    Full Text Available Abstract Deep sequencing is able to generate a complete picture of the retroviral quasi-species in a patient. We demonstrate that the unprecedented power of deep sequencing in conjunction with computational data analysis has great potential for clinical diagnostics and basic research. Specifically, we analyzed longitudinal deep sequencing data from patients in a study with Vicriviroc, a drug that blocks the HIV-1 co-receptor CCR5. Sequences covered the V3-loop of gp120, known to be the main determinant of co-receptor tropism. First, we evaluated this data with a computational model for the interpretation of V3-sequences with respect to tropism, and we found complete agreement with results from phenotypic assays. Thus, the method could be applied in cases where phenotypic assays fail. Second, computational analysis led to the discovery of a characteristic pattern in the quasi-species that foreshadows switches of co-receptor tropism. This analysis could help to unravel the mechanism of tropism switches, and to predict these switches weeks to months before they can be detected by a phenotypic assay.

  7. Quasispecies tropism and compartmentalization in gut and peripheral blood during early and chronic phases of HIV-1 infection: possible correlation with immune activation markers.

    Science.gov (United States)

    Rozera, G; Abbate, I; Vlassi, C; Giombini, E; Lionetti, R; Selleri, M; Zaccaro, P; Bartolini, B; Corpolongo, A; D'Offizi, G; Baiocchini, A; Del Nonno, F; Ippolito, G; Capobianchi, M R

    2014-03-01

    HIV quasispecies was analysed in plasma and proviral genomes hosted by duodenal mucosa and peripheral blood cells (PBMC) from patients with early or chronic infection, with respect to viral heterogeneity, tropism compartmentalization and extent of immune activation. Seventeen HIV-1-infected combined antiretroviral therapy naive patients were enrolled (11 early infection and six chronic infection). V3 and nef genomic regions were analysed by ultra-deep pyrosequencing. Sequences were used to infer co-receptor usage and to construct phylogenetic trees. As markers of immune activation, plasma sCD14 and soluble tumour necrosis factor receptor II (sTNFRII) levels were measured. Median diversity of HIV RNA was lower in patients with early infection versus chronic infection patients. Overall, direct correlation was observed between V3 diversity and X4 frequency; V3 diversity of HIV RNA was inversely correlated with CD4 T-cell count; median sCD14 and sTNFRII values were similar in early and chronic patients, but X4 frequency of HIV RNA was directly correlated with plasma sCD14. The proportion of patients harbouring X4 variants and median intra-patient X4 frequency of proviral genomes tended to be higher in chronic infection than early infection patients. More pronounced compartmentalization of proviral quasispecies in gut compared with PBMC samples was observed in patients with early infection compared with chronic patients. The loss of gut/PBMC compartmentalization in more advanced stages of HIV infection was confirmed by longitudinal observation. More studies are needed to understand the pathogenetic significance of early HIV quasispecies compartmentalization and progressive intermixing of viral variants in subsequent phases of the infection, as well as the role of immune activation in tropism switch.

  8. In vivo near-infrared imaging for the tracking of systemically delivered mesenchymal stem cells: tropism for brain tumors and biodistribution

    Directory of Open Access Journals (Sweden)

    Kim SM

    2015-12-01

    Full Text Available Seong Muk Kim,1 Chang Hyun Jeong,2 Ji Sun Woo,2 Chung Heon Ryu,1 Jeong-Hwa Lee,3 Sin-Soo Jeun1,21Postech-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Department of Neurosurgery, Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea; 3Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, KoreaAbstract: Mesenchymal stem cell (MSC-based gene therapy is a promising tool for the treatment of various neurological diseases, including brain tumors. However, the tracking of in vivo stem cell migration, distribution, and survival need to be defined for their clinical application. The systemic routes of stem cell delivery must be determined because direct intracerebral injection as a cure for brain tumors is an invasive method. In this study, we show for the first time that near-infrared (NIR imaging can reveal the distribution and tumor tropism of intravenously injected MSCs in an intracranial xenograft glioma model. MSCs were labeled with NIR fluorescent nanoparticles, and the effects of the NIR dye on cell proliferation and migratory capacity were evaluated in vitro. We investigated the tumor-targeting properties and tissue distribution of labeled MSCs introduced by intravenous injection and followed by in vivo imaging analysis, histological analysis, and real-time quantitative polymerase chain reaction. We observed no cytotoxicity or change in the overall growth rate and characteristics of labeled MSCs compared with control MSCs. NIR fluorescent imaging showed the organ distribution and targeted tumor tropism of systemically injected human MSCs. A significant number of MSCs accumulated specifically at the tumor site in the mouse brain. These results suggest that NIR-based cell tracking is a potentially useful imaging technique to visualize cell survival, migration, and distribution for the application of MSC

  9. The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors

    Directory of Open Access Journals (Sweden)

    Martín-García Julio

    2008-10-01

    Full Text Available Abstract Background HIV-1 infects macrophages and microglia in the brain and can cause neurological disorders in infected patients. We and others have shown that brain-derived envelope glycoproteins (Env have lower CD4 dependence and higher avidity for CD4 than those from peripheral isolates, and we have also observed increased fusogenicity and reduced sensitivity to the fusion inhibitor T-1249. Due to the genetic differences between brain and spleen env from one individual throughout gp120 and in gp41's heptad repeat 2 (HR2, we investigated the viral determinants for the phenotypic differences by performing functional studies with chimeric and mutant Env. Results Chimeric Env showed that the V1/V2-C2-V3 region in brain's gp120 determines the low CD4 dependence and high avidity for CD4, as well as macrophage tropism and reduced sensitivity to the small molecule BMS-378806. Changes in brain gp41's HR2 region did not contribute to the increased fusogenicity or to the reduced sensitivity to T-1249, since a T-1249-based peptide containing residues found in brain's but not in spleen's HR2 had similar potency than T-1249 and interacted similarly with an immobilized heptad repeat 1-derived peptide in surface plasmon resonance analysis. However, the increased fusogenicity and reduced T-1249 sensitivity of brain and certain chimeric Env mostly correlated with the low CD4 dependence and high avidity for CD4 determined by brain's V1-V3 region. Remarkably, most but not all of these low CD4-dependent, macrophage tropic envelopes glycoproteins also had increased sensitivity to the novel allosteric entry inhibitor HNG-105. The gp120's C2 region asparagine 283 (N283 has been previously associated with macrophage tropism, brain infection, lower CD4 dependence and higher CD4 affinity. Therefore, we introduced the N283T mutation into an env clone from a brain-derived isolate and into a brain tissue-derived env clone, and the T283N change into a spleen-derived env

  10. Brain mechanisms in early language acquisition.

    Science.gov (United States)

    Kuhl, Patricia K

    2010-09-09

    The last decade has produced an explosion in neuroscience research examining young children's early processing of language. Noninvasive, safe functional brain measurements have now been proven feasible for use with children starting at birth. The phonetic level of language is especially accessible to experimental studies that document the innate state and the effect of learning on the brain. The neural signatures of learning at the phonetic level can be documented at a remarkably early point in development. Continuity in linguistic development from infants' earliest brain responses to phonetic stimuli is reflected in their language and prereading abilities in the second, third, and fifth year of life, a finding with theoretical and clinical impact. There is evidence that early mastery of the phonetic units of language requires learning in a social context. Neuroscience on early language learning is beginning to reveal the multiple brain systems that underlie the human language faculty.

  11. Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring

    Science.gov (United States)

    Lovy, Jan; Lewis, N.L.; Hershberger, P.K.; Bennett, W.; Meyers, T.R.; Garver, K.A.

    2012-01-01

    Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring.

  12. Transduction of brain dopamine neurons by adenoviral vectors is modulated by CAR expression: rationale for tropism modified vectors in PD gene therapy.

    Directory of Open Access Journals (Sweden)

    Travis B Lewis

    Full Text Available BACKGROUND: Gene-based therapy is a new paradigm for the treatment of Parkinson disease (PD and offers considerable promise for precise targeting and flexibility to impact multiple pathobiological processes for which small molecule agents are not available. Some success has been achieved utilizing adeno-associated virus for this approach, but it is likely that the characteristics of this vector system will ultimately create barriers to progress in clinical therapy. Adenovirus (Ad vector overcomes limitations in payload size and targeting. The cellular tropism of Ad serotype 5 (Ad5-based vectors is regulated by the Ad attachment protein binding to its primary cellular receptor, the coxsackie and adenovirus receptor (CAR. Many clinically relevant tissues are refractory to Ad5 infection due to negligible CAR levels but can be targeted by tropism-modified, CAR-independent forms of Ad. Our objective was to evaluate the role of CAR protein in transduction of dopamine (DA neurons in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Ad5 was delivered to the substantia nigra (SN in wild type (wt and CAR transgenic animals. Cellular tropism was assessed by immunohistochemistry (IHC in the SN and striatal terminals. CAR expression was assessed by western blot and IHC. We found in wt animals, Ad5 results in robust transgene expression in astrocytes and other non-neuronal cells but poor infection of DA neurons. In contrast, in transgenic animals, Ad5 infects SNc neurons resulting in expression of transduced protein in their striatal terminals. Western blot showed low CAR expression in the ventral midbrain of wt animals compared to transgenic animals. Interestingly, hCAR protein localizes with markers of post-synaptic structures, suggesting synapses are the point of entry into dopaminergic neurons in transgenic animals. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate that CAR deficiency limits infection of wild type DA neurons by Ad5 and provide a rationale for the

  13. Music and the Baby's Brain: Early Experiences.

    Science.gov (United States)

    Fox, Donna Brink

    2000-01-01

    States that brain research may be too immature to use it as the only rationale for early music education. Proposes integrated instruction for music education and addresses the need for teacher preparation in early childhood music education. Discusses future collaborations providing three examples of models of childhood music collaborations and…

  14. Early signs of brain asymmetry.

    Science.gov (United States)

    Corballis, Michael C

    2013-11-01

    A new study shows a leftward asymmetry of the choroid plexus in two-thirds of first-trimester human fetuses. This is the earliest brain asymmetry so far identified and may be a precursor to other asymmetries, including that of the temporal planum, which is evident from the 31st week of gestation.

  15. Cytokine determinants of viral tropism

    OpenAIRE

    McFadden, Grant; Mohamed, Mohamed R.; Rahman, Masmudur M.; Bartee, Eric

    2009-01-01

    The specificity of a given virus for a ceil type, tissue or species — collectively known as viral tropism — is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine viral tropism has become particularly important. In this Review, we summarize our current understanding of the central role ...

  16. Early Brain Development Research Review and Update

    Science.gov (United States)

    Schiller, Pam

    2010-01-01

    Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

  17. Early Brain Development Research Review and Update

    Science.gov (United States)

    Schiller, Pam

    2010-01-01

    Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

  18. Early complement components in Alzheimer's disease brains.

    Science.gov (United States)

    Veerhuis, R; Janssen, I; Hack, C E; Eikelenboom, P

    1996-01-01

    Activation products of the early complement components C1, C4 and C3 can be found colocalized with diffuse and fibrillar beta-amyloid (beta/A4) deposits in Alzheimer's disease (AD) brains. Immunohistochemically, C1-esterase inhibitor (C1-Inh) and the C1 subcomponents C1s and C1r can not, or only occasionally, be detected in plaques or in astrocytes. The present finding that C1q, C1s and C1-Inh mRNA are present in both AD and control brains suggests that the variable immunohistochemical staining results for C1r, C1s and C1-Inh are due to a rapid consumption, and that the inability to detect C1s, C1r or C1-Inh is probably due to the dissociation of C1s-C1-Inh and C1r-C1-Inh complexes from the activator-bound C1q into the fluid phase. Employing monoclonal antibodies specific for different forms of C1-Inh, no complexed C1-Inh could be found, whereas inactivated C1-Inh seems to be present in astrocytes surrounding beta/A4 plaques in AD brains. These findings, together with our finding (using reverse transcriptase-polymerase chain reaction) that C1-Inh is locally produced in the brain, suggest that in the brain complement activation at the C1 level is regulated by C1-Inh. Immunohistochemically, no evidence for the presence of the late complement components C5, C7 and C9, or of the membrane attack complex (MAC), was found in beta/A4 plaques. In contrast to the mRNA encoding the early components, that of the late complement components appears to be hardly detectable (C7) or absent (C9). Thus, without blood-brain-barrier impairment, the late complement components are probably present at too low a concentration to allow the formation of the MAC, which is generally believed to be responsible for at least some of the neurodegenerative effects observed in AD. Therefore, the present findings support the idea that in AD, complement does not function as an inflammatory mediator through MAC formation, but through the action of early component activation products.

  19. Early Language Learning and the Social Brain.

    Science.gov (United States)

    Kuhl, Patricia K

    2014-01-01

    Explaining how every typically developing child acquires language is one of the grand challenges of cognitive neuroscience. Historically, language learning provoked classic debates about the contributions of innately specialized as opposed to general learning mechanisms. Now, new data are being brought to bear from studies that employ magnetoencephalograph (MEG), electroencephalograph (EEG), magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI) studies on young children. These studies examine the patterns of association between brain and behavioral measures. The resulting data offer both expected results and surprises that are altering theory. As we uncover what it means to be human through the lens of young children, and their ability to speak, what we learn will not only inform theories of human development, but also lead to the discovery of neural biomarkers, early in life, that indicate risk for language impairment and allow early intervention for children with developmental disabilities involving language. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

  20. Nutrition and brain development in early life.

    Science.gov (United States)

    Prado, Elizabeth L; Dewey, Kathryn G

    2014-04-01

    Presented here is an overview of the pathway from early nutrient deficiency to long-term brain function, cognition, and productivity, focusing on research from low- and middle-income countries. Animal models have demonstrated the importance of adequate nutrition for the neurodevelopmental processes that occur rapidly during pregnancy and infancy, such as neuron proliferation and myelination. However, several factors influence whether nutrient deficiencies during this period cause permanent cognitive deficits in human populations, including the child's interaction with the environment, the timing and degree of nutrient deficiency, and the possibility of recovery. These factors should be taken into account in the design and interpretation of future research. Certain types of nutritional deficiency clearly impair brain development, including severe acute malnutrition, chronic undernutrition, iron deficiency, and iodine deficiency. While strategies such as salt iodization and micronutrient powders have been shown to improve these conditions, direct evidence of their impact on brain development is scarce. Other strategies also require further research, including supplementation with iron and other micronutrients, essential fatty acids, and fortified food supplements during pregnancy and infancy. © 2014 International Life Sciences Institute.

  1. Early Brain Activity Relates to Subsequent Brain Growth in Premature Infants

    NARCIS (Netherlands)

    Benders, Manon J.; Palmu, Kirsi; Menache, Caroline; Borradori-Tolsa, Cristina; Lazeyras, Francois; Sizonenko, Stephane; Dubois, Jessica; Vanhatalo, Sampsa; Hüppi, Petra S.

    2015-01-01

    Recent experimental studies have shown that early brain activity is crucial for neuronal survival and the development of brain networks; however, it has been challenging to assess its role in the developing human brain. We employed serial quantitative magnetic resonance imaging to measure the rate o

  2. Heart Failure Protein May Signal Early Brain Damage

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_162447.html Heart Failure Protein May Signal Early Brain Damage Higher levels ... stress. Blood levels of NT-proBNP rise when heart failure worsens and fall when it gets better. Previous ...

  3. Linking Brain Principles to High-Quality Early Childhood Education

    Science.gov (United States)

    Rushton, Stephen; Juola-Rushton, Anne

    2011-01-01

    Many educators are already knowledgeable about and skilled in best practices. And much of what is happening in developmentally appropriate programs exemplifies "brain compatible" practices. Being educated in the connections between best practices and brain compatibility is an important part of the knowledge base of early childhood educators. Just…

  4. Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Brault

    2016-08-01

    Full Text Available The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV, can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4. We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV.

  5. Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex.

    Science.gov (United States)

    Brault, Jean-Baptiste; Khou, Cécile; Basset, Justine; Coquand, Laure; Fraisier, Vincent; Frenkiel, Marie-Pascale; Goud, Bruno; Manuguerra, Jean-Claude; Pardigon, Nathalie; Baffet, Alexandre D

    2016-08-01

    The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV), can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV) and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4). We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV.

  6. Early bilingualism, language attainment, and brain development.

    Science.gov (United States)

    Berken, Jonathan A; Gracco, Vincent L; Klein, Denise

    2017-04-01

    The brain demonstrates a remarkable capacity to undergo structural and functional change in response to experience throughout the lifespan. Evidence suggests that, in many domains of skill acquisition, the manifestation of this neuroplasticity depends on the age at which learning begins. The fact that most skills are acquired late in childhood or in adulthood has proven to be a limitation in studies aimed at determining the relationship between age of acquisition and brain plasticity. Bilingualism, however, provides an optimal model for discerning differences in how the brain wires when a skill is acquired from birth, when the brain circuitry for language is being constructed, versus later in life, when the pathways subserving the first language are already well developed. This review examines some of the existing knowledge about optimal periods in language development, with particular attention to the attainment of native-like phonology. It focuses on the differences in brain structure and function between simultaneous and sequential bilinguals and the compensatory mechanisms employed when bilingualism is achieved later in life, based on evidence from studies using a variety of neuroimaging modalities, including positron emission tomography (PET), task-based and resting-state functional magnetic resonance imaging (fMRI), and structural MRI. The discussion concludes with the presentation of recent neuroimaging studies that explore the concept of nested optimal periods in language development and the different neural paths to language proficiency taken by simultaneous and sequential bilinguals, with extrapolation to general notions of the relationship between age of acquisition and ultimate skill performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Early adversity and brain response to faces in young adulthood.

    Science.gov (United States)

    Lieslehto, Johannes; Kiviniemi, Vesa; Mäki, Pirjo; Koivukangas, Jenni; Nordström, Tanja; Miettunen, Jouko; Barnett, Jennifer H; Jones, Peter B; Murray, Graham K; Moilanen, Irma; Paus, Tomáš; Veijola, Juha

    2017-09-01

    Early stressors play a key role in shaping interindividual differences in vulnerability to various psychopathologies, which according to the diathesis-stress model might relate to the elevated glucocorticoid secretion and impaired responsiveness to stress. Furthermore, previous studies have shown that individuals exposed to early adversity have deficits in emotion processing from faces. This study aims to explore whether early adversities associate with brain response to faces and whether this association might associate with the regional variations in mRNA expression of the glucocorticoid receptor gene (NR3C1). A total of 104 individuals drawn from the Northern Finland Brith Cohort 1986 participated in a face-task functional magnetic resonance imaging (fMRI) study. A large independent dataset (IMAGEN, N = 1739) was utilized for reducing fMRI data-analytical space in the NFBC 1986 dataset. Early adversities were associated with deviant brain response to fearful faces (MANCOVA, P = 0.006) and with weaker performance in fearful facial expression recognition (P = 0.01). Glucocorticoid receptor gene expression (data from the Allen Human Brain Atlas) correlated with the degree of associations between early adversities and brain response to fearful faces (R(2)  = 0.25, P = 0.01) across different brain regions. Our results suggest that early adversities contribute to brain response to faces and that this association is mediated in part by the glucocorticoid system. Hum Brain Mapp 38:4470-4478, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Early invasion of brain parenchyma by African trypanosomes.

    Directory of Open Access Journals (Sweden)

    Ute Frevert

    Full Text Available Human African trypanosomiasis or sleeping sickness is a vector-borne parasitic disease that has a major impact on human health and welfare in sub-Saharan countries. Based mostly on data from animal models, it is currently thought that trypanosome entry into the brain occurs by initial infection of the choroid plexus and the circumventricular organs followed days to weeks later by entry into the brain parenchyma. However, Trypanosoma brucei bloodstream forms rapidly cross human brain microvascular endothelial cells in vitro and appear to be able to enter the murine brain without inflicting cerebral injury. Using a murine model and intravital brain imaging, we show that bloodstream forms of T. b. brucei and T. b. rhodesiense enter the brain parenchyma within hours, before a significant level of microvascular inflammation is detectable. Extravascular bloodstream forms were viable as indicated by motility and cell division, and remained detectable for at least 3 days post infection suggesting the potential for parasite survival in the brain parenchyma. Vascular inflammation, as reflected by leukocyte recruitment and emigration from cortical microvessels, became apparent only with increasing parasitemia at later stages of the infection, but was not associated with neurological signs. Extravascular trypanosomes were predominantly associated with postcapillary venules suggesting that early brain infection occurs by parasite passage across the neuroimmunological blood brain barrier. Thus, trypanosomes can invade the murine brain parenchyma during the early stages of the disease before meningoencephalitis is fully established. Whether individual trypanosomes can act alone or require the interaction from a quorum of parasites remains to be shown. The significance of these findings for disease development is now testable.

  9. Ionizing radiation augments glioma tropism of mesenchymal stem cells.

    Science.gov (United States)

    Thomas, Jonathan G; Parker Kerrigan, Brittany C; Hossain, Anwar; Gumin, Joy; Shinojima, Naoki; Nwajei, Felix; Ezhilarasan, Ravesanker; Love, Patrice; Sulman, Erik P; Lang, Frederick F

    2017-03-31

    OBJECTIVE Mesenchymal stem cells (MSCs) have been shown to localize to gliomas after intravascular delivery. Because these cells home to areas of tissue injury, the authors hypothesized that the administration of ionizing radiation (IR) to tumor would enhance the tropism of MSCs to gliomas. Additionally, they sought to identify which radiation-induced factors might attract MSCs. METHODS To assess the effect of IR on MSC migration in vitro, transwell assays using conditioned medium (CM) from an irradiated commercially available glioma cell line (U87) and from irradiated patient-derived glioma stem-like cells (GSCs; GSC7-2 and GSC11) were employed. For in vivo testing, green fluorescent protein (GFP)-labeled MSCs were injected into the carotid artery of nude mice harboring orthotopic U87, GSC7-2, or GSC17 xenografts that were treated with either 0 or 10 Gy of IR, and brain sections were quantitatively analyzed by immunofluorescence for GFP-positive cells. These GSCs were used because GSC7-2 is a weak attractor of MSCs at baseline, whereas GSC17 is a strong attractor. To determine the factors implicated in IR-induced tropism, CM from irradiated GSC7-2 and from GSC11 was assayed with a cytokine array and quantitative ELISA. RESULTS Transwell migration assays revealed statistically significant enhanced MSC migration to CM from irradiated U87, GSC7-2, and GSC11 compared with nonirradiated controls and in a dose-dependent manner. After their intravascular delivery into nude mice harboring orthotopic gliomas, MSCs engrafted more successfully in irradiated U87 (p = 0.036), compared with nonirradiated controls. IR also significantly increased the tropism of MSCs to GSC7-2 xenografts (p = 0.043), which are known to attract MSCs only poorly at baseline (weak-attractor GSCs). Ionizing radiation also increased the engraftment of MSCs in strong-attractor GSC17 xenografts, but these increases did not reach statistical significance. The chemokine CCL2 was released by GSC7-2 and GSC

  10. Traumatic Brain Injury in Early Childhood: Developmental Effects and Interventions.

    Science.gov (United States)

    Lowenthal, Barbara; Lowenthal, Barbara

    1998-01-01

    Describes the unique effects of traumatic brain injury (TBI) on development in early childhood and offers suggestions for interventions in the cognitive, language, social-emotional, motor, and adaptive domains. Urges more intensive, long-term studies on the immediate and long-term effects of TBI. (Author/DB)

  11. Early Childhood Traumatic Brain Injuries: Effects on Development and Interventions.

    Science.gov (United States)

    Lowenthal, Barbara

    1998-01-01

    Describes the variety of possible effects of traumatic brain injuries (TBI) on early childhood development in the cognitive, language, social-emotional, motor, and adaptive domains. Suggests interventions which can assist young survivors and their families. Suggests that more long-term, intensive studies be conducted on the short- and long-term…

  12. Protocadherin-19 is essential for early steps in brain morphogenesis.

    Science.gov (United States)

    Emond, Michelle R; Biswas, Sayantanee; Jontes, James D

    2009-10-01

    One of the earliest stages of brain morphogenesis is the establishment of the neural tube during neurulation. While some of the cellular mechanisms responsible for neurulation have been described in a number of vertebrate species, the underlying molecular processes are not fully understood. We have identified the zebrafish homolog of protocadherin-19, a member of the cadherin superfamily, which is expressed in the anterior neural plate and is required for brain morphogenesis. Interference with Protocadherin-19 function with antisense morpholino oligonucleotides leads to a severe disruption in early brain morphogenesis. Despite these pronounced effects on neurulation, axial patterning of the neural tube appears normal, as assessed by in situ hybridization for otx2, pax2.1 and krox20. Characterization of embryos early in development by in vivo 2-photon timelapse microscopy reveals that the observed disruption of morphogenesis results from an arrest of cell convergence in the anterior neural plate. These results provide the first functional data for protocadherin-19, demonstrating an essential role in early brain development.

  13. Early Bifrontal Brain Injury: Disturbances in Cognitive Function Development

    Directory of Open Access Journals (Sweden)

    Christine Bonnier

    2010-01-01

    Full Text Available We describe six psychomotor, language, and neuropsychological sequential developmental evaluations in a boy who sustained a severe bifrontal traumatic brain injury (TBI at 19 months of age. Visuospatial, drawing, and writing skills failed to develop normally. Gradually increasing difficulties were noted in language leading to reading and spontaneous speech difficulties. The last two evaluations showed executive deficits in inhibition, flexibility, and working memory. Those executive abnormalities seemed to be involved in the other impairments. In conclusion, early frontal brain injury disorganizes the development of cognitive functions, and interactions exist between executive function and other cognitive functions during development.

  14. Mechanical origins of rightward torsion in early chick brain development

    Science.gov (United States)

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry

    2015-03-01

    During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.

  15. Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation.

    Science.gov (United States)

    Wolff, Gretchen; Davidson, Sarah J; Wrobel, Jagoda K; Toborek, Michal

    2015-08-07

    Tumor cell extravasation into the brain requires passage through the blood-brain barrier, which is a highly protected microvascular environment fortified with tight junction (TJ) proteins. TJ integrity can be regulated under physiological and pathophysiological conditions. There is evidence that exercise can modulate oxidation status within the brain microvasculature and protect against tumor cell extravasation and metastasis formation. In order to study these events, mature male mice were given access to voluntary exercise on a running wheel (exercise) or access to a locked wheel (sedentary) for five weeks. The average running distance was 9.0 ± 0.2 km/day. Highly metastatic tumor cells (murine Lewis lung carcinoma) were then infused into the brain microvasculature through the internal carotid artery. Analyses were performed at early stage (48 h) and late stage (3 weeks) post tumor cell infusion. Immunohistochemical analysis revealed fewer isolated tumor cells extravasating into the brain at both 48 h and 3 weeks post surgery in exercised mice. Occludin protein levels were reduced in the sedentary tumor group, but maintained in the exercised tumor group at 48 h post tumor cell infusion. These results indicate that voluntary exercise may participate in modulating blood-brain barrier integrity thereby protecting the brain during metastatic progression.

  16. Early Brain and Child Development: Connections to Early Education and Child Care

    Science.gov (United States)

    Romano, Judith T.

    2013-01-01

    The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

  17. Early Brain and Child Development: Connections to Early Education and Child Care

    Science.gov (United States)

    Romano, Judith T.

    2013-01-01

    The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

  18. Early application of deep brain stimulation: clinical and ethical aspects.

    Science.gov (United States)

    Woopen, Christiane; Pauls, K Amande M; Koy, Anne; Moro, Elena; Timmermann, Lars

    2013-11-01

    Deep brain stimulation (DBS) has proven to be a successful therapeutic approach in several patients with movement disorders such as Parkinson's disease and dystonia. Hitherto its application was mainly restricted to advanced disease patients resistant to medication or with severe treatment side effects. However, there is now growing interest in earlier application of DBS, aimed at improving clinical outcomes, quality of life, and avoiding psychosocial consequences of chronic disease-related impairments. We address the clinical and ethical aspects of two "early" uses of DBS, (1) DBS early in the course of the disease, and (2) DBS early in life (i.e. in children). Possible benefits, risks and burdens are discussed and thoroughly considered. Further research is needed to obtain a careful balance between exposing vulnerable patients to potential severe surgical risks and excluding them from a potentially good outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Species differences in early patterning of the avian brain.

    Science.gov (United States)

    McGowan, Luke; Kuo, Eric; Martin, Arnaud; Monuki, Edwin S; Striedter, Georg

    2011-03-01

    The telencephalon is proportionately larger in parrots than in galliformes (chicken-like birds), whereas the midbrain tectum is proportionately smaller. We here test the hypothesis that the adult species difference in midbrain proportion is due to an evolutionary change in early brain patterning. In particular, we compare the size of the early embryonic midbrain between parakeets (Melopsittacus undulatus) and bobwhite quail (Colinus virgianus) by examining the expression domains of transcription factors Pax6 and Gbx2, which are expressed in the forebrain and hindbrain, respectively. Because these expression domains form rostral and caudal borders with the presumptive midbrain when this region is specified (Hamburger-Hamilton stages 9-11), they allow us to measure and compare the sizes of a molecularly defined presumptive midbrain in the two species. Based on published data from older embryos, we predicted that the molecularly defined midbrain territory is significantly larger in quail than parakeets. Indeed, our data show that normalized midbrain length is 33% greater in quail and that the midbrain to forebrain ratio is 28% greater. This is strong evidence of a significant species difference in early brain patterning.

  20. Non-invasive brain stimulation in early rehabilitation after stroke.

    Science.gov (United States)

    Blesneag, A V; Popa, L; Stan, A D

    2015-01-01

    The new tendency in rehabilitation involves non-invasive tools that, if applied early after stroke, promote neurorecovery. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation may correct the disruption of cortical excitability and effectively contribute to the restoration of movement and speech. The present paper analyses the results of non-invasive brain stimulation (NIBS) trials, highlighting different aspects related to the repetitive transcranial magnetic stimulation frequency, transcranial direct current stimulation polarity, the period and stimulation places in acute and subacute ischemic strokes. The risk of adverse events, the association with motor or language recovery specific training, and the cumulative positive effect evaluation are also discussed.

  1. Understanding and altering cell tropism of vesicular stomatitis virus

    Science.gov (United States)

    Hastie, Eric; Cataldi, Marcela; Marriott, Ian; Grdzelishvili, Valery Z.

    2013-01-01

    Vesicular stomatitis virus (VSV) is a prototypic nonsegmented negative-strand RNA virus. VSV’s broad cell tropism makes it a popular model virus for many basic research applications. In addition, a lack of preexisting human immunity against VSV, inherent oncotropism and other features make VSV a widely used platform for vaccine and oncolytic vectors. However, VSV’s neurotropism that can result in viral encephalitis in experimental animals needs to be addressed for the use of the virus as a safe vector. Therefore, it is very important to understand the determinants of VSV tropism and develop strategies to alter it. VSV glycoprotein (G) and matrix (M) protein play major roles in its cell tropism. VSV G protein is responsible for VSV broad cell tropism and is often used for pseudotyping other viruses. VSV M affects cell tropism via evasion of antiviral responses, and M mutants can be used to limit cell tropism to cell types defective in interferon signaling. In addition, other VSV proteins and host proteins may function as determinants of VSV cell tropism. Various approaches have been successfully used to alter VSV tropism to benefit basic research and clinically relevant applications. PMID:23796410

  2. General systems theory, brain organization, and early experiences.

    Science.gov (United States)

    Denenberg, V H

    1980-01-01

    Three hypothetical brain processes--interhemispheric coupling, hemispheric activation, and interhemispheric inhibition--are derived from an equation characterizing general systems theory. To investigate these processes, experimental rats were reared under differing early experience conditions. When adult, they had their right or left neocortex lesioned, had a sham operation, or were left undisturbed. Interhemispheric coupling was measured by means of a correlation coefficient between the right and left hemispheres. The presence of a significant positive correlation is taken as evidence of a negative feedback loop between the hemispheres. In one experimental population, in which rats did not receive any extra stimulation in infancy, the correlation was not significantly different from zero, thus implying that the two hemispheres were operating independently. In another population, in which rats had received handling stimulation in infancy, the correlation coefficient was significant (0.543), indicating that the hemispheres were coupled in a systems arrangement. The processes of hemispheric activation and interhemispheric inhibition were assessed by comparing the mean performance of the two unilateral lesion groups and the group with intact brain. The two rat populations had different forms of brain organizations as measured by these processes. These analyses show that the behavior of the isolated hemisphere cannot be directly extrapolated to the behavior of the connected hemisphere. If there is hemispheric coupling via a negative feedback loop or if there is interhemispheric inhibition, then the disconnected hemisphere may show behaviors that are not evident in the normal connected condition.

  3. Neural Basis of Brain Dysfunction Produced by Early Sleep Problems

    Directory of Open Access Journals (Sweden)

    Jun Kohyama

    2016-01-01

    Full Text Available There is a wealth of evidence that disrupted sleep and circadian rhythms, which are common in modern society even during the early stages of life, have unfavorable effects on brain function. Altered brain function can cause problem behaviors later in life, such as truancy from or dropping out of school, quitting employment, and committing suicide. In this review, we discuss findings from several large cohort studies together with recent results of a cohort study using the marshmallow test, which was first introduced in the 1960s. This test assessed the ability of four-year-olds to delay gratification and showed how this ability correlated with success later in life. The role of the serotonergic system in sleep and how this role changes with age are also discussed. The serotonergic system is involved in reward processing and interactions with the dorsal striatum, ventral striatum, and the prefrontal cortex are thought to comprise the neural basis for behavioral patterns that are affected by the quantity, quality, and timing of sleep early in life.

  4. Early Brain changes May Help Predict Autism Among High-Risk Infants

    Science.gov (United States)

    ... Media Resources Interviews & Selected Staff Profiles Multimedia Early brain changes may help predict autism among high-risk ... Share this: Page Content NIH-funded researchers link brain changes at 6 and 12 months of age ...

  5. Pain Catastrophizing Correlates with Early Mild Traumatic Brain Injury Outcome

    Science.gov (United States)

    Chaput, Geneviève; Lajoie, Susanne P.; Naismith, Laura M.; Lavigne, Gilles

    2016-01-01

    Background. Identifying which patients are most likely to be at risk of chronic pain and other postconcussion symptoms following mild traumatic brain injury (MTBI) is a difficult clinical challenge. Objectives. To examine the relationship between pain catastrophizing, defined as the exaggerated negative appraisal of a pain experience, and early MTBI outcome. Methods. This cross-sectional design included 58 patients diagnosed with a MTBI. In addition to medical chart review, postconcussion symptoms were assessed by self-report at 1 month (Time 1) and 8 weeks (Time 2) after MTBI. Pain severity, psychological distress, level of functionality, and pain catastrophizing were measured by self-report at Time 2. Results. The pain catastrophizing subscales of rumination, magnification, and helplessness were significantly correlated with pain severity (r = .31 to .44), number of postconcussion symptoms reported (r = .35 to .45), psychological distress (r = .57 to .67), and level of functionality (r = −.43 to −.29). Pain catastrophizing scores were significantly higher for patients deemed to be at high risk of postconcussion syndrome (6 or more symptoms reported at both Time 1 and Time 2). Conclusions. Higher levels of pain catastrophizing were related to adverse early MTBI outcomes. The early detection of pain catastrophizing may facilitate goal-oriented interventions to prevent or minimize the development of chronic pain and other postconcussion symptoms. PMID:27445604

  6. Pain Catastrophizing Correlates with Early Mild Traumatic Brain Injury Outcome

    Directory of Open Access Journals (Sweden)

    Geneviève Chaput

    2016-01-01

    Full Text Available Background. Identifying which patients are most likely to be at risk of chronic pain and other postconcussion symptoms following mild traumatic brain injury (MTBI is a difficult clinical challenge. Objectives. To examine the relationship between pain catastrophizing, defined as the exaggerated negative appraisal of a pain experience, and early MTBI outcome. Methods. This cross-sectional design included 58 patients diagnosed with a MTBI. In addition to medical chart review, postconcussion symptoms were assessed by self-report at 1 month (Time 1 and 8 weeks (Time 2 after MTBI. Pain severity, psychological distress, level of functionality, and pain catastrophizing were measured by self-report at Time 2. Results. The pain catastrophizing subscales of rumination, magnification, and helplessness were significantly correlated with pain severity (r=.31 to .44, number of postconcussion symptoms reported (r=.35 to .45, psychological distress (r=.57 to .67, and level of functionality (r=-.43 to -.29. Pain catastrophizing scores were significantly higher for patients deemed to be at high risk of postconcussion syndrome (6 or more symptoms reported at both Time 1 and Time 2. Conclusions. Higher levels of pain catastrophizing were related to adverse early MTBI outcomes. The early detection of pain catastrophizing may facilitate goal-oriented interventions to prevent or minimize the development of chronic pain and other postconcussion symptoms.

  7. Early exposure to traumatic stressors impairs emotional brain circuitry.

    Directory of Open Access Journals (Sweden)

    Mayuresh S Korgaonkar

    Full Text Available Exposure to early life trauma (ELT is known to have a profound impact on mental development, leading to a higher risk for depression and anxiety. Our aim was to use multiple structural imaging methods to systematically investigate how traumatic stressors early in life impact the emotional brain circuits, typically found impaired with clinical diagnosis of depression and anxiety, across the lifespan in an otherwise healthy cohort. MRI data and self-reported histories of ELT from 352 healthy individuals screened for no psychiatric disorders were analyzed in this study. The volume and cortical thickness of the limbic and cingulate regions were assessed for all participants. A large subset of the cohort also had diffusion tensor imaging data, which was used to quantify white matter structural integrity of these regions. We found a significantly smaller amygdala volume and cortical thickness in the rostral anterior cingulate cortex associated with higher ELT exposure only for the adolescence group. White matter integrity of these regions was not affected. These findings demonstrate that exposure to early life trauma is associated with alterations in the gray matter of cingulate-limbic regions during adolescence in an otherwise healthy sample. These findings are interesting in the context that the affected regions are central neuroanatomical components in the psychopathology of depression, and adolescence is a peak period for risk and onset of the disorder.

  8. ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy

    Science.gov (United States)

    El Costa, Hicham; Gouilly, Jordi; Mansuy, Jean-Michel; Chen, Qian; Levy, Claude; Cartron, Géraldine; Veas, Francisco; Al-Daccak, Reem; Izopet, Jacques; Jabrane-Ferrat, Nabila

    2016-01-01

    The outbreak of the Zika Virus (ZIKV) and its association with fetal abnormalities have raised worldwide concern. However, the cellular tropism and the mechanisms of ZIKV transmission to the fetus during early pregnancy are still largely unknown. Therefore, we ex vivo modeled the ZIKV transmission at the maternal-fetal interface using organ culture from first trimester pregnancy samples. Here, we provide evidence that ZIKV strain circulating in Brazil infects and damages tissue architecture of the maternal decidua basalis, the fetal placenta and umbilical cord. We also show that ZIKV replicates differentially in a wide range of maternal and fetal cells, including decidual fibroblasts and macrophages, trophoblasts, Hofbauer cells as well as umbilical cord mesenchymal stem cells. The striking cellular tropism of ZIKV and its cytopathic-induced tissue injury during the first trimester of pregnancy could provide an explanation for the irreversible congenital damages. PMID:27759009

  9. Auditory event-related brain potentials for an early discrimination between normal and pathological brain aging

    Institute of Scientific and Technical Information of China (English)

    Juliana Dushanova; Mario Christov

    2013-01-01

    The brain as a system with gradually decreasing resources maximizes its chances by reorganizing neural networks to ensure efficient performance. Auditory event-related potentials were recorded in 28 healthy volunteers comprising 14 young and 14 elderly subjects in auditory discrimination motor task (low frequency tone – right hand movement and high frequency tone – left hand movement). The amplitudes of the sensory event-related potential components (N1, P2) were more pronounced with increasing age for either tone and this effect for P2 amplitude was more pronounced in the frontal region. The latency relationship of N1 between the groups was tone-dependent, while that of P2 was tone-independent with a prominent delay in the elderly group over all brain regions. The amplitudes of the cognitive components (N2, P3) diminished with increasing age and the hemispheric asymmetry of N2 (but not for P3) reduced with increasing age. Prolonged N2 latency with increasing age was widespread for either tone while between-group difference in P3 latency was tone-dependent. High frequency tone stimulation and movement requirements lead to P3 delay in the elderly group. The amplitude difference of the sensory components between the age groups could be due to a general greater alertness, less expressed habituation, or decline in the ability to retreat attentional resources from the stimuli in the elderly group. With aging, a neural circuit reorganization of the brain activity affects the cognitive processes. The approach used in this study is useful for an early discrimination between normal and pathological brain aging for early treatment of cognitive alterations and dementia.

  10. Early oxygen-utilization and brain activity in preterm infants.

    Directory of Open Access Journals (Sweden)

    Maria Luisa Tataranno

    Full Text Available The combined monitoring of oxygen supply and delivery using Near-InfraRed spectroscopy (NIRS and cerebral activity using amplitude-integrated EEG (aEEG could yield new insights into brain metabolism and detect potentially vulnerable conditions soon after birth. The relationship between NIRS and quantitative aEEG/EEG parameters has not yet been investigated. Our aim was to study the association between oxygen utilization during the first 6 h after birth and simultaneously continuously monitored brain activity measured by aEEG/EEG. Forty-four hemodynamically stable babies with a GA < 28 weeks, with good quality NIRS and aEEG/EEG data available and who did not receive morphine were included in the study. aEEG and NIRS monitoring started at NICU admission. The relation between regional cerebral oxygen saturation (rScO2 and cerebral fractional tissue oxygen extraction (cFTOE, and quantitative measurements of brain activity such as number of spontaneous activity transients (SAT per minute (SAT rate, the interval in seconds (i.e. time between SATs (ISI and the minimum amplitude of the EEG in μV (min aEEG were evaluated. rScO2 was negatively associated with SAT rate (β=-3.45 [CI=-5.76- -1.15], p=0.004 and positively associated with ISI (β=1.45 [CI=0.44-2.45], p=0.006. cFTOE was positively associated with SAT rate (β=0.034 [CI=0.009-0.059], p=0.008 and negatively associated with ISI (β=-0.015 [CI=-0.026- -0.004], p=0.007. Oxygen delivery and utilization, as indicated by rScO2 and cFTOE, are directly related to functional brain activity, expressed by SAT rate and ISI during the first hours after birth, showing an increase in oxygen extraction in preterm infants with increased early electro-cerebral activity. NIRS monitored oxygenation may be a useful biomarker of brain vulnerability in high-risk infants.

  11. Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

    Science.gov (United States)

    Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

    2014-07-01

    Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Phylogenetic origins of early alterations in brain region proportions.

    Science.gov (United States)

    Charvet, Christine J; Sandoval, Alexis L; Striedter, Georg F

    2010-01-01

    Adult galliform birds (e.g. chickens) exhibit a relatively small telencephalon and a proportionately large optic tectum compared with parrots and songbirds. We previously examined the embryonic origins of these adult species differences and found that the optic tectum is larger in quail than in parakeets and songbirds at early stages of development, prior to tectal neurogenesis onset. The aim of this study was to determine whether a proportionately large presumptive tectum is a primitive condition within birds or a derived feature of quail and other galliform birds. To this end, we examined embryonic brains of several avian species (emus, parrots, songbirds, waterfowl, galliform birds), reptiles (3 lizard species, alligators, turtles) and a monotreme (platypuses). Brain region volumes were estimated from serial Nissl-stained sections. We found that the embryos of galliform birds and lizards exhibit a proportionally larger presumptive tectum than all the other examined species. The presumptive tectum of the platypus is unusually small. The most parsimonious interpretation of these data is that the expanded embryonic tectum of lizards and galliform birds is a derived feature in both of these taxonomic groups.

  13. [Early functional disorders of the brain in uncomplicated hypertensive patients].

    Science.gov (United States)

    De Quesada-Martínez, M E; Blanco-García, M; Díaz-De Quesada, L

    To detect the presence of changes in brain electrical activity that might be used as early markers in patients with risk factors for developing vascular encephalopathy. There were studied 84 uncomplicated hypertensive patients, with a normal neurological physical examination and mean age of 49 years compared to 35 functionally healthy subjects. The patients were divided into three groups: slight high blood pressure (SLHBP, n = 24) with diastolic blood pressure (DBP) between 90 and 100 mmHg, moderate high blood pressure (MHBP, n = 40) with DBP between 101 and 114 mmHg, and severe high blood pressure (SHBP, n = 20) with TAD of 115 mmHg or higher. All subjects underwent digital electroencephalogram (dEEG) with quantitative analysis (QEEG). The patients showed focal, especially frontal paroxysms, and diffuse polymorphic theta activity in these areas, mainly those with SLHBP. Posterior alpha rhythm disorganization, inter-hemispheric asymmetries and frontal monomorphic activity were more often found in SHBP patients. In QEEG was observed an increase in absolute and relative power of slow activities, and a decrease in power of alpha and beta activities. All these findings were more frequent in the left hemisphere. The hemodynamic characteristics of the Central Nervous System and the changes caused by HBP alter the functional organization of the brain cortex, especially in frontal and midline regions, irrigated by the anterior cerebral artery.

  14. Clinical factors adversely affecting early outcome after brain infarction

    Directory of Open Access Journals (Sweden)

    Charles André

    1994-06-01

    Full Text Available PURPOSE AND METHODS: One-hundred-and-nine consecutive patients admitted during the acute phase of a CT-confirmed brain infarction (BI were studied. Putative adverse influence of demographic and stroke risk factors, previous medical history, clinical presentation, initial and follow-up neurological examination, initial general evaluation, laboratory findings, chest X-ray and electrocardiographic findings, treatment, and topography and etiology of the ischemic insult was analysed. The end-point for assessment was early death (within 30 days. Statistical analysis was performed with univariate analysis and multiple regression. RESULTS: The main adverse factors related to an increased death risk during the first 30 days were, in decreasing order of importance: coma 48-72 hours after admission; stroke occuring in already hospitalized patients; Babinski sign on admission; minor degrees of impairment of consciousness 48-72 hours after admission; stroke related to large artery atherothrombosis and to embolism; a history of early impairment of consciousness; cardiac failure on admission. In 53 lucid patients on admission, only a history of congestive heart failure (CHF was associated with a reduced survival rate. In 56 patients with impaired consciousness, the presence of a Babinski sign increased death risk, but the main factor predicting a high case-fatality rate was the persistence of consciousness disturbances after48-72 hours. CONCLUSIONS: The presence of impairment of consciousness, especially coma, 2-3 days after disease onset, and a history of CHF greatly increase the early case fatality rate in patients with acute BI presenting with or without consciousness disturbances at admission, respectively. The use of a prognostic algorythm considering these few variables seems to predict the approximate 30-day fatality rates.

  15. Visualizing the blind brain: brain imaging of visual field defects from early recovery to rehabilitation techniques

    Directory of Open Access Journals (Sweden)

    Marika eUrbanski

    2014-09-01

    Full Text Available Visual field defects (VFDs are one of the most common consequences observed after brain injury, especially after a stroke in the posterior cerebral artery territory. Less frequently, tumours, traumatic brain injury, brain surgery or demyelination can also determine various visual disabilities, from a decrease in visual acuity to cerebral blindness. VFD is a factor of bad functional prognosis as it compromises many daily life activities (e.g., obstacle avoidance, driving, and reading and therefore the patient’s quality of life. Spontaneous recovery seems to be limited and restricted to the first six months, with the best chance of improvement at one month. The possible mechanisms at work could be partly due to cortical reorganization in the visual areas (plasticity and/or partly to the use of intact alternative visual routes, first identified in animal studies and possibly underlying the phenomenon of blindsight. Despite processes of early recovery, which is rarely complete, and learning of compensatory strategies, the patient’s autonomy may still be compromised at more chronic stages. Therefore, various rehabilitation therapies based on neuroanatomical knowledge have been developed to improve VFDs. These use eye-movement training techniques (e.g., visual search, saccadic eye movements, reading training, visual field restitution (the Vision Restoration Therapy, VRT, or perceptual learning. In this review, we will focus on studies of human adults with acquired VFDs, which have used different imaging techniques (Positron Emission Tomography: PET, Diffusion Tensor Imaging: DTI, functional Magnetic Resonance Imaging: fMRI, MagnetoEncephalography: MEG or neurostimulation techniques (Transcranial Magnetic Stimulation: TMS; transcranial Direct Current Stimulation, tDCS to show brain activations in the course of spontaneous recovery or after specific rehabilitation techniques.

  16. Group B Streptococcus surface proteins as major determinants for meningeal tropism.

    Science.gov (United States)

    Tazi, Asmaa; Bellais, Samuel; Tardieux, Isabelle; Dramsi, Shaynoor; Trieu-Cuot, Patrick; Poyart, Claire

    2012-02-01

    Streptococcus agalactiae (group B Streptococcus, GBS), a normal constituent of the intestinal microbiota is the major cause of human neonatal infections and a worldwide spread 'hypervirulent' clone, GBS ST-17, is strongly associated with neonatal meningitis. Adhesion to epithelial and endothelial cells constitutes a key step of the infectious process. Therefore GBS surface-anchored proteins are obvious potential adhesion mediators of barrier crossing and determinant of hypervirulence. This review addresses the most recent molecular insights gained from studies on GBS surface proteins proven to be involved in the crossing of the brain-blood barrier and emphasizes on the specificity of a hypervirulent clone that displays meningeal tropism.

  17. Thickening of spine ligamentum flavum and facet tropism

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Appolonio

    2014-03-01

    Full Text Available OBJECTIVE: This study investigated the thickening of the ligamentum flavum (LF and its correlation with facet tropism and its severity at different levels of the spine. METHOD: This retrospective study was performed with patients with chronic back pain consecutively admitted to a specialized spinal surgery service between January 2012 and January 2013. All patients underwent magnetic resonance imaging (MRI to measure the thickness of the LF and facet tropism severity (severe, moderate or absent according to the spine levels (L3 -L4, L4-L5, L5-S1. The association between the thickness of LF and facet tropism was analyzed. RESULTS: During the study period, 98 consecutive patients were enrolled with a mean age of 53.6 years, most women (59.2%. There was no significant difference between the thicknesses of the ligament and the presence of tropism in different spinal levels (p > 0.05. The thickness of LF was significantly associated with the severity of tropism only in L5-S1 level (p < 0.03. CONCLUSIONS: Our results show that there is a positive relationship between severe facet tropism and increased thickness of the LF in the L5-S1 level.

  18. Preterm birth and structural brain alterations in early adulthood

    Directory of Open Access Journals (Sweden)

    Chiara Nosarti

    2014-01-01

    Full Text Available Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM and white matter (WM maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks and 43 term-born controls aged 19–20 years, and their association with cognitive outcomes (Hayling Sentence Completion Test, Controlled Oral Word Association Test, Visual Reproduction test of the Wechsler Memory Scale-Revised and gestational age. Structural MRI data were obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with a customized study-specific template. Similarly to results obtained at adolescent assessment, VPT young adults compared to controls demonstrated reduced GM volume in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and putamen. Increases in GM volume were noted in medial/anterior frontal gyrus. Smaller subcortical WM volume in the VPT group was observed in temporal, parietal and frontal regions, and in a cluster centred on posterior corpus callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in posterior brain regions, in areas beneath the parahippocampal and occipital gyri and in cerebellum. Gestational age was associated with GM and WM volumes in areas where VPT individuals demonstrated GM and WM volumetric alterations, especially in temporal, parietal and occipital regions. VPT participants scored lower than controls on measures of IQ, executive function and non-verbal memory. When investigating GM and WM alterations and cognitive outcome scores, subcortical WM volume in an area beneath the left inferior frontal gyrus accounted for 14% of the variance of full-scale IQ (F = 12.9, p < 0.0001. WM volume in posterior corpus

  19. Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors

    Directory of Open Access Journals (Sweden)

    Simmonds Peter

    2008-01-01

    Full Text Available Abstract Background HIV-1 R5 viruses cause most of the AIDS cases worldwide and are preferentially transmitted compared to CXCR4-using viruses. Furthermore, R5 viruses vary extensively in capacity to infect macrophages and highly macrophage-tropic variants are frequently identified in the brains of patients with dementia. Here, we investigated the sensitivity of R5 envelopes to a range of inhibitors and antibodies that block HIV entry. We studied a large panel of R5 envelopes, derived by PCR amplification without culture from brain, lymph node, blood and semen. These R5 envelopes conferred a wide range of macrophage tropism and included highly macrophage-tropic variants from brain and non-macrophage-tropic variants from lymph node. Results R5 macrophage-tropism correlated with sensitivity to inhibition by reagents that inhibited gp120:CD4 interactions. Thus, increasing macrophage-tropism was associated with increased sensitivity to soluble CD4 and to IgG-CD4 (PRO 542, but with increased resistance to the anti-CD4 monoclonal antibody (mab, Q4120. These observations were highly significant and are consistent with an increased affinity of envelope for CD4 for macrophage-tropic envelopes. No overall correlations were noted between R5 macrophage-tropism and sensitivity to CCR5 antagonists or to gp41 specific reagents. Intriguingly, there was a relationship between increasing macrophage-tropism and increased sensitivity to the CD4 binding site mab, b12, but decreased sensitivity to 2G12, a mab that binds a glycan complex on gp120. Conclusion Variation in R5 macrophage-tropism is caused by envelope variation that predominantly influences sensitivity to reagents that block gp120:CD4 interactions. Such variation has important implications for therapy using viral entry inhibitors and for the design of envelope antigens for vaccines.

  20. Structural and Maturational Covariance in Early Childhood Brain Development.

    Science.gov (United States)

    Geng, Xiujuan; Li, Gang; Lu, Zhaohua; Gao, Wei; Wang, Li; Shen, Dinggang; Zhu, Hongtu; Gilmore, John H

    2017-03-01

    Brain structural covariance networks (SCNs) composed of regions with correlated variation are altered in neuropsychiatric disease and change with age. Little is known about the development of SCNs in early childhood, a period of rapid cortical growth. We investigated the development of structural and maturational covariance networks, including default, dorsal attention, primary visual and sensorimotor networks in a longitudinal population of 118 children after birth to 2 years old and compared them with intrinsic functional connectivity networks. We found that structural covariance of all networks exhibit strong correlations mostly limited to their seed regions. By Age 2, default and dorsal attention structural networks are much less distributed compared with their functional maps. The maturational covariance maps, however, revealed significant couplings in rates of change between distributed regions, which partially recapitulate their functional networks. The structural and maturational covariance of the primary visual and sensorimotor networks shows similar patterns to the corresponding functional networks. Results indicate that functional networks are in place prior to structural networks, that correlated structural patterns in adult may arise in part from coordinated cortical maturation, and that regional co-activation in functional networks may guide and refine the maturation of SCNs over childhood development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Early brain-body impact of emotional arousal

    Directory of Open Access Journals (Sweden)

    Fabien D'Hondt

    2010-04-01

    Full Text Available Current research in affective neuroscience suggests that the emotional content of visual stimuli activates brain–body responses that could be critical to general health and physical disease. The aim of this study was to develop an integrated neurophysiological approach linking central and peripheral markers of nervous activity during the presentation of natural scenes in order to determine the temporal stages of brain processing related to the bodily impact of emotions. More specifically, whole head magnetoencephalogram (MEG data and skin conductance response (SCR, a reliable autonomic marker of central activation, were recorded in healthy volunteers during the presentation of emotional (unpleasant and pleasant and neutral pictures selected from the International Affective Picture System (IAPS. Analyses of event-related magnetic fields (ERFs revealed greater activity at 180 ms in an occipitotemporal component for emotional pictures than for neutral counterparts. More importantly, these early effects of emotional arousal on cerebral activity were significantly correlated with later increases in SCR magnitude. For the first time, a neuromagnetic cortical component linked to a well-documented marker of bodily arousal expression of emotion, namely, the skin conductance response, was identified and located. This finding sheds light on the time course of the brain–body interaction with emotional arousal and provides new insights into the neural bases of complex and reciprocal mind–body links.

  2. Filovirus tropism: Cellular molecules for viral entry

    Directory of Open Access Journals (Sweden)

    Ayato eTakada

    2012-02-01

    Full Text Available In human and nonhuman primates, filoviruses (Ebola and Marburg viruses cause severe hemorrhagic fever.Recently, other animals such as pigs and some species of fruit bats have also been shown to be susceptible to these viruses. While having a preference for some cell types such as hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages, filoviruses are known to be pantropic in infection of primates. The envelope glycoprotein (GP is responsible for both receptor binding and fusion of the virus envelope with the host cell membrane. It has been demonstrated that filovirus GP interacts with multiple molecules for entry into host cells, whereas none of the cellular molecules so far identified as a receptor/coreceptor fully explains filovirus tissue tropism and host range. Available data suggest that the mucin-like region (MLR on GP plays an important role in attachment to the preferred target cells, whose infection is likely involved in filovirus pathogenesis, whereas the MLR is not essential for the fundamental function of the GP in viral entry into cells in vitro. Further studies elucidating the mechanisms of cellular entry of filoviruses may shed light on the development of strategies for prophylaxis and treatment of Ebola and Marburg hemorrhagic fevers.

  3. Structural brain abnormalities in early onset first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, A K; Baaré, W F C; Raabjerg Christensen, A M;

    2007-01-01

    BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder, delusi...

  4. Research Review: Cholinergic Mechanisms, Early Brain Development, and Risk for Schizophrenia

    Science.gov (United States)

    Ross, Randal G.; Stevens, Karen E.; Proctor, William R.; Leonard, Sherry; Kisley, Michael A.; Hunter, Sharon K.; Freedman, Robert; Adams, Catherine E.

    2010-01-01

    The onset of diagnostic symptomology for neuropsychiatric diseases is often the end result of a decades-long process of aberrant brain development. Identification of novel treatment strategies aimed at normalizing early brain development and preventing mental illness should be a major therapeutic goal. However, there are few models for how this…

  5. Effects of Experience on the Brain: The Role of Neuroscience in Early Development and Education

    Science.gov (United States)

    Twardosz, Sandra

    2012-01-01

    Research Findings: Research on the effect of experience on the structure and function of the brain across the lifespan pertains directly to the concerns of professionals involved with children's early development and education. This paper briefly reviews (a) the role of experience in shaping the developing brain, (b) individual adaptation to the…

  6. Effects of Experience on the Brain: The Role of Neuroscience in Early Development and Education

    Science.gov (United States)

    Twardosz, Sandra

    2012-01-01

    Research Findings: Research on the effect of experience on the structure and function of the brain across the lifespan pertains directly to the concerns of professionals involved with children's early development and education. This paper briefly reviews (a) the role of experience in shaping the developing brain, (b) individual adaptation to the…

  7. Early life adversity is associated with brain changes in subjects at family risk for depression.

    LENUS (Irish Health Repository)

    Carballedo, Angela

    2012-12-01

    The interplay of genetic and early environmental factors is recognized as an important factor in the aetiology of major depressive disorder (MDD). The aim of the present study was to examine whether reduced volume of hippocampus and frontal brain regions involved in emotional regulation are already present in unaffected healthy individuals at genetic risk of suffering MDD and to investigate whether early life adversity is a relevant factor interacting with these reduced brain structures.

  8. Early invasion of brain parenchyma by African trypanosomes

    National Research Council Canada - National Science Library

    Frevert, Ute; Movila, Alexandru; Nikolskaia, Olga V; Raper, Jayne; Mackey, Zachary B; Abdulla, Maha; McKerrow, James; Grab, Dennis J

    2012-01-01

    .... Based mostly on data from animal models, it is currently thought that trypanosome entry into the brain occurs by initial infection of the choroid plexus and the circumventricular organs followed days...

  9. Trajectories of Early Brain Volume Development in Fragile X and Autism RH: Trajectory of Brain Volume in Fragile X

    Science.gov (United States)

    Hazlett, Heather Cody; Poe, Michele D.; Lightbody, Amy A.; Styner, Martin; MacFall, James R.; Reiss, Allan L.; Piven, Joseph

    2012-01-01

    Objective To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared to a comparison group (controls) and a group with idiopathic autism. Method The study included 53 boys between 18–42 months of age with FXS, 68 boys with idiopathic autism (ASD), and a comparison group of 50 typically-developing and developmentally-delayed controls. We examined structural brain volumes using magnetic resonance imaging (MRI) across two timepoints between ages 2–3 and 4–5 years and examined total brain volumes and regional (lobar) tissue volumes. Additionally, we studied a selected group of subcortical structures implicated in the behavioral features of FXS (e.g., basal ganglia, hippocampus, amygdala). Results Children with FXS had greater global brain volumes compared to controls, but were not different than children with idiopathic autism, and the rate of brain growth between ages 2 and 5 paralleled that seen in controls. In contrast to the children with idiopathic autism who had generalized cortical lobe enlargement, the children with FXS showed a specific enlargement in temporal lobe white matter, cerebellar gray matter, and caudate nucleus, but significantly smaller amygdala. Conclusions This structural longitudinal MRI study of preschoolers with FXS observed generalized brain overgrowth in FXS compared to controls, evident at age 2 and maintained across ages 4–5. We also find different patterns of brain growth that distinguishes boys with FXS from children with idiopathic autism. PMID:22917205

  10. Extreme divergence of Wolbachia tropism for the stem-cell-niche in the Drosophila testis.

    Science.gov (United States)

    Toomey, Michelle E; Frydman, Horacio M

    2014-12-01

    Microbial tropism, the infection of specific cells and tissues by a microorganism, is a fundamental aspect of host-microbe interactions. The intracellular bacteria Wolbachia have a peculiar tropism for the stem cell niches in the Drosophila ovary, the microenvironments that support the cells producing the eggs. The molecular underpinnings of Wolbachia stem cell niche tropism are unknown. We have previously shown that the patterns of tropism in the ovary show a high degree of conservation across the Wolbachia lineage, with closely related Wolbachia strains usually displaying the same pattern of stem cell niche tropism. It has also been shown that tropism to these structures in the ovary facilitates both vertical and horizontal transmission, providing a strong selective pressure towards evolutionary conservation of tropism. Here we show great disparity in the evolutionary conservation and underlying mechanisms of stem cell niche tropism between male and female gonads. In contrast to females, niche tropism in the male testis is not pervasive, present in only 45% of niches analyzed. The patterns of niche tropism in the testis are not evolutionarily maintained across the Wolbachia lineage, unlike what was shown in the females. Furthermore, hub tropism does not correlate with cytoplasmic incompatibility, a Wolbachia-driven phenotype imprinted during spermatogenesis. Towards identifying the molecular mechanism of hub tropism, we performed hybrid analyses of Wolbachia strains in non-native hosts. These results indicate that both Wolbachia and host derived factors play a role in the targeting of the stem cell niche in the testis. Surprisingly, even closely related Wolbachia strains in Drosophila melanogaster, derived from a single ancestor only 8,000 years ago, have significantly different tropisms to the hub, highlighting that stem cell niche tropism is rapidly diverging in males. These findings provide a powerful system to investigate the mechanisms and evolution of

  11. Early Blood Gas Abnormalities and the Preterm Brain

    Science.gov (United States)

    Leviton, Alan; Allred, Elizabeth; Kuban, Karl C. K.; Dammann, Olaf; O'Shea, T. Michael; Hirtz, Deborah; Schreiber, Michael D.; Paneth, Nigel

    2010-01-01

    The authors explored associations between blood gas abnormalities in more than 1,000 preterm infants during the first postnatal days and indicators of neonatal brain damage. During 2002–2004, women delivering infants before 28 weeks’ gestation at one of 14 participating institutions in 5 US states were asked to enroll in the study. The authors compared infants with blood gas values in the highest or lowest quintile for gestational age and postnatal day (extreme value) on at least 1 of the first 3 postnatal days with the remainder of the subjects, with separate analyses for blood gas abnormalities on multiple days and for partial pressure of oxygen in the alveolar gas of blood gas derangement (hypoxemia, hyperoxemia, hypocapnia, hypercapnia, and acidosis) was associated with multiple indicators of brain damage. However, for some, the associations were seen with only 1 day of exposure; others were evident with 2 or more days’ exposure. Findings suggest that individual blood gas derangements do not increase brain damage risk. Rather, the multiple derangements associated with indicators of brain damage might be indicators of immaturity/vulnerability and illness severity. PMID:20807736

  12. Early Oxygen-Utilization and Brain Activity in Preterm Infants

    NARCIS (Netherlands)

    Tataranno, ML; Alderliesten, Thomas; De Vries, Linda S.; Groenendaal, Floris; Toet, MC; Lemmers, Petra M A; van de Vosse, R.; Van Bel, Frank; Benders, Manon J N L

    2015-01-01

    The combined monitoring of oxygen supply and delivery using Near-InfraRed spectroscopy (NIRS) and cerebral activity using amplitude-integrated EEG (aEEG) could yield new insights into brain metabolism and detect potentially vulnerable conditions soon after birth. The relationship between NIRS and qu

  13. MRI surveillance of cancer cell fate in a brain metastasis model after early radiotherapy.

    Science.gov (United States)

    Murrell, Donna H; Zarghami, Niloufar; Jensen, Michael D; Dickson, Fiona; Chambers, Ann F; Wong, Eugene; Foster, Paula J

    2017-10-01

    Incidence of brain metastasis attributed to breast cancer is increasing and prognosis is poor. It is thought that disseminated dormant cancer cells persist in metastatic organs and may evade treatments, thereby facilitating a mechanism for recurrence. Radiotherapy is used to treat brain metastases clinically, but assessment has been limited to macroscopic tumor volumes detectable by clinical imaging. Here, we use cellular MRI to understand the concurrent responses of metastases and nonproliferative or slowly cycling cancer cells to radiotherapy. MRI cell tracking was used to investigate the impact of early cranial irradiation on the fate of individual iron-labeled cancer cells and outgrowth of breast cancer brain metastases in the human MDA-MB-231-BR-HER2 cell model. Early whole-brain radiotherapy significantly reduced the outgrowth of metastases from individual disseminated cancer cells in treated animals compared to controls. However, the numbers of nonproliferative iron-retaining cancer cells in the brain were not significantly different. Radiotherapy, when given early in cancer progression, is effective in preventing the outgrowth of solitary cancer cells to brain metastases. Future studies of the nonproliferative cancer cells' clonogenic potentials are warranted, given that their persistent presence suggests that they may have evaded treatment. Magn Reson Med 78:1506-1512, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  14. Early monitoring of PtiO2, PtiCO2, pH and brain temperat ure in patients with brain injuries and the clinical significanc e

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To explore the regulation of early br ain tissue metabolic changing after brain injuries and the clinical significance .   Methods: There were 17 patients with brain injuries. Early dire ct monitoring of PtiO2, PtiCO2, pH and brain temperature, dynami c observation of the relation between various parameters and clinics after brai n injuries were performed.   Results: Early changes of PtiO2, PtiCO2 and pH we re closely correlated with outcome. The death rate obviously increased when P tiO2 was continuously lower than 9 mm?Hg within 24 hours after injuries. Secondary brain injury prolonged and aggravated brain tissue metabolic disturban ce. When intracerebral pressure was over 30 mm?Hg PtiO2 began to de crea se. The brain temperature in brain death patients was evidently lower than axill ary temperature.   Conclusions: The direct monitoring of PtiO2, PtiC O2, pH and brain temperature is safe and accurate and can find early anoxia da mage to brain tissue and provide reliable basis for clinical therapy. It ha s an instructive significance in selecting and studying a new treatment method i n brain injuries. And it can be taken as a criterion in clinical judging brain d eaths.

  15. Tissue tropism and parasite burden ofToxoplasma gondii RH strain in experimentally infected mice

    Institute of Scientific and Technical Information of China (English)

    Yousef Dadimoghaddam; Ahmad Daryani; Mehdi Sharif; Ehsan Ahmadpour; Zahra Hossienikhah

    2014-01-01

    ABSTRACT Objective:To evaluate parasite distribution and tissue tropism ofToxoplasma gondii tachyzoites in experimentally infected mice using real timeQPCR.Methods:In this survey16Balb/c mice were inoculated with1×104 alive tachyzoites ofToxoplasma gondiiRH strain.After1,2,3 days post infection and the last day(before death), different tissues of mice including blood, brain, eye, liver, spleen, kidney, heart and muscle were harvested.Following tissuesDNA extraction, the parasite burden was quantified using real timeQPCR targeting theB1 gene(451 bp).Results:It showed thatToxoplasmaafter intraperitoneal injection was able to movement to various tissues in 24 hours.Parasite burden was high in all tissues but the most number of parasites were observed in kidney, heart and liver, respectively.Conclusions:These data provide significant baseline information aboutToxoplasmapathogenesis, vaccine monitoring and drug efficiency.

  16. Expression of the homeobox genes OTX2 and OTX1 in the early developing human brain

    DEFF Research Database (Denmark)

    Larsen, Karen B; Lutterodt, Melissa C; Møllgård, Kjeld

    2010-01-01

    protein was found in the subcommissural organ, pineal gland, and cerebellum. The early expression of OTX2 and OTX1 in proliferative cell layers of the human fetal brain supports the concept that these homeobox genes are important in neuronal cell development and differentiation: OTX1 primarily...... of young neurons of the deeper cortical layers. We have studied the spatial and temporal expression of the two homeobox genes OTX2 and OTX1 in human fetal brains from 7 to 14 weeks postconception by in situ hybridization and immunohistochemistry. OTX2 was expressed in the diencephalon, mesencephalon...... in the neocortex, and OTX2 in the archicortex, diencephalon, rostral brain stem, and cerebellum....

  17. The temporal increase in HIV-1 non-R5 tropism frequency among newly diagnosed patients from northern Poland is associated with clustered transmissions

    Directory of Open Access Journals (Sweden)

    Miłosz Parczewski

    2015-08-01

    Full Text Available Introduction: CCR5 (R5 tropic viruses are associated with early stages of infection, whereas CXCR4 (X4 HIV-1 tropism has been associated with severe immunodeficiency. We investigated the temporal changes in the genotype-predicted tropism frequency and the phylogenetic relationships between the R5 and non-R5 clades. Methods: A cohort of 194 patients with a newly diagnosed HIV infection that was linked to their care from 2007 to 2014 was analyzed. Baseline plasma samples were used to assess the HIV-1 genotypic tropism with triplicate V3-loop sequencing. The non-R5 tropism prediction thresholds were assigned using a false positive rate (FPR of 10 and 5.75% and associated with clinical and laboratory data. The transmission clusters were analyzed using pol sequences with a maximum likelihood and Bayesian inference. Results: The overall non-R5 tropism frequency for 5.75% FPR was 15.5% (n=30 and 27.8% (n=54 for 10% FPR. The frequency of the non-R5 tropism that was predicted using 5.75% FPR increased significantly from 2007 (0% to 2014 (n=5/17, 29.4% (p=0.004, rough slope +3.73%/year and from 0% (2007 to 35.3% (2014, n=6/17 (p=0.071, rough slope +2.9%/year using 10% FPR. Increase in the asymptomatic diagnoses over time was noted (p=0.05, rough slope +3.53%/year along with a tendency to increase the lymphocyte CD4 nadir (p=0.069. Thirty-two clusters were identified, and non-R5 tropic viruses were found for 26 (30.95% sequences contained within 14 (43.8% clusters. Non-R5 tropism was associated with subtype D variants (p=0.0001 and the presence of CCR5 Δ32/wt genotype (p=0.052. Conclusions: R5 tropism predominates among the treatment of naive individuals, but the increases in the frequency of non-R5 tropic variants may limit the clinical efficacy of the co-receptor inhibitors. The rising prevalence of non-R5 HIV-1 may indicate transmission of X4 clades.

  18. Early CT signs of progressive hemorrhagic injury following acute traumatic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Wu-song; Zheng, Ping; Xu, Jun-fa; Guo, Yi-jun; Zeng, Jing-song; Yang, Wen-jin; Li, Gao-yi; He, Bin; Yu, Hui [Pudong New Area People' s Hospital, Department of Neurosurgery, Shanghai (China)

    2011-05-15

    Since progressive hemorrhagic injury (PHI) was introduced in neurosurgical literatures, several studies have been performed, the results of which have influenced doctors but do not define guidelines for the best treatment of PHI. PHI may be confirmed by a serial computerized tomography (CT) scan, and it has been shown to be associated with a fivefold increase in the risk of clinical worsening and is a significant cause of morbidity and mortality as well. So, early detection of PHI is practically important in a clinical situation. To analyze the early CT signs of progressive hemorrhagic injury following acute traumatic brain injury (TBI) and explore their clinical significances, PHI was confirmed by comparing the first and repeated CT scans. Data were analyzed and compared including times from injury to the first CT and signs of the early CT scan. Logistic regression analysis was used to show the risk factors related to PHI. A cohort of 630 TBI patients was evaluated, and there were 189 (30%) patients who suffered from PHI. For patients with their first CT scan obtained as early as 2 h post-injury, there were 116 (77.25%) cases who suffered from PHI. The differences between PHIs and non-PHIs were significant in the initial CT scans showing fracture, subarachnoid hemorrhage (SAH), brain contusion, epidural hematoma (EDH), subdural hematoma (SDH), and multiple hematoma as well as the times from injury to the first CT scan (P < 0.01). Logistic regression analysis showed that early CT scans (EDH, SDH, SAH, fracture, and brain contusion) were predictors of PHI (P < 0.01). For patients with the first CT scan obtained as early as 2 h post-injury, a follow-up CT scan should be performed promptly. If the initial CT scan shows SAH, brain contusion, and primary hematoma with brain swelling, an earlier and dynamic CT scan should be performed for detection of PHI as early as possible and the medical intervention would be enforced in time. (orig.)

  19. Multicenter trial of early hypothermia in severe brain injury.

    Science.gov (United States)

    Clifton, Guy L; Drever, Pamala; Valadka, Alex; Zygun, David; Okonkwo, David

    2009-03-01

    The North American Brain Injury Study: Hypothermia IIR (NABIS:H IIR) is a randomized clinical trial designed to enroll 240 patients with severe brain injury between the ages of 16 and 45 years. The primary outcome measure is the dichotomized Glasgow Outcome Scale (GOS) at 6 months after injury. The study has the power to detect a 17.5% absolute difference in the percentage of patients with a good outcome with a power of 80%. All patients are randomized by waiver of consent unless family is immediately available. Enrollment is within 2.5 h of injury. Patients may be enrolled in the field by emergency medical services personnel affiliated with the study or by study personnel when the patient arrives at the emergency department. Patients who do not follow commands and have no exclusion criteria and who are enrolled in the hypothermia arm of the study are cooled to 35 degrees C as rapidly as possible by intravenous administration of up to 2 liters of chilled crystalloid. Those patients who meet the criteria for the second phase of the protocol (primarily a post-resuscitation GCS 3-8 without hypotension and without severe associated injuries) are cooled to 33 degrees C. Patients enrolled in the normothermia arm receive standard management at normothermia. As of December 2007, 74 patients had been randomized into phase II of the protocol. Patients in the hypothermia arm reached 35 degrees C in 2.7 +/- 1.1 (SD) h after injury and reached 33 degrees C at 4.4 +/- 1.5 h after injury.

  20. Early life stress-induced alterations in rat brain structures measured with high resolution MRI.

    Science.gov (United States)

    Sarabdjitsingh, R Angela; Loi, Manila; Joëls, Marian; Dijkhuizen, Rick M; van der Toorn, Annette

    2017-01-01

    Adverse experiences early in life impair cognitive function both in rodents and humans. In humans this increases the vulnerability to develop mental illnesses while in the rodent brain early life stress (ELS) abnormalities are associated with changes in synaptic plasticity, excitability and microstructure. Detailed information on the effects of ELS on rodent brain structural integrity at large and connectivity within the brain is currently lacking; this information is highly relevant for understanding the mechanism by which early life stress predisposes to mental illnesses. Here, we exposed rats to 24 hours of maternal deprivation (MD) at postnatal day 3, a paradigm known to increase corticosterone levels and thereby activate glucocorticoid receptors in the brain. Using structural magnetic resonance imaging we examined: i) volumetric changes and white/grey matter properties of the whole cerebrum and of specific brain areas; and ii) whether potential alterations could be normalized by blocking glucocorticoid receptors with mifepristone during the critical developmental window of early adolescence, i.e. between postnatal days 26 and 28. The results show that MD caused a volumetric reduction of the prefrontal cortex, particularly the ventromedial part, and the orbitofrontal cortex. Within the whole cerebrum, white (relative to grey) matter volume was decreased and region-specifically in prefrontal cortex and dorsomedial striatum following MD. A trend was found for the hippocampus. Grey matter fractions were not affected. Treatment with mifepristone did not normalize these changes. This study indicates that early life stress in rodents has long lasting consequences for the volume and structural integrity of the brain. However, changes were relatively modest and-unlike behavior- not mitigated by blockade of glucocorticoid receptors during a critical developmental period.

  1. Temporal increase in HIV-1 non-R5 tropism frequency among antiretroviral-naive patients from northern Poland

    Directory of Open Access Journals (Sweden)

    Milosz Parczewski

    2014-11-01

    Full Text Available Introduction: Sequencing of the third hypervariable loop allows to identify genotype-based HIV tropism. R5-tropic viruses associated with early stages of infection are preferentially transmitted, while non-R5 HIV-1 tropism has been associated with severe immunodeficiency and lower lymphocyte CD4 nadir and may reflect delayed HIV diagnosis. In this study, we investigate the changes in tropism frequency from 2007 to 2013. Materials and Methods: Study included 194 patients with confirmed HIV infection linked to care in 2007–2013. Baseline plasma samples from treatment naive patients were used for HIV-1 genotypic tropism assessment based on triplicate V3 loop sequencing. Non-R5 tropism prediction thresholds were assigned using a false positive rate (FPR of 10% and 5.75% FPR and associated with clinical and laboratory data (age, gender, date of HIV diagnosis, route of transmission, CDC clinical category at diagnosis, pretreatment HIV viral load, baseline and nadir lymphocyte CD4 counts. For statistics, chi-square and Mann–Whitney U tests were used, time trends were examined using logistic regression (R statistical platform, v. 3.1.0 for binary variables and linear regression for continuous ones. Results: Overall non-R5 tropism frequency for the 5.75% FPR was 15.5% and 27.8% for 10% FPR. Frequency of the non-R5 tropism predicted using 5.75% FPR increased significantly from 2007 (0% to 2013 (25% [OR: 1.44 (95% CI 1.14–1.86, p=0.003, rough slope +3.89%/year] (Figure 1a. With 10% FPR, the frequency changed from 7% (2007 to 33% (2013 [OR: 1.17 (95% CI 0.99–1.39, p=0.054, rough slope +3.0%/year] (Figure 1b. Baseline lymphocyte CD4 count and nadir, as well as pretreatment HIV-1 viral loads were stable over time of observation (r=0.014, p=0.84; r=0.13, p=0.085; r=0.016, p=0.83 for CD4 baseline, nadir and HIV load, respectively. Frequency of AIDS at HIV diagnosis increased from 21.4% in 2007 to 38.0% in 2013, however trend over time was insignificant

  2. Gesturing with an Injured Brain: How Gesture Helps Children with Early Brain Injury Learn Linguistic Constructions

    Science.gov (United States)

    Ozcaliskan, Seyda; Levine, Susan C.; Goldin-Meadow, Susan

    2013-01-01

    Children with pre/perinatal unilateral brain lesions (PL) show remarkable plasticity for language development. Is this plasticity characterized by the same developmental trajectory that characterizes typically developing (TD) children, with gesture leading the way into speech? We explored this question, comparing eleven children with PL -- matched…

  3. The Role of Cancer Stem Cells in the Organ Tropism of Breast Cancer Metastasis: A Mechanistic Balance between the “Seed” and the “Soil”?

    OpenAIRE

    2012-01-01

    Breast cancer is a prevalent disease worldwide, and the majority of deaths occur due to metastatic disease. Clinical studies have identified a specific pattern for the metastatic spread of breast cancer, termed organ tropism; where preferential secondary sites include lymph node, bone, brain, lung, and liver. A rare subpopulation of tumor cells, the cancer stem cells (CSCs), has been hypothesized to be responsible for metastatic disease and therapy resistance. Current treatments are highly in...

  4. Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour.

    Science.gov (United States)

    Desbonnet, Lieve; Clarke, Gerard; Traplin, Alexander; O'Sullivan, Orla; Crispie, Fiona; Moloney, Rachel D; Cotter, Paul D; Dinan, Timothy G; Cryan, John F

    2015-08-01

    There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may

  5. Effects of early life adverse experiences on brain activity: Implications from maternal separation models in rodents

    Directory of Open Access Journals (Sweden)

    Mayumi eNishi

    2014-06-01

    Full Text Available During postnatal development, adverse early life experiences can affect the formation of neuronal circuits and exert long-lasting influences on neural function. Many studies have shown that daily repeated MS, an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA axis and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been completely elucidated. In this review, we introduce various cases of MS in rodents and illustrate the alterations in HPA axis activity by focusing on corticosterone (CORT, an end product of the HPA axis in rodents. We then present a characterization of the brain regions affected by various patterns of MS, including repeated MS and single time MS at various stages before weaning, by investigating c-Fos expression, a biological marker of neuronal activity. These CORT and c-Fos studies suggest that repeated early life stress may affect neuronal function in region- and temporal-specific manners, indicating a critical period for habituation to early life stress. Next, we discuss how early life stress can impact behavior, namely by inducing depression, anxiety or eating disorders. Furthermore, alterations in gene expression in adult mice exposed to MS, especially epigenetic changes of DNA methylation, are discussed.

  6. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    Science.gov (United States)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-03-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

  7. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    Science.gov (United States)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-01-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development. PMID:28266608

  8. Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Imam, Ayesha M; Jin, Guang; Sillesen, Martin

    2013-01-01

    Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the assoc......Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well...

  9. Media representations of early human development: protecting, feeding and loving the developing brain.

    Science.gov (United States)

    O'Connor, Cliodhna; Joffe, Helene

    2013-11-01

    The public profile of neurodevelopmental research has expanded in recent years. This paper applies social representations theory to explore how early brain development was represented in the UK print media in the first decade of the 21st century. A thematic analysis was performed on 505 newspaper articles published between 2000 and 2010 that discussed early brain development. Media coverage centred around concern with 'protecting' the prenatal brain (identifying threats to foetal neurodevelopment), 'feeding' the infant brain (indicating the patterns of nutrition that enhance brain development) and 'loving' the young child's brain (elucidating the developmental significance of emotionally nurturing family environments). The media focused almost exclusively on the role of parental action in promoting optimal neurodevelopment, rarely acknowledging wider structural, cultural or political means of supporting child development. The significance of parental care was intensified by deterministic interpretations of critical periods, which implied that inappropriate parental input would produce profound and enduring neurobiological impairments. Neurodevelopmental research was also used to promulgate normative judgements concerning the acceptability of certain gender roles and family contexts. The paper argues that media representations of neurodevelopment stress parental responsibility for shaping a child's future while relegating the contributions of genetic or wider societal factors, and examines the consequences of these representations for society and family life.

  10. Brain Network Involved in the Recognition of Facial Expressions of Emotion in the Early Blind

    Directory of Open Access Journals (Sweden)

    Ryo Kitada

    2011-10-01

    Full Text Available Previous studies suggest that the brain network responsible for the recognition of facial expressions of emotion (FEEs begins to emerge early in life. However, it has been unclear whether visual experience of faces is necessary for the development of this network. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI experiments to test the hypothesis that the brain network underlying the recognition of FEEs is not dependent on visual experience of faces. Early-blind, late-blind and sighted subjects participated in the psychophysical experiment. Regardless of group, subjects haptically identified basic FEEs at above-chance levels, without any feedback training. In the subsequent fMRI experiment, the early-blind and sighted subjects haptically identified facemasks portraying three different FEEs and casts of three different shoe types. The sighted subjects also completed a visual task that compared the same stimuli. Within the brain regions activated by the visually-identified FEEs (relative to shoes, haptic identification of FEEs (relative to shoes by the early-blind and sighted individuals activated the posterior middle temporal gyrus adjacent to the superior temporal sulcus, the inferior frontal gyrus, and the fusiform gyrus. Collectively, these results suggest that the brain network responsible for FEE recognition can develop without any visual experience of faces.

  11. [Development and the developmental disorders of human brain. I. Early development of the cerebrum

    NARCIS (Netherlands)

    Donkelaar, H.J. ten; Wesseling, P.; Lammens, M.M.Y.; Renier, W.O.; Mullaart, R.A.; Thijssen, H.O.M.

    2001-01-01

    The recent discovery of many genes that regulate brain development is revolutionizing our knowledge of neuroembryology and, moreover, our understanding of how gene defects cause human birth defects. The first 8 weeks of the development of the cerebrum can be subdivided into 23 stages, with early

  12. Serial cranial ultrasonography or early MRI for detecting preterm brain injury?

    NARCIS (Netherlands)

    Plaisier, Annemarie; Raets, Marlou M A; Ecury-Goossen, Ginette M; Govaert, Paul; Feijen-Roon, Monique; Reiss, Irwin K M; Smit, Liesbeth S; Lequin, Maarten H; Dudink, Jeroen

    2015-01-01

    OBJECTIVE: To investigate detection ability and feasibility of serial cranial ultrasonography (CUS) and early MRI in preterm brain injury. DESIGN: Prospective cohort study. SETTING: Level III neonatal intensive care unit. PATIENTS: 307 infants, born below 29 weeks of gestation. METHODS: Serial CUS a

  13. Trajectories of Early Brain Volume Development in Fragile X Syndrome and Autism

    Science.gov (United States)

    Hazlett, Heather Cody; Poe, Michele D.; Lightbody, Amy A.; Styner, Martin; MacFall, James R.; Reiss, Allan L.; Piven, Joseph

    2012-01-01

    Objective: To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared with a comparison group (controls) and a group with idiopathic autism. Method: The study included 53 boys 18 to 42 months of age with FXS, 68 boys with idiopathic autism (autism spectrum disorder), and a comparison group of 50 typically…

  14. Early diagnosis of dementia based on intersubject whole-brain dissimilarities

    DEFF Research Database (Denmark)

    Klein, S.; Loog, M.; Lijn, F. van der;

    2010-01-01

    . A kNN classifier was trained on the dissimilarity matrix and the performance was tested in a leave-one-out experiment. A classification accuracy of 81% was attained (spec. 83%, sens. 79%). This demonstrates the potential of whole-brain intersubject dissimilarities to aid in early diagnosis of dementia....

  15. Rebooting the Brain: Using Early Childhood Education to Heal Trauma from Abuse and Neglect

    Science.gov (United States)

    McLintock, Ben

    2011-01-01

    Abused and neglected children live in a world that usually includes some sort of violence, chaos, and tremendous physical and mental stress. This toxic environment wreaks havoc on a child's developing brain. This article discusses how to use early childhood education to heal trauma from abuse and neglect. It shares the story of two children, Bryce…

  16. Early Gesture Predicts Language Delay in Children with Pre- Or Perinatal Brain Lesions

    Science.gov (United States)

    Sauer, Eve; Levine, Susan C.; Goldin-Meadow, Susan

    2010-01-01

    Does early gesture use predict later productive and receptive vocabulary in children with pre- or perinatal unilateral brain lesions (PL)? Eleven children with PL were categorized into 2 groups based on whether their gesture at 18 months was within or below the range of typically developing (TD) children. Children with PL whose gesture was within…

  17. Structural brain abnormalities in early onset first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, A K; Baaré, William Frans Christian; Raabjerg Christensen, A M

    2007-01-01

    , delusional disorder or other non-organic psychosis), aged 10-18 to those of 29 matched controls, using optimized voxel-based morphometry. RESULTS: Psychotic patients had frontal white matter abnormalities, but expected (regional) gray matter reductions were not observed. Post hoc analyses revealed...... that schizophrenia patients (n = 15) had significantly larger lateral ventricles as compared to controls. Duration and dose of antipsychotics correlated negatively with global gray matter volume in minimally medicated patients (n = 18). CONCLUSION: Findings of white matter changes and enlarged lateral ventricles...... already at illness onset in young schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes in the pathogenesis of these disorders. Gray matter volume changes, however, appear not to be a key feature in early onset first-episode psychosis....

  18. Structural brain network characteristics can differentiate CIS from early RRMS

    Directory of Open Access Journals (Sweden)

    Muthuraman eMuthuraman

    2016-02-01

    Full Text Available Focal demyelinated lesions, diffuse white matter (WM damage and grey matter (GM atrophy influence directly the disease progression in patients with multiple sclerosis. The aim of this study was to identify specific characteristics of GM and WM structural networks in subjects with clinically isolated syndrome (CIS in comparison to patients with early relapsing-remitting multiple sclerosis (RRMS.Twenty patients with CIS, thirty three with RRMS and forty healthy subjects were investigated using 3 T-MRI. Diffusion tensor imaging was applied, together with probabilistic tractography and fractional anisotropy (FA maps for WM and cortical thickness correlation analysis for GM, to determine the structural connectivity patterns. A network topology analysis with the aid of graph theoretical approaches was used to characterize the network at different community levels (modularity, clustering coefficient, global and local efficiencies. Finally, we applied support vector machines (SVM to automatically discriminate the two groups. .In comparison to CIS subjects, patients with RRMS were found to have increased modular connectivity and higher local clustering, highlighting increased local processing in both GM and WM. Both groups presented increased modularity and clustering coefficients in comparison to healthy controls. SVM algorithms achieved 97% accuracy using the clustering coefficient as classifier derived from GM and 65% using WM from probabilistic tractography and 67 % from modularity of FA maps to differentiate between CIS and RRMS patients. We demonstrate a clear increase of modular and local connectivity in patients with early RRMS in comparison to CIS and healthy subjects. Based only on a single anatomic scan and without a priori information, we developed an automated and investigator-independent paradigm that can accurately discriminate between patients with these clinically similar disease entities, and could thus complement the current

  19. Patient Perspectives on Deep Brain Stimulation Clinical Research in Early Stage Parkinson's Disease.

    Science.gov (United States)

    Heusinkveld, Lauren; Hacker, Mallory; Turchan, Maxim; Bollig, Madelyn; Tamargo, Christina; Fisher, William; McLaughlin, Lauren; Martig, Adria; Charles, David

    2017-01-01

    The FDA has approved a multicenter, double-blind, Phase III, pivotal trial testing deep brain stimulation (DBS) in 280 people with very early stage Parkinson's disease (PD; IDE#G050016). In partnership with The Michael J. Fox Foundation for Parkinson's Research, we conducted a survey to investigate motivating factors, barriers, and gender differences among potentially eligible patients for participation in a trial testing DBS in early PD compared to standard medical treatment. The majority of survey respondents (72%) indicated they would consider learning more about participating. Early PD patients are therefore likely to consider enrolling in trials of invasive therapies that may slow symptom progression and help future patients.

  20. Elucidating the early signal transduction pathways leading to fetal brain injury in preterm birth.

    Science.gov (United States)

    Elovitz, Michal A; Mrinalini, Conjeevaram; Sammel, Mary D

    2006-01-01

    Adverse neurologic outcome, including cerebral palsy, is a significant contributor to long-term morbidity in preterm neonates. However, the mechanisms leading to brain injury in the setting of a preterm birth are poorly understood. In the last decade, there has been a growing body of evidence correlating infection or inflammation with preterm birth. The presence of intrauterine inflammation significantly increases the risk for adverse neurologic outcome in the neonate. These studies were performed to elucidate the early signal transduction pathways activated in the fetal brain that may result in long-term neurologic injury. Using our mouse model of localized intrauterine inflammation, the activation of TH1/TH2 pathways in the placenta, fetus corpus, fetal liver, and fetal brain was investigated. Additional studies determined whether activation of TH1/TH2 pathways could promote cell death and alter glial development. Real-time PCR studies demonstrated that a robust TH1/TH2 response occurs rapidly in the fetal brain after exposure to intrauterine inflammation. The cytokine response in the fetus and placenta was not significantly correlated with the response in the fetal brain. Along with an immune response, cell death pathways were activated early in the fetal brain in response to intrauterine LPS. Implicating TH1/TH2 and cell death pathways in permanent brain injury are our findings of an increase in GFAP mRNA and protein as well as a loss of pro-oligodendrocytes. With increased understanding of the mechanisms by which inflammation promotes brain injury in the preterm neonate, identification of potential targets to limit adverse neonatal outcomes becomes possible.

  1. Enhanced brain signal variability in children with autism spectrum disorder during early childhood

    Science.gov (United States)

    Yoshimura, Yuko; Hiraishi, Hirotoshi; Hasegawa, Chiaki; Munesue, Toshio; Higashida, Haruhiro; Minabe, Yoshio; Kikuchi, Mitsuru

    2016-01-01

    Abstract Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age‐related increase of brain signal variability in a specific timescale in TD children, whereas atypical age‐related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region‐specifically and timescale‐specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical‐developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. Hum Brain Mapp 37:1038–1050, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26859309

  2. Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host

    Science.gov (United States)

    Varela, Mariana; Schnettler, Esther; Caporale, Marco; Murgia, Claudio; Barry, Gerald; McFarlane, Melanie; McGregor, Eva; Piras, Ilaria M.; Shaw, Andrew; Lamm, Catherine; Janowicz, Anna; Beer, Martin; Glass, Mandy; Herder, Vanessa; Hahn, Kerstin; Baumgärtner, Wolfgang; Kohl, Alain; Palmarini, Massimo

    2013-01-01

    Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV. PMID:23326235

  3. Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host.

    Directory of Open Access Journals (Sweden)

    Mariana Varela

    2013-01-01

    Full Text Available Schmallenberg virus (SBV is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and "synthetic" SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV.

  4. Development of Brain EEG Connectivity across Early Childhood: Does Sleep Play a Role?

    Directory of Open Access Journals (Sweden)

    Monique K. LeBourgeois

    2013-11-01

    Full Text Available Sleep has beneficial effects on brain function and learning, which are reflected in plastic changes in the cortex. Early childhood is a time of rapid maturation in fundamental skills—e.g., language, cognitive control, working memory—that are predictive of future functioning. Little is currently known about the interactions between sleep and brain maturation during this developmental period. We propose coherent electroencephalogram (EEG activity during sleep may provide unique insight into maturational processes of functional brain connectivity. Longitudinal sleep EEG assessments were performed in eight healthy subjects at ages 2, 3 and 5 years. Sleep EEG coherence increased across development in a region- and frequency-specific manner. Moreover, although connectivity primarily decreased intra-hemispherically across a night of sleep, an inter-hemispheric overnight increase occurred in the frequency range of slow waves (0.8–2 Hz, theta (4.8–7.8 Hz and sleep spindles (10–14 Hz, with connectivity changes of up to 20% across a night of sleep. These findings indicate sleep EEG coherence reflects processes of brain maturation—i.e., programmed unfolding of neuronal networks—and moreover, sleep-related alterations of brain connectivity during the sensitive maturational window of early childhood.

  5. Early effects of lipopolysaccharide-induced inflammation on foetal brain development in rat

    Directory of Open Access Journals (Sweden)

    Cristina A Ghiani

    2011-11-01

    Full Text Available Studies in humans and animal models link maternal infection and imbalanced levels of inflammatory mediators in the foetal brain to the aetiology of neuropsychiatric disorders. In a number of animal models, it was shown that exposure to viral or bacterial agents during a period that corresponds to the second trimester in human gestation triggers brain and behavioural abnormalities in the offspring. However, little is known about the early cellular and molecular events elicited by inflammation in the foetal brain shortly after maternal infection has occurred. In this study, maternal infection was mimicked by two consecutive intraperitoneal injections of 200 μg of LPS (lipopolysaccharide/kg to timed-pregnant rats at GD15 (gestational day 15 and GD16. Increased thickness of the CP (cortical plate and hippocampus together with abnormal distribution of immature neuronal markers and decreased expression of markers for neural progenitors were observed in the LPS-exposed foetal forebrains at GD18. Such effects were accompanied by decreased levels of reelin and the radial glial marker GLAST (glial glutamate transporter, and elevated levels of pro-inflammatory cytokines in maternal serum and foetal forebrains. Foetal inflammation elicited by maternal injections of LPS has discrete detrimental effects on brain development. The early biochemical and morphological changes described in this work begin to explain the sequelae of early events that underlie the neurobehavioural deficits reported in humans and animals exposed to prenatal insults.

  6. Early Effects of Lipopolysaccharide-Induced Inflammation on Foetal Brain Development in Rat

    Directory of Open Access Journals (Sweden)

    Cristina A Ghiani

    2011-10-01

    Full Text Available Studies in humans and animal models link maternal infection and imbalanced levels of inflammatory mediators in the foetal brain to the aetiology of neuropsychiatric disorders. In a number of animal models, it was shown that exposure to viral or bacterial agents during a period that corresponds to the second trimester in human gestation triggers brain and behavioural abnormalities in the offspring. However, little is known about the early cellular and molecular events elicited by inflammation in the foetal brain shortly after maternal infection has occurred. In this study, maternal infection was mimicked by two consecutive intraperitoneal injections of 200 μg of LPS (lipopolysaccharide/kg to timed-pregnant rats at GD15 (gestational day 15 and GD16. Increased thickness of the CP (cortical plate and hippocampus together with abnormal distribution of immature neuronal markers and decreased expression of markers for neural progenitors were observed in the LPS-exposed foetal forebrains at GD18. Such effects were accompanied by decreased levels of reelin and the radial glial marker GLAST (glial glutamate transporter, and elevated levels of pro-inflammatory cytokines in maternal serum and foetal forebrains. Foetal inflammation elicited by maternal injections of LPS has discrete detrimental effects on brain development. The early biochemical and morphological changes described in this work begin to explain the sequelae of early events that underlie the neurobehavioural deficits reported in humans and animals exposed to prenatal insults.

  7. Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities

    Directory of Open Access Journals (Sweden)

    Janušonis Skirmantas

    2005-07-01

    Full Text Available Abstract Background A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin in blood platelets (platelet hyperserotonemia. The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor. Results The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals. Conclusion At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene based on currently available clinical and

  8. Fetal MRI detects early alterations of brain development in Tetralogy of Fallot.

    Science.gov (United States)

    Schellen, Christoph; Ernst, Schwartz; Gruber, Gerlinde M; Mlczoch, Elisabeth; Weber, Michael; Brugger, Peter C; Ulm, Barbara; Langs, Georg; Salzer-Muhar, Ulrike; Prayer, Daniela; Kasprian, Gregor

    2015-09-01

    Prenatal imaging has identified alterations of brain growth in fetuses with congenital heart disease. However, little is known about the timing of altered brain development and its occurrence in specific congenital heart disease subgroups. This magnetic resonance imaging study aimed to identify early (median, 25 gestational weeks [GW]) changes in fetal total brain (TBV), gray matter (GMV), and subcortical brain (SBV) volumes in Tetralogy of Fallot (TOF) cases in utero. Fetal magnetic resonance imaging (1.5 Tesla) was performed in 24 fetuses who were diagnosed with TOF and 24 normal age-matched control fetuses (20-34 GW). TBV, GMV, SBV, intracranial cavity, cerebellar, ventricular, and external cerebrospinal fluid volumes were quantified by manual segmentation based on coronal T2-weighted sequences. Mixed model analyses of variance and t-tests were conducted to compare cases and control fetuses. TBV was significantly lower (P < .001) in early (<25 GW) and late TOF cases. Both GMV (P = .003) and SBV (P = .001) were affected. The GMV-to-SBV ratio declined in fetuses with TOF (P = .026). Compared with normal fetuses, ventricular volume was increased (P = .0048). External cerebrospinal fluid was enlarged in relation to head size (P < .001). Intracranial cavity volume (P = .314) and cerebellar volume (P = .074) were not significantly reduced in fetuses with TOF. TOF is associated with smaller volumes of gray and white matter and enlarged cerebrospinal fluid spaces. These changes are present at ≤25 GW and indicate altered fetal brain growth in this pathophysiologic entity during early stages of human brain development. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Early expression of hypocretin/orexin in the chick embryo brain.

    Directory of Open Access Journals (Sweden)

    Kyle E Godden

    Full Text Available Hypocretin/Orexin (H/O neuropeptides are released by a discrete group of neurons in the vertebrate hypothalamus which play a pivotal role in the maintenance of waking behavior and brain state control. Previous studies have indicated that the H/O neuronal development differs between mammals and fish; H/O peptide-expressing cells are detectable during the earliest stages of brain morphogenesis in fish, but only towards the end of brain morphogenesis (by ∼ 85% of embryonic development in rats. The developmental emergence of H/O neurons has never been previously described in birds. With the goal of determining whether the chick developmental pattern was more similar to that of mammals or of fish, we investigated the emergence of H/O-expressing cells in the brain of chick embryos of different ages using immunohistochemistry. Post-natal chick brains were included in order to compare the spatial distribution of H/O cells with that of other vertebrates. We found that H/O-expressing cells appear to originate from two separate places in the region of the diencephalic proliferative zone. These developing cells express the H/O neuropeptide at a comparatively early age relative to rodents (already visible at 14% of the way through fetal development, thus bearing a closer resemblance to fish. The H/O-expressing cell population proliferates to a large number of cells by a relatively early embryonic age. As previously suggested, the distribution of H/O neurons is intermediate between that of mammalian and non-mammalian vertebrates. This work suggests that, in addition to its roles in developed brains, the H/O peptide may play an important role in the early embryonic development of non-mammalian vertebrates.

  10. Development of a quantitative PCR assay for monitoring Streptococcus agalactiae colonization and tissue tropism in experimentally infected tilapia.

    Science.gov (United States)

    Su, Y-L; Feng, J; Li, Y-W; Bai, J-S; Li, A-X

    2016-02-01

    Streptococcus agalactiae has become one of the most important emerging pathogens in the aquaculture industry and has resulted in large economic losses for tilapia farms in China. In this study, three pairs of specific primers were designed and tested for their specificities and sensitivities in quantitative real-time polymerase chain reactions (qPCRs) after optimization of the annealing temperature. The primer pair IGS-s/IGS-a, which targets the 16S-23S rRNA intergenic spacer region, was finally chosen, having a detection limit of 8.6 copies of S. agalactiae DNA in a 20 μL reaction mixture. Bacterial tissue tropism was demonstrated by qPCR in Oreochromis niloticus 5 days post-injection with a virulent S. agalactiae strain. Bacterial loads were detected at the highest level in brain, followed by moderately high levels in kidney, heart, spleen, intestines, and eye. Significantly lower bacterial loads were observed in muscle, gill and liver. In addition, significantly lower bacterial loads were observed in the brain of convalescent O. niloticus 14 days post-injection with several different S. agalactiae strains. The qPCR for the detection of S. agalactiae developed in this study provides a quantitative tool for investigating bacterial tissue tropism in infected fish, as well as for monitoring bacterial colonization in convalescent fish.

  11. Enhanced brain signal variability in children with autism spectrum disorder during early childhood.

    Science.gov (United States)

    Takahashi, Tetsuya; Yoshimura, Yuko; Hiraishi, Hirotoshi; Hasegawa, Chiaki; Munesue, Toshio; Higashida, Haruhiro; Minabe, Yoshio; Kikuchi, Mitsuru

    2016-03-01

    Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age-related increase of brain signal variability in a specific timescale in TD children, whereas atypical age-related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region-specifically and timescale-specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical-developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  12. Mitochondrial quality control systems sustain brain mitochondrial bioenergetics in early stages of type 2 diabetes.

    Science.gov (United States)

    Santos, R X; Correia, S C; Alves, M G; Oliveira, P F; Cardoso, S; Carvalho, C; Seiça, R; Santos, M S; Moreira, P I

    2014-09-01

    Mitochondria have a crucial role in the supply of energy to the brain. Mitochondrial alterations can lead to detrimental consequences on the function of brain cells and are thought to have a pivotal role in the pathogenesis of several neurologic disorders. This study was aimed to evaluate mitochondrial function, fusion-fission and biogenesis and autophagy in brain cortex of 6-month-old Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes (T2D). No statistically significant alterations were observed in mitochondrial respiratory chain and oxidative phosphorylation system. A significant decrease in the protein levels of OPA1, a protein that facilitates mitochondrial fusion, was observed in brain cortex of GK rats. Furthermore, a significant decrease in the protein levels of LC3-II and a significant increase in protein levels of mTOR phosphorylated at serine residue 2448 were observed in GK rats suggesting a suppression of autophagy in diabetic brain cortex. No significant alterations were observed in the parameters related to mitochondrial biogenesis. Altogether, these results demonstrate that during the early stages of T2D, brain mitochondrial function is maintained in part due to a delicate balance between mitochondrial fusion-fission and biogenesis and autophagy. However, future studies are warranted to evaluate the role of mitochondrial quality control pathways in late stages of T2D.

  13. PREVELENCE OF HIV-1 CCRS TROPISM (GENOTYPIC ASSAY: JAIPUR

    Directory of Open Access Journals (Sweden)

    Shifa

    2014-09-01

    Full Text Available : INTRODUCTION: HIV most commonly uses CCR5 and/or CXCR4 as a co-receptor to enter its target cells. Several chemokine receptors can function as viral co-receptors, but CCR5 is likely the most physiologically important co receptor during natural infection. C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. This is the process by which T cells are attracted to specific tissue and organ targets. Most forms of HIV, the virus that causes AIDS, initially use CCR5 to enter and infect host cells. We studied the prevalence of CCR5 tropism HIV1 amongst HIV positive patients attending Mahatma Gandhi hospital Jaipur. STUDY DESIGN: This was epidemiological, cross-sectional, and non-interventional study between March and April 2014 in HIV positive patients in Jaipur. METHODS: Co-receptor tropism assay was done in total nine patients who were HIV positive attending Mahatma Gandhi Hospital Dermatology &Venereology of Mahatma Gandhi Hospital OPD in one month duration time. Total nine patients were studied, seven patients were already on ART(anti-retroviral treatment and two patients were not taking any treatment as their CD4 count were above 500 cells/ULwith low viral load. Co-Receptor tropism assay (genetic assay CCR5 (with the help of Emcure pharmaceuticals was done in all of them. RESULT: Only one patient had FPR below 15 %, rest 8 patients had FPR above 15%.The study showed that the prevalence of CCR5 positivity was 88.8%, whereas CXCR4 prevalence was only 11.1%.

  14. Seizures in the de-institutionalized patients with early brain injuries.

    Science.gov (United States)

    DeToledo, J C

    1998-08-01

    The number of individuals with early brain injury and multiple disabilities discharged from institutions had increased steadily over the past 10 years. The most frequently encountered problems by patients with early brain injury and epilepsy placed in the community were reviewed. Unavailability of specialized services, inadequate reimbursement, high turnover and lack of knowledge by caregivers, lack of understanding/acceptance of the concepts of seizure intractability and pseudoseizures, unrealistic expectations by overseeing agencies and/or family, and side effects of antiepileptic medications were the most common seizure-related problems afflicting these patients. Everything else being equal, good exchange of information between the various caregivers and continued education of caregivers, both time consuming endeavors, are the crucial factors for the successful management of seizures in this population.

  15. A critical role for sonic hedgehog signaling in the early expansion of the developing brain.

    Science.gov (United States)

    Britto, Joanne; Tannahill, David; Keynes, Roger

    2002-02-01

    The mechanisms that coordinate the three-dimensional shape of the vertebrate brain during development are largely unknown. We have found that sonic hedgehog (Shh) is crucial in driving the rapid, extensive expansion of the early vesicles of the developing midbrain and forebrain. Transient displacement of the notochord from the midbrain floor plate resulted in abnormal folding and overall collapse of the vesicles, accompanied by reduced cell proliferation and increased cell death in the midbrain. Simultaneously, expression of Shh decreased locally in the notochord and floor plate, whereas overt patterning and differentiation proceeded normally. Normal midbrain expansion was restored by implantation of Shh-secreting cells in a dose-dependent manner; conversely, expansion was retarded following antagonism of the Shh signaling pathway by cyclopamine. Our results indicate that Shh signaling from the ventral midline is essential for regulating brain morphogenesis during early development.

  16. [Specialised early rehabilitation of brain injury performed in an intensive care setting].

    Science.gov (United States)

    Daugaard, Morten; Nielsen, Lars Hedemann

    2013-12-09

    In Denmark, early rehabilitation of acquired head injuries is centralised in two centres, each covering half the country as uptake area. The Regional Hospital Hammel Neurocenter (HN), which covers the western half of Denmark, traditionally receives patients for rehabilitation after discharge from the intensive care unit (ICU). In collaboration with the Regional Hospital in Silkeborg HN now offers early rehabilitation in Silkeborg's ICU setting to patients with acquired brain injury. This preliminary study discusses whether the collaboration facilitates rehabilitation at an earlier state than previously.

  17. Initial study of magnetic resonance diffusion tensor imaging in brain white matter of early AIDS patients

    Institute of Scientific and Technical Information of China (English)

    XUAN Ang; WANG Guang-bin; SHI Da-peng; XU Jun-ling; LI Yong-li

    2013-01-01

    Background HIV is a neurotropic virus which can cause brain white matter demyelination,gliosis,and other pathological changes that appear as H IV encephalitis or AIDS dementia.The purpose of this study was to investigate the change of the diffused condition of water molecules in brain white matter in early acquired immune deficiency syndrome (AIDS) patients using MR diffusion tensor imaging (DTI).Methods DTI examinations were performed on a Siemens 3.0T MR scanner in 23 AIDS patients with normal brain appearance by conventional MRI and 20 healthy volunteers as the control group.Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured in nine regions; corpus callosum (CC) knee,CC body,CC splenium,periventricular white matter,frontal lobe white matter,parietal lobe white matter,occipital lobe white matter,and the anterior and posterior limbs of the internal capsule.The mean FA and ADC values from each region were compared in three groups:the symptomatic,asymptomatic and the control.Results The mean FA values were significantly lower and the mean ADC values were significantly higher in all nine regions in patients in the symptomatic group than in the asymptomatic and control group patients.In the asymptomatic group,the mean FA values were significantly lower and the mean ADC values were significantly higher at the CC knee,CC body,CC splenium,periventricular white matter,frontal lobe white matter and parietal lobe white matter,than in the control group.There were no significant differences at other regions between the two groups.Conclusions The diffused changes of water molecules in brain white matter in AIDS patients are related to brain white matter regions.DTI examination can detect the brain white matter lesions early in AIDS patients.

  18. Deep brain stimulation effects in dystonia: time course of electrophysiological changes in early treatment.

    Science.gov (United States)

    Ruge, Diane; Tisch, Stephen; Hariz, Marwan I; Zrinzo, Ludvic; Bhatia, Kailash P; Quinn, Niall P; Jahanshahi, Marjan; Limousin, Patricia; Rothwell, John C

    2011-08-15

    Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia. Copyright © 2011 Movement Disorder Society.

  19. Comparative observation with MRI and pathology of brain edema at the early stage of severe burn

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the correlation between MRI features and pathology in brain edema at the early stage of severe burn (50% TBSA Ⅲ degree) in dogs.Methods: Fifty-two dogs were randomized into control, simple burn (SB), burn plus sodium lactate (BSL), and burn plus glucose solution groups (BGS). The manifestation of the brain of control group was compared with that of burn groups at 6, 12, 18 and 24 hours postburn with MRI and pathological examination (gross appearance, electron microscopy and light microscopy).Results: The earliest findings of brain edema were seen at 12 hours after burn in BGS group, in which brain swelling was the main feature of MRI. The decrease of SIR on T1WI was not observed until it was exceeded 10%.Signal of T2WI increased by 8.29% at 24 hours after burn.It was difficult to distinguish the gray matter from the white matter at the boundary line, which became blurred later. Histological changes of brain edema were observed as early as 6 hours after burn, being accompanied by swelling of endothelial cells and peri-vescular astrocytes, and vacuolation took place in neurons at 12 hours after burn, with different degrees of necrosis of capillary endothelimn,neurons, and axons. These changes became more marked with elapse of time. The BGS group showed the most obvious changes mentioned above at 24 hours after burn.Conclusions: The model of the brain edema after severe burn has the feature of both vasogenic edema and cytotoxic edema on the MRI and pathology. Positive MRI findings lagged behind that of the pathomorphological changes.ed

  20. Early development of arterial spin labeling to measure regional brain blood flow by MRI.

    Science.gov (United States)

    Koretsky, Alan P

    2012-08-15

    Two major avenues of work converged in the late 1980's and early 1990's to give rise to brain perfusion MRI. The development of anatomical brain MRI quickly had as a major goal the generation of angiograms using tricks to label flowing blood in macroscopic vessels. These ideas were aimed at getting information about microcirculatory flow as well. Over the same time course the development of in vivo magnetic resonance spectroscopy had as its primary goal the assessment of tissue function and in particular, tissue energetics. For this the measurement of the delivery of water to tissue was critical for assessing tissue oxygenation and viability. The measurement of the washin/washout of "freely" diffusible tracers by spectroscopic based techniques pointed the way for quantitative approaches to measure regional blood flow by MRI. These two avenues came together in the development of arterial spin labeling (ASL) MRI techniques to measure regional cerebral blood flow. The early use of ASL to measure brain activation to help verify BOLD fMRI led to a rapid development of ASL based perfusion MRI. Today development and applications of regional brain blood flow measurements with ASL continues to be a major area of activity.

  1. Brain structure abnormalities in early-onset and adolescent-onset conduct disorder.

    Science.gov (United States)

    Fairchild, Graeme; Passamonti, Luca; Hurford, Georgina; Hagan, Cindy C; von dem Hagen, Elisabeth A H; van Goozen, Stephanie H M; Goodyer, Ian M; Calder, Andrew J

    2011-06-01

    The developmental taxonomic theory proposes that neurodevelopmental factors play a critical role in the etiology of early-onset conduct disorder, whereas adolescent-onset conduct disorder arises as a result of social mimicry of deviant peers. Recent studies have challenged this theory by demonstrating that adolescents with both early- and adolescent-onset forms of conduct disorder show impaired emotional learning and abnormal neural activation during facial expression processing. The present study extends this work by investigating brain structure in both subtypes of conduct disorder. Voxel-based morphometry was used to compare gray matter volumes in four regions of interest (amygdala, insula, anterior cingulate, and orbitofrontal cortex) in male adolescents with early-onset (N=36) or adolescent-onset (N=27) conduct disorder and in healthy comparison subjects (N=27). Whole-brain structural analyses were also performed. The combined conduct disorder group displayed gray matter volume reductions in the bilateral amygdala, extending into the insula, relative to healthy comparison subjects. Separate comparisons between healthy subjects and each conduct disorder subgroup revealed lower amygdala volume in both subgroups and reduced right insula volume in the adolescent-onset subgroup. Regression analyses within the conduct disorder subjects alone demonstrated a negative correlation between conduct disorder symptoms and right insula volume. The results demonstrate that gray matter volume reductions in brain regions involved in processing socioemotional stimuli are associated with conduct disorder, regardless of age of onset. Brain structural abnormalities may contribute to the emergence of adolescent-onset as well as early-onset conduct disorder.

  2. Brain Regions Related to Impulsivity Mediate the Effects of Early Adversity on Antisocial Behavior

    OpenAIRE

    Mackey, Scott,; Chaarani, Bader; Kan, Kees-Jan; Philip A. Spechler; Orr, Catherine; Banaschewski, Tobias; Barker, Gareth; Arun L W Bokde; Bromberg, Uli; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J.; Desrivières, Sylvane; Flor, Herta; Frouin, Vincent

    2016-01-01

    IN_PRESS Export Date: 27 September 2016 Article in Press Background Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood. Methods Impulsivity was estimated with a temporal discounting task. Voxel-based morphometry was used to determine the brain structural correlates of tempora...

  3. Interdisciplinary facilitation of the minimal participation of patients with severe brain injury in early rehabilitation

    DEFF Research Database (Denmark)

    Pallesen, Hanne; Buhl, Inge

    2016-01-01

    ABSTRACT Aim: The purpose of the study was to shed light on the participatory aspect of early rehabilitation, when contact, communication and interaction between the patients and the professionals is minimal, because of the patients’ severe brain injury and complex conditions. Methodology...... by a combination of the clinicians’ professional skills, their ability to create a rehabilitation environment in which patients can perform activities, the right framework for the meeting, and a suitable approach, to facilitate fruitful interaction with the patients....

  4. Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.

    Science.gov (United States)

    Parker, Matthew O; Evans, Alexandra M-D; Brock, Alistair J; Combe, Fraser J; Teh, Muy-Teck; Brennan, Caroline H

    2016-01-01

    Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning.

  5. Facet tropism: comparison of plain film and computed tomography examinations.

    Science.gov (United States)

    Cox, J M; Aspegren, D D; Trier, K K

    1991-01-01

    This study compares the findings of plain film X-ray and computed CT examination in the diagnosis of facet orientation and the presence of tropism. Twenty consecutive patients having lumbar disc disease with sciatica were studied utilizing plain X-ray as well as CT scanning. A chiropractic radiologist read the films to determine if facet facings were sagittally, semi-sagittally or coronally oriented on both CT and plain X-ray study. CT was accepted as the most accurate method to determine the true facet orientation, and plain X-ray interpretation of facet orientation was compared to the CT reading. There was a statistically significant relationship in diagnosing tropism between plain film X-ray and CT readings, with a predictive accuracy that ranged from 58-84% across the three segmental levels. However, the exact concordance of plain film X-ray and CT readings for right and left facet facings was very low. This raises the question of how the profession defines diagnostic accuracy.

  6. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    Science.gov (United States)

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Early and Persistent Dendritic Hypertrophy in the Basolateral Amygdala following Experimental Diffuse Traumatic Brain Injury.

    Science.gov (United States)

    Hoffman, Ann N; Paode, Pooja R; May, Hazel G; Ortiz, J Bryce; Kemmou, Salma; Lifshitz, Jonathan; Conrad, Cheryl D; Currier Thomas, Theresa

    2017-01-01

    In the pathophysiology of traumatic brain injury (TBI), the amygdala remains understudied, despite involvement in processing emotional and stressful stimuli associated with anxiety disorders, such as post-traumatic stress disorder (PTSD). Because the basolateral amygdala (BLA) integrates inputs from sensory and other limbic structures coordinating emotional learning and memory, injury-induced changes in circuitry may contribute to psychiatric sequelae of TBI. This study quantified temporal changes in dendritic complexity of BLA neurons after experimental diffuse TBI, modeled by midline fluid percussion injury. At post-injury days (PIDs) 1, 7, and 28, brain tissue from sham and brain-injured adult, male rats was processed for Golgi, glial fibrillary acidic protein (GFAP), or silver stain and analyzed to quantify BLA dendritic branch intersections, activated astrocytes, and regional neuropathology, respectively. Compared to sham, brain-injured rats at all PIDs showed enhanced dendritic branch intersections in both pyramidal and stellate BLA neuronal types, as evidenced by Sholl analysis. GFAP staining in the BLA was significantly increased at PID1 and 7 in comparison to sham. However, the BLA was relatively spared from neuropathology, demonstrated by an absence of argyrophilic accumulation over time, in contrast to other brain regions. These data suggest an early and persistent enhancement of dendritic complexity within the BLA after a single diffuse TBI. Increased dendritic complexity would alter information processing into and through the amygdala, contributing to emotional symptoms post-TBI, including PTSD.

  8. DEVELOPMENTAL CHANGES IN SEROTONIN SIGNALING: IMPLICATIONS FOR EARLY BRAIN FUNCTION, BEHAVIOR AND ADAPTATION

    Science.gov (United States)

    BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.

    2017-01-01

    The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950

  9. Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

    Science.gov (United States)

    VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

    2016-01-01

    People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

  10. Early endocrine alterations reflect prolonged stress and relate to one year functional outcome in patients with severe brain injury

    DEFF Research Database (Denmark)

    Marina, Djordje; Klose, Marianne; Nordenbo, Annette

    2015-01-01

    OBJECTIVE: Severe brain injury poses a risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective was to assess the pattern and prevalence...

  11. Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs.

    Science.gov (United States)

    Perez-Caballero, L; Pérez-Egea, R; Romero-Grimaldi, C; Puigdemont, D; Molet, J; Caso, J-R; Mico, J-A; Pérez, V; Leza, J-C; Berrocoso, E

    2014-05-01

    Deep brain stimulation (DBS) in the subgenual cingulated gyrus (SCG) is a promising new technique that may provide sustained remission in resistant major depressive disorder (MDD). Initial studies reported a significant early improvement in patients, followed by a decline within the first month of treatment, an unexpected phenomenon attributed to potential placebo effects or a physiological response to probe insertion that remains poorly understood. Here we characterized the behavioural antidepressant-like effect of DBS in the rat medial prefrontal cortex, focusing on modifications to rodent SCG correlate (prelimbic and infralimbic (IL) cortex). In addition, we evaluated the early outcome of DBS in the SCG of eight patients with resistant MDD involved in a clinical trial. We found similar antidepressant-like effects in rats implanted with electrodes, irrespective of whether they received electrical brain stimulation or not. This effect was due to regional inflammation, as it was temporally correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity, and it was blocked by anti-inflammatory drugs. Indeed, inflammatory mediators and neuronal p11 expression also changed. Furthermore, a retrospective study indicated that the early response of MDD patients subjected to DBS was poorer when they received anti-inflammatory drugs. Our study demonstrates that electrode implantation up to the IL cortex is sufficient to produce an antidepressant-like effect of a similar magnitude to that observed in rats receiving brain stimulation. Moreover, both preclinical and clinical findings suggest that the use of anti-inflammatory drugs after electrode implantation may attenuate the early anti-depressive response in patients who are subjected to DBS.

  12. Early CT perfusion changes and blood-brain barrier permeability after aneurysmal subarachnoid hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Amanda; Bharatha, Aditya [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); De Oliveira Manoel, Airton Leonardo; Kouzmina, Ekaterina [St. Michael' s Hospital, Toronto (Canada); Burgers, Kyle; Lee, Ting [Robarts Research Institute, London (Canada); Macdonald, R.L. [St. Michael' s Hospital, Department of Neurosurgery, Toronto (Canada)

    2015-08-15

    Early brain injury (EBI) can occur within 72 h of aneurysmal subarachnoid hemorrhage (aSAH). The objective of this study was to determine if there are differences in early CTP parameters (<72 h) with respect to delayed cerebral ischemia (DCI), cerebral infarction, and functional outcome. We performed a prospective cohort study of aSAH patients admitted to a single tertiary care center. MTT, CBF and blood-brain barrier permeability (PS) were quantified with CTP within 72 h of aneurysm rupture. Primary outcomes were functional outcome by the Modified Rankin Scale (mRS) at 3 months and cerebral infarction. Secondary outcome was the development of DCI. Differences between early CTP parameters were determined with respect to primary and secondary outcomes. Fifty aSAH patients were included in the final analysis. MTT was significantly higher in patients who developed DCI (6.7 ± 1.2 vs 5.9 ± 1.0; p = 0.03) and cerebral infarction (7.0 ± 1.2 vs 5.9 ± 0.9; p = 0.007); however, no difference in MTT was found between patients with and without a poor outcome (mRS > 2). Early CBF and PS did not differ with respect to functional outcome, DCI, and cerebral infarction. Elevated MTT within 72 h of aneurysm rupture is associated with DCI and cerebral infarction but not with long-term functional outcome. Blood-brain barrier permeability, as assessed by CT perfusion, was not associated with DCI or worse outcome in this cohort. (orig.)

  13. Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats.

    Science.gov (United States)

    Cui, Yonghua; Duan, Xiaochun; Li, Haiying; Dang, Baoqi; Yin, Jia; Wang, Yang; Gao, Anju; Yu, Zhengquan; Chen, Gang

    2016-08-01

    Increasing studies have demonstrated the neuroprotective effect of hydrogen sulfide (H2S) in central nervous system (CNS) diseases. However, the potential application value of H2S in the therapy of subarachnoid hemorrhage (SAH) is still not well known. This study was to investigate the potential effect of H2S on early brain injury (EBI) induced by SAH and explore the underlying mechanisms. The role of sodium hydrosulfide (NaHS), a donor of H2S, in SAH-induced EBI, was investigated in both in vivo and in vitro. A prechiasmatic cistern single injection model was used to produce experimental SAH in vivo. In vitro, cultured primary rat cortical neurons and human umbilical vein endothelial cells (HUVECs) were exposed to OxyHb at concentration of 10 μM to mimic SAH. Endogenous production of H2S in the brain was significantly inhibited by SAH. The protein levels of the predominant H2S-generating enzymes in the brain, including cystathionineb-synthase (CBS) and 3-mercaptopyruvate sulfur transferase (3MST), were also correspondingly reduced by SAH, while treatment with NaHS restored H2S production and the expressions of CBS and 3MST. More importantly, NaHS treatment could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, brain cell apoptosis, inflammatory response, and cerebral vasospasm) after SAH. In vitro, H2S protects neurons and endothelial function by functioning as an antioxidant and antiapoptotic mediator. Our results suggest that NaSH as an exogenous H2S donor could significantly reduce EBI induced by SAH.

  14. Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder.

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    Shen, Mark D; Nordahl, Christine W; Young, Gregory S; Wootton-Gorges, Sandra L; Lee, Aaron; Liston, Sarah E; Harrington, Kayla R; Ozonoff, Sally; Amaral, David G

    2013-09-01

    Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 'high-risk' infants having an older sibling with autism spectrum disorder and 22 'low-risk' infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic

  15. Early human speciation, brain expansion and dispersal influenced by African climate pulses.

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    Susanne Shultz

    Full Text Available Early human evolution is characterised by pulsed speciation and dispersal events that cannot be explained fully by global or continental paleoclimate records. We propose that the collated record of ephemeral East African Rift System (EARS lakes could be a proxy for the regional paleoclimate conditions experienced by early hominins. Here we show that the presence of these lakes is associated with low levels of dust deposition in both West African and Mediterranean records, but is not associated with long-term global cooling and aridification of East Africa. Hominin expansion and diversification seem to be associated with climate pulses characterized by the precession-forced appearance and disappearance of deep EARS lakes. The most profound period for hominin evolution occurs at about 1.9 Ma; with the highest recorded diversity of hominin species, the appearance of Homo (sensu stricto and major dispersal events out of East Africa into Eurasia. During this period, ephemeral deep-freshwater lakes appeared along the whole length of the EARS, fundamentally changing the local environment. The relationship between the local environment and hominin brain expansion is less clear. The major step-wise expansion in brain size around 1.9 Ma when Homo appeared was coeval with the occurrence of ephemeral deep lakes. Subsequent incremental increases in brain size are associated with dry periods with few if any lakes. Plio-Pleistocene East African climate pulses as evinced by the paleo-lake records seem, therefore, fundamental to hominin speciation, encephalisation and migration.

  16. Identification of cellular infiltrates during early stages of brain inflammation with magnetic resonance microscopy.

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    Helmar Waiczies

    Full Text Available A comprehensive view of brain inflammation during the pathogenesis of autoimmune encephalomyelitis can be achieved with the aid of high resolution non-invasive imaging techniques such as microscopic magnetic resonance imaging (μMRI. In this study we demonstrate the benefits of cryogenically-cooled RF coils to produce μMRI in vivo, with sufficient detail to reveal brain pathology in the experimental autoimmune encephalomyelitis (EAE model. We could visualize inflammatory infiltrates in detail within various regions of the brain, already at an early phase of EAE. Importantly, this pathology could be seen clearly even without the use of contrast agents, and showed excellent correspondence with conventional histology. The cryogenically-cooled coil enabled the acquisition of high resolution images within short scan times: an important practical consideration in conducting animal experiments. The detail of the cellular infiltrates visualized by in vivo μMRI allows the opportunity to follow neuroinflammatory processes even during the early stages of disease progression. Thus μMRI will not only complement conventional histological examination but will also enable longitudinal studies on the kinetics and dynamics of immune cell infiltration.

  17. Caffeic acid ameliorates early and delayed brain injuries after focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Yu ZHOU; San-hua FANG; Yi-lu YE; Li-sheng CHU; Wei-ping ZHANG; Meng-ling WANG; Er-qing WEI

    2006-01-01

    Aim: To investigate the effects of caffeic acid on early and delayed injuries after focal cerebral ischemia in rats, and the possible relation to 5-lipoxygenase inhibition. Methods: Transient focal cerebral ischemia was induced by middle cerebral artery occlusion in Sprague-Dawley rats. Caffeic acid (10 and 50 mg/kg) was ip injected for 5 d after ischemia. The brain injuries were observed, and the levels of cysteinyl leukotrienes and leukotriene B4 in the brain tissue were measured. Results: Caffeic acid (50 mg/kg) ameliorated neurological dysfunction and neuron loss, and decreased infarct volume 24 h after ischemia; it attenuated brain atrophy, infarct volume, and particularly astrocyte proliferation 14 d after ischemia. In addition, it reduced the production of leukotrienes (5-lipoxygenase metabolites) in the ischemic hemispheres 3 h and 7 d after ischemia. Conclusion: Caffeic acid has protective effect on both early and delayed injuries after focal cerebral ischemia in rats; and this effect may partly relate to 5-lipoxygenase inhibition.

  18. Second-order projection from the posterior lateral line in the early zebrafish brain

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    Ghysen Alain

    2006-11-01

    Full Text Available Abstract Background Mechanosensory information gathered by hair cells of the fish lateral-line system is collected by sensory neurons and sent to the ipsilateral hindbrain. The information is then conveyed to other brain structures through a second-order projection. In the adult, part of the second-order projection extends to the contralateral hindbrain, while another part connects to a midbrain structure, the torus semicircularis. Results In this paper we examine the second-order projection from the posterior lateral-line system in late embryonic/early larval zebrafish. At four days after fertilization the synaptic field of the sensory neurons can be accurately targeted, allowing a very reproducible labeling of second-order neurons. We show that second-order projections are highly stereotyped, that they vary according to rhombomeric identity, and that they are almost completely lateralized. We also show that the projections extend not only to the contralateral hindbrain and torus semicircularis but to many other brain centers as well, including gaze- and posture-controlling nuclei in the midbrain, and presumptive thalamic nuclei. Conclusion We propose that the extensive connectivity observed in early brain development reveals a basic scaffold common to most vertebrates, from which different subsets are later reinforced in various vertebrate groups. The large repertoire of projection targets provides a promising system to study the genetic encoding of this differential projection capacity.

  19. HIV tropism and decreased risk of breast cancer.

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    Nancy A Hessol

    Full Text Available BACKGROUND: During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection. METHODS AND FINDINGS: We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR and 95% confidence intervals (CI for breast cancer were estimated by exact conditional logistic regression. Two (9% of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28% of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84 and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83. Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer. CONCLUSIONS: Low

  20. Disruption of brain connectivity in acute stroke patients with early impairment in consciousness

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    Yuan-Hsiung eTsai

    2014-01-01

    Full Text Available Impairment in consciousness is common in acute stroke patients and is correlated with the clinical outcome after stroke. The underlying mechanism is not completely understood, with little known about brain activity and connectivity changes in acute stroke patients having impaired consciousness. In this study, we investigated changes in regional brain activity and brain networks of consciousness impaired stroke patients, as well as the amplitude of spontaneous low frequency fluctuation (ALFF of each time series. Regional homogeneity (ReHo of each voxel was measured, and resting state network analysis was consequently conducted. Results from this study demonstrate that, compared to normal subjects, the intensities of ALFF and ReHo, as well as the strength of the default mode network (DMN connectivity, were significantly decreased in the precuneus and posterior cingulate cortex regions among stroke patients with impaired consciousness. Furthermore, the strength of the DMN was highly correlated with differences in the Glasgow Coma Scale (GCS scores between the onset time and the scanning time. Results from this study suggest that the resting state fMRI is a feasible tool for the evaluation of acute stroke patients with an early impairment of consciousness. The detailed mechanisms, implications of these brain activities and networks exhibiting changes will require further investigation.

  1. Divergence in brain composition during the early stages of ecological specialization in Heliconius butterflies.

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    Montgomery, S H; Merrill, R M

    2017-03-01

    During speciation across ecological gradients, diverging populations are exposed to contrasting sensory and spatial information that present new behavioural and perceptive challenges. These challenges may be met by heritable or environmentally induced changes in brain function which mediate behaviour. However, few studies have investigated patterns of neural divergence at the early stages of speciation, inhibiting our understanding of the relative importance of these processes. Here, we provide a novel case study. The incipient species pair, Heliconius erato and H. himera, are parapatric across an environmental and altitudinal gradient. Despite ongoing gene flow, these species have divergent ecological, behavioural and physiological traits. We demonstrate that these taxa also differ significantly in brain composition, in particular in the relative levels of investment in structures that process sensory information. These differences are not explained solely by environmentally-induced plasticity, but include heritable, nonallometric shifts in brain structure. We suggest these differences reflect divergence to meet the demands of contrasting sensory ecologies. This conclusion would support the hypothesis that the evolution of brain structure and function play an important role in facilitating the emergence of ecologically distinct species.

  2. Early brain injury and subarachnoid hemorrhage: Where are we at present?

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    Tumul Chowdhury

    2013-01-01

    Full Text Available The current era has adopted many new innovations in nearly every aspect of management of subarachnoid hemorrhage (SAH; however, the neurological outcome has still not changed significantly. These major therapeutic advances mainly addressed the two most important sequels of the SAH-vasospasm and re-bleed. Thus, there is a possibility of some different pathophysiological mechanism that would be responsible for causing poor outcome in these patients. In this article, we have tried to compile the current role of this different yet potentially treatable pathophysiological mechanism in post-SAH patients. The main pathophysiological mechanism for the development of early brain injury (EBI is the apoptotic pathways. The macro-mechanism includes increased intracranial pressure, disruption of the blood-brain barrier, and finally global ischemia. Most of the treatment strategies are still in the experimental phase. Although the role of EBI following SAH is now well established, the treatment modalities for human patients are yet to be testified.

  3. Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis

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    López-Góngora, Mariana; Escartín, Antonio; Martínez-Horta, Saul; Fernández-Bobadilla, Ramón; Querol, Luis; Romero, Sergio; Mañanas, Miquel Àngel; Riba, Jordi

    2015-01-01

    Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes. PMID:26322632

  4. Brain signatures of early lexical and morphological learning of a new language.

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    Havas, Viktória; Laine, Matti; Rodríguez Fornells, Antoni

    2017-07-01

    Morphology is an important part of language processing but little is known about how adult second language learners acquire morphological rules. Using a word-picture associative learning task, we have previously shown that a brief exposure to novel words with embedded morphological structure (suffix for natural gender) is enough for language learners to acquire the hidden morphological rule. Here we used this paradigm to study the brain signatures of early morphological learning in a novel language in adults. Behavioural measures indicated successful lexical (word stem) and morphological (gender suffix) learning. A day after the learning phase, event-related brain potentials registered during a recognition memory task revealed enhanced N400 and P600 components for stem and suffix violations, respectively. An additional effect observed with combined suffix and stem violations was an enhancement of an early N2 component, most probably related to conflict-detection processes. Successful morphological learning was also evident in the ERP responses to the subsequent rule-generalization task with new stems, where violation of the morphological rule was associated with an early (250-400ms) and late positivity (750-900ms). Overall, these findings tend to converge with lexical and morphosyntactic violation effects observed in L1 processing, suggesting that even after a short exposure, adult language learners can acquire both novel words and novel morphological rules. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer's disease.

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    Leskovjan, Andreana C; Kretlow, Ariane; Lanzirotti, Antonio; Barrea, Raul; Vogt, Stefan; Miller, Lisa M

    2011-03-01

    Elevated brain iron content, which has been observed in late-stage human Alzheimer's disease, is a potential target for early diagnosis. However, the time course for iron accumulation is currently unclear. Using the PSAPP mouse model of amyloid plaque formation, we conducted a time course study of metal ion content and distribution [iron (Fe), copper (Cu), and zinc (Zn)] in the cortex and hippocampus using X-ray fluorescence microscopy (XFM). We found that iron in the cortex was 34% higher than age-matched controls at an early stage, corresponding to the commencement of plaque formation. The elevated iron was not associated with the amyloid plaques. Interestingly, none of the metal ions were elevated in the amyloid plaques until the latest time point (56 weeks), where only the Zn content was significantly elevated by 38%. Since neuropathological changes in human Alzheimer's disease are presumed to occur years before the first cognitive symptoms appear, quantification of brain iron content could be a powerful marker for early diagnosis of Alzheimer's disease.

  6. Comparison of Human Immunodeficiency Virus Type 1 Tropism Profiles in Clinical Samples by the Trofile and MT-2 Assays▿

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    Coakley, Eoin; Reeves, Jacqueline D.; Huang, Wei; Mangas-Ruiz, Marga; Maurer, Irma; Harskamp, Agnes M.; Gupta, Soumi; Lie, Yolanda; Petropoulos, Christos J.; Schuitemaker, Hanneke; van 't Wout, Angélique B.

    2009-01-01

    The recent availability of CCR5 antagonists as anti-human immunodeficiency virus (anti-HIV) therapeutics has highlighted the need to accurately identify CXCR4-using variants in patient samples when use of this new drug class is considered. The Trofile assay (Monogram Biosciences) has become the method that is the most widely used to define tropism in the clinic prior to the use of a CCR5 antagonist. By comparison, the MT-2 assay has been used since early in the HIV epidemic to define tropism in clinical specimens. Given that there are few data from direct comparisons of these two assays, we evaluated the performance of the plasma-based Trofile assay and the peripheral blood mononuclear cell (PBMC)-based MT-2 assay for the detection of CXCR4 use in defining the tropism of HIV isolates derived from clinical samples. The various samples used for this comparison were derived from participants of the Amsterdam Cohort Studies on HIV infection and AIDS who underwent consecutive MT-2 assay testing of their PBMCs at approximately 3-month intervals. This unique sample set was specifically selected because consecutive MT-2 assays had demonstrated a shift from negative to positive in PBMCs, reflecting the first emergence of CXCR4-using virus in PBMCs above the level of detection of the assay in these individuals. Trofile testing was performed with clonal HIV type 1 (HIV-1) variants (n = 21), MT-2 cell culture-derived cells (n = 20) and supernatants (n = 42), and plasma samples (n = 76). Among the clonal HIV-1 variants and MT-2 cell culture-derived samples, the results of the Trofile and MT-2 assays demonstrated a high degree of concordance (95% to 98%). Among consecutive plasma samples, detection of CXCR4-using virus was at or before the time of first detection by the MT-2 assay in 5/10 patients by the original Trofile assay and in 9/10 patients by the enhanced-sensitivity Trofile assay. Differences in the time to the first detection of CXCR4 use between the MT-2 assay (PBMCs

  7. Long-term therapy with nevirapine and tropism

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    S Bressan

    2012-11-01

    Full Text Available Objective: A more potent effect on the residual viraemia was ascribed to nevirapine (NVP with respect to other antiretroviral drugs; moreover a selection of X4 strains was described in patients (pts with undetectable viraemia; our aim was to study viro-immunological parameters and tropism for co-receptor in pts on a long term successful therapy with NVP. Methods: 14 pts on HAART from 130 months (GL, median value, range 118–156 months without occurrence of blips, as assessable with the available methods at that time, were retrospectively selected from a single center cohort (Bolzano. Tropism for V3 was determined by population sequencing on blood, and using geno2pheno algorithm; cellular HIV DNA load was analysed by in-house Real-Time. A further eighteen months (mo follow up was then observed. Data were compared with those obtained from a control group of 50 naïve pts (GS, evaluated after a 36-mo successful therapy (median, range 12–84 with various drug combinations, with median baseline (BL CD4 of 50/μl, comparable value with the GL cohort. Results: In 7 pts a R5-tropic (GLR5, FPR median 84.8% and in 7 an X4-tropic strain (GLX4, FPR median 1.1% was demonstrated. BL data of GLR5 were 46 y old, CD4 54/l, HIV-RNA 104,000 cps/ml; HAART from 142 mo, with NVP from 125 (one after 70 mo on NVP switched to protease from 57; at follow up CD4 were 679/l, HIV-DNA 60 cps/106 PBMCs (range<5–252. GLX4 were 46 y, at BL 38 CD4/l, HIV-RNA 250,000 cps/ml; in HAART from 121 mo, with NVP from 97; at follow up CD4 902/l, HIV-DNA 60 cps/106 PBMCs (range<5–225. Six out of seven pts of the two groups were on treatment with abacavir+lamivudine (ABC+3TC and one with tenofovir+emtricitabine. In the subsequent 18 mo four blips were observed (21–71 cps/ml; the backbone was changed to raltegravir in two GLR5 and one GLX4 for convenience. In the 50 GS pts at follow up an X4 strain was found in 50% of 14 efavirenz-treated, in 16% of 6 NVP, and 63% of 30 protease

  8. LCMV glycosylation modulates viral fitness and cell tropism.

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    Cyrille J Bonhomme

    Full Text Available The glycoprotein (GP of arenaviruses is glycosylated at 11 conserved N-glycosylation sites. We constructed recombinant lymphocytic choriomeningitis virus (rLCMV featuring either additions or deletions of these N-glycans to investigate their role in the viral life cycle. N-glycosylation at two sites, T87 and S97, were found to be necessary to rescue rLCMV. Three of nine successfully rescued mutants, S116A, T234A, and S373A, under selective pressures in either epithelial, neuronal, or macrophage cells reverted to WT sequence. Of the seven stable N-glycan deletion mutants, five of these led to altered viral fitness and cell tropism, assessed as growth in either mouse primary cortical neurons or bone marrow derived macrophages. These results demonstrate that the deletion of N-glycans in LCMV GP may confer an advantage to the virus for infection of neurons but a disadvantage in macrophages.

  9. Face and location processing in children with early unilateral brain injury.

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    Paul, Brianna; Appelbaum, Mark; Carapetian, Stephanie; Hesselink, John; Nass, Ruth; Trauner, Doris; Stiles, Joan

    2014-07-01

    Human visuospatial functions are commonly divided into those dependent on the ventral visual stream (ventral occipitotemporal regions), which allows for processing the 'what' of an object, and the dorsal visual stream (dorsal occipitoparietal regions), which allows for processing 'where' an object is in space. Information about the development of each of the two streams has been accumulating, but very little is known about the effects of injury, particularly very early injury, on this developmental process. Using a set of computerized dorsal and ventral stream tasks matched for stimuli, required response, and difficulty (for typically-developing individuals), we sought to compare the differential effects of injury to the two systems by examining performance in individuals with perinatal brain injury (PBI), who present with selective deficits in visuospatial processing from a young age. Thirty participants (mean=15.1 years) with early unilateral brain injury (15 right hemisphere PBI, 15 left hemisphere PBI) and 16 matched controls participated. On our tasks children with PBI performed more poorly than controls (lower accuracy and longer response times), and this was particularly prominent for the ventral stream task. Lateralization of PBI was also a factor, as the dorsal stream task did not seem to be associated with lateralized deficits, with both PBI groups showing only subtle decrements in performance, while the ventral stream task elicited deficits from RPBI children that do not appear to improve with age. Our findings suggest that early injury results in lesion-specific visuospatial deficits that persist into adolescence. Further, as the stimuli used in our ventral stream task were faces, our findings are consistent with what is known about the neural systems for face processing, namely, that they are established relatively early, follow a comparatively rapid developmental trajectory (conferring a vulnerability to early insult), and are biased toward the right

  10. Early upregulation of matrix metalloproteinases following reperfusion triggers neuroinflammatory mediators in brain ischemia in rat.

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    Amantea, Diana; Russo, Rossella; Gliozzi, Micaela; Fratto, Vincenza; Berliocchi, Laura; Bagetta, G; Bernardi, G; Corasaniti, M Tiziana

    2007-01-01

    Abnormal expression of matrix metalloproteinases (MMPs) has been implicated in the pathophysiology of neuroinflammatory processes that accompany most central nervous system disease. In particular, early upregulation of the gelatinases MMP-2 and MMP-9 has been shown to contribute to disruption of the blood-brain barrier and to death of neurons in ischemic stroke. In situ zymography reveals a significant increase in gelatinolytic MMPs activity in the ischemic brain hemisphere after 2-h middle cerebral artery occlusion (MCAo) followed by 2-h reperfusion in rat. Accordingly, gel zymography demonstrates that expression and activity of MMP-2 and MMP-9 are enhanced in cortex and striatum ipsilateral to the ischemic insult. The latter effect appears to be instrumental for development of delayed brain damage since administration of a broad spectrum, highly specific MMPs inhibitor, GM6001, but not by its negative control, results in a significant (50%) reduction in ischemic brain volume. Increased gelatinase activity in the ischemic cortex coincides with elevation (166% vs sham) of mature interleukin-1beta (IL-1beta) after 2-h reperfusion and this does not appear to implicate a caspase-1-dependent processing of pro(31kDa)-IL-1beta to yield mature (17kDa) IL-1beta. More importantly, when administered at a neuroprotective dose GM6001 abolishes the early IL-1beta increase in the ischemic cortex and reduces the cleavage of the cytokine proform supporting the deduction that MMPs may initiate IL-1beta processing. In conclusion, development of tissue damage that follows transient ischemia implicates a crucial interplay between MMPs and mediators of neuroinflammation (e.g., IL-1beta), and this further underscores the therapeutic potential of MMPs inhibitors in the treatment of stroke.

  11. Neuroprotective effects of edaravone on early brain injury in rats after subarachnoid hemorrhage

    Institute of Scientific and Technical Information of China (English)

    GAO Yang; DING Xin-sheng; XU Shu; WANG Wei; ZUO Qi-long; KUAI Feng

    2009-01-01

    Background The underlying mechanism of early neurobiological impairment after subarachnoid hemorrhage (SAH) is not well understood,but the system of reactive oxygen superoxide (ROS) might be involved.Edaravone (MC1-186),a potent free radical scavenger that prevents apoptosis of neurons,was thus used in this study to see its possible therapeutic effect in early brain injury due to SAH in a rat model.Methods One hundred and twenty male Sprague-Dawley rats were randomly assigned to four groups:group 1,control rats receiving sham operation only;group 2,rats with SAH treated by saline;group 3,rats with SAH treated with 1 mg/kg MCI-186 injected intraperitoneally;and group 4,rats with SAH treated with 3 mg/kg MC1-186.Treated with either saline or MC1-186 twice daily for two consecutive days after SAH,the rats were sacrificed for measurements of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and histological analysis of caspase-3 protein by Western blotting and immunohistochemical staining.In addition,mortality and neurological scores were statistically analyzed by the chi-square test and Dunn's procedure respectively for each group.One-way analysis of variance followed by the Tukey's procedure was also used in data analysis.Results The rats in group 2 that received saline only showed neurological impairment as well as elevated mortality,and were found to have significantly increased levels of MDA and caspase-3,but reduced SOD activities in brain tissues (P<0.05).When treated with MC1-186 at two different dosages,the rats in groups 3 and 4 had markedly decreased levels of MDA and caspase-3 but increased SOD activities in the brain tissue (P<0.05),along with improved scores of neurological evaluation (P<0.05).Conclusions This study sheds some lights on the therapy of SAH-induced early brain injury by providing the promising data indicating that MC1-186,a radical scavenger,can efficiently diminish apoptosis of neurons and thus prevent the function

  12. Early and later life stress alter brain activity and sleep in rats.

    Directory of Open Access Journals (Sweden)

    Jelena Mrdalj

    Full Text Available Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min or brief maternal separation (10 min. Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.

  13. Early and later life stress alter brain activity and sleep in rats.

    Science.gov (United States)

    Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

    2013-01-01

    Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.

  14. The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants.

    Science.gov (United States)

    Dubois, J; Dehaene-Lambertz, G; Kulikova, S; Poupon, C; Hüppi, P S; Hertz-Pannier, L

    2014-09-12

    Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the baby's brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio.

  15. Brain-derived neurotrophic factor and early-life stress: Multifaceted interplay

    Indian Academy of Sciences (India)

    NATALYA P BONDAR; TATIANA I MERKULOVA

    2016-12-01

    The brain-derived neurotrophic factor (BDNF) is a key regulator of neural development and plasticity. Longtermchanges in the BDNF pathway are associated with childhood adversity and adult depression symptoms.Initially, stress-induced decreases in the BDNF pathway were found in some studies, but subsequent reportsindicated the relationship between stress and BDNF to be much more complex, and the concept wassignificantly revised. In the present mini-review, we focus on the structure and regulation of the Bbnf geneas well as on the stress–BDNF interactions under early-life adverse conditions.

  16. Research progress of early rehabilitation therapy on severe traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Yang YU

    2014-06-01

    Full Text Available In recent years, the mortality rates after severe traumatic brain injury (TBI have decreased because of advances in emergency medicine. Despite these positive achievements, the disability due to TBI has not appreciably reduced. TBI results in impairment of neurological and cognitive functions leading to activity restriction of patients. The current focus is to rehabilitate them so that they can regain their premorbid functional status as much as possible. This paper would like to review the treatment mechanism, methods and clinical advantages of early rehabilitation therapy in patients with severe TBI. doi: 10.3969/j.issn.1672-6731.2014.06.017

  17. Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised clinical trial.

    Science.gov (United States)

    Kahn, Elyne; D'Haese, Pierre-Francois; Dawant, Benoit; Allen, Laura; Kao, Chris; Charles, P David; Konrad, Peter

    2012-02-01

    Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may have a disease modifying effect in early Parkinson's disease (PD). A randomised, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. 15 of 30 early PD patients were randomised to receive STN-DBS implants in an institutional review board approved protocol. Operative technique, location of DBS leads and perioperative adverse events are reported. Active contact used for stimulation in these patients was compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. 14 of the 15 patients did not sustain any long term (>3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior -1.1±1.7 mm, lateral 10.7±1.7 mm and superior -3.3±2.5 mm (anterior and posterior commissure coordinates). This location is statistically no different (0.77 mm, p>0.05) than the optimal contact used in the treatment of 47 advanced PD patients. The perioperative adverse events in this trial of subjects with early stage PD are comparable with those reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomised, surgical versus best medical therapy trial for the early treatment of PD.

  18. [Analysis of the cellular tropism of JC virus with archetypal regulatory region].

    Science.gov (United States)

    Hasegawa, Y

    1997-07-01

    JC virus (JCV) with an archetypal regulatory region (archetype) has been cloned from urines of a healthy individual. It has been suggested that the regulatory region of prototype JC virus (PML type) isolated from brain of PML patient was derived from that of the archetype by deletion and duplication. Biological characteristics of archetypal JCV, however, have not been fully studied. In the present study we examined the infectivity of archetypal JCV (CY), PML-type JCV (Mad-1) and Chimera JCV (Mad-1/CR-CY), in which the regulatory region is composed of CY and the other region Mad-1. DNAs from the three JCV types were transfected into COS-7 (monkey kidney cells transformed with SV40 T) and IMR-32 (human neuroblastoma cell). COS-7 was permissive for all three types, but IMR-32 was only infected with Mad-1. Infected DNAs were confirmed by Southern blotting, and the constancy of the regulatory regions before and after transmission was verified by DNA sequencing. The results showed that the viral regulatory region was related to viral cell tropism and that PML type regulatory region would be necessary for IMR-32 to propagate. The fact that COS-7 was susceptible for all three types may be explained by the function of SV40 T protein. In addition, we first succeeded in the propagation of CY in COS-7, which would provide a useful system to analyze the mechanism of persistent infection of archetypal JCV.

  19. Experimental studies on pathogenesis of the brain radiation injury in early stage

    Energy Technology Data Exchange (ETDEWEB)

    Ye Tian [Suzhou Medical Coll., Jiangsu (China). 2nd Affiliated Hospital; Shiyao Bao; Weibo Yin; Chunfeng Liu; Zhilin Zhang

    2000-05-01

    To investigate the pathogenesis of the brain radiation injury in the early stage, a series of experiments were performed as below. The SD rats halfbrain were irradiated by the single dose of 10, 20, and 30 Gy of 4 MeV electron, all those experiments were performed in 1 day to 3 months after radiation. The neurological symptoms, the weight and the skin response inside the field of all the rats were evaluated sequentially. The measurement of regional cerebral blood flow (rCBF) using hydrogen gas generated by electrolysis, the calculation of the brain water content percentage with wet-dry weight formula. The DNA contents and the quantities of bcl-2 protein were analyzed by flow cytometry. The brain histological sections were scanned to assess the present or absence of white matter necrosis in the region of hippocampus, and then the hippocampus region was observed for the morphological changes of the blood vessel, neuroglial, and the neurons. Some of the data were analyzed by the Student t test. Intra-portal alopecia was observed in all rats which received 30 Gy and some rats which received 20 Gy, the abnormal neurological signs were not found in all the rats, but the tend of weight increase was less pronounced in 1-3 months in the irradiated rats than those unirradiated. By comparison the unirradiated hemisphere, the rCBF of the contralateral brain decreased in most of the rats. In 20 Gy and 30 Gy groups, rCBF decreased areas expand gradually along with the prolong of observation time, from the nucleus caudate putamen, to the frontal cortex and then the hippocampus, the rCBF of whole the irradiated hemibrain was reduced significantly at 3 month after radiation. The water content of the irradiated halfbrain increased progressively, it means the brain edema exists in the meantime. By comparison the unirradiation halfbrain, the apoptosis of the hippocampus cells in the irradiated brain increased, and the expression of bcl-2 protein decreased at the meantime, and those

  20. Neuroimaging, a new tool for investigating the effects of early diet on cognitive and brain development

    Directory of Open Access Journals (Sweden)

    Elizabeth B Isaacs

    2013-08-01

    Full Text Available Nutrition is crucial to the initial development of the central nervous system, and then to its maintenance, because both depend on dietary intake to supply the elements required to develop and fuel the system. Diet in early life is often seen in the context of programming where a stimulus occurring during a vulnerable period can have long-lasting or even lifetime effects on some aspect of the organism’s structure or function. Nutrition was first shown to be a programing stimulus for growth, and then for cognitive behaviour, in animal studies that were also able to employ methods that allowed the demonstration of neural effects of early nutrition. Such research raised the question of whether nutrition could also programme cognition/brain structure in humans. Initial studies of cognitive effects were observational, usually in developing countries where the presence of confounding factors made it difficult to interpret the role of nutrition in the cognitive deficits that were seen. Attributing causality to nutrition required randomised controlled trials and these, often in developed countries, started to appear around 30 years ago. Most demonstrated convincingly that early nutrition could affect subsequent cognition. Until the advent of neuroimaging techniques that allowed in vivo examination of the brain, however, we could determine very little about the neural effects of early diet in humans. The combination of well-designed trials with neuroimaging tools means that we are now able to pose and answer questions that would have seemed impossible only recently. This review discusses various neuroimaging methods that are suitable for use in nutrition studies, while pointing out some of the limitations that they may have. The existing literature is small, but examples of studies that have used these methods are presented. Finally, some considerations that have arisen from previous studies, as well as suggestions for future research, are discussed.

  1. TALE transcription factors during early development of the vertebrate brain and eye.

    Science.gov (United States)

    Schulte, Dorothea; Frank, Dale

    2014-01-01

    Our brain's cognitive performance arises from the coordinated activities of billions of nerve cells. Despite a high degree of morphological and functional differences, all neurons of the vertebrate central nervous system (CNS) arise from a common field of multipotent progenitors. Cell fate specification and differentiation are directed by multistep processes that include inductive/external cues, such as the extracellular matrix or growth factors, and cell-intrinsic determinants, such as transcription factors and epigenetic modulators of proteins and DNA. Here we review recent findings implicating TALE-homeodomain proteins in these processes. Although originally identified as HOX-cofactors, TALE proteins also contribute to many physiological processes that do not require HOX-activity. Particular focus is, therefore, given to HOX-dependent and -independent functions of TALE proteins during early vertebrate brain development. Additionally, we provide an overview about known upstream and downstream factors of TALE proteins in the developing vertebrate brain and discuss general concepts of how TALE proteins function to modulate neuronal cell fate specification.

  2. Molecular diagnosis of Chagas' disease and use of an animal model to study parasite tropism.

    Science.gov (United States)

    Vera-Cruz, J M; Magallón-Gastelum, E; Grijalva, G; Rincón, A R; Ramos-García, C; Armendáriz-Borunda, J

    2003-04-01

    Chagas' disease, which is an important health problem in humans, is caused by the protozoan Trypanosoma cruzi. The cellular and molecular mechanisms, involved in the selective tropism of T. cruzi to different organs remain largely unknown. In this study we designed a PCR-based molecular diagnosis method in order to study the tropism and growth kinetics of T. cruzi in a murine model infected with parasites isolated from an endemic area of Mexico. The growth kinetics and parasite tropism of T. cruzi were also evaluated in the blood and other tissues. We observed that T. cruzi isolates from the Western Mexico showed a major tropism to mouse heart and skeletal muscles in this murine model.

  3. Blood-brain barrier P-glycoprotein function is not impaired in early Parkinson's disease.

    Science.gov (United States)

    Bartels, A L; van Berckel, B N M; Lubberink, M; Luurtsema, G; Lammertsma, A A; Leenders, K L

    2008-08-01

    The cause of Parkinson's disease (PD) is unknown. Genetic susceptibility and exposure to environmental toxins contribute to specific neuronal loss in PD. Decreased blood-brain barrier (BBB) P-glycoprotein (P-gp) efflux function has been proposed as a possible causative link between toxin exposure and PD neurodegeneration. In the present study BBB P-gp function was investigated in vivo in 10 early stage PD patients and 8 healthy control subjects using (R)-[(11)C]-verapamil and PET. Cerebral volume of distribution (V(d)) of verapamil was used as measure of P-gp function. Both region of interest (ROI) analysis and voxel analysis using statistical parametric mapping (SPM) were performed to assess regional brain P-gp function. In addition, MDR1 genetic polymorphism was assessed. In the present study, a larger variation in V(d) of (R)-[(11)C]-verapamil was seen in the PD group as compared to the control group. However, decreased BBB P-gp function in early stage PD patients could not be confirmed.

  4. Tackling the 'dyslexia paradox': reading brain and behavior for early markers of developmental dyslexiax.

    Science.gov (United States)

    Ozernov-Palchik, Ola; Gaab, Nadine

    2016-01-01

    Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5-17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in pre-reading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure.

  5. Relationship between CAG repeat length and brain volume in premanifest and early Huntington's disease.

    Science.gov (United States)

    Henley, Susie M D; Wild, Edward J; Hobbs, Nicola Z; Scahill, Rachael I; Ridgway, Gerard R; Macmanus, David G; Barker, Roger A; Fox, Nick C; Tabrizi, Sarah J

    2009-02-01

    Huntington's disease (HD) is caused by an expanded CAG repeat on the gene encoding for the protein huntingtin. There are conflicting findings about the extent to which repeat length predicts signs of the disease or severity of disease progression in adults. This study examined the relationship between CAG repeat length and brain volume in a large cohort of pre- and post-motor onset HD gene carriers, using voxel-based morphometry (VBM), an approach which allowed us to investigate the whole brain without defining a priori regions of interest. We also used VBM to examine group differences between 20 controls, 21 premanifest, and 40 early HD subjects. In the 61 mutation-positive subjects higher CAG repeat length was significantly associated with reduced volume of the body of the caudate nucleus bilaterally, left putamen, right insula, right parahippocampal gyrus, right anterior cingulate, and right occipital lobe, after correcting for age. The group contrasts showed significant reduction in grey matter volume in the early HD group relative to controls in widespread cortical as well as subcortical areas but there was no evidence of difference between controls and premanifest subjects. Overall we have demonstrated that increased CAG repeat length is associated with atrophy in extra-striatal as well as striatal regions, which has implications for the monitoring of disease-modifying therapies in the condition.

  6. A diagnosis model for early Tourette syndrome children based on brain structural network characteristics

    Science.gov (United States)

    Wen, Hongwei; Liu, Yue; Wang, Jieqiong; Zhang, Jishui; Peng, Yun; He, Huiguang

    2016-03-01

    Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder characterized by the presence of multiple motor and vocal tics. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of action. The aim of our work is to select topological characteristics of structural network which were most efficient for estimating the classification models to identify early TS children. Here we employed the diffusion tensor imaging (DTI) and deterministic tractography to construct the structural networks of 44 TS children and 48 age and gender matched healthy children. We calculated four different connection matrices (fiber number, mean FA, averaged fiber length weighted and binary matrices) and then applied graph theoretical methods to extract the regional nodal characteristics of structural network. For each weighted or binary network, nodal degree, nodal efficiency and nodal betweenness were selected as features. Support Vector Machine Recursive Feature Extraction (SVM-RFE) algorithm was used to estimate the best feature subset for classification. The accuracy of 88.26% evaluated by a nested cross validation was achieved on combing best feature subset of each network characteristic. The identified discriminative brain nodes mostly located in the basal ganglia and frontal cortico-cortical networks involved in TS children which was associated with tic severity. Our study holds promise for early identification and predicting prognosis of TS children.

  7. Tackling the ‘dyslexia paradox’: reading brain and behavior for early markers of developmental dyslexia

    Science.gov (United States)

    Ozernov-Palchik, Ola; Gaab, Nadine

    2016-01-01

    Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5–17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in prereading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure. PMID:26836227

  8. Microstructural Changes of the Human Brain from Early to Mid-Adulthood.

    Science.gov (United States)

    Tian, Lixia; Ma, Lin

    2017-01-01

    Despite numerous studies on the microstructural changes of the human brain throughout life, we have indeed little direct knowledge about the changes from early to mid-adulthood. The aim of this study was to investigate the microstructural changes of the human brain from early to mid-adulthood. We performed two sets of analyses based on the diffusion tensor imaging (DTI) data of 111 adults aged 18-55 years. Specifically, we first correlated age with skeletonized fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) at global and regional level, and then estimated individuals' ages based on each DTI metric using elastic net, a kind of multivariate pattern analysis (MVPA) method that aims at selecting the model that achieves the best trade-off between goodness of fit and model complexity. We observed statistically significant negative age-vs-FA correlations and relatively less changes of MD. The negative age-vs-FA correlations were associated with negative age-vs-AD and positive age-vs-RD correlations. Regional negative age-vs-FA correlations were observed in the bilateral genu of the corpus callosum (CCg), the corticospinal tract (CST), the fornix and several other tracts, and these negative correlations may indicate the earlier changes of the fibers with aging. In brain age estimation, the chronological-vs-estimated-age correlations based on FA, MD, AD and RD were R = 0.62, 0.44, 0.63 and 0.69 (P = 0.002, 0.008, 0.002 and 0.002 based on 500 permutations), respectively, and these results indicate that even the microstructural changes from early to mid-adulthood alone are sufficiently specific to decode individuals' ages. Overall, the current results not only demonstrated statistically significant FA decreases from early to mid-adulthood and clarified the driving factors of the FA decreases (RD increases and AD decreases, in contrast to increases of both measures in late-adulthood), but highlighted the necessity of

  9. Clinical Evaluation of Brain Perfusion SPECT with Brodmann Areas Mapping in Early Diagnosis of Alzheimer's Disease.

    Science.gov (United States)

    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Psimadas, Dimitrios; Fezoulidis, Ioannis; Kapsalaki, Eftychia; Hadjigeorgiou, George; Georgoulias, Panagiotis

    2015-01-01

    Early diagnosis of Alzheimer's disease (AD) based on clinical criteria alone may be problematic, while current and future treatments should be administered earlier in order to be more effective. Thus, various disease biomarkers could be used for early detection of AD. We evaluated brain perfusion with 99mTc-HMPAO single photon emission computed tomography (SPECT) and Brodmann areas (BAs) mapping in mild AD using an automated software (NeuroGam) for the semi-quantitative evaluation of perfusion in BAs and the comparison with the software's normal database. We studied 34 consecutive patients with mild AD: 9 men, 25 women, mean age 70.9 ± 8.1 years, mean Mini-Mental State Examination 22.6 ± 2.5. BAs 25L, 25R, 38L, 38R, 28L, 28R, 36L, and 36R had the lower mean perfusion values, while BAs 31L, 31R, 19R, 18L, 18R, 17L, and 17R had the higher mean values. Compared with healthy subjects of the same age, perfusion values in BAs 25L, 25R, 28R, 28L, 36L, and 36R had the greatest deviations from the healthy sample, while the lowest deviations were found in BAs 32L, 32R, 19R, 24L, 17L, 17R, 18L, and 18R. A percentage of ≥94% of patients had perfusion values more than -2SDs below the mean of healthy subjects in BAs 38R, 38L, 36L, 36R, 23L, 23R, 22L, 44L, 28L, 28R, 25L, and 25R. The corresponding proportion was less than 38% for BAs 11L, 19R, 32L, 32R, 18L, 18R, 24L, and 17R. In conclusion, brain SPECT studies with automated perfusion mapping could be useful as an ancillary tool in daily practice, revealing perfusion impairments in early AD.

  10. Exercise in the Early Stage after Stroke Enhances Hippocampal Brain-Derived Neurotrophic Factor Expression and Memory Function Recovery.

    Science.gov (United States)

    Himi, Naoyuki; Takahashi, Hisashi; Okabe, Naohiko; Nakamura, Emi; Shiromoto, Takashi; Narita, Kazuhiko; Koga, Tomoshige; Miyamoto, Osamu

    2016-12-01

    Exercise in the early stage after stroke onset has been shown to facilitate the recovery from physical dysfunction. However, the mechanism of recovery has not been clarified. In this study, the effect of exercise on spatial memory function recovery in the early stage was shown, and the mechanism of recovery was discussed using a rat model of brain embolism. Intra-arterial microsphere (MS) injection induced small emboli in the rat brain. Treadmill exercise was started at 24 hours (early group) or 8 days (late group) after MS injection. The non-exercise (NE) and sham-operated groups were included as controls. Memory function was evaluated by the Morris water maze test, and hippocampal levels of brain-derived neurotrophic factor (BDNF) were measured by enzyme-linked immunosorbent assays. To further investigate the effect of BDNF on memory function, BDNF was continuously infused into the hippocampus via implantable osmotic pumps in the early or late stage after stroke. Memory function significantly improved only in the early group compared with the late and the NE groups, although hippocampal BDNF concentrations were temporarily elevated after exercise in both the early and the late groups. Rats infused with BDNF in the early stage exhibited significant memory function recovery; however, rats that received BDNF infusion in the late stage showed no improvement. Exercise elevates hippocampal BDNF levels in the early stage after cerebral embolism, and this event facilitates memory function recovery. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  11. The role of the sonic hedgehog signaling pathway in early brain injury after experimental subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Li, Tao; Zhang, Jie; Liu, Rong-Yao; Lian, Zhi-Gang; Chen, Xiao-Lin; Ma, Li; Sun, Hao-Min; Zhao, Yuan-Li

    2013-09-27

    Previous studies have demonstrated that the sonic hedgehog (Shh) pathway plays a neuro-protective role. However, whether the Shh pathway is induced by subarachnoid hemorrhage (SAH) has not been investigated. We sought to investigate Shh activation in the cortex in the early stage of SAH, and assessed the effect of cyclopamine (a specific inhibitor of the Shh pathway) on Shh pathway regulation and evaluated the impact of cyclopamine on SAH. We found that the Shh pathway was up-regulated in the cortex after SAH, and that blocking the Shh pathway increased cell apoptosis. Early brain damages, including brain edema, blood-brain barrier impairment, and cortical apoptosis were significantly aggravated following with cyclopamine treatment compared with vehicle treatment. Our results suggest that the Shh pathway should be activated in the brain after SAH, and plays a beneficial role in SAH development, possibly by inhibiting cerebral oxidative stress through induction of antioxidant and detoxifying enzymes.

  12. Early enrichment effects on brain development in hatchery-reared Atlantic salmon (Salmo salar): no evidence for a critical period

    DEFF Research Database (Denmark)

    Näslund, Joacim; Aarestrup, Kim; Thomassen, Søren T.;

    2012-01-01

    In hatcheries, fish are normally reared in barren environments, which have been reported to affect their phenotypic development compared with wild conspecifics. In this study, Atlantic salmon (Salmo salar) alevins were reared in conventional barren hatchery trays or in either of two types...... of structurally enriched trays. We show that increased structural complexity during early rearing increased brain size in all investigated brain substructures. However, these effects disappeared over time after transfer to barren tanks for external feeding. Parallel to the hatchery study, a group of salmon parr...... was released into nature and recaptured at smoltification. These stream-reared smolts developed smaller brains than the hatchery reared smolts, irrespective of initial enrichment treatment. These novel findings do not support the hypothesis that there is a critical early period determining the brain growth...

  13. Clinical Observation on Combined Tuina and Medicated Bath for Early Intervention of Neonatal Brain Injuries

    Institute of Scientific and Technical Information of China (English)

    刘振寰; 丁建英; 韩丑萍

    2010-01-01

    目的:观察推拿、药浴等中医疗法早期干预对婴儿脑损伤的临床疗效.方法:对60例中重度脑损伤婴儿进行小儿健脑推拿及中药浴式水疗,同时配合中医传统五行音乐聆听及运动疗法等治疗.分别于治疗前、治疗3个月后采用Gesell测查法进行发育商(Development Quotient,DQ)评估,并在治疗1年半后进行远期随访.结果:治疗前、治疗3个月及一年半后发育商分别为(34.98±28.94),(66.17±14.91)和(75.40±14.69),与治疗前比较,治疗3个月及一年半后发育商各指标均有显著提高(P=0.000).结论:对脑损伤婴儿进行推拿中医早期干预可促进大脑发育,修复神经损伤,促进运动、认知的发育,有效预防神经系统后遗症的发生.%Objective: To observe the clinical effect of early intervention of combined tuina with medicated bath for neonatal brain injuries.Methods: Brain-benefiting tuina manipulations,medicated bath and music plus exercise therapies were employed in 60 infants with medium or severe brain injuries.The Gesell measurement methods were adopted prior to and 3 months after treatment to evaluate the development quotient(DQ).In addition,the long-term follow-up was made after one and a half years.Result: The scores of DQ prior to treatment,3 month after treatment and 1.5 years after treatment were(34.98±28.94),(66.17±14.91)and(75.40±14.69)respectively,showing a marked improvement after 3months and 1.5 years of treatment(P=0.000).Conclusion: Early intervention using tuina manipulations could enhance the brain development,repair the nerve injury,improve the motion and cognitive ability and prevent the sequela of the nervous system.

  14. The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation

    Directory of Open Access Journals (Sweden)

    K.A. Sagar

    2015-12-01

    Full Text Available Marijuana (MJ use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n = 24 and late onset (age 16 or later; n = 26, and 34 healthy control participants (HCs. All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth.

  15. Task relevance effects in electrophysiological brain activity: early, but not first.

    Science.gov (United States)

    Fellrath, Julia; Manuel, Aurélie L; Ptak, Radek

    2014-11-01

    A current controversy surrounds the question whether high-level features of a stimulus such as its relevance to the current task may affect early attentional processes. According to one view abruptly appearing stimuli gain priority during an initial feedforward processing stage and therefore capture attention even if they are irrelevant to the task. Alternatively, only stimuli that share a relevant property with the target may capture attention of the observer. Here, we used high-density EEG to test whether task relevance may modulate early feedforward brain activity, or whether it only becomes effective once the physical characteristics of the stimulus have been processed. We manipulated task relevance and visual saliency of distracters presented left or right of an upcoming central target. We found that only the relevance of distracters had an effect on manual reaction times to the target. However, the analysis of electrocortical activity revealed three discrete processing stages during which pure effects of distracter saliency (~80-160 ms), followed by an interaction between saliency and relevance (~130-240 ms) and finally pure effects of relevance (~230-370 ms) were observed. Electrical sources of early saliency effects and later relevance effects were localized in the posterior parietal cortex, predominantly over the right hemisphere. These findings support the view that during the initial feedforward stage only physical (bottom-up) factors determine cortical responses to visual stimuli, while top-down effects interfere at later processing stages.

  16. Early- versus Late-Onset Fetal Growth Restriction Differentially Affects the Development of the Fetal Sheep Brain.

    Science.gov (United States)

    Alves de Alencar Rocha, Anna Karynna; Allison, Beth J; Yawno, Tamara; Polglase, Graeme R; Sutherland, Amy E; Malhotra, Atul; Jenkin, Graham; Castillo-Melendez, Margie; Miller, Suzanne L

    2017-01-01

    Fetal growth restriction (FGR) is a common complication of pregnancy, principally caused by suboptimal placental function, and is associated with high rates of perinatal mortality and morbidity. Clinical studies suggest that the time of onset of placental insufficiency is an important contributor towards the neurodevelopmental impairments that are evident in children who had FGR. It is however currently unknown how early-onset and late-onset FGR differentially affect brain development. The aim of this study was to examine neuropathology in early-onset and late-onset FGR fetal sheep and to determine whether they differentially alter brain development. We induced placental insufficiency and FGR via single umbilical artery ligation at either 88 days (early-onset) or 105 days (late-onset) of fetal sheep gestation (term is approx. 147 days), reflecting a period of rapid white matter brain development. Fetal blood samples were collected for the first 10 days after surgery, and all fetuses were sacrificed at 125 days' gestation for brain collection and subsequent histopathology. Our results show that early-onset FGR fetuses became progressively hypoxic over the first 10 days after onset of placental insufficiency, whereas late-onset FGR fetuses were significantly hypoxic compared to controls from day 1 after onset of placental insufficiency (SaO2 46.7 ± 7.4 vs. 65.7 ± 3.9%, respectively, p = 0.03). Compared to control brains, early-onset FGR brains showed widespread white matter injury, with a reduction in both CNPase-positive and MBP-positive density of staining in the periventricular white matter (PVWM), subcortical white matter, intragyral white matter (IGWM), subventricular zone (SVZ), and external capsule (p development that principally mediates altered brain development associated with FGR. © 2017 S. Karger AG, Basel.

  17. Recent Observations on Australian Bat Lyssavirus Tropism and Viral Entry

    Directory of Open Access Journals (Sweden)

    Dawn L. Weir

    2014-02-01

    Full Text Available Australian bat lyssavirus (ABLV is a recently emerged rhabdovirus of the genus lyssavirus considered endemic in Australian bat populations that causes a neurological disease in people indistinguishable from clinical rabies. There are two distinct variants of ABLV, one that circulates in frugivorous bats (genus Pteropus and the other in insectivorous microbats (genus Saccolaimus. Three fatal human cases of ABLV infection have been reported, the most recent in 2013, and each manifested as acute encephalitis but with variable incubation periods. Importantly, two equine cases also arose recently in 2013, the first occurrence of ABLV in a species other than bats or humans. Similar to other rhabdoviruses, ABLV infects host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion facilitated by its single fusogenic envelope glycoprotein (G. Recent studies have revealed that proposed rabies virus (RABV receptors are not sufficient to permit ABLV entry into host cells and that the unknown receptor is broadly conserved among mammalian species. However, despite clear tropism differences between ABLV and RABV, the two viruses appear to utilize similar endocytic entry pathways. The recent human and horse infections highlight the importance of continued Australian public health awareness of this emerging pathogen.

  18. Spaceflight studies of tropisms in the European Modular Cultivation System

    Science.gov (United States)

    Kiss, J. Z.; Correll, M. J.; Edelmann, R. E.

    Phototropism and gravitropism play key roles in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. The blue-light response is controlled by the phototropins while the red-light response is mediated by the phytochrome family of photoreceptors. In order to better characterize root phototropism, we plan to perform experiments in microgravity so that this tropism can be more effectively studied without the interactions with the gravity response. Our experiments are to be performed on the European Modular Cultivation System (EMCS), which provides an incubator, lighting system, and high resolution video that are on a centrifuge palette. These experiments will be performed at μ g, 1g (control) and fractional g-levels. In order to ensure success of this mission on the International Space Station (ISS), we have been performing ground-based studies on growth, phototropism, and gravitropism in experimental unique equipment (EUE) that was designed for our experiments that will use Arabidopsis seedlings. Currently, the EMCS and our EUE are scheduled for launch on space shuttle mission STS-121. This project should provide insight into how the blue-light and red-light signaling systems interact with each other, and also with the gravisensing system.

  19. Fatty acid binding protein 7 and n-3 poly unsaturated fatty acid supply in early rat brain development.

    Science.gov (United States)

    Maximin, Elise; Langelier, Bénédicte; Aïoun, Josiane; Al-Gubory, Kaïs H; Bordat, Christian; Lavialle, Monique; Heberden, Christine

    2016-03-01

    Fatty acid binding protein 7 (FABP7), abundant in the embryonic brain, binds with the highest affinity to docosahexaenoic acid (DHA) and is expressed in the early stages of embryogenesis. Here, we have examined the consequences of the exposure to different DHA levels and of the in utero depletion of FABP7 on early rat brain development. Neurodevelopment was evaluated through the contents of two proteins, connexin 43 (Cx43) and cyclin-dependent kinase 5 (CDK5), both involved in neuroblast proliferation, differentiation, and migration. The dams were fed with diets presenting different DHA contents, from deficiency to supplementation. DHA brain embryos contents already differed at embryonic day 11.5 and the differences kept increasing with time. Cx43 and CDK5 contents were positively associated with the brain DHA levels. When FABP7 was depleted in vivo by injections of siRNA in the telencephalon, the enhancement of the contents of both proteins was lost in supplemented animals, but FABP7 depletion did not modify phospholipid compositions regardless of the diets. Thus, FABP7 is a necessary mediator of the effect of DHA on these proteins synthesis, but its role in DHA uptake is not critical, although FABP7 is localized in phospholipid-rich areas. Our study shows that high contents of DHA associated with FABP7 are necessary to promote early brain development, which prompted us to recommend DHA supplementation early in pregnancy.

  20. Early planarian brain regeneration is independent of blastema polarity mediated by the Wnt/β-catenin pathway.

    Science.gov (United States)

    Iglesias, Marta; Almuedo-Castillo, Maria; Aboobaker, A Aziz; Saló, Emili

    2011-10-01

    Analysis of anteroposterior (AP) axis specification in regenerating planarian flatworms has shown that Wnt/β-catenin signaling is required for posterior specification and that the FGF-like receptor molecule nou-darake (ndk) may be involved in restricting brain regeneration to anterior regions. The relationship between re-establishment of AP identity and correct morphogenesis of the brain is, however, still poorly understood. Here we report the characterization of two axin paralogs in the planarian Schmidtea mediterranea. Although Axins are well known negative regulators of Wnt/β-catenin signaling, no role in AP specification has previously been reported for axin genes in planarians. We show that silencing of Smed-axin genes by RNA interference (RNAi) results in two-tailed planarians, a phenotype previously reported after silencing of Smed-APC-1, another β-catenin inhibitor. More strikingly, we show for the first time that while early brain formation at anterior wounds remains unaffected, subsequent development of the brain is blocked in the two-tailed planarians generated after silencing of Smed-axin genes and Smed-APC-1. These findings suggest that the mechanisms underlying early brain formation can be uncoupled from the specification of AP identity by the Wnt/β-catenin pathway. Finally, the posterior expansion of the brain observed following Smed-ndk RNAi is enhanced by silencing Smed-APC-1, revealing an indirect relationship between the FGFR/Ndk and Wnt/β-catenin signaling systems in establishing the posterior limits of brain differentiation.

  1. Ethical Considerations for Deep Brain Stimulation Trials in Patients with Early-Onset Alzheimer's Disease.

    Science.gov (United States)

    Viaña, John Noel M; Bittlinger, Merlin; Gilbert, Frederic

    2017-01-01

    Several studies of deep brain stimulation (DBS) of the fornix or the nucleus basalis of Meynert have been recently conducted in people with Alzheimer's disease, with several recruiting participants early-onset Alzheimer's disease (EOAD). Although EOAD accounts for less than 5.5% of AD cases, ethical considerations must still be made when performing DBS trials including these participants since a portion of people with EOAD, especially those possessing autosomal-dominant mutations, have an atypical and more aggressive disease progression. These considerations include appropriate patient selection and signing of an informed consent for genetic testing; appropriate study design; potential outcomes that people with EOAD could expect; and accurate interpretation and balanced discussion of trial results. Finally, recommendations for future DBS for AD trials will be made to ensure that EOAD patients will not experience avoidable harms should they be enrolled in these experimental studies.

  2. Early learning shapes the memory networks for arithmetic: evidence from brain potentials in bilinguals.

    Science.gov (United States)

    Salillas, Elena; Wicha, Nicole Y Y

    2012-07-01

    Language and math are intertwined during children's learning of arithmetic concepts, but the importance of language in adult arithmetic processing is less clear. To determine whether early learning plays a critical role in the math-language connection in adults, we tested retrieval of simple multiplication in adult bilinguals who learned arithmetic in only one language. We measured electrophysiological and behavioral responses during correctness judgments for problems presented as digits or as number words in Spanish or English. Problems presented in the language in which participants learned arithmetic elicited larger, more graded, and qualitatively different brain responses than did problems presented in participants' other language, and these responses more closely resembled responses for digits, even when participants' other language was more dominant. These findings suggest that the memory networks for simple multiplication are established when arithmetic concepts are first learned and are independent of language dominance in adulthood.

  3. Early rehabilitation for severe acquired brain injury in intensive care unit: multicenter observational study.

    Science.gov (United States)

    Bartolo, Michelangelo; Bargellesi, Stefano; Castioni, Carlo A; Bonaiuti, Donatella; Antenucci, Roberto; Benedetti, Angelo; Capuzzo, Valeria; Gamna, Federica; Radeschi, Giulio; Citerio, Giuseppe; Colombo, Carolina; Del Casale, Laura; Recubini, Elena; Toska, Saimir; Zanello, Marco; D'Aurizio, Carlo; Spina, Tullio; Del Gaudio, Alredo; Di Rienzo, Filomena; Intiso, Domenico; Dallocchio, Giulia; Felisatti, Giovanna; Lavezzi, Susanna; Zoppellari, Roberto; Gariboldi, Valentina; Lorini, Luca; Melizza, Giovanni; Molinero, Guido; Mandalà, Giorgio; Pignataro, Amedeo; Montis, Andrea; Napoleone, Alessandro; Pilia, Felicita; Pisu, Marina; Semerjian, Monica; Pagliaro, Giuseppina; Nardin, Lorella; Scarponi, Federico; Zampolini, Mauro; Zava, Raffaele; Massetti, Maria A; Piccolini, Carlo; Aloj, Fulvio; Antonelli, Sergio; Zucchella, Chiara

    2016-02-01

    The increased survival after a severe acquired brain injury (sABI) raise the problem of making most effective the treatments in Intensive Care Unit (ICU)/Neurointensive Care Unit (NICU), also integrating rehabilitation care. Despite previous studies reported that early mobilization in ICU was effective in preventing complications and reducing hospital stay, few studies addressed the rehabilitative management of sABI patients in ICU/NICU. To collect clinical and functional data about the early rehabilitative management of sABI patients during ICU/NICU stay. Prospective, observational, multicenter study. Fourteen facilities supplied by intensive neurorehabilitation units and ICU/NICUs. Consecutive sABI patients admitted to ICU/NICU. Patients were evaluated at admission and then every 3-5 days. Clinical, functional and rehabilitative data, including Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), The Rancho Los Amigos Levels of Cognitive Functioning Scale (LCF), Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome scale (GOS) and Functional Independence Measure (FIM) were collected. One hundred and two patients (F/M 44/58) were enrolled. The mean duration of ICU stay was 24.7±13.9 days and the first rehabilitative evaluation occurred after 8.7±8.8 days. Regular postural changes and multijoint mobilization were prescribed in 63.7% and 64.7% cases, respectively. The mean session duration was 38±11.5 minutes. Swallowing evaluation was performed in 14.7% patients, psychological support was provided to 12.7% of patients' caregivers, while 17.6% received a psycho-educational intervention, and 28.4% were involved in interdisciplinary team meetings. The main discharge destinations were Severe Acquired Brain Injury rehabilitation units for 43.7%, intensive neurorehabilitation units for 20.7%. Data showed that early rehabilitation was not diffusely performed in sABI subjects in ICU/NICU and rehabilitative interventions were variable; one-third of subjects were

  4. Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson's Disease.

    Science.gov (United States)

    Hacker, Mallory L; Currie, Amanda D; Molinari, Anna L; Turchan, Maxim; Millan, Sarah M; Heusinkveld, Lauren E; Roach, Jonathon; Konrad, Peter E; Davis, Thomas L; Neimat, Joseph S; Phibbs, Fenna T; Hedera, Peter; Byrne, Daniel W; Charles, David

    2016-01-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson's disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD.

  5. Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson’s Disease

    Science.gov (United States)

    Hacker, Mallory L.; Currie, Amanda D.; Molinari, Anna L.; Turchan, Maxim; Millan, Sarah M.; Heusinkveld, Lauren E.; Roach, Jonathon; Konrad, Peter E.; Davis, Thomas L.; Neimat, Joseph S.; Phibbs, Fenna T.; Hedera, Peter; Byrne, Daniel W.; Charles, David

    2016-01-01

    Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson’s disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). Objective: The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Methods: Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Results: Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p <  0.05; OR = 0.2; 95% CI: 0.04–0.97). Conclusions: STN-DBS in early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD. PMID:26967937

  6. Development of the brain's structural network efficiency in early adolescence: A longitudinal DTI twin study.

    Science.gov (United States)

    Koenis, Marinka M G; Brouwer, Rachel M; van den Heuvel, Martijn P; Mandl, René C W; van Soelen, Inge L C; Kahn, René S; Boomsma, Dorret I; Hulshoff Pol, Hilleke E

    2015-12-01

    The brain is a network and our intelligence depends in part on the efficiency of this network. The network of adolescents differs from that of adults suggesting developmental changes. However, whether the network changes over time at the individual level and, if so, how this relates to intelligence, is unresolved in adolescence. In addition, the influence of genetic factors in the developing network is not known. Therefore, in a longitudinal study of 162 healthy adolescent twins and their siblings (mean age at baseline 9.9 [range 9.0-15.0] years), we mapped local and global structural network efficiency of cerebral fiber pathways (weighted with mean FA and streamline count) and assessed intelligence over a three-year interval. We find that the efficiency of the brain's structural network is highly heritable (locally up to 74%). FA-based local and global efficiency increases during early adolescence. Streamline count based local efficiency both increases and decreases, and global efficiency reorganizes to a net decrease. Local FA-based efficiency was correlated to IQ. Moreover, increases in FA-based network efficiency (global and local) and decreases in streamline count based local efficiency are related to increases in intellectual functioning. Individual changes in intelligence and local FA-based efficiency appear to go hand in hand in frontal and temporal areas. More widespread local decreases in streamline count based efficiency (frontal cingulate and occipital) are correlated with increases in intelligence. We conclude that the teenage brain is a network in progress in which individual differences in maturation relate to level of intellectual functioning.

  7. Speech disorders in Parkinson's disease: early diagnostics and effects of medication and brain stimulation.

    Science.gov (United States)

    Brabenec, L; Mekyska, J; Galaz, Z; Rektorova, Irena

    2017-03-01

    Hypokinetic dysarthria (HD) occurs in 90% of Parkinson's disease (PD) patients. It manifests specifically in the areas of articulation, phonation, prosody, speech fluency, and faciokinesis. We aimed to systematically review papers on HD in PD with a special focus on (1) early PD diagnosis and monitoring of the disease progression using acoustic voice and speech analysis, and (2) functional imaging studies exploring neural correlates of HD in PD, and (3) clinical studies using acoustic analysis to evaluate effects of dopaminergic medication and brain stimulation. A systematic literature search of articles written in English before March 2016 was conducted in the Web of Science, PubMed, SpringerLink, and IEEE Xplore databases using and combining specific relevant keywords. Articles were categorized into three groups: (1) articles focused on neural correlates of HD in PD using functional imaging (n = 13); (2) articles dealing with the acoustic analysis of HD in PD (n = 52); and (3) articles concerning specifically dopaminergic and brain stimulation-related effects as assessed by acoustic analysis (n = 31); the groups were then reviewed. We identified 14 combinations of speech tasks and acoustic features that can be recommended for use in describing the main features of HD in PD. While only a few acoustic parameters correlate with limb motor symptoms and can be partially relieved by dopaminergic medication, HD in PD seems to be mainly related to non-dopaminergic deficits and associated particularly with non-motor symptoms. Future studies should combine non-invasive brain stimulation with voice behavior approaches to achieve the best treatment effects by enhancing auditory-motor integration.

  8. Computed tomography of the brain in children with early infantile autism

    Energy Technology Data Exchange (ETDEWEB)

    Hoshino, Yoshihiko; Manome, Taei; Kaneko, Motohisa; Yashima, Yuko; Kumashiro, Hisashi

    1984-01-01

    In order to examine the cranial CT of autistic children and investigate the etiological significance of CT scan findings, the CT of the brain was surveyed in 24 children with early infantile autism (3 to 17 years with a mean age of 7.6), and 179 children with the normal CT despite their medical histories such as headaches or febrile convulsions. According to their ages, the autistic and normal children were divided into the following three groups: Group I (age ranging from 3 to 5), Group II (age: 6 to 9) and Group III (age: 10 to 17). 1) There was no significant difference between the bifrontal CVI of the autistic children and that of the normal children. However, in Group III, the bifrontal CVI of the autistic children was significantly higher than that of the normal children. 2) There was no significant difference between the bicaudate CVI of the autistic children and that of the normal children. However, in Groups I and II, the bicaudate CVI of the autistic children was significantly lower than that of the normal children. 3) The maximum widths of the third ventricle showed no significant difference between the autistic and normal children. However, in Groups II and III, those of the autistic children were wider than those of the normal children. In the autistic children, as the age increases, the difference becomes significantly wider. A positive correlation was observed between the width of the third ventricle and ages of the autistic children. 4) An examination of the right-left ratio of maximum transverse diameter of the brain showed that there was no significant difference between the autistic and normal children. The above mentioned results (1)-4)) might suggest a progressive disorder of the brain structure surrounding the third ventricle or lateral ventricles in the autistic children. (author).

  9. Early complement activation increases in the brain in some aged normal subjects.

    Science.gov (United States)

    Loeffler, David A; Camp, Dianne M; Schonberger, Michael B; Singer, Daniel J; LeWitt, Peter A

    2004-09-01

    Complement activation is increased in Alzheimer's disease (AD) and may contribute to the development and progression of this disorder. To compare early complement activation between normal and AD brain specimens, C4d and iC3b concentrations were measured in hippocampus, entorhinal cortex, temporal cortex, parietal cortex, and cerebellum from aged normal and AD subjects n=10-14 for both), and in hippocampus and entorhinal cortex from younger normal subjects (n=5-6). C4d and iC3b levels increased 2.3- to 4.6-fold in AD versus aged normal specimens (all P hippocampus or entorhinal cortex. However, the concentrations of these proteins were markedly increased in several aged normal specimens. Normal subject age was moderately associated with both C4d (r=0.49) and iC3b (r=0.53) concentrations in the hippocampus. Increased brain complement activation in some elderly individuals may promote the subsequent development of AD.

  10. Brain-derived neurotrophic factor Val66Met polymorphism and early life adversity affect hippocampal volume.

    Science.gov (United States)

    Carballedo, Angela; Morris, Derek; Zill, Peter; Fahey, Ciara; Reinhold, Elena; Meisenzahl, Eva; Bondy, Brigitta; Gill, Michael; Möller, Hans-Jürgen; Frodl, Thomas

    2013-03-01

    The interaction between adverse life events during childhood and genetic factors is associated with a higher risk to develop major depressive disorder (MDD). One of the polymorphisms found to be associated with MDD is the Val66MET polymorphism of brain-derived neurotrophic factor (BDNF). The aim of our two-center study was to determine how the BDNF Val66Met polymorphism and childhood adversity affect the volumetric measures of the hippocampus in healthy individuals and people with MDD. In this two-center study, 62 adult patients with MDD and 71 healthy matched controls underwent high-resolution magnetic resonance imaging. We used manual tracing of the bilateral hippocampal structure with help of the software BRAINS2, assessed childhood adversity using the Childhood Trauma Questionnaire and genotyped Val66Met BDNF SNP (rs6265). MDD patients had smaller hippocampal volumes, both in the left and right hemispheres (F = 5.4, P = 0.022). We also found a significant interaction between BDNF allele and history of childhood adversity (F = 6.1, P = 0.015): Met allele carriers in our samples showed significantly smaller hippocampal volumes when they did have a history of childhood adversity, both in patients and controls. Our results highlight how relevant stress-gene interactions are for hippocampal volume reductions. Subjects exposed to early life adversity developed smaller hippocampal volumes when they carry the Met-allele of the BDNF polymorphism.

  11. The impact of early aerobic exercise on brain microvascular alterations induced by cerebral hypoperfusion.

    Science.gov (United States)

    Leardini-Tristão, Marina; Borges, Juliana Pereira; Freitas, Felipe; Rangel, Raquel; Daliry, Anissa; Tibiriçá, Eduardo; Estato, Vanessa

    2017-02-15

    The therapeutic potential of early exercise training following cerebral hypoperfusion was investigated on brain perfusion and inflammation in rats with permanent bilateral occlusion of the common carotid arteries (2VO). Wistar rats were subjected to 2VO or sham surgery and each group was then subdivided randomly into sedentary or exercise groups. Early exercise training was initiated after three days of 2VO or sham surgery and consisted of seven days of treadmill training (30min/day at ∼60% of maximal exercise test), composing four groups: 1) Sham sedentary (Sham-Sed), 2) Sham exercised (Sham-Ex), 3) 2VO sedentary (2VO-Sed) and 4) 2VO exercised (2VO-Ex). Microvascular cerebral blood flow (MCBF) and NADPH oxidase and eNOS gene expression were evaluated by laser speckle contrast imaging and RT-PCR, respectively, and brain functional capillary density and endothelial-leukocyte interactions were evaluated by fluorescence intravital video-microscopy. The 2VO-Sed group presented a decrease in MCBF (Sham-Sed: 230.9±12.2 vs. 2VO-Sed: 183.6±10.6 arbitrary perfusion units, Pexercise was able to prevent the cerebral microvascular inflammation by decreasing endothelial-leukocyte interactions (2VO-Ex: 0.9±0.3 vs. 2VO-Sed: 5±0.6cells/min/100μm, Pbrain NADPH oxidase gene expression (2VO-Ex: 1.7±0.1 arbitrary units, Pexercise may represent a means of preventing the microvascular alterations induced by chronic cerebral hypoperfusion.

  12. Advanced fiber tracking in early acquired brain injury causing cerebral palsy.

    Science.gov (United States)

    Lennartsson, F; Holmström, L; Eliasson, A-C; Flodmark, O; Forssberg, H; Tournier, J-D; Vollmer, B

    2015-01-01

    Diffusion-weighted MR imaging and fiber tractography can be used to investigate alterations in white matter tracts in patients with early acquired brain lesions and cerebral palsy. Most existing studies have used diffusion tensor tractography, which is limited in areas of complex fiber structures or pathologic processes. We explored a combined normalization and probabilistic fiber-tracking method for more realistic fiber tractography in this patient group. This cross-sectional study included 17 children with unilateral cerebral palsy and 24 typically developing controls. DWI data were collected at 1.5T (45 directions, b=1000 s/mm(2)). Regions of interest were defined on a study-specific fractional anisotropy template and mapped onto subjects for fiber tracking. Probabilistic fiber tracking of the corticospinal tract and thalamic projections to the somatosensory cortex was performed by using constrained spherical deconvolution. Tracts were qualitatively assessed, and DTI parameters were extracted close to and distant from lesions and compared between groups. The corticospinal tract and thalamic projections to the somatosensory cortex were realistically reconstructed in both groups. Structural changes to tracts were seen in the cerebral palsy group and included splits, dislocations, compaction of the tracts, or failure to delineate the tract and were associated with underlying pathology seen on conventional MR imaging. Comparisons of DTI parameters indicated primary and secondary neurodegeneration along the corticospinal tract. Corticospinal tract and thalamic projections to the somatosensory cortex showed dissimilarities in both structural changes and DTI parameters. Our proposed method offers a sensitive means to explore alterations in WM tracts to further understand pathophysiologic changes following early acquired brain injury. © 2015 by American Journal of Neuroradiology.

  13. Brain networks disconnection in early multiple sclerosis cognitive deficits: an anatomofunctional study.

    Science.gov (United States)

    Louapre, Céline; Perlbarg, Vincent; García-Lorenzo, Daniel; Urbanski, Marika; Benali, Habib; Assouad, Rana; Galanaud, Damien; Freeman, Léorah; Bodini, Benedetta; Papeix, Caroline; Tourbah, Ayman; Lubetzki, Catherine; Lehéricy, Stéphane; Stankoff, Bruno

    2014-09-01

    Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large-scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3-5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age-matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage.

  14. Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation in Adolescence.

    Science.gov (United States)

    French, Leon; Gray, Courtney; Leonard, Gabriel; Perron, Michel; Pike, G Bruce; Richer, Louis; Séguin, Jean R; Veillette, Suzanne; Evans, C John; Artiges, Eric; Banaschewski, Tobias; Bokde, Arun W L; Bromberg, Uli; Bruehl, Ruediger; Buchel, Christian; Cattrell, Anna; Conrod, Patricia J; Flor, Herta; Frouin, Vincent; Gallinat, Jurgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Lemaitre, Herve; Martinot, Jean-Luc; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Pangelinan, Melissa Marie; Poustka, Luise; Rietschel, Marcella; Smolka, Michael N; Walter, Henrik; Whelan, Robert; Timpson, Nic J; Schumann, Gunter; Smith, George Davey; Pausova, Zdenka; Paus, Tomáš

    2015-10-01

    Cannabis use during adolescence is known to increase the risk for schizophrenia in men. Sex differences in the dynamics of brain maturation during adolescence may be of particular importance with regard to vulnerability of the male brain to cannabis exposure. To evaluate whether the association between cannabis use and cortical maturation in adolescents is moderated by a polygenic risk score for schizophrenia. Observation of 3 population-based samples included initial analysis in 1024 adolescents of both sexes from the Canadian Saguenay Youth Study (SYS) and follow-up in 426 adolescents of both sexes from the IMAGEN Study from 8 European cities and 504 male youth from the Avon Longitudinal Study of Parents and Children (ALSPAC) based in England. A total of 1577 participants (aged 12-21 years; 899 [57.0%] male) had (1) information about cannabis use; (2) imaging studies of the brain; and (3) a polygenic risk score for schizophrenia across 108 genetic loci identified by the Psychiatric Genomics Consortium. Data analysis was performed from March 1 through December 31, 2014. Cortical thickness derived from T1-weighted magnetic resonance images. Linear regression tests were used to assess the relationships between cannabis use, cortical thickness, and risk score. Across the 3 samples of 1574 participants, a negative association was observed between cannabis use in early adolescence and cortical thickness in male participants with a high polygenic risk score. This observation was not the case for low-risk male participants or for the low- or high-risk female participants. Thus, in SYS male participants, cannabis use interacted with risk score vis-à-vis cortical thickness (P = .009); higher scores were associated with lower thickness only in males who used cannabis. Similarly, in the IMAGEN male participants, cannabis use interacted with increased risk score vis-à-vis a change in decreasing cortical thickness from 14.5 to 18.5 years of age (t137 = -2.36; P

  15. Distinct transformation tropism exhibited by human T lymphotropic virus type 1 (HTLV-1) and HTLV-2 is the result of postinfection T cell clonal expansion.

    Science.gov (United States)

    Kannian, Priya; Yin, Han; Doueiri, Rami; Lairmore, Michael D; Fernandez, Soledad; Green, Patrick L

    2012-04-01

    Human T lymphotropic virus type 1 (HTLV-1) and HTLV-2 are related but pathogenically distinct viruses. HTLV-1 mainly causes adult T cell leukemia, while HTLV-2 is not associated with leukemia. In vitro, HTLV-1 and HTLV-2 predominantly transform CD4(+) and CD8(+) T cells, respectively: the genetic determinant maps to the viral envelope. Herein, we investigate whether this transformation tropism occurs during initial infection or subsequently during the cellular transformation process. Since most individuals are chronically infected at the time of detection, we utilized an established rabbit model to longitudinally measure the early HTLV-1 and HTLV-2 infection and replication kinetics in purified CD4(+) and CD8(+) T cells. HTLV-1 and HTLV-2 were detected in both CD4(+) and CD8(+) T cells within 1 week postinoculation. In HTLV-1-infected rabbit CD4(+) T cells, proviral burden and tax/rex mRNA expression peaked early, and expression levels were directly proportional to each other. The late expression of the antisense transcript (Hbz or Aph-2) correlated directly with a late proviral burden peak in HTLV-1- or HTLV-2-infected rabbit CD8(+) T cells, respectively. This study provides the first in vivo evidence that these viruses do not exhibit cellular preference during initial infection. We further evaluated the transformation tropism of HTLV-1 and HTLV-2 over a 9-week period using in vitro cell growth/immortalization assays. At the early weeks, both HTLV-1 and HTLV-2 showed proportionate growth of CD4(+) and CD8(+) T cells. However, beyond week 5, the predominance of one particular T cell type emerged, supporting the conclusion that transformation tropism is a postinfection event due to selective clonal expansion over time.

  16. Traumatic Brain Injury Pathophysiology and Treatments: Early, Intermediate, and Late Phases Post-Injury

    Directory of Open Access Journals (Sweden)

    Hanna Algattas

    2013-12-01

    Full Text Available Traumatic Brain Injury (TBI affects a large proportion and extensive array of individuals in the population. While precise pathological mechanisms are lacking, the growing base of knowledge concerning TBI has put increased emphasis on its understanding and treatment. Most treatments of TBI are aimed at ameliorating secondary insults arising from the injury; these insults can be characterized with respect to time post-injury, including early, intermediate, and late pathological changes. Early pathological responses are due to energy depletion and cell death secondary to excitotoxicity, the intermediate phase is characterized by neuroinflammation and the late stage by increased susceptibility to seizures and epilepsy. Current treatments of TBI have been tailored to these distinct pathological stages with some overlap. Many prophylactic, pharmacologic, and surgical treatments are used post-TBI to halt the progression of these pathologic reactions. In the present review, we discuss the mechanisms of the pathological hallmarks of TBI and both current and novel treatments which target the respective pathways.

  17. Early environmental therapy rescues brain development in a mouse model of Down syndrome.

    Science.gov (United States)

    Begenisic, Tatjana; Sansevero, Gabriele; Baroncelli, Laura; Cioni, Giovanni; Sale, Alessandro

    2015-10-01

    Down syndrome (DS), the most common genetic disorder associated with intellectual disabilities, is an untreatable condition characterized by a number of developmental defects and permanent deficits in the adulthood. Ts65Dn mice, the major animal model for DS, display severe cognitive and synaptic plasticity defects closely resembling the human phenotype. Here, we employed a multidisciplinary approach to investigate, for the first time in developing Ts65Dn mice, the effects elicited by early environmental enrichment (EE) on brain maturation and function. We report that exposure to EE resulted in a robust increase in maternal care levels displayed by Ts65Dn mothers and led to a normalization of declarative memory abilities and hippocampal plasticity in trisomic offspring. The positive effects of EE on Ts65Dn phenotype were not limited to the cognitive domain, but also included a rescue of visual system maturation. The beneficial EE effects were accompanied by increased BDNF and correction of over-expression of the GABA vesicular transporter vGAT. These findings highlight the beneficial impact of early environmental stimuli and their potential for application in the treatment of major functional deficits in children with DS.

  18. Gene expression in the mouse brain following early pregnancy exposure to ethanol

    Directory of Open Access Journals (Sweden)

    Christine R. Zhang

    2016-12-01

    Full Text Available Exposure to alcohol during early embryonic or fetal development has been linked with a variety of adverse outcomes, the most common of which are structural and functional abnormalities of the central nervous system [1]. Behavioural and cognitive deficits reported in individuals exposed to alcohol in utero include intellectual impairment, learning and memory difficulties, diminished executive functioning, attention problems, poor motor function and hyperactivity [2]. The economic and social costs of these outcomes are substantial and profound [3,4]. Improvement of neurobehavioural outcomes following prenatal alcohol exposure requires greater understanding of the mechanisms of alcohol-induced damage to the brain. Here we use a mouse model of relatively moderate ethanol exposure early in pregnancy and profile gene expression in the hippocampus and caudate putamen of adult male offspring. The effects of offspring sex and age on ethanol-sensitive hippocampal gene expression were also examined. All array data are available at the Gene Expression Omnibus (GEO repository under accession number GSE87736.

  19. A Pilot Project of Early Integrated Traumatic Brain Injury Rehabilitation in Singapore

    Directory of Open Access Journals (Sweden)

    Siew Kwaon Lui

    2014-01-01

    Full Text Available Objective. Document acute neurosurgical and rehabilitation parameters of patients of all traumatic brain injury (TBI severities and determine whether early screening along with very early integrated TBI rehabilitation changes functional outcomes. Methods. Prospective study involving all patients with TBI admitted to a neurosurgical department of a tertiary hospital. They were assessed within 72 hours of admission by the rehabilitation team and received twice weekly rehabilitation reviews. Patients with further rehabilitation needs were then transferred to the attached acute inpatient TBI rehabilitation unit (TREATS and their functional outcomes were compared against a historical group of patients. Demographic variables, acute neurosurgical characteristics, medical complications, and rehabilitation outcomes were recorded. Results. There were 298 patients screened with an average age of 61.8±19.1 years. The most common etiology was falls (77.5%. Most patients were discharged home directly (67.4% and 22.8% of patients were in TREATS. The TREATS group functionally improved (P<0.001. Regression analysis showed by the intervention of TREATS, that there was a statistically significant FIM functional gain of 18.445 points (95% CI −30.388 to −0.6502, P=0.03. Conclusion. Our study demonstrated important epidemiological data on an unselected cohort of patients with TBI in Singapore and functional improvement in patients who further received inpatient rehabilitation.

  20. cis p-tau: early driver of brain injury and tauopathy blocked by antibody

    Science.gov (United States)

    Mannix, Rebekah; Qiu, Jianhua; Moncaster, Juliet; Chen, Chun-Hau; Yao, Yandan; Lin, Yu-Min; Driver, Jane A; Sun, Yan; Wei, Shuo; Luo, Man-Li; Albayram, Onder; Huang, Pengyu; Rotenberg, Alexander; Ryo, Akihide; Goldstein, Lee E; Pascual-Leone, Alvaro; McKee, Ann C.; Meehan, William; Zhou, Xiao Zhen; Lu, Kun Ping

    2015-01-01

    Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy (CTE) and Alzheimer's disease (AD), whose defining pathologic features include tauopathy made of phosphorylated tau (p-tau). However, tauopathy has not been detected in early stages after TBI and how TBI leads to tauopathy is unknown. Here we find robust cis p-tau pathology after sport- and military-related TBI in humans and mice. Acutely after TBI in mice and stress in vitro, neurons prominently produce cis p-tau, which disrupts axonal microtubule network and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, termed “cistauosis”, appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis p-tau is a major early driver after TBI and leads to tauopathy in CTE and AD, and cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury. PMID:26176913

  1. STATISTICAL GROWTH MODELING OF LONGITUDINAL DT-MRI FOR REGIONAL CHARACTERIZATION OF EARLY BRAIN DEVELOPMENT.

    Science.gov (United States)

    Sadeghi, Neda; Prastawa, Marcel; Fletcher, P Thomas; Gilmore, John H; Lin, Weili; Gerig, Guido

    2012-01-01

    A population growth model that represents the growth trajectories of individual subjects is critical to study and understand neurodevelopment. This paper presents a framework for jointly estimating and modeling individual and population growth trajectories, and determining significant regional differences in growth pattern characteristics applied to longitudinal neuroimaging data. We use non-linear mixed effect modeling where temporal change is modeled by the Gompertz function. The Gompertz function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to growth. Our proposed framework combines nonlinear modeling of individual trajectories, population analysis, and testing for regional differences. We apply this framework to the study of early maturation in white matter regions as measured with diffusion tensor imaging (DTI). Regional differences between anatomical regions of interest that are known to mature differently are analyzed and quantified. Experiments with image data from a large ongoing clinical study show that our framework provides descriptive, quantitative information on growth trajectories that can be directly interpreted by clinicians. To our knowledge, this is the first longitudinal analysis of growth functions to explain the trajectory of early brain maturation as it is represented in DTI.

  2. The relationship between clinical phenotype and early staged bilateral deep brain stimulation in Parkinson disease.

    Science.gov (United States)

    Sung, Victor W; Watts, Ray L; Schrandt, Christian J; Guthrie, Stephanie; Wang, Deli; Amara, Amy W; Guthrie, Barton L; Walker, Harrison C

    2013-12-01

    While many centers place bilateral deep brain stimulation (DBS) systems simultaneously, unilateral subthalamic nucleus (STN) DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However, little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite STN will be required. The authors aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second STN DBS electrode in patients who undergo unilateral STN DBS for Parkinson disease (PD). Eighty-two consecutive patients with advanced PD underwent unilateral STN DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression analysis determined preoperative characteristics that predicted staged placement of a second electrode in the opposite STN. Preoperative measurements included aspects of the Unified Parkinson's Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. At 2-year follow-up, 28 (34%) of the 82 patients had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and Part 3 scores were retained at the end of the 2-year follow-up period in both subsets of patients. Multivariate logistic regression analysis showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (OR 13.4, 95% CI 2.8-64.9), high tremor subscore (OR 7.2, CI 1.5-35.0), and low body weight (OR 5.5, 95% CI 1.4-22.3). This single-center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral STN DBS. These data may aid in the management of patients with advanced PD who undergo STN DBS.

  3. Evidence of vertical transmission and tissue tropism of Streptococcosis from naturally infected red tilapia (Oreochromis spp.

    Directory of Open Access Journals (Sweden)

    Padmaja Jayaprasad Pradeep

    2016-05-01

    Full Text Available Streptococcosis is a highly problematic disease in the aquaculture of freshwater fishes, especially for tilapia. The possibility of vertical transmission of streptococcosis and the pattern of tissue tropism of this pathogen in various organs was examined in red tilapia (Oreochromis sp.. Healthy broodstock without any clinical signs of Streptococcus spp. were selected from a farm earlier reported to have the disease and a total of 10 pairs were forced spawned to provide samples of gametes and progeny for pathogen testing. A colorimetric LAMP assay was used to confirm whether the bacterial pathogens Streptococcus. agalactiae and Streptococcus. iniae was present in samples of milt, unfertilized eggs, fertilized eggs, and offspring at various stages of development, as well as internal organs of broodstock (reproductive organs, gill, liver, spleen, kidney and brain as well as samples of water from culture systems. The majority of samples of milt (9/10 and unfertilized eggs (7/10 collected from the broodstock were infected with S. iniae at the time of spawning and was transmitted to all of their offspring. Nevertheless, when the same samples of gametes were analyzed for S. agalactiae, they were all found to be negative but the pathogen was found to be present in some 10-day-old larval offspring (4/10. However, when the pathogenic presence was analyzed from the reproductive organs of the parents, both S. agalactiae (11/20 and S. iniae (18/20 bacterium were common. Although, all broodstock were asymptomatic, almost all broodstock harboured the bacteria in many organs. Confirmation of vertical transmission of streptococcosis in tilapia means that intergenerational break cannot be used as a reliable and simple means of reducing or eliminating the prevalence of these difficult pathogens in aquaculture stock.

  4. Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

    Science.gov (United States)

    Fundament, Tomasz; Eldridge, Paul R; Green, Alexander L; Whone, Alan L; Taylor, Rod S; Williams, Adrian C; Schuepbach, W M Michael

    2016-01-01

    Parkinson's disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost

  5. Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

    Directory of Open Access Journals (Sweden)

    Tomasz Fundament

    Full Text Available Parkinson's disease (PD is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT, among PD patients with early onset of motor complications, from a United Kingdom (UK payer perspective.We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY. One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty.Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs, resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values.These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental

  6. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors: A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, S.C.; Schouten-van Meeteren, A.Y.; Boot, A.M.; Claahsen-van der Grinten, H.L.; Granzen, B.; Han, K.; Janssens, G.O.; Michiels, E.M.; Trotsenburg, A.S. van; Vandertop, W.P.; Vuurden, D.G. van; Kremer, L.C.; Caron, H.N.; Santen, H.M. van

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >/= 2 years after diagnosis.

  7. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C; Schouten-van Meeteren, Antoinette Y N; Boot, Annemieke M; Claahsen-van der Grinten, Hedy L; Granzen, Bernd; Sen Han, K; Janssens, Geert O; Michiels, Erna M; van Trotsenburg, A S Paul; Vandertop, W Peter; van Vuurden, Dannis G; Kremer, Leontien C M; Caron, Hubert N; van Santen, Hanneke M

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients

  8. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C.; Schouten-van Meeteren, Antoinette Y. N.; Boots, Annemieke; Claahsen-van der Grinten, Hedy L.; Granzen, Bernd; Sen Han, K.; Janssens, Geert O.; Michiels, Erna M.; van Trotsenburg, A. S. Paul; Vandertop, W. Peter; van Vuurden, Dannis G.; Kremer, Leontien C. M.; Caron, Hubert N.; van Santen, Hanneke M.

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >= 2 years after diagnosis. Patients

  9. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C.; Schouten-van Meeteren, Antoinette Y. N.; Boots, Annemieke; Claahsen-van der Grinten, Hedy L.; Granzen, Bernd; Sen Han, K.; Janssens, Geert O.; Michiels, Erna M.; van Trotsenburg, A. S. Paul; Vandertop, W. Peter; van Vuurden, Dannis G.; Kremer, Leontien C. M.; Caron, Hubert N.; van Santen, Hanneke M.

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >= 2 years after diagnosis. Patients wi

  10. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C; Schouten-van Meeteren, Antoinette Y N; Boot, Annemieke M; Claahsen-van der Grinten, Hedy L; Granzen, Bernd; Sen Han, K; Janssens, Geert O; Michiels, Erna M; van Trotsenburg, A S Paul; Vandertop, W Peter; van Vuurden, Dannis G; Kremer, Leontien C M; Caron, Hubert N; van Santen, Hanneke M

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients wit

  11. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors: A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, S.C.; Schouten-van Meeteren, A.Y.; Boot, A.M.; Claahsen-van der Grinten, H.L.; Granzen, B.; Han, K.; Janssens, G.O.; Michiels, E.M.; Trotsenburg, A.S. van; Vandertop, W.P.; Vuurden, D.G. van; Kremer, L.C.; Caron, H.N.; Santen, H.M. van

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >/= 2 years after diagnosis. Patient

  12. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C; Schouten-van Meeteren, Antoinette Y N; Boot, Annemieke M; Claahsen-van der Grinten, Hedy L; Granzen, Bernd; Sen Han, K; Janssens, Geert O; Michiels, Erna M; van Trotsenburg, A S Paul; Vandertop, W Peter; van Vuurden, Dannis G; Kremer, Leontien C M; Caron, Hubert N; van Santen, Hanneke M

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients wit

  13. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C.; Schouten-van Meeteren, Antoinette Y. N.; Boots, Annemieke; Claahsen-van der Grinten, Hedy L.; Granzen, Bernd; Sen Han, K.; Janssens, Geert O.; Michiels, Erna M.; van Trotsenburg, A. S. Paul; Vandertop, W. Peter; van Vuurden, Dannis G.; Kremer, Leontien C. M.; Caron, Hubert N.; van Santen, Hanneke M.

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >= 2 years after diagnosis. Patients wi

  14. Association analysis of the brain-derived neurotrophic factor gene polymorphisms with early-onset schizophrenia in the Chinese population

    Institute of Scientific and Technical Information of China (English)

    易正辉

    2012-01-01

    Objective To investigate the relationship between the brain-derived neurotrophic factor (BDNF) gene Tag SNPs(rs 11030101 and rs6265) and early-onset schizophrenia in the Chinese Han population. Methods The tag single nucleotide polymorphisms (tag SNPs) rs11030101 and rs6265 in the BDNF gene were genotyped

  15. Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Aibek E. Mirrakhimov

    2012-01-01

    Full Text Available We present a case of early onset pancreatic cancer related extra-axial brain metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites, and a history of a pulmonary embolism was admitted to the hospital because of a new onset headache, nausea, and vomiting which started 2 days prior to the encounter. Brain MRI was ordered, which showed acute bihemispheric subdural hematomas and left hemispheric extra-axial heterogeneously enhancing lesions consisting with metastatic disease. The patient was started on ondansentron, metoclopramide, and dexamethasone. The cranial irradiation was started, and the patient’s headache and nausea significantly improved. There are only 9 published reports of extra-axial brain metastases related to the pancreatic cancer, whereas our paper is the first such case reported on a patient with epidural metastases and early onset pancreatic cancer.

  16. Brain Basics

    Medline Plus

    Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ... grow there are differences in brain development in children who develop bipolar disorder than children who do ...

  17. Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5

    Energy Technology Data Exchange (ETDEWEB)

    Mefford, Megan E., E-mail: megan_mefford@hms.harvard.edu [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA (United States); Kunstman, Kevin, E-mail: kunstman@northwestern.edu [Northwestern University Medical School, Chicago, IL (United States); Wolinsky, Steven M., E-mail: s-wolinsky@northwestern.edu [Northwestern University Medical School, Chicago, IL (United States); Gabuzda, Dana, E-mail: dana_gabuzda@dfci.harvard.edu [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA (United States); Department of Neurology (Microbiology and Immunobiology), Harvard Medical School, Boston, MA (United States)

    2015-07-15

    Macrophages express low levels of the CD4 receptor compared to T-cells. Macrophage-tropic HIV strains replicating in brain of untreated patients with HIV-associated dementia (HAD) express Envs that are adapted to overcome this restriction through mechanisms that are poorly understood. Here, bioinformatic analysis of env sequence datasets together with functional studies identified polymorphisms in the β3 strand of the HIV gp120 bridging sheet that increase M-tropism. D197, which results in loss of an N-glycan located near the HIV Env trimer apex, was detected in brain in some HAD patients, while position 200 was estimated to be under positive selection. D197 and T/V200 increased fusion and infection of cells expressing low CD4 by enhancing gp120 binding to CCR5. These results identify polymorphisms in the HIV gp120 bridging sheet that overcome the restriction to macrophage infection imposed by low CD4 through enhanced gp120–CCR5 interactions, thereby promoting infection of brain and other macrophage-rich tissues. - Highlights: • We analyze HIV Env sequences and identify amino acids in beta 3 of the gp120 bridging sheet that enhance macrophage tropism. • These amino acids at positions 197 and 200 are present in brain of some patients with HIV-associated dementia. • D197 results in loss of a glycan near the HIV Env trimer apex, which may increase exposure of V3. • These variants may promote infection of macrophages in the brain by enhancing gp120–CCR5 interactions.

  18. A longitudinal analysis of regional brain volumes in macaques exposed to X-irradiation in early gestation.

    Directory of Open Access Journals (Sweden)

    Kristina Aldridge

    Full Text Available BACKGROUND: Early gestation represents a period of vulnerability to environmental insult that has been associated with adult psychiatric disease. However, little is known about how prenatal perturbation translates into adult brain dysfunction. Here, we use a longitudinal study design to examine the effects of disruption of early gestational neurogenesis on brain volume in the non-human primate. METHODS AND PRINCIPAL FINDINGS: Five Rhesus macaques were exposed to x-irradiation in early gestation (E30-E41, and four control monkeys were sham-irradiated at comparable ages. Whole brain magnetic resonance imaging was performed at 6 months, 12 months, and 3 and 5 years of age. Volumes of whole cerebrum, cortical gray matter, caudate, putamen, and thalamus were estimated using semi-automated segmentation methods and high dimensional brain mapping. Volume reductions spanning all ages were observed in irradiated monkeys in the putamen (15-24%, p = 0.01 and in cortical gray matter (6-15%, p = 0.01. Upon covarying for whole cerebral volume, group differences were reduced to trend levels (putamen: p = 0.07; cortical gray matter: p = 0.08. No group-by-age effects were significant. CONCLUSIONS: Due to the small number of observations, the conclusions drawn from this study must be viewed as tentative. Early gestational irradiation may result in non-uniform reduction of gray matter, mainly affecting the putamen and cerebral cortex. This may be relevant to understanding how early prenatal environmental insult could lead to brain morphological differences in neurodevelopmental diseases.

  19. Increase in estrogen signaling in the early brain of orange-spotted grouper Epinephelus coioides: a mini-review.

    Science.gov (United States)

    Nagarajan, Ganesan; Aruna, Adimoolam; Chang, Ching-Fong

    2013-02-01

    Despite neurosteroidogenic enzymes are playing important roles in the regulation of brain development and function, the potential link between brain and gonad by the action of steroid hormones during gonadal sex differentiation is still not clear in teleosts. In this mini-review, we summarized our understanding on the early brain development related to the synthesis of neurosteroids and receptor signaling during gonadal sex differentiation in protogynous orange-spotted grouper, Epinephelus coioides (functional females for the first 6 years of life and start to sex change around the age of 7 years) and protandrous black porgy (functional males for the first 2 years of life but begin to change sex during the third year). We found a similar profile in the increased expression of brain aromatase gene (aromatatse B or cyp19a1b), aromatase activity, estradiol (E(2)), and estrogen signaling in the brain of both grouper and black porgy fish during gonadal sex differentiation. In contrast to mammals, teleost fish Cyp19a1b expressed in a unique cell type, a radial glial cell, which is acted as progenitors in the brain of developing and adult fish. In agreement with these pioneer studies, we demonstrated that the grouper cyp19a1b/Cyp19a1b was expressed in radial glial cells. Further, in vivo data in the grouper brain showed that exogenous E(2) upregulated Cyp19a1b immunoreactivity (ir) in radial glial cells. These data suggest the possible roles of Cyp19a1b and E(2) in early brain development which is presumably related to gonadal sex differentiation.

  20. Early transient mild hypothermia attenuates neurological deficits and brain damage after experimental subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Lilla, Nadine; Rinne, Christoph; Weiland, Judith; Linsenmann, Thomas; Ernestus, Ralf-Ingo; Westermaier, Thomas

    2017-09-23

    Metabolic exhaustion in ischemic tissue is the basis for a detrimental cascade of cell damage. In the acute stage of subarachnoid hemorrhage (SAH), a sequence of global and focal ischemia occurs, threatening brain tissue to undergo ischemic damage. This study was conducted to investigate whether early therapy with moderate hypothermia can offer neuroprotection after experimental SAH. 20 male Sprague-Dawley rats were subjected to SAH and treated by active cooling (34° C) or served as controls by continuous maintenance of normothermia (37.0° C). Mean arterial blood pressure (MABP), intracranial pressure (ICP) and local cerebral blood flow (CBF) over both hemispheres were continuously measured. Neurological assessment was performed 24 hours later. Hippocampal damage was assessed by hematoxylin and eosin and Caspase-3 staining. By a slight increase of MABP in the cooling phase and a significant reduction of ICP, hypothermia improved cerebral perfusion pressure (CPP) in the first 60 minutes after SAH. Accordingly, a trend to increased CBF was observed during this period. The rate of injured neurons was significantly reduced in hypothermia-treated animals compared to normothermic controls. The results of this series cannot finally answer whether this form of treatment permanently attenuates or only delays ischemic damage. In the latter case, slowing down metabolic exhaustion by hypothermia may still be a valuable treatment during this state of ischemic brain damage and prolong the therapeutic window for possible causal treatments of the acute perfusion deficit. Therefore, it may be useful as a first-tier therapy in suspected SAH. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Maternal sensitivity and the empathic brain: Influences of early life maltreatment.

    Science.gov (United States)

    Mielke, Emilia L; Neukel, Corinne; Bertsch, Katja; Reck, Corinna; Möhler, Eva; Herpertz, Sabine C

    2016-06-01

    One of the most striking characteristics of early life maltreatment (ELM) is the risk of transmission across generations, which could be linked to differences in maternal behavior. Maternal sensitivity includes appropriate and positive affective exchanges between mother and child. Mothers with a history of ELM have been found to show a lower sensitivity representing a significant risk factor for maltreating their own children. 25 mothers with and 28 mothers without sexual and/or physical childhood maltreatment (as assessed with the Childhood Experience of Care and Abuse interview) and their children participated in a standardized mother-child interaction task. Videotaped interactions were rated by two independent trained raters based on the Emotional Availability Scales. In addition, empathic capabilities were assessed with the Interpersonal Reactivity Index. High resolution structural magnetic resonance brain images of the mothers were analyzed with unbiased voxel-based morphometry and correlated with maternal sensitivity. Results indicate that mothers with ELM were less sensitive in the standardized interaction with their own child. In non-maltreated control mothers, maternal sensitivity was positively related to anterior insular grey matter volume, a region which is crucially involved in emotional empathy, while there was a positive association between maternal sensitivity and grey matter volume in parts of the cognitive empathy network such as the superior temporal sulcus and temporal pole region in mothers with ELM. These results implicate that neurostructural alterations associated with poor maternal sensitivity might be a sequelae of ELM and that mothers with ELM may try to compensate deficits in emotional empathy by recruiting brain regions involved in cognitive empathy when interacting with their child. Thus, findings suggest possible coping strategies of mother with ELM to prevent an intergenerational transmission of abuse.

  2. Brain structural substrates of cognitive procedural learning in alcoholic patients early in abstinence

    Science.gov (United States)

    Ritz, Ludivine; Segobin, Shailendra; Le Berre, Anne Pascale; Lannuzel, Coralie; Boudehent, Céline; Vabret, François; Eustache, Francis; Pitel, Anne Lise; Beaunieux, Hélène

    2014-01-01

    Background Procedural learning allows for the acquisition of new behavioral skills. Previous studies have shown that chronic alcoholism is characterized by impaired cognitive procedural learning and brain abnormalities affecting regions that are involved in the automation of new cognitive procedures in healthy individuals. The goal of the present study was to investigate the brain structural substrates of cognitive procedural learning in alcoholic patients (ALs) early in abstinence. Methods Thirty-one ALs and 31 control participants (NCs) performed the Tower of Toronto task (4 daily learning sessions, each comprising 10 trials) to assess cognitive procedural learning. We also assessed episodic and working memory, executive functions, and visuospatial abilities. ALs underwent 1.5T structural magnetic resonance imaging. Results The initial cognitive phase was longer in the AL group than in the NC group, whereas the autonomous phase was shorter. In ALs, the longer cognitive phase was predicted by poorer planning and visuospatial working memory abilities, and by smaller gray matter (GM) volumes in the angular gyrus and caudate nucleus. ALs’ planning abilities correlated with smaller GM volume in the angular gyrus. Conclusions Cognitive procedural learning was impaired in ALs, with a delayed transition from the cognitive to the autonomous phase. This slowdown in the automation of the cognitive procedure was related to lower planning abilities, which may have hampered the initial generation of the procedure to be learned. In agreement with this neuropsychological finding, a persistent relationship was found between learning performance and the GM volumes of the angular gyrus and caudate nucleus, which are usually regarded as markers of planning and initial learning of the cognitive procedure. PMID:25156613

  3. Early platelet dysfunction in a rodent model of blunt traumatic brain injury reflects the acute traumatic coagulopathy found in humans.

    Science.gov (United States)

    Donahue, Deborah L; Beck, Julia; Fritz, Braxton; Davis, Patrick; Sandoval-Cooper, Mayra J; Thomas, Scott G; Yount, Robert A; Walsh, Mark; Ploplis, Victoria A; Castellino, Francis J

    2014-02-15

    Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and is of uncertain etiology because of the complex nature of TBI. However, recent work has shown a correlation between mortality and abnormal hemostasis resulting from early platelet dysfunction. The aim of the current study was to develop and characterize a rodent model of TBI that mimics the human coagulopathic condition so that mechanisms of the early acute coagulopathy in TBI can be more readily assessed. Studies utilizing a highly reproducible constrained blunt-force brain injury in rats demonstrate a strong correlation with important postinjury pathological changes that are observed in human TBI patients, namely, diminished platelet responses to agonists, especially adenosine diphosphate (ADP), and subarachnoid bleeding. Additionally, administration of a direct thrombin inhibitor, preinjury, recovers platelet functionality to ADP stimulation, indicating a direct role for excess thrombin production in TBI-induced early platelet dysfunction.

  4. Tissue and host tropism of influenza viruses:Importance of quantitative analysis

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    It is generally accepted that human influenza viruses preferentially bind to cell-surface glycoproteins/ glycolipids containing sialic acids in α2,6-linkage; while avian and equine influenza viruses preferentially bind to those containing sialic acids in α2,3-linkage. Even though this generalized view is accurate for H3 subtype isolates, it may not be accurate and absolute for all subtypes of influenza A viruses and, therefore, needs to be reevaluated carefully and realistically. Some of the studies published in major scientific journals on the subject of tissue tropism of influenza viruses are inconsistent and caused confusion in the scientific community. One of the reasons for the inconsistency is that most studies were quantitative descriptions of sialic acid receptor distributions based on lectin or influenza virus immunohistochemistry results with limited numbers of stained cells. In addition, recent studies indicate that α2,3- and α2,6-linked sialic acids are not the sole receptors determining tissue and host tropism of influenza viruses. In fact, determinants for tissue and host tropism of human, avian and animal influenza viruses are more complex than what has been generally accepted. Other factors, such as glycan topology, concentration of invading viruses, local density of receptors, lipid raft microdomains, coreceptors or sialic acid-independent receptors, may also be important. To more efficiently control the global spread of pandemic influenza such as the current circulating influenza A H1N1, it is crucial to clarify the determinants for tissue and host tropism of influenza viruses through quantitative analysis of experimental results. In this review, I will comment on some conflicting issues related to tissue and host tropism of influenza viruses, discuss the importance of quantitative analysis of lectin and influenza virus immunohistochemistry results and point out directions for future studies in this area, which should lead to a better

  5. Neuroaxonal regeneration is more pronounced in early multiple sclerosis than in traumatic brain injury lesions.

    Science.gov (United States)

    Schirmer, Lucas; Merkler, Doron; König, Fatima B; Brück, Wolfgang; Stadelmann, Christine

    2013-01-01

    The extent of irreversible neuroaxonal damage is the key determinant of permanent disability in traumatic and inflammatory conditions of the central nervous system (CNS). Structural damage is nevertheless in part compensated by neuroplastic events. However, it is unknown whether the same kinetics and mechanisms of neuroaxonal de- and regeneration take place in inflammatory and traumatic conditions. We analyzed neuroaxonal degeneration and plasticity in early multiple sclerosis (MS) lesions and traumatic brain injury (TBI). Neuroaxonal degeneration identified by the presence of SMI31+ chromatolytic neurons and SMI32+ axonal profiles were characteristic features of leukocortical TBI lesions. Axonal transport disturbances as determined by amyloid precursor protein (APP)+ spheroids were present in both TBI and MS lesions to a similar degree. Neurons expressing growth-associated protein 43 (GAP43) and synaptophysin (Syn) were found under both pathological conditions. However, axonal swellings immunopositive for GAP43 and Syn clearly prevailed in subcortical MS lesions, suggesting a higher regenerative potential in MS. In this context, GAP43+/APP+ axonal spheroid ratios correlated with macrophage infiltration in TBI and MS lesions, supporting the idea that phagocyte activation might promote neuroplastic events. Furthermore, axonal GAP43+ and Syn+ swellings correlated with prolonged survival after TBI, indicating a sustained regenerative response.

  6. An availability of brain magnetic resonance imaging (MRI) in the early diagnosis of latent hepatic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kuwahara, Noaki; Tanabe, Masako; Fujiwara, Akiko; Minato, Takeshi; Sasaki, Hiromasa [Hiroshima Posts and Telecommunications Hospital (Japan); Higashi, Toshihiro; Tsuji, Takao

    1996-03-01

    Brain MRI was carried out in patients with chronic liver diseases. No abnormal findings were recognized in patients with chronic viral hepatitis, while 59.2% of cirrhotics showed a symmetrically strong signal in basal ganglia on T1 weighted image in MRI. This finding significantly related with lowered Fischer`s ratio of serum amino acid, increased levels of serum phenylalanine, tyrosine and hyaluronic acid, prolonged prothrombin time and decreased platelet counts in the peripheral blood. Overt hepatic encephalopathy was observed in 6 of 34 patients with the strong signal in MRI during follow-up period, while none of patients without that finding developed hepatic encephalopathy. These results have indicated that the strong signal in basal ganglia on MRI appears in cirrhotic patients with severe liver dysfunction, and it is an useful index in the early diagnosis of latent hepatic encephalopathy. An improvement of this MRI finding was not observed by long-term oral administration of branched-chain amino acid. (author).

  7. Early attention impairment and recovery profiles after childhood traumatic brain injury.

    Science.gov (United States)

    Anderson, Vicki; Eren, Senem; Dob, Rian; Le Brocque, Robyne; Iselin, Greg; Davern, Timothy J; McKinlay, Lynne; Kenardy, Justin

    2012-01-01

    To examine recovery of attention from 3 to 6 months postinjury; to identify effects of injury severity and time since injury on performance; to explore whether complex attention skills (eg, shifting, divided attention, attentional control) are more vulnerable to traumatic brain injury (TBI), and slower to recover than simple attention skills (eg, attentional capacity, selective attention, sustained attention). Prospective longitudinal investigation. A total of 205 school-aged children with TBI were divided into groups according to injury severity (mild = 63%, moderate = 27%, severe = 10%). Emergency departments of 3 metropolitan children's hospitals across Australia. Standardized clinical measures of both simple and complex attention were administered at 3 months and 6 months postinjury. Attention skills were vulnerable to the impact of TBI. More severe injury affected attention skills most negatively. Significant recovery was observed over time. There were few interaction effects, with severity groups exhibiting similar levels of recovery over the 6 months post-TBI. No differences in recovery trajectories were detected for simple and complex attention. These findings have important clinical and educational implications, suggesting that children with TBI, and particularly those with more serious injuries, are most vulnerable to attention deficits in the acute stages postinjury. It is important that schools and families are aware of these limitations and structure expectations accordingly. For example, gradual return to school should be considered, and in the early stages of recovery, children should be provided with sufficient rest time, with reduced expectations for tasks such as homework.

  8. Emotion labeling and socio-emotional outcomes 18 months after early childhood traumatic brain injury.

    Science.gov (United States)

    Tlustos, Sarah J; Chiu, C-Y Peter; Walz, Nicolay Chertkoff; Taylor, H Gerry; Yeates, Keith Owen; Wade, Shari L

    2011-11-01

    A growing body of literature has documented evidence for emotion labeling (EL) deficits after traumatic brain injury (TBI); however, long-term effects of TBI on EL abilities, particularly among young children, are unclear. We investigated EL abilities and socio-emotional outcomes in 32 children with moderate-severe TBI, 23 with complicated-mild TBI, and 82 children with orthopedic injuries (OI), shortly after injury and at 18 months post-injury. All children were between 3:0 and 6:11 years of age at the time of injury. Repeated measures analyses indicated that all groups showed improved EL performance between acute and 18-month assessments, but that the moderate-severe TBI group improved at a slower rate than the OI group, so that the two groups showed significantly different performance at 18 months. Emotion labeling ability did not significantly contribute to the prediction of socio-emotional outcomes after controlling for pre-injury functioning. These results provide preliminary evidence of emerging EL deficits after early childhood TBI that are related to injury severity but that do not predict social and behavioral outcomes.

  9. The early signal substances induced by heat stress in brains of mice

    Institute of Scientific and Technical Information of China (English)

    Chunxu WANG; Hanxing WANG

    2008-01-01

    To study the effects of early signal substances induced by heat stress in brains of Kunming mice, six-month-old mice (n=72) were pretreated with heat stress and subsequent ischemia/reperfusion by clipping of their bilateral cervical common arteries for 7 min. According to different treatments, animals were randomly divided into four groups: (1) normal control group; (2) heat stress pre-treatment followed by ischemia and reperfusion group (HS/IR); (3) ischemia and reperfusion group (IR); (4) heat stress group (HS). Animals in the later three groups were subdivided into 3 subgroups (1 day, 4 days, 14 days), respectively. The changes in the expression of cAMP res-ponse element binding protein (CREB) and calcitonin gene-related peptide (CGRP) were detected by immuno-histochemistry and computer image analysis methods. The results showed that compared with the normal group, the expressions of CREB in the hippocampal CA1 region increased significantly in the HS, HS/IR and IR groups (P<0.05). Compared to the normal group, heat stress could result in CGRP excretion and redistribution in the cerebrum, with the highest level in the 4 d HS/IR group. Following heat stress, CGRP immunoreactivity was observed in varicose fibers and neuronal perikarya within the CA1 region. The results indicate that heat stress can induce CREB expression, which in turn stimulates CGRP secretion.

  10. Mild traumatic brain injuries in early adolescent rugby players: Long-term neurocognitive and academic outcomes.

    Science.gov (United States)

    Alexander, D G; Shuttleworth-Edwards, A B; Kidd, M; Malcolm, C M

    2015-01-01

    Information is scant concerning enduring brain injury effects of participation in the contact sport of Rugby Union (hereafter rugby) on early adolescents. The objective was prospectively to investigate differences between young adolescent male rugby players and non-contact sports controls on neurocognitive test performance over 3 years and academic achievement over 6 years. A sample of boys from the same school and grade was divided into three groups: rugby with seasonal concussions (n = 45), rugby no seasonal concussions (n = 21) and non-contact sports controls (n = 30). Baseline neurocognitive testing was conducted pre-season in Grade 7 and post-season in Grades 8 and 9. Year-end academic grades were documented for Grades 6-9 and 12 (pre-high school to year of school leaving). A mixed model repeated measures ANOVA was conducted to investigate comparative neurocognitive and academic outcomes between the three sub-groups. Compared with controls, both rugby groups were significantly lower on the WISC-III Coding Immediate Recall sub-test. There was a significant interaction effect on the academic measure, with improved scores over time for controls, that was not in evidence for either rugby group. Tentatively, the outcome suggests cognitive vulnerability in association with school level participation in rugby.

  11. Early-life exercise may promote lasting brain and metabolic health through gut bacterial metabolites.

    Science.gov (United States)

    Mika, Agnieszka; Fleshner, Monika

    2016-02-01

    The 100 trillion microorganisms residing within our intestines contribute roughly 5 million additional genes to our genetic gestalt, thus posing the potential to influence many aspects of our physiology. Microbial colonization of the gut shortly after birth is vital for the proper development of immune, neural and metabolic systems, while sustaining a balanced, diverse gut flora populated with beneficial bacteria is necessary for maintaining optimal function of these systems. Although symbiotic host-microbial interactions are important throughout the lifespan, these interactions can have greater and longer lasting impacts during certain critical developmental periods. A better understanding of these sensitive periods is necessary to improve the impact and effectiveness of health-promoting interventions that target the microbial ecosystem. We have recently reported that exercise initiated in early life increases gut bacterial species involved in promoting psychological and metabolic health. In this review, we emphasize the ability of exercise during this developmentally receptive time to promote optimal brain and metabolic function across the lifespan through microbial signals.

  12. Role of Mitochondrial Calcium Uniporter in Early Brain Injury After Experimental Subarachnoid Hemorrhage.

    Science.gov (United States)

    Yan, Huiying; Zhang, Dingding; Hao, Shuangying; Li, Kuanyu; Hang, Chun-Hua

    2015-12-01

    Previous studies have shown that mitochondrial Ca(2+) is undertaken by mitochondrial calcium uniporter (MCU), and its accumulation is associated with the development of many diseases. However, little was known about the role of MCU in early brain injury (EBI) after subarachnoid hemorrhage (SAH). MCU can be opened by spermine under a physiological condition and inhibited by ruthenium red (RR). Herein, we investigated the effects of RR and spermine to reveal the role of MCU in SAH animal model. The data obtained with biochemical and histological assays showed that mitochondrial Ca(2+) concentration was significantly increased in the temporal cortex of rats 1, 2, and 3 days after SAH, consistent with constant high levels of cellular Ca(2+) concentration. In agreement with the observation in the acute phase, SAH rats showed an obvious increase of reactive oxygen species (ROS) level and decrease of ATP production. Blockage of MCU prevented Ca(2+) accumulation, abated the level of oxidative stress, and improved the energy supply. Translocation of cytochrome c, increased cleaved caspase-3, and a large amount of apoptotic cells after SAH were reversed by RR administration. Surprisingly, exogenous spermine did not increase cellular Ca(2+) concentration, but lessened the Ca(2+) accumulation after SAH to benefit the rats. Taken together, our results demonstrated that blockage of MCU or prevention of Ca(2+) accumulation after SAH is essential in EBI after SAH. These findings suggest that MCU is considered to be a therapeutic target for patients suffering from SAH.

  13. Early integration processing between faces and vowel sounds in human brain: an MEG investigation.

    Science.gov (United States)

    Nakamura, Itta; Hirano, Yoji; Ohara, Naotoshi; Hirano, Shogo; Ueno, Takefumi; Tsuchimoto, Rikako; Kanba, Shigenobu; Onitsuka, Toshiaki

    2015-01-01

    Unconscious fast integration of face and voice information is a crucial brain function necessary for communicating effectively with others. Here, we investigated for evidence of rapid face-voice integration in the auditory cortex. Magnetic fields (P50m and N100m) evoked by visual stimuli (V), auditory stimuli (A) and audiovisual stimuli (VA), i.e. by face, vowel and simultaneous vowel-face stimuli, were recorded in 22 healthy subjects. Magnetoencephalographic data from 28 channels around bilateral auditory cortices were analyzed. In both hemispheres, AV - V showed significantly larger P50m amplitudes than A. Additionally, compared with A, the N100m amplitudes and dipole moments of AV - V were significantly smaller in the left hemisphere, but not in the right hemisphere. Differential changes in P50m (bilateral) and N100m (left hemisphere) that occur when V (faces) are associated with A (vowel sounds) indicate that AV (face-voice) integration occurs in early processing, likely enabling us to communicate effectively in our lives. © 2015 S. Karger AG, Basel.

  14. Effects of Repetitive Transcranial Magnetic Stimulation on Behavioral Recovery during Early Stage of Traumatic Brain Injury in Rats.

    Science.gov (United States)

    Yoon, Kyung Jae; Lee, Yong-Taek; Chung, Pil-Wook; Lee, Yun Kyung; Kim, Dae Yul; Chun, Min Ho

    2015-10-01

    Repetitive transcranial magnetic stimulation (rTMS) is a promising technique that modulates neural networks. However, there were few studies evaluating the effects of rTMS in traumatic brain injury (TBI). Herein, we assessed the effectiveness of rTMS on behavioral recovery and metabolic changes using brain magnetic resonance spectroscopy (MRS) in a rat model of TBI. We also evaluated the safety of rTMS by measuring brain swelling with brain magnetic resonance imaging (MRI). Twenty male Sprague-Dawley rats underwent lateral fluid percussion and were randomly assigned to the sham (n=10) or the rTMS (n=10) group. rTMS was applied on the fourth day after TBI and consisted of 10 daily sessions for 2 weeks with 10 Hz frequency (total pulses=3,000). Although the rTMS group showed an anti-apoptotic effect around the peri-lesional area, functional improvements were not significantly different between the two groups. Additionally, rTMS did not modulate brain metabolites in MRS, nor was there any change of brain lesion or edema after magnetic stimulation. These data suggest that rTMS did not have beneficial effects on motor recovery during early stages of TBI, although an anti-apoptosis was observed in the peri-lesional area.

  15. Apigenin protects blood-brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats.

    Science.gov (United States)

    Zhang, Tingting; Su, Jingyuan; Guo, Bingyu; Wang, Kaiwen; Li, Xiaoming; Liang, Guobiao

    2015-09-01

    Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Inflammation has been considered as the major contributor to brain damage after SAH. SAH induces a systemic increase in pro-inflammatory cytokines and chemokines. Disruption of blood-brain barrier (BBB) facilitates the influx of inflammatory cells. It has been reported that the activation of toll-like receptor 4 (TLR4)/NF-κB signaling pathway plays a vital role in the central nervous system diseases. Apigenin, a common plant flavonoid, possesses anti-inflammation effect. In this study, we focused on the effects of apigenin on EBI following SAH and its anti-inflammation mechanism. Our results showed that apigenin (20mg/kg) administration significantly attenuated EBI (including brain edema, BBB disruption, neurological deficient, severity of SAH, and cell apoptosis) after SAH in rats by suppressing the expression of TLR4, NF-κB and their downstream pro-inflammatory cytokines in the cortex and by up-regulating the expression of tight junction proteins of BBB. Double immunofluorescence staining demonstrated that TLR4 was activated following SAH in neurons, microglia cells, and endothelial cells but not in astrocytes. Apigenin could suppress the activation of TLR4 induced by SAH and inhibit apoptosis of cells in the cortex. These results suggested that apigenin could attenuate EBI after SAH in rats by suppressing TLR4-mediated inflammation and protecting against BBB disruption. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Hyperglycemia induces protein nonenzymeatic glycosylation in brain neurons of diabetic rats at early stage

    Institute of Scientific and Technical Information of China (English)

    Jingsheng Hu; Xueyi Ma; Shuli Sheng

    2007-01-01

    BACKGROUND: Protein nonenzymatic glycosylation is supposed to be one of mechanisms for chronic complications development in diabetes mellitus, and therefore, might play an important role in the neuronal degeneration.OBJECTIVE: To study the protein nonenzymatic glycosylation in brain neurons of diabetic rats, and to analyze the pathway of neuronal degeneration at the early stage of hyperglymecia.DESIGN: Randomized controlled animal experiment.SETTING: Department of Endocrinology, First hospital Affiliated to General Hospital of Chinese PLA and Beijing Laboratory for Brain Aging, Xuanwu Hospital Affiliated to Capital Medical University.MATERIALS: Thirty-five male Wistar rats (grade Ⅱ), aged 3 months old, and 11 male purebred Kunming mice (grade Ⅲ) without special pathogen, aged 3 months old, were provided by the Animal Room of Capital Medical University.METHODS: This experiment was carried out in the Beijing Laboratory for Brain Aging, Xuanwu Hospital Affiliated to Capital Medical University in 1998. The rats in the diabetic model group were intraperitoneally injected into 10 g/L STZ according to 60 mg/kg to establish rat models of diabetes mellitus. The blood glucose and body mass of rats in each group were determined respectively at 1, 2 and 3 months after modeling. The antibodies of advanced glycosylation end products (AGEs) of bovine serum albumin (anti-BSA) were self-prepared: ①The antigen of AGEs-BSA was prepared.②Eleven male Kuming mice (grade Ⅱ) of 3 months old without special pathogen were selected to inoculate AGEs-BSA. ③ The animals were immunized. ④Primary purification and detection of poly-antibodies of AGEs: the AGEs were performed immunohistochemical examination at 1 month after diabetic modeling by ELISA method.MAIN OUTCOME MEASURES: ① Detection results of blood glucose and body mass of rats in two groups at different time points. ② Determination of polyclonal antibody titer of AGEs-BSA. ③ Changes in immunohistochemical image of

  17. Manganese-enhanced magnetic resonance imaging (MEMRI) of brain activity and applications to early detection of brain ischemia.

    Science.gov (United States)

    Aoki, Ichio; Naruse, Shoji; Tanaka, Chuzo

    2004-12-01

    Divalent manganese ion (Mn2+) has been reported to be a useful contrast agent for functional MRI, through a technique named activity-induced manganese-dependent MRI (AIM). In AIM, signal enhancement is related to functional increases in calcium influx, and therefore AIM is, thus far, the only MRI method able to map brain activation in vivo independently of the surrogate hemodynamic changes used in functional MRI. Because of its high signal-to-noise ratio (SNR) and high sensitivity, AIM allows the use of multi-slice or three-dimensional MRI techniques to map functional activity at high spatial resolution. In the present review, we define AIM as a functional MRI tool based on the administration of divalent ionized manganese through an open or disrupted blood-brain barrier (BBB). The adequacy and efficacy of AIM in detecting neural activation is described in light of supporting experiments on inhibition of calcium channels, FOS expression, and on direct comparison to BOLD- and perfusion-based functional MRI. Two main applications of AIM, mapping brain activation in rat somatosensory cortex, as well stroke research based on the well-established middle cerebral artery occlusion model, are described in detail. Methodological problems associated with a strong dependence on anesthetic conditions, potential corruption due to disruption of the BBB, and unspecific increase of the baseline signal due to acoustical noise are discussed. Finally, recommended preparation methods and experimental protocols for AIM are introduced.

  18. Vojta and Bobath combined treatment for high risk infants with brain damage at early period

    Institute of Scientific and Technical Information of China (English)

    Chunyan Wu; Xiaohui Peng; Xuesong Li; Qingling Niu; Hong Guo; Huitao Huang

    2007-01-01

    BACKGROUND: In the process of early screening and interventions to high risk infants with brain damage,the occasion and choosing methods of interventions and the combined application of different interventions are still at the exploratory phase.OBJECTIVE: To observe the efficacy of early intervention using Vojta and Bobath combined treatment in high risk infants with brain damage, and investigate the effect of early rehabilitation on the prognosis.DESIGN: A randomized controlled comparative observation.SETTING: Daqing Oil Field General Hospital of Heilongjiang Province.PARTICIPANTS: Eighty-four high risk infants younger than 1 year were selected from the Department of Pediatrics, Daqing Oil Field General Hospital of Heilongjiang Province from October 2005 to October 2006,including 52 boys (62%) and 32 girls (38%). The treatment started at the age of 0 - 3 months in 11 cases (13%), 4 - 6 months in 28 cases (33%), 7 - 9 months in 35 cases (42%), and 10 - 12 months in 10 cases (12%). Infants with at least two of the followings were enrolled, including 7 Vojta abnormal postural reflexes,slow or disorder of motor development, increase of muscular tension, postural abnormality, primary reflection residual and CT/MRI abnormalities. Informed consents were obtained from their guardians. The 84 infants were randomly divided into treatment group (n =42) and control group (n =42).METHODS: All the children were intravenously injected with cerebroprotein hydrolysate injection or cattle encephalon glycoside and ignotin injection, 10 times as a course for 2 - 5 courses; Besides, the infants in the treatment group also received early rehabilitative training of Vojta and Bobath combined treatment, once a day, 40 minutes per time, 5 times a week followed by a 2-day rest, 1 month as a course, and totally 2 - 5 courses. The Vojta method was to facilitate the automatic regulation by reflexlocomotion. Bobath method was to inhibit abnormal posture but facilitate the normal one, thus it is

  19. Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial

    DEFF Research Database (Denmark)

    Plomgaard, Anne M; Alderliesten, Thomas; Austin, Topun

    2017-01-01

    ,4,7,14, and 35 and at term. Electroencephalogram (EEG) was recorded at 64h. Blood-samples taken at 6 and 64 hours were analysed for the brain injury biomarkers; S100beta, brain-fatty-acid-binding-protein, and neuroketal. All analyses were conducted post hoc. RESULTS: Significantly more infants with a cerebral...... significantly associated with cerebral hyperoxia. The blood biomarkers were not significantly associated with the burden of cerebral hypo- or hyperoxia. CONCLUSIONS: The explorative analysis showed that early burden of cerebral hypoxia, but not hyperoxia was significantly associated with low brain electrical...... activity and severe intracranial haemorrhage while none of the three blood biomarkers were associated with the burden of either cerebral hypo- or hyperoxia....

  20. Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments.

    Directory of Open Access Journals (Sweden)

    Justin Wang

    Full Text Available Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min. Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute

  1. Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments.

    Science.gov (United States)

    Wang, Justin; Wu, Chiping; Peng, Jessie; Patel, Nisarg; Huang, Yayi; Gao, Xiaoxing; Aljarallah, Salman; Eubanks, James H; McDonald, Robert; Zhang, Liang

    2015-01-01

    Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic) and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI) model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min). Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG) monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex) with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute mortality in aging

  2. Electrical resistance increases at the tissue-electrode interface as an early response to nucleus accumbens deep brain stimulation.

    Science.gov (United States)

    Kale, Rajas P; Kouzani, Abbas Z; Berk, Julian; Walder, Ken; Berk, Michael; Tye, Susannah J

    2016-08-01

    The therapeutic actions of deep brain stimulation are not fully understood. The early inflammatory response of electrode implantation is associated with symptom relief without electrical stimulation, but is negated by anti-inflammatory drugs. Early excitotoxic necrosis and subsequent glial scarring modulate the conductivity of the tissue-electrode interface, which can provide some detail into the inflammatory response of individual patients. The feasibility of this was demonstrated by measuring resistance values across a bipolar electrode which was unilaterally implanted into the nucleus accumbens of a rat while receiving continuous deep brain stimulation with a portable back-mounted device using clinical parameters (130Hz, 200μA, 90μs) for 3 days. Daily resistance values rose significantly (pstimulation.

  3. Electrical resistance increases at the tissue-electrode interface as an early response to nucleus accumbens deep brain stimulation.

    Science.gov (United States)

    Kale, Rajas P; Kouzani, Abbas Z; Berk, Julian; Walder, Ken; Berk, Michael; Tye, Susannah J; Kale, Rajas P; Kouzani, Abbas Z; Berk, Julian; Walder, Ken; Berk, Michael; Tye, Susannah J; Berk, Julian; Berk, Michael; Tye, Susannah J; Kouzani, Abbas Z; Kale, Rajas P; Walder, Ken

    2016-08-01

    The therapeutic actions of deep brain stimulation are not fully understood. The early inflammatory response of electrode implantation is associated with symptom relief without electrical stimulation, but is negated by anti-inflammatory drugs. Early excitotoxic necrosis and subsequent glial scarring modulate the conductivity of the tissue-electrode interface, which can provide some detail into the inflammatory response of individual patients. The feasibility of this was demonstrated by measuring resistance values across a bipolar electrode which was unilaterally implanted into the nucleus accumbens of a rat while receiving continuous deep brain stimulation with a portable back-mounted device using clinical parameters (130Hz, 200μA, 90μs) for 3 days. Daily resistance values rose significantly (pstimulation.

  4. Brain MRI and SPECT in the diagnosis of early neurological involvement in Wilson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Piga, Mario; Satta, Loredana; Serra, Alessandra; Loi, Gianluigi [Policlinico Universitario, University of Cagliari, Nuclear Medicine, Department of Medical Science, Monserrato, Cagliari (Italy); Murru, Alessandra; Demelia, Luigi [Policlinico Universitario, University of Cagliari, Gastroenterology, Department of Medical Science, Monserrato, Cagliari (Italy); Sias, Alessandro [Policlinico Universitario, University of Cagliari, Radiology, Department of Medical Science, Monserrato, Cagliari (Italy); Marrosu, Francesco [Policlinico Universitario, University of Cagliari, Neurology, Department of Medical Science, Monserrato, Cagliari (Italy)

    2008-04-15

    To evaluate the impact of brain MRI and single-photon emission computed tomography (SPECT) in early detection of central nervous system abnormalities in patients affected by Wilson's disease (WD) with or without neurological involvement. Out of 25 consecutive WD patients, 13 showed hepatic involvement, ten hepatic and neurological manifestations, and twp hepatic, neurological, and psychiatric symptoms, including mainly movement disorders, major depression, and psychosis. Twenty-four healthy, age-gender matched subjects served as controls. All patients underwent brain MRI and {sup 99m}Tc-ethyl-cysteinate dimer (ECD) SPECT before starting specific therapy. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare differences in {sup 99m}Tc-ECD brain uptake between the two groups. Brain MRI showed T2-weighted hyperintensities in seven patients (28%), six of whom were affected by hepatic and neurological forms. Brain perfusion SPECT showed pathological data in 19 patients (76%), revealing diffuse or focal hypoperfusion in superior frontal (Brodmann area (BA) 6), prefrontal (BA 9), parietal (BA 40), and occipital (BA 18, BA 39) cortices in temporal gyri (BA 37, BA 21) and in caudatus and putamen. Moreover, hepatic involvement was detected in nine subjects; eight presented both hepatic and neurological signs, while two exhibited WD-correlated hepatic, neurological, and psychiatric alterations. All but one patient with abnormal MRI matched with abnormal ECD SPECT. Pathologic MRI findings were obtained in six out of ten patients with hepatic and neurological involvement while abnormal ECD SPECT was revealed in eight patients. Both patients with hepatic, neurological, and psychiatric involvement displayed abnormal ECD SPECT and one displayed an altered MRI. These findings suggest that ECD SPECT might be useful in detecting early brain damage in WD, not only in the perspective of assessing and treating motor impairment but also in evaluating

  5. Conventional 3T brain MRI and diffusion tensor imaging in the diagnostic workup of early stage parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Meijer, Frederick J.A. [Radboud University Nijmegen Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Rumund, Anouke van; Tuladhar, Anil M.; Aerts, Marjolein B.; Titulaer, Imke; Esselink, Rianne A.J.; Bloem, Bastiaan R. [Radboud University Nijmegen Medical Center, Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Nijmegen (Netherlands); Verbeek, Marcel M. [Radboud University Nijmegen Medical Center, Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Nijmegen (Netherlands); Radboud University Nijmegen Medical Center, Department of Laboratory Medicine, Nijmegen (Netherlands); Goraj, Bozena [Radboud University Nijmegen Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Medical Center of Postgraduate Education, Department of Diagnostic Imaging, Warsaw (Poland)

    2015-07-15

    The aim of this study is to evaluate whether the diagnostic accuracy of 3 T brain MRI is improved by region of interest (ROI) measures of diffusion tensor imaging (DTI), to differentiate between neurodegenerative atypical parkinsonism (AP) and Parkinson's disease (PD) in early stage parkinsonism. We performed a prospective observational cohort study of 60 patients presenting with early stage parkinsonism and initial uncertain diagnosis. At baseline, patients underwent a 3 T brain MRI including DTI. After clinical follow-up (mean 28.3 months), diagnoses could be made in 49 patients (30 PD and 19 AP). Conventional brain MRI was evaluated for regions of atrophy and signal intensity changes. Tract-based spatial statistics and ROI analyses of DTI were performed to analyze group differences in mean diffusivity (MD) and fractional anisotropy (FA), and diagnostic thresholds were determined. Diagnostic accuracy of conventional brain MRI and DTI was assessed with the receiver operating characteristic (ROC). Significantly higher MD of the centrum semiovale, body corpus callosum, putamen, external capsule, midbrain, superior cerebellum, and superior cerebellar peduncles was found in AP. Significantly increased MD of the putamen was found in multiple system atrophy-parkinsonian form (MSA-P) and increased MD in the midbrain and superior cerebellar peduncles in progressive supranuclear palsy (PSP). The diagnostic accuracy of brain MRI to identify AP as a group was not improved by ROI measures of MD, though the diagnostic accuracy to identify MSA-P was slightly increased (AUC 0.82 to 0.85). The diagnostic accuracy of brain MRI to identify AP as a group was not improved by the current analysis approach to DTI, though DTI measures could be of added value to identify AP subgroups. (orig.)

  6. Linking Influenza Virus Tissue Tropism to Population-Level Reproductive Fitness

    NARCIS (Netherlands)

    L.A. Reperant (Leslie); T. Kuiken (Thijs); B.T. Grenfell (Bryan); A.D.M.E. Osterhaus (Albert); A.P. Dobson (Andrew)

    2012-01-01

    textabstractInfluenza virus tissue tropism defines the host cells and tissues that support viral replication and contributes to determining which regions of the respiratory tract are infected in humans. The location of influenza virus infection along the respiratory tract is a key determinant of vir

  7. [Study on meridian tropism of medicinal property theory for Chines medicines by supramolecular chemistry (I)].

    Science.gov (United States)

    He, Fu-yuan; Deng, Kai-wen; Yang, Yan-tao; Zhou, Yi-qun; Shi, Ji-lian; Liu, Wen-long; Tang, Yu

    2015-04-01

    In this paper, based on the special influence of supramolecular chemistry on the basic theory of Chinese medicines ( CM) , the authors further analyzed the history of meridian tropism and natural origins of CM organisms and explained CM ingredients and the universal regularity of the automatic action of the supramolecular "imprinting templates" hole channel structure. After entering human bodies, CMs, as the aggregation of supramolecular "imprinting templates" , automatically seek supramolecular subjects that are matched with their "imprinting templates" in human meridians and organs for the purpose of self-recognition, self-organization, self-assembly and self-replication, so as to generate specific efficacy in meridians and organs, which is reflected as the meridian tropism phenomena at macro level. This regularity can be studied by in vitro and in vivo experimental studies. In vitro methods are mostly supra molecular structure analysis and kinetic and thermodynamic parameter calculation; Whereas in vivo methods are dominated by the analysis on object component distribution, chromatopharmacodynamic parameters and network chromatopharmacodynamic parameters; Particularly, the acupoint-medicine method can simplify to study the supramolecular subject-object relations. Consequently, CM's'meridian tropism reveals the universal regularity for interactions of macromolecular and micromolecular "imprinting templates" of subjects and objects in natural organisms. As the first barrier for the material base of the CM theory and breakthrough in the modernization of the basic CM theory, meridian tropism plays an important role in studies on basic theories of the basic CM theory.

  8. Dengue tropism for macrophages and dendritic cells : the host cell effect

    NARCIS (Netherlands)

    Flipse, Jacky; Torres, Silvia; Diosa-Toro, Mayra; van der Ende-Metselaar, Heidi; Herrera-Rodriguez, Jose; Urcuqui-Inchima, Silvio; Huckriede, Anke; Rodenhuis-Zybert, Izabela A; Smit, Jolanda M

    2016-01-01

    Dengue virus infects immune cells, including monocytes, macrophages and dendritic cells (DC). We compared virus infectivity in macrophages and DC, and found that the virus-origin determined the cell tropism of progeny virus. The highest efficiency of re-infection was seen for macrophage-derived deng

  9. Linking Influenza Virus Tissue Tropism to Population-Level Reproductive Fitness

    NARCIS (Netherlands)

    L.A. Reperant (Leslie); T. Kuiken (Thijs); B.T. Grenfell (Bryan); A.D.M.E. Osterhaus (Albert); A.P. Dobson (Andrew)

    2012-01-01

    textabstractInfluenza virus tissue tropism defines the host cells and tissues that support viral replication and contributes to determining which regions of the respiratory tract are infected in humans. The location of influenza virus infection along the respiratory tract is a key determinant of

  10. Changes in cerebral blood flow and psychometric indicators in veterans with early forms of chronic brain ischemia

    Directory of Open Access Journals (Sweden)

    Vasilenko Т.М.

    2015-09-01

    Full Text Available The goal is to study the cerebral blood flow and psychometric characteristics in veterans of Afghanistan with early forms of chronic brain ischemia. Material and Methods. The study included 74 veterans of the Afghan war aged from 45 to 55 years: group 1, 28 people with NPNKM; Group 2-28 patients with circulatory encephalopathy stage 1; group 3-18 healthy persons. Doppler examination of cerebral vessels was carried out on the unit «Smart-lite». Reactive and personal anxiety of patients was assessed using the scale of Spielberger, evaluation of the quality of life through the test SAN. Determining the level of neuroticism and psychoticism was conducted by the scale of neuroticism and psy-choticism. Results: The study of cerebral blood flow in the Afghan war veterans showed signs of insolvency of carotid and carotid-basilar anastomoses, hypoperfusion phenomenon with the depletion of autoregulation, violation of the outflow of venous blood at the level of the microvasculature, accompanied by cerebral arteries spasm. More than 40% of patients with early forms of chronic brain ischemia had high personal anxiety, low levels of well-being and activity, with maximum expression of dyscirculatory hypoxia. Conclusion. Readaptation of veterans of Afghanistan is accompanied by the changes in psychometric performance and the formation of the earliest forms of brain chronic ischemia associated with inadequate hemodynamics providing increased functional activity of the brain and the inefficiency of compensatory-adaptive reactions.

  11. Early Clinical Predictors of 5-Year Outcome After Concussive Blast Traumatic Brain Injury.

    Science.gov (United States)

    Mac Donald, Christine L; Barber, Jason; Jordan, Mary; Johnson, Ann M; Dikmen, Sureyya; Fann, Jesse R; Temkin, Nancy

    2017-07-01

    The long-term clinical effects of wartime traumatic brain injuries (TBIs), most of which are mild, remain incompletely described. Current medical disability cost estimates from world conflicts continually surpass projections. Additional information regarding long-term functional trajectory is needed to reduce this extensive public health burden. To examine 5-year clinical outcomes leveraging existing clinical data collected at 1 year after injury in the same patients and to identify early risk factors for long-term disability. This prospective, longitudinal study enrolled active-duty US military after concussive blast injury (n = 50) in the acute to subacute stage and combat-deployed control individuals (n = 44) in Afghanistan or after medical evacuation to Germany from November 1, 2008, through July 1, 2013. One- and 5-year clinical evaluations were completed in the United States. All concussive blast injuries met the Department of Defense definition of mild, uncomplicated TBI. In-person clinical evaluations included standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden that were essentially identical to the evaluations completed at 1-year follow-up. Data were analyzed from October 1 through November 30, 2016. Changes in the in-person standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden from the 1- to 5-year follow-up. Predictive modeling was used to identify early risk factors for long-term disability. Among the 94 participants (87 men [93%] and 7 women [7%]; mean [SD] age, 34 [8] years), global disability, satisfaction with life, neurobehavioral symptom severity, psychiatric symptom severity, and sleep impairment were significantly worse in patients with concussive blast TBI compared with combat-deployed controls, whereas performance on cognitive measures was no different between groups at the 5-year evaluation. Logistic regression on the dichotomized Extended

  12. Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pulsifer, Margaret B., E-mail: mpulsifer@mgh.harvard.edu [Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts (United States); Sethi, Roshan V. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kuhlthau, Karen A. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2015-10-01

    Purpose: To report, from a longitudinal study, cognitive outcome in pediatric patients treated with proton radiation therapy (PRT) for central nervous system (CNS) tumors. Methods and Materials: Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥6 years at baseline to ensure consistency in neurocognitive measures. Results: Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton radiation therapy included craniospinal irradiation (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged <12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy, or history of surgical resection. Conclusions: Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon radiation therapy.

  13. Brain function decline in healthy retired athletes who sustained their last sports concussion in early adulthood.

    Science.gov (United States)

    De Beaumont, Louis; Théoret, Hugo; Mongeon, David; Messier, Julie; Leclerc, Suzanne; Tremblay, Sébastien; Ellemberg, Dave; Lassonde, Maryse

    2009-03-01

    Recent studies have shown that the detrimental effects of sports concussions on cognitive and motor function may persist up to a few years post-injury. The present study sought to investigate the effects of having sustained a sports concussion more than 30 years prior to testing on cognitive and motor functions. Nineteen healthy former athletes, in late adulthood (mean age = 60.79; SD = 5.16), who sustained their last sport-related concussion in early adulthood (mean age = 26.05; SD = 9.21) were compared with 21 healthy former athletes with no history of concussion (mean age = 58.89; SD = 9.07). Neuropsychological tests sensitive to age-related changes in cognition were administered. An auditory oddball paradigm was used to evoke P3a and P3b brain responses. Four TMS paradigms were employed to assess motor cortex excitability: (i) resting motor threshold; (ii) paired-pulse intracortical inhibition and intracortical facilitation; (iii) input/output curve and (iv) cortical silent period (CSP). A rapid alternating movement task was also used to characterize motor system dysfunctions. Relative to controls, former athletes with a history of concussion had: (i) lower performance on neuropsychological tests of episodic memory and response inhibition; (ii) significantly delayed and attenuated P3a/P3b components; (iii) significantly prolonged CSP and (iv) significantly reduced movement velocity (bradykinesia). The finding that the P3, the CSP as well as neuropsychological and motor indices were altered more than three decades post-concussion provides evidence for the chronicity of cognitive and motor system changes consecutive to sports concussion.

  14. Plasticity in the development of handedness: evidence from normal development and early asymmetric brain injury.

    Science.gov (United States)

    Corbetta, Daniela; Williams, Joshua; Snapp-Childs, Winona

    2006-09-01

    Previous research revealed that shifting patterns of hand preference in the first year of life are linked to infants' sensory-motor experiences as they learn to sit, creep, and walk. In this report, we examine whether new and different forms of locomotion and sensory-motor experiences similarly contribute to alter patterns of hand preference in early development. We examined the cases of three infants with unique developmental histories. Two infants adopted distinctive forms of locomotion in lieu of typical hands-and-knees crawling. One infant scooted using both hands and legs in a coupled fashion, while the other infant performed an asymmetrical, left-biased belly-crawl using only one arm to drag his body. The third infant suffered damage to his left-brain hemisphere shortly after birth and received intense physical therapy to his right arm as a result of it. We followed all three infants on a weekly basis and tracked changes in their reaching behavior, mode of locomotion, and postural achievements. The two infants with unique locomotor patterns displayed changes in hand preference that reciprocated the arm patterns that they used during locomotion. The infant who coupled his body for scooting began to reach bimanually, while the infant who adopted the left-biased belly-crawl developed a strong unimanual, right-hand, preference. The infant with left-hemisphere damage initially displayed a right-hand preference, then a temporary decline in preferred hand use as he began to cruise and walk, and ultimately resumed a right-hand preference in the 2nd year of life. This data is consistent with previous work showing that the development of hand preference in the 1st year of life is highly malleable and sensitive to a variety of new sensory-motor experiences.

  15. Discrimination of timbre in early auditory responses of the human brain.

    Directory of Open Access Journals (Sweden)

    Jaeho Seol

    Full Text Available BACKGROUND: The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1-testing (S2 paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2 for both same and different conditions in the both hemispheres. CONCLUSIONS/SIGNIFICANCES: Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre.

  16. A Bayesian framework for early risk prediction in traumatic brain injury

    Science.gov (United States)

    Chaganti, Shikha; Plassard, Andrew J.; Wilson, Laura; Smith, Miya A.; Patel, Mayur B.; Landman, Bennett A.

    2016-03-01

    Early detection of risk is critical in determining the course of treatment in traumatic brain injury (TBI). Computed tomography (CT) acquired at admission has shown latent prognostic value in prior studies; however, no robust clinical risk predictions have been achieved based on the imaging data in large-scale TBI analysis. The major challenge lies in the lack of consistent and complete medical records for patients, and an inherent bias associated with the limited number of patients samples with high-risk outcomes in available TBI datasets. Herein, we propose a Bayesian framework with mutual information-based forward feature selection to handle this type of data. Using multi-atlas segmentation, 154 image-based features (capturing intensity, volume and texture) were computed over 22 ROIs in 1791 CT scans. These features were combined with 14 clinical parameters and converted into risk likelihood scores using Bayes modeling. We explore the prediction power of the image features versus the clinical measures for various risk outcomes. The imaging data alone were more predictive of outcomes than the clinical data (including Marshall CT classification) for discharge disposition with an area under the curve of 0.81 vs. 0.67, but less predictive than clinical data for discharge Glasgow Coma Scale (GCS) score with an area under the curve of 0.65 vs. 0.85. However, in both cases, combining imaging and clinical data increased the combined area under the curve with 0.86 for discharge disposition and 0.88 for discharge GCS score. In conclusion, CT data have meaningful prognostic value for TBI patients beyond what is captured in clinical measures and the Marshall CT classification.

  17. Myocardial function at the early phase of traumatic brain injury: a prospective controlled study

    OpenAIRE

    Cuisinier, Adrien; Maufrais, Claire; Payen, Jean-François; Nottin, Stephane; Walther, Guillaume; Bouzat, Pierre

    2016-01-01

    Background The concept of brain-heart interaction has been described in several brain injuries. Traumatic brain injury (TBI) may also lead to cardiac dysfunction but evidences are mainly based upon experimental and clinical retrospective studies. Methods We conducted a prospective case-control study in a level I trauma center. Twenty consecutive adult patients with severe TBI were matched according to age and gender with 20 control patients. The control group included adult patients undergoin...

  18. Astaxanthin Alleviates Early Brain Injury Following Subarachnoid Hemorrhage in Rats: Possible Involvement of Akt/Bad Signaling

    Directory of Open Access Journals (Sweden)

    Xiang-Sheng Zhang

    2014-07-01

    Full Text Available Apoptosis has been proven to play a crucial role in early brain injury pathogenesis and to represent a target for the treatment of subarachnoid hemorrhage (SAH. Previously, we demonstrated that astaxanthin (ATX administration markedly reduced neuronal apoptosis in the early period after SAH. However, the underlying molecular mechanisms remain obscure. In the present study, we tried to investigate whether ATX administration is associated with the phosphatidylinositol 3-kinase-Akt (PI3K/Akt pathway, which can play an important role in the signaling of apoptosis. Our results showed that post-SAH treatment with ATX could cause a significant increase of phosphorylated Akt and Bad levels, along with a significant decrease of cleaved caspase-3 levels in the cortex after SAH. In addition to the reduced neuronal apoptosis, treatment with ATX could also significantly reduce secondary brain injury characterized by neurological dysfunction, cerebral edema and blood-brain barrier disruption. In contrast, the PI3K/Akt inhibitor, LY294002, could partially reverse the neuroprotection of ATX in the early period after SAH by downregulating ATX-induced activation of Akt/Bad and upregulating cleaved caspase-3 levels. These results provided the evidence that ATX could attenuate apoptosis in a rat SAH model, potentially, in part, through modulating the Akt/Bad pathway.

  19. Concordance between two phenotypic assays and ultradeep pyrosequencing for determining HIV-1 tropism.

    Science.gov (United States)

    Saliou, Adrien; Delobel, Pierre; Dubois, Martine; Nicot, Florence; Raymond, Stéphanie; Calvez, Vincent; Masquelier, Bernard; Izopet, Jacques

    2011-06-01

    There have been few studies on the concordance between phenotypic assays for predicting human immunodeficiency virus type 1 (HIV-1) coreceptor usage. The sensitivity of ultradeep pyrosequencing combined with genotyping tools is similar to that of phenotypic assays for detecting minor CXCR4-using variants. We evaluated the agreement between two phenotypic assays, the Toulouse tropism test (TTT) and the Trofile assay, and ultradeep pyrosequencing for determining the tropism of HIV-1 quasispecies. The concordance between the TTT and Trofile assays was assessed for 181 samples successfully phenotyped by both assays. The TTT was 86% concordant with the standard Trofile assay and 91.7% with its enhanced-sensitivity version. The concordance between phenotypic characterization of HIV-1 tropism and ultradeep pyrosequencing genotypic prediction was further studied in selected samples. The HIV-1 tropism inferred from ultradeep pyrosequencing of 11 samples phenotyped as X4 and dualtropic and 12 phenotyped as R5-tropic agreed closely with the results of phenotyping. However, ultradeep pyrosequencing detected minor CXCR4-using variants in 3 of 12 samples phenotyped as R5-tropic. Ultradeep pyrosequencing also detected minor CXCR4-using variants that had been missed by direct sequencing in 6 of 9 samples phenotyped as X4-tropic but genotyped as R5-tropic by direct sequencing. Ultradeep pyrosequencing was 87% concordant with the Trofile and TTT phenotypic assays and was in the same range of sensitivity (0.4%) than these two phenotypic assays (0.3 to 0.5%) for detecting minor CXCR4-using variants. Ultradeep pyrosequencing provides a new way to improve the performance of genotypic prediction of HIV-1 tropism to match that of the phenotypic assays.

  20. CpG sites with continuously increasing or decreasing methylation from early to late human fetal brain development.

    Science.gov (United States)

    Schneider, Eberhard; Dittrich, Marcus; Böck, Julia; Nanda, Indrajit; Müller, Tobias; Seidmann, Larissa; Tralau, Tim; Galetzka, Danuta; El Hajj, Nady; Haaf, Thomas

    2016-10-30

    Normal human brain development is dependent on highly dynamic epigenetic processes for spatial and temporal gene regulation. Recent work identified wide-spread changes in DNA methylation during fetal brain development. We profiled CpG methylation in frontal cortex of 27 fetuses from gestational weeks 12-42, using Illumina 450K methylation arrays. Sites showing genome-wide significant correlation with gestational age were compared to a publicly available data set from gestational weeks 3-26. Altogether, we identified 2016 matching developmentally regulated differentially methylated positions (m-dDMPs): 1767m-dDMPs were hypermethylated and 1149 hypomethylated during fetal development. M-dDMPs are underrepresented in CpG islands and gene promoters, and enriched in gene bodies. They appear to cluster in certain chromosome regions. M-dDMPs are significantly enriched in autism-associated genes and CpGs. Our results promote the idea that reduced methylation dynamics during fetal brain development may predispose to autism. In addition, m-dDMPs are enriched in genes with human-specific brain expression patterns and/or histone modifications. Collectively, we defined a subset of dDMPs exhibiting constant methylation changes from early to late pregnancy. The same epigenetic mechanisms involving methylation changes in cis-regulatory regions may have been adopted for human brain evolution and ontogeny. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein.

    Science.gov (United States)

    Tang, Maoxue; Gao, Guangping; Rueda, Carlos B; Yu, Hang; Thibodeaux, David N; Awano, Tomoyuki; Engelstad, Kristin M; Sanchez-Quintero, Maria-Jose; Yang, Hong; Li, Fanghua; Li, Huapeng; Su, Qin; Shetler, Kara E; Jones, Lynne; Seo, Ryan; McConathy, Jonathan; Hillman, Elizabeth M; Noebels, Jeffrey L; De Vivo, Darryl C; Monani, Umrao R

    2017-01-20

    Haploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). There is little to suggest how reduced Glut1 causes cognitive dysfunction and no optimal treatment for Glut1 DS. We used model mice to demonstrate that low Glut1 protein arrests cerebral angiogenesis, resulting in a profound diminution of the brain microvasculature without compromising the blood-brain barrier. Studies to define the temporal requirements for Glut1 reveal that pre-symptomatic, AAV9-mediated repletion of the protein averts brain microvasculature defects and prevents disease, whereas augmenting the protein late, during adulthood, is devoid of benefit. Still, treatment following symptom onset can be effective; Glut1 repletion in early-symptomatic mutants that have experienced sustained periods of low brain glucose nevertheless restores the cerebral microvasculature and ameliorates disease. Timely Glut1 repletion may thus constitute an effective treatment for Glut1 DS.

  2. Determinants of HIV-induced brain changes in three different periods of the early clinical course: A data mining analysis

    Directory of Open Access Journals (Sweden)

    Bokai Cao

    2015-01-01

    Full Text Available To inform an understanding of brain status in HIV infection, quantitative imaging measurements were derived at structural, microstructural and macromolecular levels in three different periods of early infection and then analyzed simultaneously at each stage using data mining. Support vector machine recursive feature elimination was then used for simultaneous analysis of subject characteristics, clinical and behavioral variables, and immunologic measures in plasma and CSF to rank features associated with the most discriminating brain alterations in each period. The results indicate alterations beginning in initial infection and in all periods studied. The severity of immunosuppression in the initial virus host interaction was the most highly ranked determinant of earliest brain alterations. These results shed light on the initial brain changes induced by a neurotropic virus and their subsequent evolution. The pattern of ongoing alterations occurring during and beyond the period in which virus is suppressed in the systemic circulation supports the brain as a viral reservoir that may preclude eradication in the host. Data mining capabilities that can address high dimensionality and simultaneous analysis of disparate information sources have considerable utility for identifying mechanisms underlying onset of neurological injury and for informing new therapeutic targets.

  3. Determinants of HIV-induced brain changes in three different periods of the early clinical course: A data mining analysis.

    Science.gov (United States)

    Cao, Bokai; Kong, Xiangnan; Kettering, Casey; Yu, Philip; Ragin, Ann

    2015-01-01

    To inform an understanding of brain status in HIV infection, quantitative imaging measurements were derived at structural, microstructural and macromolecular levels in three different periods of early infection and then analyzed simultaneously at each stage using data mining. Support vector machine recursive feature elimination was then used for simultaneous analysis of subject characteristics, clinical and behavioral variables, and immunologic measures in plasma and CSF to rank features associated with the most discriminating brain alterations in each period. The results indicate alterations beginning in initial infection and in all periods studied. The severity of immunosuppression in the initial virus host interaction was the most highly ranked determinant of earliest brain alterations. These results shed light on the initial brain changes induced by a neurotropic virus and their subsequent evolution. The pattern of ongoing alterations occurring during and beyond the period in which virus is suppressed in the systemic circulation supports the brain as a viral reservoir that may preclude eradication in the host. Data mining capabilities that can address high dimensionality and simultaneous analysis of disparate information sources have considerable utility for identifying mechanisms underlying onset of neurological injury and for informing new therapeutic targets.

  4. Middle cerebral artery remodeling following transient brain ischemia is linked to early postischemic hyperemia: a target of uric acid treatment.

    Science.gov (United States)

    Onetti, Yara; Dantas, Ana P; Pérez, Belén; Cugota, Roger; Chamorro, Angel; Planas, Anna M; Vila, Elisabet; Jiménez-Altayó, Francesc

    2015-04-15

    Ischemia impairs blood supply to the brain, and reperfusion is important to restore cerebral blood flow (CBF) and rescue neurons from cell death. However, reperfusion can induce CBF values exceeding the basal values before ischemia. This hyperemic effect has been associated with a worse ischemic brain damage, albeit the mechanisms that contribute to infarct expansion are not clear. In this study, we investigated the influence of early postischemic hyperemia on brain damage and middle cerebral artery (MCA) properties and the effect of treatment with the endogenous antioxidant uric acid (UA). The MCA was occluded for 90 min followed by 24 h reperfusion in adult male Sprague-Dawley rats. Cortical CBF increases at reperfusion beyond 20% of basal values were taken as indicative of hyperemia. UA (16 mg/kg) or vehicle (Locke's buffer) was administered intravenously 135 min after MCA occlusion. Hyperemic compared with nonhyperemic rats showed MCA wall thickening (sham: 22.4 ± 0.8 μm; nonhyperemic: 23.1 ± 1.2 μm; hyperemic: 27.8 ± 0.9 at 60 mmHg; P < 0.001, hyperemic vs. sham) involving adventitial cell proliferation, increased oxidative stress, and interleukin-18, and more severe brain damage. Thus MCA remodeling after ischemia-reperfusion takes place under vascular oxidative and inflammatory stress conditions linked to hyperemia. UA administration attenuated MCA wall thickening, induced passive lumen expansion, and reduced brain damage in hyperemic rats, although it did not increase brain UA concentration. We conclude that hyperemia at reperfusion following brain ischemia induces vascular damage that can be attenuated by administration of the endogenous antioxidant UA. Copyright © 2015 the American Physiological Society.

  5. Cyclophilin A/Cluster of Differentiation 147 Interactions Participate in Early Brain Injury After Subarachnoid Hemorrhage in Rats.

    Science.gov (United States)

    Dang, Baoqi; Li, Haiying; Xu, Xiang; Shen, Haitao; Wang, Yang; Gao, Anju; He, Weichun; Wang, Zhong; Chen, Gang

    2015-09-01

    Cyclophilin A has been found to be involved in many inflammatory diseases via its receptor, cluster of differentiation 147 (CD147). This study was designed to estimate the potential role of cyclophilin A/CD147 in subarachnoid hemorrhage-induced early brain injury. Controlled in vivo laboratory study. Animal research laboratory. Two hundred ninety adult male Sprague-Dawley rats weighing 300-350 g. A prechiasmatic cistern single-injection model was used to produce experimental subarachnoid hemorrhage in Sprague-Dawley rats. The expressions of cyclophilin A and CD147, the interaction between cyclophilin A and CD147, and the secretion of cyclophilin A were assessed using immunofluorescence staining, Western blot analysis, and coimmunoprecipitation analysis. Down-regulation of cyclophilin A expression by small interfering RNA was performed, and recombinant human cyclophilin A and monoclonal antibody of CD147 were exploited to study the role of cyclophilin A/CD147 in subarachnoid hemorrhage-induced early brain injury. The expressions of cyclophilin A and CD147 in neurons were higher than that of the sham group and peaked at 24 hours after subarachnoid hemorrhage. Compared with sham group, subarachnoid hemorrhage was found to increase the secretion of cyclophilin A and the interaction between cyclophilin A and CD147. Cyclophilin A small interfering RNA and anti-CD147 treatments were found to ameliorate subarachnoid hemorrhage-induced early brain injury, including cortical apoptosis and necrosis, brain edema, blood-brain barrier damage, and neurobehavioral deficits. Cyclophilin A small interfering RNA and anti-CD147 treatments also decreased the phosphorylation of extracellular signal-regulated protein kinase 1/2, the protein levels of p53 and caspase-3, and the level of active nuclear factor-κB. Finally, recombinant human cyclophilin A treatment resulted in an opposite effect, which was inhibited by anti-CD147 treatment. Cyclophilin A/CD147 interactions may participate

  6. Maternal Support and Brain Development: Neuroscience Validation for the Importance of Early Caregiving Relationships

    Science.gov (United States)

    Luby, Joan; Rogers, Cynthia

    2013-01-01

    Advances in brain imaging methods and technology over the last 2 decades have opened an unprecedented window into the understanding of the structure and function of the human brain. In this article, the authors describe their investigation of the relationship between maternal support, observed during the preschool period, and the size of key brain…

  7. Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage

    Institute of Scientific and Technical Information of China (English)

    MA Chun-xiao; YIN Wei-ning; CAI Bo-wen; WU Jian; WANG Jun-yi; HE Min; SUN Hong; DING Jun-li; YOU Chao

    2009-01-01

    Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-kappa B (NF-KB) regulates many genes essential for inflammation and immunity and is activated by toll-like receptor (TLR). This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-KB) signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-KB activity and concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-lbeta (IL-β) and intedeukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein: an initial peak (2-6 hours) and a sustained elevation (12-48 hours). Immunohistochemical staining showed the inducible expression of TLR4-1ike immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-KB subunit p65 as well as the production of NF-KB-regulated proinflammatory cytokines (TNF-α, IL-1β and IL-6) were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-KB signaling in early brain injury. Activation of the TLR4/NF-KB signaling may regulate the inflammatory responses after SAH.

  8. Early diagnosis of neurodegenerative diseases - the long awaited Holy Grail and bottleneck of modern brain research - 19th HUPO BPP workshop: May 22-24, 2013, Dortmund, Germany.

    Science.gov (United States)

    Schrötter, Andreas; Magraoui, Fouzi El; Gröttrup, Bernd; Wiltfang, Jens; Heinsen, Helmut; Marcus, Katrin; Meyer, Helmut E; Grinberg, Lea T; Park, Young Mok

    2013-10-01

    The HUPO Brain Proteome Project (HUPO BPP) held its 19th workshop in Dortmund, Germany, from May 22 to 24, 2013. The focus of the spring workshop was on strategies and developments concerning early diagnosis of neurodegenerative diseases.

  9. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index.

    Science.gov (United States)

    Millan, Sarah H; Hacker, Mallory L; Turchan, Maxim; Molinari, Anna L; Currie, Amanda D; Charles, David

    2017-01-01

    Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50-75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but 0.05). BMI change over two years was not different between the groups (p = 0.62, ODT = -0.89; DBS+ODT = -0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152).

  10. Brain Basics

    Medline Plus

    Full Text Available ... and plays an important role during early brain development. It may also assist in learning and memory. Problems in making or using glutamate ... increases neuronal activity, is involved in early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain ...

  11. The International Society for Developmental Psychobiology annual meeting symposium: Impact of early life experiences on brain and behavioral development.

    Science.gov (United States)

    Sullivan, Regina; Wilson, Donald A; Feldon, Joram; Yee, Benjamin K; Meyer, Urs; Richter-Levin, Gal; Avi, Avital; Michael, Tsoory; Gruss, Michael; Bock, Jörg; Helmeke, Carina; Braun, Katharina

    2006-11-01

    Decades of research in the area of developmental psychobiology have shown that early life experience alters behavioral and brain development, which canalizes development to suit different environments. Recent methodological advances have begun to identify the mechanisms by which early life experiences cause these diverse adult outcomes. Here we present four different research programs that demonstrate the intricacies of early environmental influences on behavioral and brain development in both pathological and normal development. First, an animal model of schizophrenia is presented that suggests prenatal immune stimulation influences the postpubertal emergence of psychosis-related behavior in mice. Second, we describe a research program on infant rats that demonstrates how early odor learning has unique characteristics due to the unique functioning of the infant limbic system. Third, we present work on the rodent Octodon degus, which shows that early paternal and/or maternal deprivation alters development of limbic system synaptic density that corresponds to heightened emotionality. Fourth, a juvenile model of stress is presented that suggests this developmental period is important in determining adulthood emotional well being. The approach of each research program is strikingly different, yet all succeed in delineating a specific aspect of early development and its effects on infant and adult outcome that expands our understanding of the developmental impact of infant experiences on emotional and limbic system development. Together, these research programs suggest that the developing organism's developmental trajectory is influenced by environmental factors beginning in the fetus and extending through adolescence, although the specific timing and nature of the environmental influence has unique impact on adult mental health.

  12. Early metabolic/cellular-level resuscitation following terminal brain stem herniation: implications for organ transplantation.

    Science.gov (United States)

    Arbour, Richard B

    2013-01-01

    Patients with terminal brain stem herniation experience global physiological consequences and represent a challenging population in critical care practice as a result of multiple factors. The first factor is severe depression of consciousness, with resulting compromise in airway stability and lung ventilation. Second, with increasing severity of brain trauma, progressive brain edema, mass effect, herniation syndromes, and subsequent distortion/displacement of the brain stem follow. Third, with progression of intracranial pathophysiology to terminal brain stem herniation, multisystem consequences occur, including dysfunction of the hypothalamic-pituitary axis, depletion of stress hormones, and decreased thyroid hormone bioavailability as well as biphasic cardiovascular state. Cardiovascular dysfunction in phase 1 is a hyperdynamic and hypertensive state characterized by elevated systemic vascular resistance and cardiac contractility. Cardiovascular dysfunction in phase 2 is a hypotensive state characterized by decreased systemic vascular resistance and tissue perfusion. Rapid changes along the continuum of hyperperfusion versus hypoperfusion increase risk of end-organ damage, specifically pulmonary dysfunction from hemodynamic stress and high-flow states as well as ischemic changes consequent to low-flow states. A pronounced inflammatory state occurs, affecting pulmonary function and gas exchange and contributing to hemodynamic instability as a result of additional vasodilatation. Coagulopathy also occurs as a result of consumption of clotting factors as well as dilution of clotting factors and platelets consequent to aggressive crystalloid administration. Each consequence of terminal brain stem injury complicates clinical management within this patient demographic. In general, these multisystem consequences are managed with mechanism-based interventions within the context of caring for the donor's organs (liver, kidneys, heart, etc.) after death by neurological

  13. Early detection of human glioma sphere xenografts in mouse brain using diffusion MRI at 14.1 T.

    Science.gov (United States)

    Porcari, P; Hegi, M E; Lei, H; Hamou, M-F; Vassallo, I; Capuani, S; Gruetter, R; Mlynarik, V

    2016-11-01

    Glioma models have provided important insights into human brain cancers. Among the investigative tools, MRI has allowed their characterization and diagnosis. In this study, we investigated whether diffusion MRI might be a useful technique for early detection and characterization of slow-growing and diffuse infiltrative gliomas, such as the proposed new models, LN-2669GS and LN-2540GS glioma sphere xenografts. Tumours grown in these models are not visible in conventional T2 -weighted or contrast-enhanced T1 -weighted MRI at 14.1 T. Diffusion-weighted imaging and diffusion tensor imaging protocols were optimized for contrast by exploring long diffusion times sensitive for probing the microstructural alterations induced in the normal brain by the slow infiltration of glioma sphere cells. Compared with T2 -weighted images, tumours were properly identified in their early stage of growth using diffusion MRI, and confirmed by localized proton MR spectroscopy as well as immunohistochemistry. The first evidence of tumour presence was revealed for both glioma sphere xenograft models three months after tumour implantation, while no necrosis, oedema or haemorrhage were detected either by MRI or by histology. Moreover, different values of diffusion indices, such as mean diffusivity and fractional anisotropy, were obtained in tumours grown from LN-2669GS and LN-2540GS glioma sphere lines. These observations highlighted diverse tumour microstructures for both xenograft models, which were reflected in histology. This study demonstrates the ability of diffusion MRI techniques to identify and investigate early stages of slow-growing, invasive tumours in the mouse brain, thus providing a potential imaging biomarker for early detection of tumours in humans. Copyright © 2016 John Wiley & Sons, Ltd.

  14. [Cognitive and brain development of memory from infancy to early adulthood].

    Science.gov (United States)

    Dégeilh, Fanny; Eustache, Francis; Guillery-Girard, Bérengère

    2015-01-01

    Cognitive and brain development are closely linked from infancy to adulthood. The purpose of this article is to review the current state of knowledge on behavioral and brain substrates of memory development. First, we will review cognitive development of different memory systems, from procedural to autobiographical memory. We will discuss how the development of other cognitive functions (language, attention, executive functions and metamemory) participates in memory development. Second, we will describe how structural and functional changes in two core brain regions of memory, i.e. the hippocampus and the prefrontal cortex, impact the protracted development of memory throughout childhood. © Société de Biologie, 2016.

  15. Location and expression of neurotrophin-3 and its receptor in the brain of human embryos during early development

    Institute of Scientific and Technical Information of China (English)

    Jian Li; Yongjie Mi; Dajun Ma

    2008-01-01

    BACKGROUND: Cell culture in vitro trials have demonstrated that neurotrophin-3 (NT-3) can enhance the survival of sensory neurons and sympathetic neurons, and can also support embryo-derived motor neurons.This effect is dependent on nerve growth factor on the surface of cells. Understanding the role of NT-3 and its receptor in the early development of human embryonic brains will help to investigate the correlation between early survival of nerve cells and the microenvironment of neural regeneration.OBJECTIVE: To observe the proliferation of cerebral neurons in the development of human embryonic brain, and to investigate the location, expression and distribution of NT-3 and its receptor TrkC during human brain development.DESIGN, TIME AND SETTING: An observation study on cells was performed in the Department of Human Anatomy, Histology and Embryology, Chengdu Medical College in September 2007.MATERIALS: Fifteen specimens of fresh human embryo, aged 6 weeks, were used in this study.METHODS: The proliferation of cerebral neurons was detected using proliferating cell nuclear antigen, and the immunocytochemistry ABC technique was applied to observe the location, expression and distribution of NT-3 and its receptor TrkC in the brain of the human embryo.MAIN OUTCOME MEASURES: Location, expression and distribution of NT-3 and its receptor in the brain of the human embryo.RESULTS: In the early period (aged 6 weeks) of human embryonic development, proliferating cell nuclear antigen-positive reactive substances were mainly observed in the nucleus of the forebrain ventricular zone and subventricular zone, and the intensity was stronger in the subventricular zone than the forebrain ventricle.NT-3 positive reactive substance was mainly distributed in the cytoblastema of the forebrain neuroepithelial layer and nerve cell process, while TrkC was mainly distributed in the cell membrane of the forebrain ventricular zone and subventricular zone. During embryonic development, NT-3 and

  16. Turing Revisited: Decoding the microRNA Messages in Brain Extracellular Vesicles for Early Detection of Neurodevelopmental Disorders.

    Science.gov (United States)

    Gillet, Virginie; Hunting, Darel John; Takser, Larissa

    2016-09-01

    The prevention of neurodevelopmental disorders (NDD) of prenatal origin suffers from the lack of objective tools for early detection of susceptible individuals and the long time lag, usually in years, between the neurotoxic exposure and the diagnosis of mental dysfunction. Human data on the effects of alcohol, lead, and mercury and experimental data from animals on developmental neurotoxins and their long-term behavioral effects have achieved a critical mass, leading to the concept of the Developmental Origin of Health and Disease (DOHaD). However, there is currently no way to evaluate the degree of brain damage early after birth. We propose that extracellular vesicles (EVs) and particularly exosomes, released by brain cells into the fetal blood, may offer us a non-invasive means of assessing brain damage by neurotoxins. We are inspired by the strategy applied by Alan Turing (a cryptanalyst working for the British government), who created a first computer to decrypt German intelligence communications during World War II. Given the growing evidence that microRNAs (miRNAs), which are among the molecules carried by EVs, are involved in cell-cell communication, we propose that decrypting messages from EVs can allow us to detect damage thus offering an opportunity to cure, reverse, or prevent the development of NDD. This review summarizes recent findings on miRNAs associated with selected environmental toxicants known to be involved in the pathophysiology of NDD.

  17. Early environmental enrichment affects neurobehavioral development and prevents brain damage in rats submitted to neonatal hypoxia-ischemia.

    Science.gov (United States)

    Schuch, Clarissa Pedrini; Diaz, Ramiro; Deckmann, Iohanna; Rojas, Joseane Jiménez; Deniz, Bruna Ferrary; Pereira, Lenir Orlandi

    2016-03-23

    Our previous results demonstrated improved cognition in adolescent rats housed in environmental enrichment (EE) that underwent neonatal hypoxia-ischemia (HI). The aim of this study was to investigate the effects of early EE on neurobehavioral development and brain damage in rats submitted to neonatal HI. Wistar rats were submitted to the HI procedure on the 7th postnatal day (PND) and housed in an enriched environment (8th-20th PND). The maturation of physical characteristics and the neurological reflexes were evaluated and the volume of striatum, corpus callosum and neocortex was measured. Data analysis demonstrated a clear effect of EE on neurobehavioral development; also, daily performance was improved in enriched rats on righting, negative geotaxis and cliff aversion reflex. HI caused a transient motor deficit on gait latency. Brain atrophy was found in HI animals and this damage was partially prevented by the EE. In conclusion, early EE stimulated neurobehavioral development in neonate rats and also protects the neocortex and the corpus callosum from atrophy following HI. These findings reinforce the potential of EE as a strategy for rehabilitation following neonatal HI and provide scientific support to the use of this therapeutic strategy in the treatment of neonatal brain injuries in humans.

  18. A CLINICAL STUDY FOR EVALUATING EARLY RADIOTHERAPY EFFECT IN PATIENTS WITH BRAIN TUMOR USING 99Tcm-HL91 SPECT

    Institute of Scientific and Technical Information of China (English)

    ZHAO Ming; ZHANG Yong-xue; ZHANG Cheng-gang; LAN Sheng-min; WANG Zhong-min; ZHANG Xiu-fu

    2006-01-01

    Objective: The purpose of this study was to evaluate the early radiotherapy effect using 99Tcm-HL91 SPECT in patients with brain tumors. Methods: Twenty-one patients with brain tumors who were treated by radiotherapy were studied. KPS grade, tumor size on 99Tcm-HL91 SPECT , tumor size on MRI, and ratio of T/N (tumor counts/sec over normal brain tissue counts/sec) were investigated before ,during and after radiotherapy. Results: The average tumor size on 99Tcm-HL91 SPECT and MRI was 11.34(5.88 cm2, 9.46(5.66 cm2, respectively before radiotherapy. The tumor size on 99Tcm-HL91 SPECT was not in accordance with to that on MRI (P<0.05). KPS grade, tumor size on 99Tcm-HL91 SPECT and ratio of T/N had significance differences before, during and after radiotherapy (P<0.05), but the tumor size on MRI imaging had no significance differences before, during and after radiotherapy (P>0.05). The rate of symptom improvement was 80% during radiotherapy and 100% after radiotherapy. The rates of imaging remission based on the brain tumor size on 99Tcm-HL91 SPECT, MRI and T/N were 75%, 15%, and 80%, respectively during radiotherapy. The agreement rates between imaging remission diagnosed by those three methods and symptom improvement were 70%, 40%, and 60% respectively during radiotherapy. The rates of imaging remission based on the brain tumor sizes on 99Tcm-HL91 SPECT, MRI and T/N were 100%, 25%, and 95% respectively after radiotherapy. The agreement rates between imaging remission diagnosed by those three methods and symptoms improvement were 100%, 20%, and 95% respectively after radiotherapy. Conclusion: The tumor size on 99Tcm-HL91 SPECT is a valuable tool for evaluating early radiotherapy effect of brain tumor in process of radiotherapy. T/N is not a feasible method in evaluating radiotherapy effect of brain tumor because it may show elevation unrelated to the curative effect during radiotherapy.

  19. Left Hemisphere Regions Are Critical for Language in the Face of Early Left Focal Brain Injury

    Science.gov (United States)

    Beharelle, Anjali Raja; Dick, Anthony Steven; Josse, Goulven; Solodkin, Ana; Huttenlocher, Peter R.; Levine, Susan C.; Small, Steven L.

    2010-01-01

    A predominant theory regarding early stroke and its effect on language development, is that early left hemisphere lesions trigger compensatory processes that allow the right hemisphere to assume dominant language functions, and this is thought to underlie the near normal language development observed after early stroke. To test this theory, we…

  20. Improving HIV-1 tropism determination by combining geno2pheno and V3 net charge calculation

    Directory of Open Access Journals (Sweden)

    G Antonelli

    2012-11-01

    Full Text Available Genotypic tests are the most common methods to identify patients eligible for CCR5 inhibitors administration in Europe. Among the available tools geno2pheno coreceptor (G2P is the most used online system in routine diagnostics. This study was conceived to assess if the combination of G2P prediction with V3 peptide net charge (NC value could improve the accuracy of tropism prediction. Sequences (129 were analyzed by G2P according to European Guidelines. NC values were calculated by the online software Peptide Property Calculator. Phenotypic assay was performed cloning the complete env gene into pcDNA 3.1 TOPO vector; infectivity of pseudotyped virions was tested on U87_CD4+CCR5+ and U87_CD4+CXCR4+ cells lines to assess viral tropism. Sequences were stratified into 3 groups according to the agreement between NC values and G2P results. Group 1: sequences assigned to the same group by both tools, group 2: sequences assigned to one group by G2P but indeterminate by NC and group 3: sequences for which G2P and NC gave discordant results. 61% of sequences predicted as X4 by G2P showed NC values higher than 5; similarly, 76% of sequences predicted as R5 by G2P had NC values below 4 (Group 1. Sequences with NC values between 4 and 5 (Group 2 were associated to different G2P predictions: 59% samples were predicted as R5-tropic and 41% sequences as X4-tropic. These data support the hypothesis that 4 to 5 NC values could be associated to the presence of dual/mixed-tropic variants (DM. Sequences identified as X4 by NC value had at least one positive residue in positions known to be involved in tropism prediction (58% and positive residues in position 32 (39%. To further verify NC-based prediction, phenotypic assay was performed on a subset of sequences from each group. The assay confirmed the tropism prediction for group 1 sequences and demonstrated that the variants with net charge between 4 and 5 have DM tropism. Moreover, in vitro phenotyping of discordant

  1. Brain Basics

    Medline Plus

    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

  2. [Protective effect of mitochondria-targeted antioxidant SS31 on early brain injury following subarachnoid hemorrhage in rats].

    Science.gov (United States)

    Zhou, Jian; Li, Zhengzheng; Chen, Zhenggang; Yang, Kun

    2017-09-28

    To evaluate protective effects of SS31 on early brain injury (EBI) induced by subarachnoid hemorrhage (SAH) in rats.
 Methods: A total of 96 Sprague-Dawley rats were randomly divided into 4 groups: A sham group, an SAH group, an SAH+vehicle group (SAH+V), and an SAH+SS31 group. The SAH-induced prechiasmatic cistern rat model was established in this study. Neurological deficit scores were evaluated at 24 h after SAH. The SS31 (5 mg/kg) as well as equal volume of vehicle were administrated intraperitoneally at 2 h after SAH. The neurological scores, brain edema, blood-brain barrier (BBB) permeability, apoptosis, malondialdehyde (MDA), glutathione peroxidase (GPx) activity, superoride dismutase (SOD) activity, and the expression of cytosolic cytochrome c (Cyt C) and Bax were analyzed at 24 h after SAH.
 Results: Treatment with SS31 could significantly reduce MDA levels, and restored the activities of GPx and SOD in the cortex following SAH when compared with the SAH+V group. In addition, Bax SS31 trearment increased or decreased the levels of mitochondrial Cyt C or Bax, respectively. Moreover, SS31 treatment ameliorated brain edema and Evans blue dye extravasation, improved neurological deficits, and decreased neuronal apoptosis at 24 h after SAH.
 Conclusion: SS31 could alleviate EBI after SAH through its antioxidant property and ability in inhibition of neuronal apoptosis.

  3. Prostaglandin E2 EP4 Receptor Activation Attenuates Neuroinflammation and Early Brain Injury Induced by Subarachnoid Hemorrhage in Rats.

    Science.gov (United States)

    Xu, Jie; Xu, Zhen; Yan, Ai

    2017-02-27

    Activation of E prostanoid 4 receptor (EP4) shows neuroprotective effects in multiple central nervous system (CNS) lesions, but the roles of EP4 receptor in subarachnoid hemorrhage (SAH) are not explored. This study was designed to research the effects of EP4 modulation on early brain injury (EBI) after experimental SAH in rats. We found that the administration of EP4 selective agonist AE1-329 significantly improved neurological dysfunction, blood brain barrier (BBB) damage and brain edema at 24 h after SAH. Furthermore, AE1-329 obviously reduced the number of activated microglia and the mRNA and protein levels of pro-inflammatory cytokines, and increased Ser1177 phosphorylated endothelial nitric oxide synthase (Ser1177 p-eNOS). Moreover, AE1-329 significantly reduced the number of TUNEL-positive cells and active caspase-3 in cortex after SAH. The EP4 selective antagonist AE3-208 was also administrated and the opposite effects were achieved. Our results indicate that activation of EP4 protects brain from EBI through downregulating neuroinflammation reaction after SAH.

  4. Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling.

    Science.gov (United States)

    Dong, Yushu; Fan, Chongxi; Hu, Wei; Jiang, Shuai; Ma, Zhiqiang; Yan, Xiaolong; Deng, Chao; Di, Shouyin; Xin, Zhenlong; Wu, Guiling; Yang, Yang; Reiter, Russel J; Liang, Guobiao

    2016-04-01

    Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti-inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood-brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-1β (IL-1β), and interleukin-6 (IL-6); these changes were also associated with an increase in the anti-apoptotic factor (Bcl2) and reduction in the pro-apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome-associated apoptosis.

  5. Simulation of blast-induced, early-time intracranial wave physics leading to traumatic brain injury.

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Paul Allen; Ford, Corey C. (University of New Mexico, Albuquerque, NM)

    2008-04-01

    U.S. soldiers are surviving blast and impacts due to effective body armor, trauma evacuation and care. Blast injuries are the leading cause of traumatic brain injury (TBI) in military personnel returning from combat. Understanding of Primary Blast Injury may be needed to develop better means of blast mitigation strategies. The objective of this paper is to investigate the effects of blast direction and strength on the resulting mechanical stress and wave energy distributions generated in the brain.

  6. Use of Early Biomarkers in Neonatal Brain Damage and Sepsis: State of the Art and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Iliana Bersani

    2015-01-01

    Full Text Available The identification of early noninvasive biochemical markers of disease is a crucial issue of the current scientific research, particularly during the first period of life, since it could provide useful and precocious diagnostic information when clinical and radiological signs are still silent. The ideal biomarker should be practical and sensitive in the precocious identification of at risk patients. An earlier diagnosis may lead to a larger therapeutic window and improve neonatal outcome. Brain damage and sepsis are common causes of severe morbidity with poor outcome and mortality during the perinatal period. A large number of potential biomarkers, including neuroproteins, calcium binding proteins, enzymes, oxidative stress markers, vasoactive agents, and inflammatory mediators, have been so far investigated. The aim of the present review was to provide a brief overview of some of the more commonly investigated biomarkers used in case of neonatal brain damage and sepsis.

  7. Use of Early Biomarkers in Neonatal Brain Damage and Sepsis: State of the Art and Future Perspectives

    Science.gov (United States)

    Bersani, Iliana; Auriti, Cinzia; Ronchetti, Maria Paola; Prencipe, Giusi; Gazzolo, Diego; Dotta, Andrea

    2015-01-01

    The identification of early noninvasive biochemical markers of disease is a crucial issue of the current scientific research, particularly during the first period of life, since it could provide useful and precocious diagnostic information when clinical and radiological signs are still silent. The ideal biomarker should be practical and sensitive in the precocious identification of at risk patients. An earlier diagnosis may lead to a larger therapeutic window and improve neonatal outcome. Brain damage and sepsis are common causes of severe morbidity with poor outcome and mortality during the perinatal period. A large number of potential biomarkers, including neuroproteins, calcium binding proteins, enzymes, oxidative stress markers, vasoactive agents, and inflammatory mediators, have been so far investigated. The aim of the present review was to provide a brief overview of some of the more commonly investigated biomarkers used in case of neonatal brain damage and sepsis. PMID:25685774

  8. Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

    Science.gov (United States)

    Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M.; Bindels, Laure B.; Cambier, Emmanuel; Ben-Amram, Hila; Koren, Omry; Forsythe, Paul; Bienenstock, John

    2017-01-01

    There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria. PMID:28375200

  9. Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage.

    Science.gov (United States)

    Malinova, Vesna; Dolatowski, Karoline; Schramm, Peter; Moerer, Onnen; Rohde, Veit; Mielke, Dorothee

    2016-07-01

    OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.

  10. Regional characterization of longitudinal DT-MRI to study white matter maturation of the early developing brain.

    Science.gov (United States)

    Sadeghi, Neda; Prastawa, Marcel; Fletcher, P Thomas; Wolff, Jason; Gilmore, John H; Gerig, Guido

    2013-03-01

    The human brain undergoes rapid and dynamic development early in life. Assessment of brain growth patterns relevant to neurological disorders and disease requires a normative population model of growth and variability in order to evaluate deviation from typical development. In this paper, we focus on maturation of brain white matter as shown in diffusion tensor MRI (DT-MRI), measured by fractional anisotropy (FA), mean diffusivity (MD), as well as axial and radial diffusivities (AD, RD). We present a novel methodology to model temporal changes of white matter diffusion from longitudinal DT-MRI data taken at discrete time points. Our proposed framework combines nonlinear modeling of trajectories of individual subjects, population analysis, and testing for regional differences in growth pattern. We first perform deformable mapping of longitudinal DT-MRI of healthy infants imaged at birth, 1 year, and 2 years of age, into a common unbiased atlas. An existing template of labeled white matter regions is registered to this atlas to define anatomical regions of interest. Diffusivity properties of these regions, presented over time, serve as input to the longitudinal characterization of changes. We use non-linear mixed effect (NLME) modeling where temporal change is described by the Gompertz function. The Gompertz growth function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to quantitative analysis of growth patterns. Results suggest that our proposed framework provides descriptive and quantitative information on growth trajectories that can be interpreted by clinicians using natural language terms that describe growth. Statistical analysis of regional differences between anatomical regions which are known to mature differently demonstrates the potential of the proposed method for quantitative assessment of brain growth and differences thereof. This will

  11. Brain Basics

    Medline Plus

    Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain ... studies show that brain growth in children with autism appears to peak early. And as they grow ...

  12. Brain Basics

    Medline Plus

    Full Text Available ... and her husband questions about Sarah's symptoms and family medical history. Epigenetic changes from stress or early- ... and techniques are giving scientists a more detailed understanding of the brain than ever before. Brain Imaging ...

  13. Brain Basics

    Medline Plus

    Full Text Available ... affect many aspects of life. Scientists are continually learning more about how the brain grows and works ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate ...

  14. Brain Basics

    Medline Plus

    Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain ... studies show that brain growth in children with autism appears to peak early. And as they grow ...

  15. Brain Basics

    Medline Plus

    Full Text Available ... affect many aspects of life. Scientists are continually learning more about how the brain grows and works ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... all. She was happily married and successful in business. Then, after a serious setback at work, she ... of the brain's structure, studies show that brain growth in children with autism appears to peak early. ...

  17. Development of maraviroc, a CCR5 antagonist for treatment of HIV, using a novel tropism assay.

    Science.gov (United States)

    van der Ryst, Elna; Heera, Jayvant; Demarest, James; Knirsch, Charles

    2015-06-01

    Assays to identify infectious organisms are critical for diagnosis and enabling the development of therapeutic agents. The demonstration that individuals with a 32-bp deletion within the CCR5 locus were resistant to human immunodeficiency virus (HIV) infection, while those heterozygous for the mutation progressed more slowly, led to the discovery of maraviroc (MVC), a CCR5 antagonist. As MVC is only active against CCR5-tropic strains of HIV, it was critical to develop a diagnostic assay to identify appropriate patients. Trofile™, a novel phenotypic tropism assay, was used to identify patients with CCR5-tropic virus for the MVC development program. Results of these clinical studies demonstrated that the assay correctly identified patients likely to respond to MVC. Over time, the performance characteristics of the phenotypic assay were enhanced, necessitating retesting of study samples. Genotypic tropism tests that have the potential to allow for local use and more rapid turnaround times are also being developed.

  18. Plasma HIV-1 tropism and risk of short-term clinical progression to AIDS or death

    Directory of Open Access Journals (Sweden)

    Maria Casadellà Fontdevila

    2014-11-01

    Full Text Available Introduction: It is uncertain if plasma HIV-1 tropism is an independent predictor of short-term risk of clinical progression / death, in addition to the CD4 count and HIV RNA level. We conducted a nested case-control study within EuroSIDA to assess this question amongst people with current HIV RNA level >1000 copies/mL, including both people on ART and those ART naïve. Methods: People with an AIDS diagnosis or who died from any causes for whom there was a stored plasma sample with HIV-1 RNA (VL≥1,000 copies/mL available in the time window of 3–12 months prior to the event were identified. At least one control was selected for each case matched for age, VL and HCV status at the time of sampling. Controls were event-free after a matched duration of time from the date of sampling. Plasma HIV tropism was estimated using 454 and population sequencing (PS. Non-R5 HIV was defined as: (a ≥2% of sequences with a Geno2Pheno (G2P FPR≤3.75% by 454, and (b a G2P FPR≤10% by PS. We also compared CD4 slopes over the 12 months following the date of sampling using a linear mixed model with random intercept according to HIV tropism and ART status. Results: The study included 266 subjects, 100 cases and 166 controls, with sample taken on average in 2006; 23% and 24% had non-R5 HIV by 454 and PS respectively. There were 19% women, 25% MSM, 92% Caucasians, 22% HCV+. At the time of sampling, 26% were ART-naïve, 25% had started but were off ART and 49% were receiving ART. The median age, CD4 and viral load was 41 years, 350 cells/mm3 and 4.81 log c/mL, respectively. Baseline characteristics were well balanced by tropism. Factors independently associated with clinical progression or death were female gender (OR=2.12; 95% CI=1.04, 4.36; p=0.038, CD4+ count (OR=0.90 per 100 cells/mm3 higher; 95% CI 0.80, 1.00; p=0.058, being on ART (OR=2.72; 95% CI 1.15, 6.41; p=0.022 and calendar year of sample (OR=0.84 per more recent year; 95% CI=0.77, 0.91; p<0

  19. Increase in FLAIR Signal of the Fluid Within the Resection Cavity as Early Recurrence Marker: Also Valid for Brain Metastases?

    Science.gov (United States)

    Bette, Stefanie; Gempt, Jens; Wiestler, Benedikt; Huber, Thomas; Specht, Hanno; Meyer, Bernhard; Zimmer, Claus; Kirschke, Jan S; Boeckh-Behrens, Tobias

    2017-01-01

    Purpose Increase in FLAIR signal of the fluid within the resection cavity is described as a highly specific and early sign for tumor recurrence in gliomas. The aim of this study was to assess the prognostic value of FLAIR signal increase in partially or completely resected brain metastases. Materials and Methods 209 cases of surgery for brain metastases were assessed. 41 cases with at least two follow-up MRIs were retrospectively included in this study. Quantitative and qualitative assessment of the FLAIR signal intensity of the fluid within the resection cavity was performed in the MRI examination at recurrent disease/last contact and in the previous MRI examination. Results 3 of 6 cases with local tumor recurrence showed a FLAIR signal increase (sensitivity 50.0 %, specificity 100.0 %). In one case, this sign was observed even about 3 months before tumor recurrence. The specificity of FLAIR signal increase for overall tumor recurrence (local and distant) was also 100.0 %, but with a lower sensitivity of 13.0 %. Quantitative analysis showed significant differences for signal intensity of the resection cavity as well as for the change of signal intensity of the resection cavity in cases with or without local tumor recurrence. Conclusion An increase in FLAIR signal of the fluid within the resection cavity might be a highly specific and early sign of local tumor recurrence/tumor progression also for brain metastases. Key points: · An increase in FLAIR signal intensity of the fluid within the resection cavity is also observed in previously resected brain metastases.. · The pathophysiology of this sign might be due to a cell-proliferative process.. Citation Format · Bette S, Gempt J, Wiestler B et al. Increase of the FLAIR Signal of the Fluid within the Resection Cavity as Early Recurrence Marker: Also Valid for Brain Metastases?. Fortschr Röntgenstr 2017; 189: 63 - 70. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Traumatic Brain Injury and Delayed Sequelae: A Review - Traumatic Brain Injury and Mild Traumatic Brain Injury (Concussion) are Precursors to Later-Onset Brain Disorders, Including Early-Onset Dementia

    OpenAIRE

    Kiraly, Michael A.; Kiraly, Stephen J.

    2007-01-01

    Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI) and mild traumatic brain injury (MTBI). Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzh...

  1. The influence of complex and threatening environments in early life on brain size and behaviour.

    Science.gov (United States)

    DePasquale, C; Neuberger, T; Hirrlinger, A M; Braithwaite, V A

    2016-01-27

    The ways in which challenging environments during development shape the brain and behaviour are increasingly being addressed. To date, studies typically consider only single variables, but the real world is more complex. Many factors simultaneously affect the brain and behaviour, and whether these work independently or interact remains untested. To address this, zebrafish (Danio rerio) were reared in a two-by-two design in housing that varied in structural complexity and/or exposure to a stressor. Fish experiencing both complexity (enrichment objects changed over time) and mild stress (daily net chasing) exhibited enhanced learning and were less anxious when tested as juveniles (between 77 and 90 days). Adults tested (aged 1 year) were also less anxious even though fish were kept in standard housing after three months of age (i.e. no chasing or enrichment). Volumetric measures of the brain using magnetic resonance imaging (MRI) showed that complexity alone generated fish with a larger brain, but this increase in size was not seen in fish that experienced both complexity and chasing, or chasing alone. The results highlight the importance of looking at multiple variables simultaneously, and reveal differential effects of complexity and stressful experiences during development of the brain and behaviour.

  2. Tissue tropism and molecular characterization of a Japanese encephalitis virus strain isolated from pigs in southwest China.

    Science.gov (United States)

    Yuan, Lei; Wu, Rui; Liu, Hanyang; Wen, Xintian; Huang, Xiaobo; Wen, Yiping; Ma, Xiaoping; Yan, Qigui; Huang, Yong; Zhao, Qin; Cao, Sanjie

    2016-04-02

    Since September 2012, an epidemic has been spreading among swine in a pig farm located in Sichuan province, southwest China, which has resulted in abortion, stillbirth, and fetal mummification. The brains of stillborn pigs were collected and a previously unknown Japanese encephalitis virus (JEV), namely SCYA201201, was isolated. According to the results of agarose gel diffusion precipitation, indirect immunofluorescence analysis, neutralization testing, reverse transcription PCR (RT-PCR) amplification, and physical and chemical testing, the virus was conformed to have the characteristics of JEV. The virus titer in BHK-21 cells was 10(8.47)PFU/ml and the median lethal dose (LD50) to 3-week-old and 7-day-old mice was 1.99 log10 and 1.02 log10 PFU/LD50, respectively. The results of tissue tropism for mice showed that the viral load in the brain was significantly higher than other organs, indicating that the isolate was strongly neurotropic. Additionally, the complete genome sequence of the isolate was determined and compared with other JEV strains. Phylogenetic analysis showed that the isolate belongs to genotype I and may be an imported virus. The isolate had 88.4% nucleotide identity with the Chinese vaccine strain SA14-14-2. However, there were 69 amino acid substitutions compared with the strain SA14-14-2. Some substitutions indicated that SCYA201201 was highly neurovirulent and infective, in accordance with the results of animal testing. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

    Science.gov (United States)

    Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

    2012-01-01

    Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

  4. Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer’s disease

    OpenAIRE

    Leskovjan, Andreana C.; Kretlow, Ariane; Lanzirotti, Antonio; Barrea, Raul; Vogt, Stefan; Miller, Lisa M.

    2010-01-01

    Elevated brain iron content, which has been observed in late stage human Alzheimer’s disease, is a potential target for early diagnosis. However, the time course for iron accumulation is currently unclear. Using the PSAPP mouse model of amyloid plaque formation, we conducted a time course study of metal ion content and distribution [iron (Fe), copper (Cu), and zinc (Zn)] in the cortex and hippocampus using X-ray fluorescence microscopy (XFM). We found that iron in the cortex was 34% higher th...

  5. Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism.

    Science.gov (United States)

    Archer, John; Weber, Jan; Henry, Kenneth; Winner, Dane; Gibson, Richard; Lee, Lawrence; Paxinos, Ellen; Arts, Eric J; Robertson, David L; Mimms, Larry; Quiñones-Mateu, Miguel E

    2012-01-01

    HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4-tropic (non-R5) viruses prior treatment with CCR5 antagonists. Phenotypic (e.g., Trofile™, Monogram Biosciences) and genotypic (e.g., population sequencing linked to bioinformatic algorithms) assays are the most widely used. Although several next-generation sequencing (NGS) platforms are available, to date all published deep sequencing HIV-1 tropism studies have used the 454™ Life Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454™, PacBio® RS (Pacific Biosciences), Illumina®, and Ion Torrent™ (Life Technologies). Cross-platform variation was evaluated, including number of reads, read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule and compared with Trofile™ and virologic response to antiretroviral therapy. Error rates related to insertions/deletions (indels) and nucleotide substitutions introduced by the four NGS platforms were low compared to the actual HIV-1 sequence variation. Each platform detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used), compared to Trofile (80%) and population sequencing (70%). In conclusion, all four NGS platforms were able to detect minority non-R5 variants at comparable levels suggesting that any NGS-based method can be used to predict HIV-1 coreceptor usage.

  6. Mechanisms of foot-and-mouth disease virus tropism inferred from differential tissue gene expression.

    Directory of Open Access Journals (Sweden)

    James J Zhu

    Full Text Available Foot-and-mouth disease virus (FMDV targets specific tissues for primary infection, secondary high-titer replication (e.g. foot and mouth where it causes typical vesicular lesions and long-term persistence at some primary replication sites. Although integrin αVβ6 receptor has been identified as primary FMDV receptors in animals, their tissue distribution alone fails to explain these highly selective tropism-driven events. Thus, other molecular mechanisms must play roles in determining this tissue specificity. We hypothesized that differences in certain biological activities due to differential gene expression determine FMDV tropism and applied whole genome gene expression profiling to identify genes differentially expressed between FMDV-targeted and non-targeted tissues in terms of supporting primary infection, secondary replication including vesicular lesions, and persistence. Using statistical and bioinformatic tools to analyze the differential gene expression, we identified mechanisms that could explain FMDV tissue tropism based on its association with differential expression of integrin αVβ6 heterodimeric receptor (FMDV receptor, fibronectin (ligand of the receptor, IL-1 cytokines, death receptors and the ligands, and multiple genes in the biological pathways involved in extracellular matrix turnover and interferon signaling found in this study. Our results together with reported findings indicate that differences in (1 FMDV receptor availability and accessibility, (2 type I interferon-inducible immune response, and (3 ability to clear virus infected cells via death receptor signaling play roles in determining FMDV tissue tropism and the additional increase of high extracellular matrix turnover induced by FMDV infection, likely via triggering the signaling of highly expressed IL-1 cytokines, play a key role in the pathogenesis of vesicular lesions.

  7. Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism.

    Directory of Open Access Journals (Sweden)

    John Archer

    Full Text Available HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4-tropic (non-R5 viruses prior treatment with CCR5 antagonists. Phenotypic (e.g., Trofile™, Monogram Biosciences and genotypic (e.g., population sequencing linked to bioinformatic algorithms assays are the most widely used. Although several next-generation sequencing (NGS platforms are available, to date all published deep sequencing HIV-1 tropism studies have used the 454™ Life Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454™, PacBio® RS (Pacific Biosciences, Illumina®, and Ion Torrent™ (Life Technologies. Cross-platform variation was evaluated, including number of reads, read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule and compared with Trofile™ and virologic response to antiretroviral therapy. Error rates related to insertions/deletions (indels and nucleotide substitutions introduced by the four NGS platforms were low compared to the actual HIV-1 sequence variation. Each platform detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used, compared to Trofile (80% and population sequencing (70%. In conclusion, all four NGS platforms were able to detect minority non-R5 variants at comparable levels suggesting that any NGS-based method can be used to predict HIV-1 coreceptor usage.

  8. A Unified Model of Shoot Tropism in Plants: Photo-, Gravi- and Propio-ception

    OpenAIRE

    Renaud Bastien; Stéphane Douady; Bruno Moulia

    2015-01-01

    Land plants rely mainly on gravitropism and phototropism to control their posture and spatial orientation. In natural conditions, these two major tropisms act concurrently to create a photogravitropic equilibrium in the responsive organ. Recently, a parsimonious model was developed that accurately predicted the complete gravitropic and proprioceptive control over the movement of different organs in different species in response to gravitational stimuli. Here we show that the framework of this...

  9. Concordance of HIV type 1 tropism phenotype to predictions using web-based analysis of V3 sequences: composite algorithms may be needed to properly assess viral tropism.

    Science.gov (United States)

    Cabral, Gabriela Bastos; Ferreira, João Leandro de Paula; Coelho, Luana Portes Osório; Fonsi, Mylva; Estevam, Denise Lotufo; Cavalcanti, Jaqueline Souza; Brígido, Luis Fernando de Macedo

    2012-07-01

    Genotypic prediction of HIV-1 tropism has been considered a practical surrogate for phenotypic tests and recently an European Consensus has set up recommendations for its use in clinical practice. Twenty-five antiretroviral-experienced patients, all heavily treated cases with a median of 16 years of antiretroviral therapy, had viral tropism determined by the Trofile assay and predicted by HIV-1 sequencing of partial env, followed by interpretation using web-based tools. Trofile determined 17/24 (71%) as X4 tropic or dual/mixed viruses, with one nonreportable result. The use of European consensus recommendations for single sequences (geno2pheno false-positive rates 20% cutoff) would lead to 4/24 (16.7%) misclassifications, whereas a composite algorithm misclassified 1/24 (4%). The use of the geno2pheno clinical option using CD4 T cell counts at collection was useful in resolving some discrepancies. Applying the European recommendations followed by additional web-based tools for cases around the recommended cutoff would resolve most misclassifications.

  10. Controlling AAV Tropism in the Nervous System with Natural and Engineered Capsids

    Science.gov (United States)

    Castle, Michael J.; Turunen, Heikki T.; Vandenberghe, Luk H.; Wolfe, John H.

    2016-01-01

    More than one hundred naturally occurring variants of adeno-associated virus (AAV) have been identified, and this library has been further expanded by an array of techniques for modification of the viral capsid. AAV capsid variants possess unique antigenic profiles and demonstrate distinct cellular tropisms driven by differences in receptor binding. AAV capsids can be chemically modified to alter tropism, can be produced as hybrid vectors that combine the properties of multiple serotypes, and can carry peptide insertions that introduce novel receptor-binding activity. Furthermore, directed evolution of shuffled genome libraries can identify engineered variants with unique properties, and rational modification of the viral capsid can alter tropism, reduce blockage by neutralizing antibodies, or enhance transduction efficiency. This large number of AAV variants and engineered capsids provides a varied toolkit for gene delivery to the CNS and retina, with specialized vectors available for many applications, but selecting a capsid variant from the array of available vectors can be difficult. This chapter describes the unique properties of a range of AAV variants and engineered capsids, and provides a guide for selecting the appropriate vector for specific applications in the CNS and retina. PMID:26611584

  11. Peste des petits ruminants virus tissue tropism and pathogenesis in sheep and goats following experimental infection.

    Science.gov (United States)

    Truong, Thang; Boshra, Hani; Embury-Hyatt, Carissa; Nfon, Charles; Gerdts, Volker; Tikoo, Suresh; Babiuk, Lorne A; Kara, Pravesh; Chetty, Thireshni; Mather, Arshad; Wallace, David B; Babiuk, Shawn

    2014-01-01

    Peste des petits ruminants (PPR) is a viral disease which primarily affects small ruminants, causing significant economic losses for the livestock industry in developing countries. It is endemic in Saharan and sub-Saharan Africa, the Middle East and the Indian sub-continent. The primary hosts for peste des petits ruminants virus (PPRV) are goats and sheep; however recent models studying the pathology, disease progression and viremia of PPRV have focused primarily on goat models. This study evaluates the tissue tropism and pathogenesis of PPR following experimental infection of sheep and goats using a quantitative time-course study. Upon infection with a virulent strain of PPRV, both sheep and goats developed clinical signs and lesions typical of PPR, although sheep displayed milder clinical disease compared to goats. Tissue tropism of PPRV was evaluated by real-time RT-PCR and immunohistochemistry. Lymph nodes, lymphoid tissue and digestive tract organs were the predominant sites of virus replication. The results presented in this study provide models for the comparative evaluation of PPRV pathogenesis and tissue tropism in both sheep and goats. These models are suitable for the establishment of experimental parameters necessary for the evaluation of vaccines, as well as further studies into PPRV-host interactions.

  12. Peste des petits ruminants virus tissue tropism and pathogenesis in sheep and goats following experimental infection.

    Directory of Open Access Journals (Sweden)

    Thang Truong

    Full Text Available Peste des petits ruminants (PPR is a viral disease which primarily affects small ruminants, causing significant economic losses for the livestock industry in developing countries. It is endemic in Saharan and sub-Saharan Africa, the Middle East and the Indian sub-continent. The primary hosts for peste des petits ruminants virus (PPRV are goats and sheep; however recent models studying the pathology, disease progression and viremia of PPRV have focused primarily on goat models. This study evaluates the tissue tropism and pathogenesis of PPR following experimental infection of sheep and goats using a quantitative time-course study. Upon infection with a virulent strain of PPRV, both sheep and goats developed clinical signs and lesions typical of PPR, although sheep displayed milder clinical disease compared to goats. Tissue tropism of PPRV was evaluated by real-time RT-PCR and immunohistochemistry. Lymph nodes, lymphoid tissue and digestive tract organs were the predominant sites of virus replication. The results presented in this study provide models for the comparative evaluation of PPRV pathogenesis and tissue tropism in both sheep and goats. These models are suitable for the establishment of experimental parameters necessary for the evaluation of vaccines, as well as further studies into PPRV-host interactions.

  13. Communication of brain network core connections altered in behavioral variant frontotemporal dementia but possibly preserved in early-onset Alzheimer's disease

    Science.gov (United States)

    Daianu, Madelaine; Jahanshad, Neda; Mendez, Mario F.; Bartzokis, George; Jimenez, Elvira E.; Thompson, Paul M.

    2015-03-01

    Diffusion imaging and brain connectivity analyses can assess white matter deterioration in the brain, revealing the underlying patterns of how brain structure declines. Fiber tractography methods can infer neural pathways and connectivity patterns, yielding sensitive mathematical metrics of network integrity. Here, we analyzed 1.5-Tesla wholebrain diffusion-weighted images from 64 participants - 15 patients with behavioral variant frontotemporal dementia (bvFTD), 19 with early-onset Alzheimer's disease (EOAD), and 30 healthy elderly controls. Using whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We evaluated the brain's networks focusing on the most highly central and connected regions, also known as hubs, in each diagnostic group - specifically the "high-cost" structural backbone used in global and regional communication. The high-cost backbone of the brain, predicted by fiber density and minimally short pathways between brain regions, accounted for 81-92% of the overall brain communication metric in all diagnostic groups. Furthermore, we found that the set of pathways interconnecting high-cost and high-capacity regions of the brain's communication network are globally and regionally altered in bvFTD, compared to healthy participants; however, the overall organization of the high-cost and high-capacity networks were relatively preserved in EOAD participants, relative to controls. Disruption of the major central hubs that transfer information between brain regions may impair neural communication and functional integrity in characteristic ways typical of each subtype of dementia.

  14. Traumatic Brain Injury and Delayed Sequelae: A Review - Traumatic Brain Injury and Mild Traumatic Brain Injury (Concussion are Precursors to Later-Onset Brain Disorders, Including Early-Onset Dementia

    Directory of Open Access Journals (Sweden)

    Michael A. Kiraly

    2007-01-01

    Full Text Available Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI and mild traumatic brain injury (MTBI. Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer's disease (AD and Parkinson's disease (PD. Objectives of this summary are, therefore, to instill appreciation regarding the importance of brain injury prevention, diagnosis, and treatment, and to increase awareness regarding the long-term delayed consequences following TBI.

  15. Risk factors and early diagnosis of cerebral venous sinus occlusion secondary to traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Jun Li

    2015-01-01

    Conclusions: Paying close attention to the past medical history of DVT, skull fracture, and the imaging finding of an epidural hematoma that crosses the sinus are necessary for the early diagnosis of CVSO. CTV and MRV help in making an early diagnosis of CVSO.

  16. Early specialization for voice and emotion processing in the infant brain

    NARCIS (Netherlands)

    Blasi, A.; Mercure, E.; Lloyd-Fox, S.; Thomson, A.; Brammer, M.; Sauter, D.; Deeley, Q.; Barker, G.J.; Renvall, V.; Deoni, S.; Gasston, D.; Williams, S.C.R.; Johnson, M.H.; Simmons, A.; Murphy, D.G.M.

    2011-01-01

    Human voices play a fundamental role in social communication, and areas of the adult "social brain" show specialization for processing voices and their emotional content (superior temporal sulcus, inferior prefrontal cortex, premotor cortical regions, amygdala, and insula) [ [1], [2], [3], [4], [5],

  17. Age-Related Changes in Transient and Oscillatory Brain Responses to Auditory Stimulation during Early Adolescence

    Science.gov (United States)

    Poulsen, Catherine; Picton, Terence W.; Paus, Tomas

    2009-01-01

    Maturational changes in the capacity to process quickly the temporal envelope of sound have been linked to language abilities in typically developing individuals. As part of a longitudinal study of brain maturation and cognitive development during adolescence, we employed dense-array EEG and spatiotemporal source analysis to characterize…

  18. Blood-brain barrier P-glycoprotein function is not impaired in early Parkinson's disease

    NARCIS (Netherlands)

    Bartels, A. L.; van Berckel, B. N. M.; Lubberink, M.; Luurtsema, G.; Lammertsma, A. A.; Leenders, K. L.

    2008-01-01

    The cause of Parkinson's disease (PD) is unknown. Genetic susceptibility and exposure to environmental toxins contribute to specific neuronal loss in PD. Decreased blood-brain barrier (BBB) P-glycoprotein (P-gp) efflux function has been proposed as a possible causative link between toxin exposure an

  19. Early referential context effects in sentence processing: Evidence from event-related brain potentials

    NARCIS (Netherlands)

    Berkum, J.J.A. van; Brown, C.M.; Hagoort, P.

    1999-01-01

    An event-related brain potentials experiment was carried out to examine the interplay of referential and structural factors during sentence processing in discourse. Subjects read (Dutch) sentences beginning like “David told the girl that … ” in short story contexts that had introduced either one or

  20. Age-Related Changes in Transient and Oscillatory Brain Responses to Auditory Stimulation during Early Adolescence

    Science.gov (United States)

    Poulsen, Catherine; Picton, Terence W.; Paus, Tomas

    2009-01-01

    Maturational changes in the capacity to process quickly the temporal envelope of sound have been linked to language abilities in typically developing individuals. As part of a longitudinal study of brain maturation and cognitive development during adolescence, we employed dense-array EEG and spatiotemporal source analysis to characterize…

  1. Development of the brain's structural network efficiency in early adolescence : A longitudinal DTI twin study

    NARCIS (Netherlands)

    Koenis, Marinka M G; Brouwer, Rachel M.; van den Heuvel, Martijn P.; Mandl, René C W; van Soelen, Inge L C; Kahn, René S.; Boomsma, Dorret I.; Hulshoff Pol, Hilleke E.

    2015-01-01

    The brain is a network and our intelligence depends in part on the efficiency of this network. The network of adolescents differs from that of adults suggesting developmental changes. However, whether the network changes over time at the individual level and, if so, how this relates to intelligence,

  2. Development of the brain's structural network efficiency in early adolescence : A longitudinal DTI twin study

    NARCIS (Netherlands)

    Koenis, Marinka M G; Brouwer, Rachel M.; van den Heuvel, Martijn P.; Mandl, René C W; van Soelen, Inge L C; Kahn, René S.; Boomsma, Dorret I.; Hulshoff Pol, Hilleke E.

    2015-01-01

    The brain is a network and our intelligence depends in part on the efficiency of this network. The network of adolescents differs from that of adults suggesting developmental changes. However, whether the network changes over time at the individual level and, if so, how this relates to intelligence,

  3. The early puberal brain: Work in progress. A study on genetic and hormonal influences

    NARCIS (Netherlands)

    Peper, J.S.

    2008-01-01

    The timing and speed of developmental processes during healthy puberty might be of critical importance to optimal adult functioning. Indeed, diseases that affect the brain at a young age, such as schizophrenia, are likely to have their origin in this period. The general aim of this thesis was to exp

  4. Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.

    Science.gov (United States)

    Hadar, Ravit; Dong, Le; Del-Valle-Anton, Lucia; Guneykaya, Dilansu; Voget, Mareike; Edemann-Callesen, Henriette; Schweibold, Regina; Djodari-Irani, Anais; Goetz, Thomas; Ewing, Samuel; Kettenmann, Helmut; Wolf, Susanne A; Winter, Christine

    2017-07-01

    In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Zinc and glutamine improve brain development in suckling mice subjected to early postnatal malnutrition.

    Science.gov (United States)

    Ladd, Fernando V L; Ladd, Aliny A B L; Ribeiro, Antônio Augusto C M; Costa, Samuel B C; Coutinho, Bruna P; Feitosa, George André S; de Andrade, Geanne M; de Castro-Costa, Carlos Maurício; Magalhães, Carlos Emanuel C; Castro, Ibraim C; Oliveira, Bruna B; Guerrant, Richard L; Lima, Aldo Angelo M; Oriá, Reinaldo B

    2010-06-01

    The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80 microL) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin and myelin basic protein brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal gamma-aminobutyric acid and synaptophysin levels on day 14. We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments. Copyright 2010 Elsevier Inc. All rights reserved.

  6. ZINC AND GLUTAMINE IMPROVE BRAIN DEVELOPMENT IN SUCKLING MICE SUBJECTED TO EARLY POST-NATAL MALNUTRITION

    Science.gov (United States)

    Ladd, Fernando V.L.; Ladd, Aliny A.B.L.; Ribeiro, Antônio Augusto C.M.; Costa, Samuel B.C.; Coutinho, Bruna P.; Feitosa, George André S.; de Andrade, Geanne M.; de Castro-Costa, Carlos Maurício; Magalhães, Carlos Emanuel C.; Castro, Ibraim C.; Oliveira, Bruna B.; Guerrant, Richard L.; Lima, Aldo Ângelo M.; Oriá, Reinaldo B.

    2009-01-01

    Objective The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. Methods Malnutrition was induced by clustering the litter size from 6–7 pups/dam (nourished control) to 12–14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40–80μl) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin (SYN) and myelin basic protein (MBP) brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Results Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal GABA and SYN levels on day 14. Conclusion We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments. PMID:20371167

  7. Brain size and encephalization in early to Mid-Pleistocene Homo.

    Science.gov (United States)

    Rightmire, G Philip

    2004-06-01

    Important changes in the brain have occurred during the course of human evolution. Both absolute and relative size increases can be documented for species of Homo, culminating in the appearance of modern humans. One species that is particularly well-represented by fossil crania is Homo erectus. The mean capacity for 30 individuals is 973 cm(3). Within this group there is substantial variation, but brain size increases slightly in specimens from later time periods. Other Middle Pleistocene crania differ from those of Homo erectus. Characters of the facial skeleton, vault, and cranial base suggest that fossils from sites such as Arago Cave in France, the Sima de los Huesos in Spain, Bodo in Ethiopia, Broken Hill in Zambia, and perhaps Dali in China belong to the taxon Homo heidelbergensis. Ten of these mid-Quaternary hominins have brains averaging 1,206 cm(3) in volume, and many fall beyond the limits of size predicted for Homo erectus of equivalent age. When orbit height is used to construct an index of relative brain size, it is apparent that the (significant) increase in volume documented for the Middle Pleistocene individuals is not simply a consequence of larger body mass. Encephalization quotient values confirm this finding. These changes in absolute and relative brain size can be taken as further corroborative evidence for a speciation event, in which Homo erectus produced a daughter lineage. It is probable that Homo heidelbergensis originated in Africa or western Eurasia and then ranged widely across the Old World. Archaeological traces indicate that these populations differed in their technology and behavior from earlier hominins. Copyright 2003 Wiley-Liss, Inc.

  8. Integrating early life experience, gene expression, brain development, and emergent phenotypes: unraveling the thread of nature via nurture.

    Science.gov (United States)

    Weaver, Ian C G

    2014-01-01

    Adaptation to environmental changes is based on the perpetual generation of new phenotypes. Modern biology has focused on the role of epigenetic mechanisms in facilitating the adaptation of organisms to changing environments through alterations in gene expression. Inherited and/or acquired epigenetic factors are relatively stable and have regulatory roles in numerous genomic activities that translate into phenotypic outcomes. Evidence that dietary and pharmacological interventions have the potential to reverse environment-induced modification of epigenetic states (e.g., early life experience, nutrition, medication, infection) has provided an additional stimulus for understanding the biological basis of individual differences in cognitive abilities and disorders of the brain. It has been suggested that accurate quantification of the relative contribution of heritable genetic and epigenetic variation is essential for understanding phenotypic divergence and adaptation in changing environments, a process requiring stable modulation of gene expression. The main challenge for epigenetics in psychology and psychiatry is to determine how experiences and environmental cues, including the nature of our nurture, influence the expression of neuronal genes to produce long-term individual differences in behavior, cognition, personality, and mental health. To this end, focusing on DNA and histone modifications and their initiators, mediators and readers may provide new inroads for understanding the molecular basis of phenotypic plasticity and disorders of the brain. In this chapter, we review recent discoveries highlighting epigenetic aspects of normal brain development and mental illness, as well as discuss some future directions in the field of behavioral epigenetics.

  9. Oligoclonal bands in the cerebrospinal fluid and increased brain atrophy in early stages of relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2012-08-01

    Full Text Available OBJECTIVE: To determine if the presence of oligoclonal bands (OB at early stages of multiple sclerosis was associated with higher brain atrophy, when compared with patients without OB. METHODS: Relapsing-remitting multiple sclerosis (RRMS patients with less than two years of disease onset and OB detection in cerebrospinal fluid (CSF were included. SIENAX was used for total brain volume (TBV, gray matter volume (GMV, and white matter volume (WMV. RESULTS: Forty patients were included, 29 had positive IgG-OB. No differences were found between positive and negative patients in gender, expanded disability status scale (EDSS, treatment received, and T2/T1 lesion load. TBV in positive IgG-OB patients was 1.5 mm³ x 10(6 compared with 1.64 mm³ x 10(6 in the negative ones (p=0.02. GMV was 0.51 mm³ x 10(6 in positive IgG-OB compared with 0.62 mm³ x 10(6 in negative ones (p=0.002. No differences in WMV (p=0.09 were seen. CONCLUSIONS: IgG-OB in the CSF was related to neurodegeneration magnetic resonance (MR markers in early RRMS.

  10. Emotion recognition in early Parkinson's disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants.

    Science.gov (United States)

    McIntosh, Lindsey G; Mannava, Sishir; Camalier, Corrie R; Folley, Bradley S; Albritton, Aaron; Konrad, Peter E; Charles, David; Park, Sohee; Neimat, Joseph S

    2014-01-01

    Parkinson's disease (PD) is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits. In addition, contrasting this with a group of healthy aging individuals demonstrates changes in emotion processing specific to the degeneration of basal ganglia circuitry in PD. Early PD patients (EPD) were recruited from a randomized clinical trial testing the safety and tolerability of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) in early-staged PD. EPD patients were previously randomized to receive optimal drug therapy only (ODT), or drug therapy plus STN-DBS (ODT + DBS). Matched healthy elderly controls (HEC) and young controls (HYC) also participated in this study. Participants completed two control tasks and three emotion recognition tests that varied in stimulus domain. EPD patients were impaired on all emotion recognition tasks compared to HEC. Neither therapy type (ODT or ODT + DBS) nor therapy state (ON/OFF) altered emotion recognition performance in this study. Finally, HEC were impaired on vocal emotion recognition relative to HYC, suggesting a decline related to healthy aging. This study supports the existence of impaired emotion recognition early in the PD course, implicating an early disruption of fronto-striatal loops mediating emotional function.

  11. Home Environment as a Predictor of Long-Term Executive Functioning following Early Childhood Traumatic Brain Injury.

    Science.gov (United States)

    Durish, Christianne Laliberté; Yeates, Keith Owen; Stancin, Terry; Taylor, H Gerry; Walz, Nicolay C; Wade, Shari L

    2017-07-20

    This study examined the relationship of the home environment to long-term executive functioning (EF) following early childhood traumatic brain injury (TBI). Participants (N=134) were drawn from a larger parent study of 3- to 6-year-old children hospitalized for severe TBI (n=16), complicated mild/moderate TBI (n=44), or orthopedic injury (OI; n=74), recruited prospectively at four tertiary care hospitals in the United States and followed for an average of 6.8 years post-injury. Quality of the home environment, caregiver psychological distress, and general family functioning were assessed shortly after injury (i.e., early home) and again at follow-up (i.e., late home). Participants completed several performance-based measures of EF at follow-up. Hierarchical regression analyses examined the early and late home environment measures as predictors of EF, both as main effects and as moderators of group differences. The early and late home environment were inconsistent predictors of long-term EF across groups. Group differences in EF were significant for only the TEA-Ch Walk/Don't Walk subtest, with poorer performance in the severe TBI group. However, several significant interactions suggested that the home environment moderated group differences in EF, particularly after complicated mild/moderate TBI. The home environment is not a consistent predictor of long-term EF in children with early TBI and OI, but may moderate the effects of TBI on EF. The findings suggest that interventions designed to improve the quality of stimulation in children's home environments might reduce the long-term effects of early childhood TBI on EF. (JINS, 2017, 23, 1-11).

  12. Emotion recognition in early Parkinson's disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants

    Directory of Open Access Journals (Sweden)

    Lindsey G. McIntosh

    2015-01-01

    Full Text Available Parkinson’s disease (PD is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits. In addition, contrasting this with a group of healthy aging individuals demonstrates changes in emotion processing specific to the degeneration of basal ganglia circuitry in PD. Early PD patients (EPD were recruited from a randomized clinical trial testing the safety and tolerability of deep brain stimulation of the subthalamic nucleus (STN-DBS in early-staged PD. EPD patients were previously randomized to receive optimal drug therapy only (ODT, or drug therapy plus STN-DBS (ODT+DBS. Matched healthy elderly controls (HEC and young controls (HYC also participated in this study. Participants completed two control tasks and three emotion recognition tests that varied in stimulus domain. EPD patients were impaired on all emotion recognition tasks compared to HEC. Neither therapy type (ODT or ODT+DBS nor therapy state (ON/OFF altered emotion recognition performance in this study. Finally, HEC were impaired on vocal emotion recognition relative to HYC, suggesting a decline related to healthy aging. This study supports the existence of impaired emotion recognition early in the PD course, implicating an early disruption of fronto-striatal loops mediating emotional function.

  13. Consequences of early life stress on the expression of endocannabinoid-related genes in the rat brain.

    Science.gov (United States)

    Marco, Eva M; Echeverry-Alzate, Victor; López-Moreno, Jose Antonio; Giné, Elena; Peñasco, Sara; Viveros, Maria Paz

    2014-09-01

    The endocannabinoid system is involved in several physiological and pathological states including anxiety, depression, addiction and other neuropsychiatric disorders. Evidence from human and rodent studies suggests that exposure to early life stress may increase the risk of psychopathology later in life. Indeed, maternal deprivation (MD) (24 h at postnatal day 9) in rats induces behavioural alterations associated with depressive-like and psychotic-like symptoms, as well as important changes in the endocannabinoid system. As most neuropsychiatric disorders first appear at adolescence, and show remarkable sexual dimorphisms in their prevalence and severity, in the present study, we analysed the gene expression of the main components of the brain cannabinoid system in adolescent (postnatal day 46) Wistar male and female rats reared under standard conditions or exposed to MD. For this, we analysed, by real-time quantitative PCR, the expression of genes encoding for CB1 and CB2 receptors, TRPV1 and GPR55 (Cnr1, Cnr2a, Cnr2b, Trpv1, and Gpr55), for the major enzymes of synthesis, N-acyl phosphatidyl-ethanolamine phospholipase D (NAPE-PLD) and diacylglycerol lipase (DAGL) (Nape-pld, Dagla and Daglb), and degradation, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) (Faah, Magl and Cox-2), in specific brain regions, that is, the frontal cortex, ventral and dorsal striatum, dorsal hippocampus and amygdala. In males, MD increased the genetic expression of all the genes studied within the frontal cortex, whereas in females such an increase was observed only in the hippocampus. In conclusion, the endocannabinoid system is sensitive to early life stress at the gene expression level in a sex-dependent and region-dependent manner, and these changes are already evident in the adolescent brain.

  14. Early changes in Huntington's disease patient brains involve alterations in cytoskeletal and synaptic elements.

    Science.gov (United States)

    DiProspero, Nicholas A; Chen, Er-Yun; Charles, Vinod; Plomann, Markus; Kordower, Jeffrey H; Tagle, Danilo A

    2004-09-01

    Huntington's disease (HD) is caused by a polyglutamine repeat expansion in the N-terminus of the huntingtin protein. Huntingtin is normally present in the cytoplasm where it may interact with structural and synaptic elements. The mechanism of HD pathogenesis remains unknown but studies indicate a toxic gain-of-function possibly through aberrant protein interactions. To investigate whether early degenerative changes in HD involve alterations of cytoskeletal and vesicular components, we examined early cellular changes in the frontal cortex of HD presymptomatic (PS), early pathological grade (grade 1) and late-stage (grade 3 and 4) patients as compared to age-matched controls. Morphologic analysis using silver impregnation revealed a progressive decrease in neuronal fiber density and organization in pyramidal cell layers beginning in presymptomatic HD cases. Immunocytochemical analyses for the cytoskeletal markers alpha -tubulin, microtubule-associated protein 2, and phosphorylated neurofilament demonstrated a concomitant loss of staining in early grade cases. Immunoblotting for synaptic proteins revealed a reduction in complexin 2, which was marked in some grade 1 HD cases and significantly reduced in all late stage cases. Interestingly, we demonstrate that two synaptic proteins, dynamin and PACSIN 1, which were unchanged by immunoblotting, showed a striking loss by immunocytochemistry beginning in early stage HD tissue suggesting abnormal distribution of these proteins. We propose that mutant huntingtin affects proteins involved in synaptic function and cytoskeletal integrity before symptoms develop which may influence early disease onset and/or progression.

  15. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  16. Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma - a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Lau, S.K.; Wei, W.I.; Sham, J.S.T.; Choy, D.T.K.; Hui, Y. (Queen Mary Hospital, Hong Kong (Hong Kong))

    1992-10-01

    A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway. (Author).

  17. Perceptions of physical activity and walking in an early stage after stroke or acquired brain injury.

    Science.gov (United States)

    Törnbom, Karin; Sunnerhagen, Katharina S; Danielsson, Anna

    2017-01-01

    Physical activity has been established as being highly beneficial for health after stroke. There are considerable global efforts to find rehabilitation programs that encourage increased physical activity for persons with stroke. However, many persons with stroke or acquired brain injury do not reach recommended levels of physical activity and increased knowledge about why is needed. We aimed to explore views and experiences of physical activity and walking among persons with stroke or acquired brain injury. A qualitative study was conducted, among persons with stroke (n = 8) or acquired brain injury (n = 2) from a rehabilitation unit at Sahlgrenska University Hospital in Sweden. Semi-structured in-depth interviews were held about perceptions and experiences of walking and physical activity in general. Data were analyzed using qualitative content analysis, with categories that were determined inductively. Physical activity in general and walking ability more specifically were considered very important by the participants. However, physical activity was, regardless of exercising habits pre-injury, associated with different kinds of negative feelings and experiences. Commonly reported internal barriers in the current study were; fatigue, fear of falling or getting hurt in traffic, lack of motivation and depression. Reported external barriers were mostly related to walking, for example; bad weather, uneven ground, lack of company or noisy or too busy surroundings. Persons with stroke or acquired brain injury found it difficult to engage in and sustain an eligible level of physical activity. Understanding individual concerns about motivators and barriers surrounding physical activity may facilitate the work of forming tailor-made rehabilitation for these groups, so that the levels of physical activity and walking can increase.

  18. Perceptions of physical activity and walking in an early stage after stroke or acquired brain injury

    Science.gov (United States)

    2017-01-01

    Background Physical activity has been established as being highly beneficial for health after stroke. There are considerable global efforts to find rehabilitation programs that encourage increased physical activity for persons with stroke. However, many persons with stroke or acquired brain injury do not reach recommended levels of physical activity and increased knowledge about why is needed. We aimed to explore views and experiences of physical activity and walking among persons with stroke or acquired brain injury. Method A qualitative study was conducted, among persons with stroke (n = 8) or acquired brain injury (n = 2) from a rehabilitation unit at Sahlgrenska University Hospital in Sweden. Semi-structured in-depth interviews were held about perceptions and experiences of walking and physical activity in general. Data were analyzed using qualitative content analysis, with categories that were determined inductively. Results Physical activity in general and walking ability more specifically were considered very important by the participants. However, physical activity was, regardless of exercising habits pre-injury, associated with different kinds of negative feelings and experiences. Commonly reported internal barriers in the current study were; fatigue, fear of falling or getting hurt in traffic, lack of motivation and depression. Reported external barriers were mostly related to walking, for example; bad weather, uneven ground, lack of company or noisy or too busy surroundings. Conclusion Persons with stroke or acquired brain injury found it difficult to engage in and sustain an eligible level of physical activity. Understanding individual concerns about motivators and barriers surrounding physical activity may facilitate the work of forming tailor-made rehabilitation for these groups, so that the levels of physical activity and walking can increase. PMID:28273158

  19. Large-scale brain networks underlying language acquisition in early infancy

    Directory of Open Access Journals (Sweden)

    Fumitaka eHomae

    2011-05-01

    Full Text Available A critical issue in human development is that of whether the language-related areas in the left frontal and temporal regions work as a functional network in preverbal infants. Here, we used 94-channel near-infrared spectroscopy (NIRS to reveal the functional networks in the brains of sleeping 3-month-old infants with and without presenting speech sounds. During the first 3 min, we measured spontaneous brain activation (period 1. After period 1, we provided stimuli by playing Japanese sentences for 3 min (period 2. Finally, we measured brain activation for 3 min without providing the stimulus (period 3, as in period 1. We found that not only the bilateral temporal and temporoparietal regions but also the prefrontal and occipital regions showed oxygenated hemoglobin (oxy-Hb signal increases and deoxygenated hemoglobin (deoxy-Hb signal decreases when speech sounds were presented to infants. By calculating time-lagged cross-correlations and coherences of oxy-Hb signals between channels, we tested the functional connectivity for the 3 periods. The oxy-Hb signals in neighboring channels, as well as their homologous channels in the contralateral hemisphere, showed high correlation coefficients in period 1. Similar correlations were observed in period 2; however, the number of channels showing high correlations was higher in the ipsilateral hemisphere, especially in the anterior-posterior direction. The functional connectivity in period 3 showed a close relationship between the frontal and temporal regions, which was less prominent in period 1, indicating that these regions form the functional networks and work as a hysteresis system that has memory of the previous inputs. We propose a hypothesis that the spatiotemporally large-scale brain networks, including the frontal and temporal regions, underlie speech processing in infants and they might play important roles in language acquisition during infancy.

  20. Multimodal imaging enables early detection and characterization of changes in tumor permeability of brain metastases.

    Science.gov (United States)

    Thorsen, Frits; Fite, Brett; Mahakian, Lisa M; Seo, Jai W; Qin, Shengping; Harrison, Victoria; Johnson, Sarah; Ingham, Elizabeth; Caskey, Charles; Sundstrøm, Terje; Meade, Thomas J; Harter, Patrick N; Skaftnesmo, Kai Ove; Ferrara, Katherine W

    2013-12-28

    Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases. A pharmacokinetic model was applied to estimate vascular permeability. Bioluminescent imaging after injecting d-luciferin (molecular weight (MW) 320 D) suggested that tumor cell extravasation had already occurred at week 1, which was confirmed by histology. 7T T1w MRI at week 4 was able to detect non-leaky 100 μm sized lesions and leaky tumors with diameters down to 200 μm after contrast injection at week 5. PET imaging showed that (18)F-FLT (MW 244 Da) accumulated in the brain at week 4. Gadolinium-based MRI tracers (MW 559 Da and 2.066 kDa) extravasated after 5 weeks (tumor diameter 600 μm), and the lower MW agent cleared more rapidly from the tumor (mean apparent permeabilities 2.27 × 10(-5)cm/s versus 1.12 × 10(-5)cm/s). PET imaging further demonstrated tumor permeability to (64)Cu-BSA (MW 65.55 kDa) at week 6 (tumor diameter 700 μm). In conclusion, high field T1w MRI without contrast may improve the detection limit of small brain metastases, allowing for earlier diagnosis of patients, although the smallest lesions detected with T1w MRI were permeable only to d-luciferin and the amphipathic small molecule (18)F-FLT. Different-sized MR and PET contrast agents demonstrated the gradual increase in leakiness of the blood tumor barrier during metastatic progression, which could guide clinicians in choosing tailored treatment strategies.

  1. Second-order projection from the posterior lateral line in the early zebrafish brain.

    OpenAIRE

    Ghysen Alain; Brajon Carole; Fame Ryann M

    2006-01-01

    Abstract Background Mechanosensory information gathered by hair cells of the fish lateral-line system is collected by sensory neurons and sent to the ipsilateral hindbrain. The information is then conveyed to other brain structures through a second-order projection. In the adult, part of the second-order projection extends to the contralateral hindbrain, while another part connects to a midbrain structure, the torus semicircularis. Results In this paper we examine the second-order projection ...

  2. Sex-dependent gene expression in early brain development of chicken embryos

    Directory of Open Access Journals (Sweden)

    Stigson Michael

    2006-02-01

    Full Text Available Abstract Background Differentiation of the brain during development leads to sexually dimorphic adult reproductive behavior and other neural sex dimorphisms. Genetic mechanisms independent of steroid hormones produced by the gonads have recently been suggested to partly explain these dimorphisms. Results Using cDNA microarrays and real-time PCR we found gene expression differences between the male and female embryonic brain (or whole head that may be independent of morphological differentiation of the gonads. Genes located on the sex chromosomes (ZZ in males and ZW in females were common among the differentially expressed genes, several of which (WPKCI-8, HINT, MHM non-coding RNA have previously been implicated in avian sex determination. A majority of the identified genes were more highly expressed in males. Three of these genes (CDK7, CCNH and BTF2-P44 encode subunits of the transcription factor IIH complex, indicating a role for this complex in neuronal differentiation. Conclusion In conclusion, this study provides novel insights into sexually dimorphic gene expression in the embryonic chicken brain and its possible involvement in sex differentiation of the nervous system in birds.

  3. Early Cerebral Circulation Disturbance in Patients Suffering from Severe Traumatic Brain Injury (TBI): A Xenon CT and Perfusion CT Study

    Science.gov (United States)

    HONDA, Mitsuru; ICHIBAYASHI, Ryo; YOKOMURO, Hiroki; YOSHIHARA, Katsunori; MASUDA, Hiroyuki; HAGA, Daisuke; SEIKI, Yoshikatsu; KUDOH, Chiaki; KISHI, Taichi

    2016-01-01

    Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). Ischemia is a common and deleterious secondary injury following TBI. Detecting early ischemia in TBI patients is important to prevent further advancement and deterioration of the brain tissue. The purpose of this study was to clarify the cerebral circulatory disturbance during the early phase and whether it can be used to predict patient outcome. A total of 90 patients with TBI underwent a xenon-computed tomography (Xe-CT) and subsequently perfusion CT to evaluate the cerebral circulation on days 1–3. We measured CBF using Xe-CT and mean transit time (MTT: the width between two inflection points [maximum upward slope and maximum downward slope from inflow to outflow of the contrast agent]) using perfusion CT and calculated the cerebral blood volume (CBV) using the AZ-7000W98 computer system. The relationships of the hemodynamic parameters CBF, MTT, and CBV to the Glasgow Coma Scale (GCS) score and the Glasgow Outcome Scale (GOS) score were examined. There were no significant differences in CBF, MTT, and CBV among GCS3–4, GCS5–6, and GCS7–8 groups. The patients with a favorable outcome (GR and MD) had significantly higher CBF and lower MTT than those with an unfavorable one (SD, VS, or D). The discriminant analysis of these parameters could predict patient outcome with a probability of 70.6%. During the early phase, CBF reduction and MTT prolongation might influence the clinical outcome of TBI. These parameters are helpful for evaluating the severity of cerebral circulatory disturbance and predicting the outcome of TBI patients. PMID:27356957

  4. Early Cerebral Circulation Disturbance in Patients Suffering from Severe Traumatic Brain Injury (TBI): A Xenon CT and Perfusion CT Study.

    Science.gov (United States)

    Honda, Mitsuru; Ichibayashi, Ryo; Yokomuro, Hiroki; Yoshihara, Katsunori; Masuda, Hiroyuki; Haga, Daisuke; Seiki, Yoshikatsu; Kudoh, Chiaki; Kishi, Taichi

    2016-08-15

    Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). Ischemia is a common and deleterious secondary injury following TBI. Detecting early ischemia in TBI patients is important to prevent further advancement and deterioration of the brain tissue. The purpose of this study was to clarify the cerebral circulatory disturbance during the early phase and whether it can be used to predict patient outcome. A total of 90 patients with TBI underwent a xenon-computed tomography (Xe-CT) and subsequently perfusion CT to evaluate the cerebral circulation on days 1-3. We measured CBF using Xe-CT and mean transit time (MTT: the width between two inflection points [maximum upward slope and maximum downward slope from inflow to outflow of the contrast agent]) using perfusion CT and calculated the cerebral blood volume (CBV) using the AZ-7000W98 computer system. The relationships of the hemodynamic parameters CBF, MTT, and CBV to the Glasgow Coma Scale (GCS) score and the Glasgow Outcome Scale (GOS) score were examined. There were no significant differences in CBF, MTT, and CBV among GCS3-4, GCS5-6, and GCS7-8 groups. The patients with a favorable outcome (GR and MD) had significantly higher CBF and lower MTT than those with an unfavorable one (SD, VS, or D). The discriminant analysis of these parameters could predict patient outcome with a probability of 70.6%. During the early phase, CBF reduction and MTT prolongation might influence the clinical outcome of TBI. These parameters are helpful for evaluating the severity of cerebral circulatory disturbance and predicting the outcome of TBI patients.

  5. Subthalamic nucleus-deep brain stimulation for early motor complications in Parkinson's disease-the EARLYSTIM trial: early is not always better.

    Science.gov (United States)

    Mestre, Tiago A; Espay, Alberto J; Marras, Connie; Eckman, Mark H; Pollak, Pierre; Lang, Anthony E

    2014-12-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) has revolutionized the management of disabling motor complications in Parkinson's disease. The EARLYSTIM trial applied this treatment to patients who had been experiencing motor complications for less than three years. STN-DBS significantly improved all primary and secondary outcome measures while best medical therapy failed to provide any improvement at the two-year follow-up time point. On face value these results strongly favor the application of STN-DBS far earlier than is currently applied, when patients are just beginning to experience problems with motor complications. Here we review the application of early DBS and the EARLYSTIM trial from the perspectives of clinical issues, health economics and study design and patient expectation of benefit. We conclude that the most relevant issue is not when to operate but on whom and that early is not always better. © 2014 International Parkinson and Movement Disorder Society. © 2014 International Parkinson and Movement Disorder Society.

  6. Protective effects and time course of Huangqion early-stage free radical injury following brain trauma in rats

    Institute of Scientific and Technical Information of China (English)

    Hongjie Wang; Xingbo Liu; Xun Wang

    2008-01-01

    BACKGROUND: Huangqi (Astragalus mongholicus), a Chinese herb, has already been included in the "Chinese Pharmacopoeia" for the treatment of ischemic cerebrovascular disease. Secondary injury following brain injury is associated with free radical production, and Huangqi possesses the ability to ameliorate free radical-mediated injury. OBJECTIVE: This study was designed to observe the correlation between anti-free-radical properties of Huangqi and early histological changes of brain tissues following traumatic brain injury. DESIGN, TIME AND SETTING: This study, a randomized, controlled, animal experiment, was performed from May 2006 to June 2007 at the Experimental Center of Science and Technology, School of Basic Science, Liaoning Medical University, Jinzhou City, Liaoning Province, China. MATERIALS: Healthy, adult, Sprague Dawley rats of either gender were included. Huangqi injection was purchased from Heilongjiang Provincial Zhenbaodao Pharmaceutical Co., Ltd., China (National License Medical Number: Z23020781). Na+-K+-adenosine triphosphatase (ATPase), Ca2+-ATPase, and Mg2+-ATPase, as well as kits to measure superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, were purchased from Nanjing Jiancheng Biological Reagent Company, China. METHODS: Seventy-two rats were randomly divided into three groups, with 24 rats in each group: (1) sham-operated group: rats were only exposed, but not injured; (2) model group: brain focal laceration rat models were established by free-falling. These groups were intraperitoneally injected with saline, once every 10 hours; (3) Huangqi group: rats were intraperitoneally injected with 4 mL/kg Huangqi (2 g/mL), once every 10 hours, following brain focal laceration by free-falling. MAIN OUTCOME MEASURES: Ultrastructural changes in brain tissue were observed under an electron microscope 24 hours after injury. The water content of brain tissue was measured using the dry-wet weight method. In addition, the activity of ATPase

  7. Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5.

    Science.gov (United States)

    Mefford, Megan E; Kunstman, Kevin; Wolinsky, Steven M; Gabuzda, Dana

    2015-07-01

    Macrophages express low levels of the CD4 receptor compared to T-cells. Macrophage-tropic HIV strains replicating in brain of untreated patients with HIV-associated dementia (HAD) express Envs that are adapted to overcome this restriction through mechanisms that are poorly understood. Here, bioinformatic analysis of env sequence datasets together with functional studies identified polymorphisms in the β3 strand of the HIV gp120 bridging sheet that increase M-tropism. D197, which results in loss of an N-glycan located near the HIV Env trimer apex, was detected in brain in some HAD patients, while position 200 was estimated to be under positive selection. D197 and T/V200 increased fusion and infection of cells expressing low CD4 by enhancing gp120 binding to CCR5. These results identify polymorphisms in the HIV gp120 bridging sheet that overcome the restriction to macrophage infection imposed by low CD4 through enhanced gp120-CCR5 interactions, thereby promoting infection of brain and other macrophage-rich tissues.

  8. Early-Stage Hyperoxia Is Associated with Favorable Neurological Outcomes and Survival after Severe Traumatic Brain Injury: A Post-Hoc Analysis of the Brain Hypothermia Study.

    Science.gov (United States)

    Fujita, Motoki; Oda, Yasutaka; Yamashita, Susumu; Kaneda, Kotaro; Kaneko, Tadashi; Suehiro, Eiichi; Dohi, Kenji; Kuroda, Yasuhiro; Kobata, Hitoshi; Tsuruta, Ryosuke; Maekawa, Tsuyoshi

    2017-01-19

    The effects of hyperoxia on the neurological outcomes of patients with severe traumatic brain injury (TBI) are still controversial. We examined whether the partial pressure of arterial oxygen (PaO2) and hyperoxia were associated with neurological outcomes and survival by conducting post-hoc analyses of the Brain Hypothermia (B-HYPO) study, a multi-center randomized controlled trial of mild therapeutic hypothermia for severe TBI. The differences in PaO2 and PaO2/fraction of inspiratory oxygen (P/F) ratio on the 1st day of admission were compared between patients with favorable (n = 64) and unfavorable (n = 65) neurological outcomes and between survivors (n = 90) and deceased patients (n = 39). PaO2 and the P/F ratio were significantly greater in patients with favorable outcomes than in patients with unfavorable neurological outcomes (PaO2: 252 ± 122 vs. 202 ± 87 mm Hg, respectively, p = 0.008; P/F ratio: 455 ± 171 vs. 389 ± 155, respectively, p = 0.022) and in survivors than in deceased patients (PaO2: 242 ± 117 vs. 193 ± 75 mm Hg, respectively, p = 0.005; P/F ratio: 445 ± 171 vs. 370 ± 141, respectively, p = 0.018). Similar tendencies were observed in subgroup analyses in patients with fever control and therapeutic hypothermia, and in patients with an evacuated mass or other lesions (unevacuated lesions). PaO2 was independently associated with survival (odds ratio 1.008, p = 0.037). These results suggested that early-stage hyperoxia might be associated with favorable neurological outcomes and survival following severe TBI.

  9. Event-related brain potentials reveal the time-course of language change detection in early bilinguals.

    Science.gov (United States)

    Kuipers, Jan-Rouke; Thierry, Guillaume

    2010-05-01

    Using event-related brain potentials, we investigated the temporal course of language change detection in proficient bilinguals as compared to matched controls. Welsh-English bilingual participants and English controls were presented with a variant of the oddball paradigm involving picture-word pairs. The language of the spoken word was manipulated such that English was the frequent stimulus (75%) and Welsh the infrequent stimulus (25%). We also manipulated semantic relatedness between pictures and words, such that only half of the pictures were followed by a word that corresponded with the identity of the picture. The P2 wave was significantly modulated by language in the bilingual group only, suggesting that this group detected a language change as early as 200 ms after word onset. Monolinguals also reliably detected the language change, but at a later stage of semantic integration (N400 range), since Welsh words were perceived as meaningless. The early detection of a language change in bilinguals triggered stimulus re-evaluation mechanisms reflected by a significant P600 modulation by Welsh words. Furthermore, compared to English unrelated words, English words matching the picture identity elicited significantly greater P2 amplitudes in the bilingual group only, suggesting that proficient bilinguals validate an incoming word against their expectation based on the context. Overall, highly proficient bilinguals appear to detect language changes very early on during speech perception and to consciously monitor language changes when they occur.

  10. Perinatal and early postnatal risk factors for malignant brain tumours in New South Wales children.

    Science.gov (United States)

    McCredie, M; Maisonneuve, P; Boyle, P

    1994-01-02

    A population-based case-control study of incident primary malignant brain tumours diagnosed during 1985-1989 in children aged 0 to 14 years was carried out in the coastal conurbation of New South Wales comprising Sydney, Wollongong and Newcastle in the period 1988 to 1990. Personal interviews were conducted using a structured questionnaire with mothers of 82 cases and 164 control children individually matched to the cases by sex and age. Among the hypotheses examined were those related to: N-nitroso compounds (sources included diet, dummies, medications, tobacco smoke); factors associated with the birth of the child; trauma to the head; and irradiation (X-rays and electromagnetic radiation through electric blankets or water beds). Reported ever-use of a dummy increased the risk of childhood brain tumours (OR = 2.9, 95% CI 1.6 to 5.4), although there did not appear to be any consistent indication of rising risk with reported increased levels of use. Compared with children who had never used a dummy, categories of use during the first year of life of a maximum of "no more than 1 hour per day or night", "several hours per day or night", and "most of the day or night" had statistically significant odds ratios of 2.6, 3.4, and 2.7 respectively. Consumption of fruit by the child before the age of one appeared to be protective. No association was found between childhood brain tumours and birth weight, being the first-born child, or factors linked with the child's birth; head injuries; exposure to X-rays; contact with horses, or living on a farm; pesticide treatment of the house during the child's lifetime; or exposure to burning incense.

  11. Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases. Plan comparison and early clinical evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Rieber, J.; Tonndorf-Martini, E.; Schramm, O.; Rhein, B.; Stefanowicz, S.; Lindel, K.; Debus, J.; Rieken, S. [University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology, Heidelberg (Germany); Kappes, J. [Heidelberg University, Translational Research Unit, Thoraxklinik, Heidelberg (Germany); Heidelberg University, Department of Pneumology, Thoraxklinik, Heidelberg (Germany); Member of the German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); Hoffmann, H. [Heidelberg University, Translational Research Unit, Thoraxklinik, Heidelberg (Germany); Heidelberg University, Department of Thoracic Surgery, Thoraxklinik, Heidelberg (Germany); Member of the German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany)

    2016-11-15

    Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques. Between November 2014 and June 2015, 21 consecutive patients with 25 brain metastases were treated with stereotactic radiosurgery (SRS) in FFF mode. Brain metastases received dose-fractionation schedules of 1 x 20 Gy or 1 x 18 Gy, delivered to the conformally enclosing 80 % isodose. Three patients with critically localized or large (>3 cm) brain metastases were treated with 6 x 5 Gy. Plan quality and efficiency were evaluated by analyzing conformity, dose gradients, dose to healthy brain tissue, treatment delivery time, and number of monitor units. FFF plans were compared to those using the FF method, and early clinical outcome and toxicity were assessed. FFF mode resulted in significant reductions in beam-on time (p < 0.001) and mean brain dose (p = 0.001) relative to FF-mode comparison plans. Furthermore, significant improvements in dose gradients and sharper dose falloffs were found for SRS in FFF mode (-1.1 %, -29.6 %; p ≤ 0.003), but conformity was slightly superior in SRS in FF mode (-1.3 %; p = 0.001). With a median follow-up time of 5.1 months, 6-month overall survival was 63.3 %. Local control was observed in 24 of 25 brain metastases (96 %). SRS in FFF mode is time efficient and provides similar plan quality with the opportunity of slightly reduced dose exposure to healthy brain tissue when compared to SRS in FF mode. Clinical outcomes appear promising and show only modest treatment-related toxicity. (orig.) [German] Die radiochirurgische Behandlung (SRS) von Hirnmetastasen wird vielfach in der klinischen Routine durchgefuehrt. Die zusaetzliche Anwendung von ausgleichsfilterfreien Bestrahlungstechniken (FFF) kann die Bestrahlungszeit

  12. Short-Term Second Language and Music Training Induces Lasting Functional Brain Changes in Early Childhood

    Science.gov (United States)

    Moreno, Sylvain; Lee, Yunjo; Janus, Monika; Bialystok, Ellen

    2015-01-01

    Immediate and lasting effects of music or second-language training were examined in early childhood using event-related potentials. Event-related potentials were recorded for French vowels and musical notes in a passive oddball paradigm in thirty-six 4- to 6-year-old children who received either French or music training. Following training, both…

  13. Short-Term Second Language and Music Training Induces Lasting Functional Brain Changes in Early Childhood

    Science.gov (United States)

    Moreno, Sylvain; Lee, Yunjo; Janus, Monika; Bialystok, Ellen

    2015-01-01

    Immediate and lasting effects of music or second-language training were examined in early childhood using event-related potentials. Event-related potentials were recorded for French vowels and musical notes in a passive oddball paradigm in thirty-six 4- to 6-year-old children who received either French or music training. Following training, both…

  14. Early Childhood Brain Development and Elementary Music Curricula: Are They in Tune?

    Science.gov (United States)

    Scott, Larissa K.

    2004-01-01

    This article examines elementary music curricula. It presents an overview of research on childhood mental development; the importance of the early experiences of children on childhood development; the impact of environmental factors on language development; children's acquisition of music ability; enhancing elementary music curriculum; and…

  15. CYTOMETRIC ANALYSIS OF THE SPECTRUM SUBPOPULATION OF T LYMPHOCYTES IN THE EARLY FORMS OF CHRONIC BRAIN ISCHEMIA VETERANS OF MODERN WARS

    Directory of Open Access Journals (Sweden)

    A. V. Zurochka

    2015-01-01

    Full Text Available Formation of the earliest forms of chronic brain ischemia veterans of modern wars accompanied by an increase in the systemic circulation of the population of T lymphocytes and monocytes, reflecting the activation of central mechanisms lymphopoiesis. In step vascular encephalopathy is an increase in circulating pool of T lymphocytes expressing the activation markers early positive reflecting readiness cells to IL-2 dependent proliferation. When progessirovanii chronic brain ischemia decreased levels of circulating T-regulatory cells, which may reflect a violation of self-tolerance in relation to brain antigens.

  16. No need to talk, I know you: familiarity influences early multisensory integration in a songbird's brain

    Directory of Open Access Journals (Sweden)

    Isabelle GEORGE

    2011-01-01

    Full Text Available It is well known that visual information can affect auditory perception, as in the famous McGurk effect, but little is known concerning the processes involved. To address this issue, we used the best-developed animal model to study language-related processes in the brain: songbirds. European starlings were exposed to audiovisual compared to auditory-only playback of conspecific songs, while electrophysiological recordings were made in their primary auditory area (Field L. The results show that the audiovisual condition modulated the auditory responses. Enhancement and suppression were both observed, depending on the stimulus familiarity. Seeing a familiar bird led to suppressed auditory responses while seeing an unfamiliar bird led to response enhancement, suggesting that unisensory perception may be enough if the stimulus is familiar while redundancy may be required for unfamiliar items. This is to our knowledge the first evidence that multisensory integration may occur in a low-level, putatively unisensory area of a non-mammalian vertebrate brain, and also that familiarity of the stimuli may influence modulation of auditory responses by vision.

  17. [Cerebral activation during Stroop's test in a case of early focal brain injury].

    Science.gov (United States)

    Salgado-Pineda, P; Román, F; Sánchez-Navarro, J P; López-Hernández, F; Bargalló, N; Falcón, C; Ramírez-Ruiz, B; Caldú-Ferrús, X; Martínez-Lage, J

    Functional magnetic resonance imaging (fMRI) offers an important advantage over other functional neuroimaging techniques used with children because of its harmlessness. Previous studies conducted with adults with alexia suggested two ways the brain can reorganise reading after a brain injury affecting the left hemisphere, one contralateral and the other ipsilateral. We describe a study carried out using fMRI of a 10 year old girl with an injury to the left hemisphere caused by a fishing harpoon when she was 6 years old. As a result of the accident the girl presented a right hemiparesia. The girl s parents and teachers also reported difficulties in the acquisition of reading writing and arithmetic, as well as a certain degree of attentional deficit. An fMRI exploration was performed while the girl was doing the Stroop test. The structural MR images showed left hemisphere cortical lesions in the orbital and angular gyrus regions, in addition to the caudate and putamen nuclei, and in the inferior longitudinal bundle. The fRMI revealed a strong overactivation of the right dorsolateral frontal cortex, in the evaluation of interference, and activations of the right angular and bilateral supramarginal gyri, in the evaluation of word reading. The functional study suggests the existence of a reorganisation of reading that is both intra and inter hemispheric.

  18. Functional brain imaging in the dementias: role in early detection, differential diagnosis, and longitudinal studies

    Energy Technology Data Exchange (ETDEWEB)

    Devous, M.D. Sr. [Nuclear Medicine Center and Department of Radiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX (United States)

    2002-12-01

    This review considers the role of functional brain imaging techniques in the dementias. The substantial assistance that especially single-photon emission tomography and positron emission tomography can play in the initial diagnosis of dementia and in the differential diagnosis of the specific dementing disorder is discussed. These techniques alone essentially match the sensitivity and specificity of clinical diagnoses in distinguishing Alzheimer's dementia (AD) from age-matched controls, from frontal lobe dementia and vascular dementia, and even from Lewy body dementia. Newer analytic techniques such as voxel-based correlational analyses and discriminant function analyses enhance the power of such differential diagnoses. Functional brain imaging techniques can also significantly assist in patient screening for clinical trials. The correlation of the observed deficits with specific patterns of cognitive abnormalities permits enhanced patient management and treatment planning and improved longitudinal assessment of outcome. It is also noteworthy that the classic abnormalities of temporoparietal and posterior cingulate hypoperfusion or hypometabolism appear to be present prior to symptom onset. These abnormalities predict progression to AD in the presence of the earliest of symptoms, and are present even in cognitively normal but at-risk subjects, with a severity proportional to the risk status. Even greater predictive ability for progression to AD is obtained by combining measures of perfusion or metabolism with risk factors, tau protein levels, hippocampal N-Acetyl aspartate concentrations, or hippocampal volume measures. (orig.)

  19. Preterm white matter brain injury is prevented by early administration of umbilical cord blood cells.

    Science.gov (United States)

    Li, Jingang; Yawno, Tamara; Sutherland, Amy; Loose, Jan; Nitsos, Ilias; Bischof, Robert; Castillo-Melendez, Margie; McDonald, Courtney A; Wong, Flora Y; Jenkin, Graham; Miller, Suzanne L

    2016-09-01

    Infants born very preterm are at high risk for neurological deficits including cerebral palsy. In this study we assessed the neuroprotective effects of umbilical cord blood cells (UCBCs) and optimal administration timing in a fetal sheep model of preterm brain injury. 50 million allogeneic UCBCs were intravenously administered to fetal sheep (0.7 gestation) at 12h or 5d after acute hypoxia-ischemia (HI) induced by umbilical cord occlusion. The fetal brains were collected at 10d after HI. HI (n=7) was associated with reduced number of oligodendrocytes (Olig2+) and myelin density (CNPase+), and increased density of activated microglia (Iba-1+) in cerebral white matter compared to control fetuses (Pcerebral inflammation. Activated microglial density showed a correlation with decreasing oligodendrocyte number (Pcell death (TUNEL+) in the internal capsule and cell proliferation (Ki-67+) in the subventricular zone compared to control (P<0.05), while UCBCs at 12h or 5d ameliorated these effects. Additionally, UCBCs at 12h induced a significant systemic increase in interleukin-10 at 10d, and reduced oxidative stress (malondialdehyde) following HI (P<0.05). UCBC administration at 12h after HI reduces preterm white matter injury, via anti-inflammatory and antioxidant actions. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  20. Dynamic Regulation of the Adenosine Kinase Gene during Early Postnatal Brain Development and Maturation

    Science.gov (United States)

    Kiese, Katharina; Jablonski, Janos; Boison, Detlev; Kobow, Katja

    2016-01-01

    The ubiquitous metabolic intermediary and nucleoside adenosine is a “master regulator” in all living systems. Under baseline conditions adenosine kinase (ADK) is the primary enzyme for the metabolic clearance of adenosine. By regulating the availability of adenosine, ADK is a critical upstream regulator of complex homeostatic and metabolic networks. Not surprisingly, ADK dysfunction is involved in several pathologies, including diabetes, epilepsy, and cancer. ADK protein exists in the two isoforms nuclear ADK-L, and cytoplasmic ADK-S, which are subject to dynamic expression changes during brain development and in response to brain injury; however, gene expression changes of the Adk gene as well as regulatory mechanisms that direct the cell-type and isoform specific expression of ADK have never been investigated. Here we analyzed potential gene regulatory mechanisms that may influence Adk expression including DNA promoter methylation, histone modifications and transcription factor binding. Our data suggest binding of transcription factor SP1 to the Adk promoter influences the regulation of Adk expression. PMID:27812320

  1. Increased Brain Connectivity In Early Postmenopausal Women with Subjective Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Jennifer N Vega

    2016-09-01

    Full Text Available Cognitive changes after menopause are a common complaint, especially as the loss of estradiol at menopause has been hypothesized to contribute to the higher rates of dementia in women. To explore the neural processes related to subjective cognitive complaints, this study examined resting state functional connectivity in 31 postmenopausal women (aged 50-60 in relationship to cognitive complaints following menopause. A cognitive complaint index was calculated using responses to a 120-item questionnaire. Seed regions were identified for resting state brain networks important for higher-order cognitive processes and for areas that have shown differences in volume and functional activity associated with cognitive complaints in prior studies. Results indicated a positive correlation between the executive control network and cognitive complaint score, weaker negative functional connectivity within the frontal cortex, and stronger positive connectivity within the right middle temporal gyrus in postmenopausal women who report more cognitive complaints. While longitudinal studies are needed to confirm this hypothesis, these data are consistent with previous findings suggesting that high levels of cognitive complaints may reflect changes in brain connectivity and may be a potential marker for the risk of late-life cognitive dysfunction in postmenopausal women with otherwise normal cognitive performance.

  2. Radiographic patterns and survival of patients with early and late brain metastases in EGFR wild type and mutant non small cell lung cancer

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    Yuan, Ren; Yamada, Andrew; Weber, Britta

    2016-01-01

    Brain metastasis (BM) in NSCLC is a negative prognostic indicator. In the era of EGFR mutations we evaluated the difference between early (≤6 months from diagnosis) versus late BM (>6 months), in EGFR wild type (WT) and mutant (MT) NSCLC patients with respect to radiographic patterns and overall...... BM, EGFR MT have an OS comparable to late BM. In contrast, early BM EGFR WT have a significantly reduced survival compared to late BM. The positive outcome in EGFR MT may be secondary to systemic control and EGFR TKI penetrance across the blood brain barrier....

  3. Phylodynamic Characterization of an Ocular-Tropism Coxsackievirus A24 Variant

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    Lu, Po-Liang; Lin, Yung-Cheng; Shi, Yong-Ying; Chou, Li-Chiu; Wang, Chu-Feng; Lin, Yi-Ying; Su, Hui-Ju; Lin, Chien-Ching; Zeng, Jing-Yun; Tyan, Yu-Chang; Ke, Guan-Ming

    2016-01-01

    Recent phylodynamic studies have focused on using tree topology patterns to elucidate interactions among the epidemiological, evolutionary, and demographic characteristics of infectious agents. However, because studies of viral phylodynamics tend to focus on epidemic outbreaks, tree topology signatures of tissue-tropism pathogens might not be clearly identified. Therefore, this study used a novel Bayesian evolutionary approach to analyze the A24 variant of coxsackievirus (CV-A24v), an ocular-tropism agent of acute hemorrhagic conjunctivitis. Analyses of the 915-nucleotide VP1 and 690-nt 3Dpol regions of 21 strains isolated in Taiwan and worldwide during 1985–2010 revealed a clear chronological trend in both the VP1 and 3Dpol phylogenetic trees: the emergence of a single dominant cluster in each outbreak. The VP1 sequences included three genotypes: GI (prototype), GIII (isolated 1985–1999), and GIV (isolated after 2000); no VP1 sequences from GII strains have been deposited in GenBank. Another five genotypes identified in the 3Dpol region had support values >0.9. Geographic and demographic transitions among CV-A24v clusters were clearly identified by Bayes algorithm. The transmission route was mapped from India to China and then to Taiwan, and each prevalent viral population declined before new clusters emerged. Notably, the VP1 and 3Dpol genes had high nucleotide sequence similarities (94.1% and 95.2%, respectively). The lack of co-circulating lineages and narrow tissue tropism affected the CV-A24v gene pool. PMID:27529556

  4. Tropism and infectivity of duck-derived egg drop syndrome virus in chickens.

    Science.gov (United States)

    Kang, Min; Cha, Se-Yeoun; Jang, Hyung-Kwan

    2017-01-01

    Egg drop syndrome virus (EDSV) can markedly decrease egg production in laying hens. Duck is the natural host of EDSV. EDSV derived from ducks abrogate egg drop in laying hens. We have previously confirmed that duck-derived EDSVs have a variety of replication activities in chick embryo liver (CEL) cells. However, it is currently unclear whether duck-derived EDSV could display tropism and adaptation in laying hens. This study assessed whether duck-derived EDSV can adapt to laying hens, and estimated the inducing factors. Complete genome sequences of duck-derived EDSVs (D11-JW-012, D11-JW-017, and D11-JW-032 isolates) with various replication efficiency in CEL cells and C10-GY-001 isolate causing disease in laying hens were analyzed to find their differences. Phylogenetic analysis of complete genome sequence revealed that C10-GY-001, D11-JW-032, and strain 127 virus as vaccine were clustered into the same group, with D11-JW-012 and D11-JW-017 clustered in another group. Comparison between D11-JW-012 isolate that poorly replicated and D11-JW-017 isolate that replicated well in CEL cells in same cluster revealed six amino acid differences on IVa2, DNA polymerase, endopeptidase, and DNA-binding protein. These amino acids might be key candidates enhancing cellular tropism in chicken. When the pathogenicities of these isolates in laying hens were compared, D11-JW-032 showed severe signs similar to 127 virus, D11-JW-017 showed intermediate signs, while D11-JW-012 showed almost no sign. Eleven amino acids differed between D11-JW-032 and D11-JW-017, and 17 amino acids were different between D11-JW-032 and D11-JW-012. These results suggest that EDSVs derived from ducks have various pathogenicities in laying hens. Key amino acid candidates might have altered their affinity to tropism of laying hens, causing difference pathogenicities.

  5. Selective tropism of liver stem cells to hepatocellular carcinoma in vivo

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the selective tropism of liver stem cells to hepatocellular carcinoma (HCC) in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS: WB-F344, a kind of rat liver stem cell,was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein (EGFP). An animal model of HCC in Wistar rats was established by implanting HCC cells (CBRH7919) combined with an immunosuppressive drug.EGFP labeled liver stem cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells.Furthermore, hepatic stem cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stem cells within the tumor tissue were observed and analyzed.RESULTS: Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line,named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo.According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration,localization, and proliferation of the hepatic stem cells within the tumor tissue.CONCLUSION: Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted

  6. Variation in Streptococcus pyogenes NAD+ glycohydrolase is associated with tissue tropism.

    Science.gov (United States)

    Riddle, David J; Bessen, Debra E; Caparon, Michael G

    2010-07-01

    Streptococcus pyogenes is an important pathogen that causes a variety of diseases. The most common infections involve the throat (pharyngitis) or skin (impetigo); however, the factors that determine tissue tropism and severity are incompletely understood. The S. pyogenes NAD(+) glycohydrolase (SPN) is a virulence factor that has been implicated in contributing to the pathogenesis of severe infections. However, the role of SPN in determining the bacterium's tissue tropism has not been evaluated. In this report, we examine the sequences of spn and its endogenous inhibitor ifs from a worldwide collection of S. pyogenes strains. Analysis of average pairwise nucleotide diversity, average number of nucleotide differences, and ratio of nonsynonymous to synonymous substitutions revealed significant diversity in spn and ifs. Application of established models of molecular evolution shows that SPN is evolving under positive selection and diverging into NAD(+) glycohydrolase (NADase)-active and -inactive subtypes. Additionally, the NADase-inactive SPN subtypes maintain the characteristics of a functional gene while ifs becomes a pseudogene. Thus, NADase-inactive SPN continues to evolve under functional constraint. Furthermore, NADase activity did not correlate with invasive disease in our collection but was associated with tissue tropism. The ability to cause infection at both the pharynx and the skin ("generalist" strains) is correlated with NADase-active SPN, while the preference for causing infection at either the throat or the skin ("specialist" strains) is associated with NADase-inactive SPN. These findings suggest that SPN has a NADase-independent function and prompt a reevaluation of the role of SPN in streptococcal pathogenesis.

  7. Enzyme alterations in brain tissue during the early postmortal interval with reference to the histomorphology: review of the literature.

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    Oehmichen, M

    1980-01-01

    The state of research on enzyme alterations in brain tissue during the early postmortal interval is surveyed with special reference to the histomorphology; the questions currently discussed in the literature are given special consideration. The type of alterations appearing during the postmortal interval and their dependency on the length of the interval are described so that practically applicable conclusions may be drawn. The findings on enzyme alterations presented in the literature (enzymes of the oxidative metabolism, transmitter, enzymes) are compiled in tables. It could be shown that important structural alterations ascertainable with light microscopy and quantitative alterations in enzyme activity ascertainable with biochemical methods do not usually occur during a 6- to 8-h postmortal interval. Qualitative investigations (i.e., histoenzymatic studies) with longer postmortal intervals and with positive findings are applicable.

  8. Neuropsychological effects of deep brain stimulation in subjects with early stage Parkinson's disease in a randomized clinical trial.

    Science.gov (United States)

    Tramontana, Michael G; Molinari, Anna L; Konrad, Peter E; Davis, Thomas L; Wylie, Scott A; Neimat, Joseph S; May, Alexandra T; Phibbs, Fenna T; Hedera, Peter; Gill, Chandler E; Salomon, Ronald M; Wang, Lily; Song, Yanna; Charles, David

    2015-01-01

    Deep brain stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor symptom complications. Recently, attention has been focused on whether offering DBS earlier in the course of PD is beneficial. The purpose of this study was to determine the effects of DBS on neuropsychological functioning in subjects with early stage PD. Thirty subjects with early PD (Hoehn & Yahr Stage II off medication) were randomized to optimal drug therapy (ODT) (n = 15) or bilateral subthalamic nucleus (STN) DBS+ODT (n = 15) after completing an expanded informed consent process specially designed for the study and administered by a medical ethicist and the study team. Comprehensive neuropsychological testing was completed in the treatment-withdrawn state at baseline and at 12 month and 24 month follow-ups. Two serious adverse events occurred in the DBS+ODT group. One subject experienced a stroke and another developed infected hardware that contributed to specific declines in cognitive functioning. However, compared to the ODT group, the remaining subjects in the DBS+ODT group exhibited modest reductions on a few measures of attention, executive function, and word fluency at 12 months. These differences were largely diminished at 24 months, especially when those with the adverse events were excluded. The results of this trial provide novel data regarding the effects of DBS on cognitive function in early PD. We believe that the findings and insights from this trial can help guide the safety analysis and risk-benefit evaluations in future discussions of DBS in early stage PD.

  9. Cognitive control deficit in patients with first-episode schizophrenia is associated with complex deviations of early brain development

    Science.gov (United States)

    Gay, Olivier; Plaze, Marion; Oppenheim, Catherine; Gaillard, Raphael; Olié, Jean-Pierre; Krebs, Marie-Odile; Cachia, Arnaud

    2017-01-01

    Background Several clinical and radiological markers of early neurodevelopmental deviations have been independently associated with cognitive impairment in patients with schizophrenia. The aim of our study was to test the cumulative and/or interactive effects of these early neurodevelopmental factors on cognitive control (CC) deficit, a core feature of schizophrenia. Methods We recruited patients with first-episode schizophrenia-spectrum disorders, who underwent structural MRI. We evaluated CC efficiency using the Trail Making Test (TMT). Several markers of early brain development were measured: neurological soft signs (NSS), handedness, sulcal pattern of the anterior cingulate cortex (ACC) and ventricle enlargement. Results We included 41 patients with schizophrenia in our analysis, which revealed a main effect of ACC morphology (p = 0.041) as well as interactions between NSS and ACC morphology (p = 0.005), between NSS and handedness (p = 0.044) and between ACC morphology and cerebrospinal fluid (CSF) volume (p = 0.005) on CC measured using the TMT-B score – the TMT-A score. Limitations No 3- or 4-way interactions were detected between the 4 neurodevelopmental factors. The sample size was clearly adapted to detect main effects and 2-way interactions, but may have limited the statistical power to investigate higher-order interactions. The effects of treatment and illness duration were limited as the study design involved only patients with first-episode psychosis. Conclusion To our knowledge, our study provides the first evidence of cumulative and interactive effects of different neurodevelopmental markers on CC efficiency in patients with schizophrenia. Such findings, in line with the neurodevelopmental model of schizophrenia, support the notion that CC impairments in patients with schizophrenia may be the final common pathway of several early neurodevelopmental mechanisms. PMID:28245174

  10. How healthcare provider talk with parents of children following severe traumatic brain injury is perceived in early acute care.

    Science.gov (United States)

    Roscigno, Cecelia I; Savage, Teresa A; Grant, Gerald; Philipsen, Gerry

    2013-08-01

    Healthcare provider talk with parents in early acute care following children's severe traumatic brain injury (TBI) affects parents' orientations to these locales, but this connection has been minimally studied. This lack of attention to this topic in previous research may reflect providers' and researchers' views that these locales are generally neutral or supportive to parents' subsequent needs. This secondary analysis used data from a larger descriptive phenomenological study (2005-2007) with parents of children following moderate to severe TBI recruited from across the United States. Parents of children with severe TBI consistently had strong negative responses to the early acute care talk processes they experienced with providers, while parents of children with moderate TBI did not. Transcript data were independently coded using discourse analysis in the framework of ethnography of speaking. The purpose was to understand the linguistic and paralinguistic talk factors parents used in their meta-communications that could give a preliminary understanding of their cultural expectations for early acute care talk in these settings. Final participants included 27 parents of children with severe TBI from 23 families. We found the human constructed talk factors that parents reacted to were: a) access to the child, which is where information was; b) regular discussions with key personnel; c) updated information that is explained; d) differing expectations for talk in this context; and, e) perceived parental involvement in decisions. We found that the organization and nature of providers' talk with parents was perceived by parents to positively or negatively shape their early acute care identities in these locales, which influenced how they viewed these locales as places that either supported them and decreased their workload or discounted them and increased their workload for getting what they needed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Neuroprotective Effects of a Smoothened Receptor Agonist against Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats

    Science.gov (United States)

    Hu, Quan; Li, Tong; Wang, Lingxiao; Xie, Yunkai; Liu, Song; Bai, Xuemei; Zhang, Tiantian; Bo, Shishi; Xin, Danqing; Xue, Hao; Li, Gang; Wang, Zhen

    2017-01-01

    The sonic hedgehog (Shh) signaling pathway plays a fundamental role in the central nervous system (CNS) development, but its effects on neural cell survival and brain repair after subarachnoid hemorrhage (SAH) has not been well-investigated. The present study was undertaken to evaluate the influence of an agonist of the Shh co-receptor Smoothened (Smo), purmorphamine (PUR), on early brain injury (EBI) as well as the underlying mechanisms after SAH. PUR was administered via an intraperitoneal injection with a dose of 0.5, 1, and 5 mg/kg at 2, 6, 24, and 46 h after SAH in rat model. The results showed that PUR treatment significantly ameliorated brain edema, improved neurobehavioral function, and attenuated neuronal cell death in the prefrontal cortex (PFC), associated with a decrease in Bax/Bcl-2 ratio and suppression of caspase-3 activation at 48 h after SAH. PUR also promoted phospho-ERK levels. Additionally, PUR treatment markedly decreased MDA concentration accompanied with the elevation in the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in PFC. Notably, PUR treatment significantly reversed the changes of Shh pathway mediators containing Patched, Gli1, and Shh by SAH insult, and the neuroprotection of PUR on SAH was blocked by Smo antagonist cyclopamine. These results indicated that PUR exerts neuroprotection against SAH-evoked injury in rats, mediated in part by anti-apoptotic and anti-oxidant mechanism, up-regulating phospho-ERK levels, mediating Shh signaling molecules in the PFC. PMID:28149272

  12. Motor impairments related to brain injury timing in early hemiparesis. Part II: abnormal upper extremity joint torque synergies.

    Science.gov (United States)

    Sukal-Moulton, Theresa; Krosschell, Kristin J; Gaebler-Spira, Deborah J; Dewald, Julius P A

    2014-01-01

    Extensive neuromotor development occurs early in human life, and the timing of brain injury may affect the resulting motor impairment. In Part I of this series, it was demonstrated that the distribution of weakness in the upper extremity depended on the timing of brain injury in individuals with childhood-onset hemiparesis. The goal of this study was to characterize how timing of brain injury affects joint torque synergies, or losses of independent joint control. Twenty-four individuals with hemiparesis were divided into 3 groups based on the timing of their injury: before birth (PRE-natal, n = 8), around the time of birth (PERI-natal, n = 8), and after 6 months of age (POST-natal, n = 8). Individuals with hemiparesis and 8 typically developing peers participated in maximal isometric shoulder, elbow, wrist, and finger torque generation tasks while their efforts were recorded by a multiple degree-of-freedom load cell. Motor output in 4 joints of the upper extremity was concurrently measured during 8 primary torque generation tasks to quantify joint torque synergies. There were a number of significant coupling patterns identified in individuals with hemiparesis that differed from the typically developing group. POST-natal differences were most noted in the coupling of shoulder abductors with elbow, wrist, and finger flexors, while the PRE-natal group demonstrated significant distal joint coupling with elbow flexion. The torque synergies measured provide indirect evidence for the use of bulbospinal pathways in the POST-natal group, while those with earlier injury may use relatively preserved ipsilateral corticospinal motor pathways.

  13. Topiramate attenuates early brain injury following subarachnoid haemorrhage in rats via duplex protection against inflammation and neuronal cell death.

    Science.gov (United States)

    Tian, Yong; Guo, Song-Xue; Li, Jian-Ru; Du, Hang-Gen; Wang, Chao-Hui; Zhang, Jian-Min; Wu, Qun

    2015-10-05

    Early brain injury (EBI) following aneurysmal subarachnoid haemorrhage (SAH) insults contributes to the poor prognosis and high mortality observed in SAH patients. Topiramate (TPM) is a novel, broad-spectrum, antiepileptic drug with a reported protective effect against several brain injuries. The current study aimed to investigate the potential of TPM for neuroprotection against EBI after SAH and the possible dose-dependency of this effect. An endovascular perforation SAH model was established in rats, and TPM was administered by intraperitoneal injection after surgery at three different doses (20mg/kg, 40mg/kg, and 80mg/kg). The animals' neurological scores and brain water content were evaluated, and ELISA, Western blotting and immunostaining assays were conducted to assess the effect of TPM. The results revealed that TPM lowers the elevated levels of myeloperoxidase and proinflammatory mediators observed after SAH in a dose-related fashion, and the nuclear factor-kappa B (NF-κB) signalling pathway is the target of neuroinflammation regulation. In addition, TPM ameliorated SAH-induced cortical neuronal apoptosis by influencing Bax, Bcl-2 and cleaved caspase-3 protein expression, and the effect of TPM was enhanced in a dose-dependent manner. Various dosages of TPM also upregulated the protein expression of the γ-aminobutyric acid (GABA)-ergic signalling molecules, GABAA receptor (GABAAR) α1, GABAAR γ2, and K(+)-Cl(-) co-transporter 2 (KCC2) together and downregulated Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1) expression. Thus, TPM may be an effective neuroprotectant in EBI after SAH by regulating neuroinflammation and neuronal cell death.

  14. Modeling and simulation of blast-induced, early-time intracranial wave physics leading to traumatic brain injury.

    Energy Technology Data Exchange (ETDEWEB)

    Ford, Corey C. (University of New Mexico, Albuquerque, NM); Taylor, Paul Allen

    2008-02-01

    The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution (1 mm{sup 3} voxels), 5 material model of the human head was created by segmentation of color cryosections from the Visible Human Female dataset. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH, and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior and lateral directions. Three dimensional plots of maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric (shear) stress within the first 2 milliseconds of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 msec time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.

  15. Cell tropism and molecular epidemiology of Anaplasma platys-like strains in cats.

    Science.gov (United States)

    Zobba, R; Anfossi, A G; Visco, S; Sotgiu, F; Dedola, C; Pinna Parpaglia, M L; Battilani, M; Pittau, M; Alberti, A

    2015-04-01

    Bacterial species of the genus Anaplasma are tick transmitted pathogens that negatively impact on animal productions and generate veterinary and public health concerns. This paper reports the identification, molecular characterization and phylogeny of novel unclassified A. platys-like strains in cats. Interestingly, these novel strains are closely related to conspecific strains recently identified in ruminants, and significantly differ from A. platys. A. platys-like strains in cats, unlike ruminants strains, show tropism for platelets. Results have implications in the diagnostic scenario of animal anaplasmosis and provide background for reconstructing the evolutionary history of species genetically related to A. platys. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. Motor impairment factors related to brain injury timing in early hemiparesis. Part I: expression of upper-extremity weakness.

    Science.gov (United States)

    Sukal-Moulton, Theresa; Krosschell, Kristin J; Gaebler-Spira, Deborah J; Dewald, Julius P A

    2014-01-01

    Extensive neuromotor development occurs early in human life, but the time that a brain injury occurs during development has not been rigorously studied when quantifying motor impairments. This study investigated the impact of timing of brain injury on the magnitude and distribution of weakness in the paretic arm of individuals with childhood-onset hemiparesis. A total of 24 individuals with hemiparesis were divided into time periods of injury before birth (PRE-natal, n = 8), around the time of birth (PERI-natal, n = 8), or after 6 months of age (POST-natal, n = 8). They, along with 8 typically developing peers, participated in maximal isometric shoulder, elbow, wrist, and finger torque generation tasks using a multiple-degree-of-freedom load cell to quantify torques in 10 directions. A mixed-model ANOVA was used to determine the effect of group and task on a calculated relative weakness ratio between arms. There was a significant effect of both time of injury group (P < .001) and joint torque direction (P < .001) on the relative weakness of the paretic arm. Distal joints were more affected compared with proximal joints, especially in the POST-natal group. The distribution of weakness provides evidence for the relative preservation of ipsilateral corticospinal motor pathways to the paretic limb in those individuals injured earlier, whereas those who sustained later injury may rely more on indirect ipsilateral corticobulbospinal projections during the generation of torques with the paretic arm.

  17. Motor impairment factors related to brain injury timing in early hemiparesis Part I: expression of upper extremity weakness

    Science.gov (United States)

    Sukal-Moulton, Theresa; Krosschell, Kristin J.; Gaebler-Spira, Deborah J.; Dewald, Julius P.A.

    2014-01-01

    Background Extensive neuromotor development occurs early in human life, but the time that a brain injury occurs during development has not been rigorously studied when quantifying motor impairments. Objective This study investigated the impact of timing of brain injury on magnitude and distribution of weakness in the paretic arm of individuals with childhood-onset hemiparesis. Methods Twenty-four individuals with hemiparesis were divided into time periods of injury before birth (PRE-natal, n=8), around the time of birth (PERI-natal, n=8) or after 6 months of age (POST-natal, n=8). They, along with 8 typically developing peers, participated in maximal isometric shoulder, elbow, wrist, and finger torque generation tasks using a multiple degree-of-freedom load cell to quantify torques in 10 directions. A mixed model ANOVA was used to determine the effect of group and task on a calculated relative weakness ratio between arms. Results There was a significant effect of both time of injury group (p<0.001) and joint torque direction (p<0.001) on the relative weakness of the paretic arm. Distal joints were more affected compared to proximal joints, especially in the POST-natal group. Conclusions The distribution of weakness provides evidence for the relative preservation of ipsilateral corticospinal motor pathways to the paretic limb in those individuals injured earlier, while those who sustained later injury may rely more on indirect ipsilateral cortico-bulbospinal projections during the generation of torques with the paretic arm. PMID:24009182

  18. Real world navigation independence in the early blind correlates with differential brain activity associated with virtual navigation.

    Science.gov (United States)

    Halko, Mark A; Connors, Erin C; Sánchez, Jaime; Merabet, Lotfi B

    2014-06-01

    Navigating is a complex cognitive task that places high demands on spatial abilities, particularly in the absence of sight. Significant advances have been made in identifying the neural correlates associated with various aspects of this skill; however, how the brain is able to navigate in the absence of visual experience remains poorly understood. Furthermore, how neural network activity relates to the wide variability in navigational independence and skill in the blind population is also unknown. Using functional magnetic resonance imaging, we investigated the neural correlates of audio-based navigation within a large scale, indoor virtual environment in early profoundly blind participants with differing levels of spatial navigation independence (assessed by the Santa Barbara Sense of Direction scale). Performing path integration tasks in the virtual environment was associated with activation within areas of a core network implicated in navigation. Furthermore, we found a positive relationship between Santa Barbara Sense of Direction scores and activation within right temporal parietal junction during the planning and execution phases of the task. These findings suggest that differential navigational ability in the blind may be related to the utilization of different brain network structures. Further characterization of the factors that influence network activity may have important implications regarding how this skill is taught in the blind community.

  19. Effect of the Nerve Growth Factor Mimetic GK-2 on Brain Structural and Functional State in the Early Postresuscitation Period

    Directory of Open Access Journals (Sweden)

    M. Sh. Avrushchenko

    2012-01-01

    Full Text Available Objective: to evaluate the efficacy of the nerve growth factor mimetic GK-2 used to improve the structural and functional state of the brain in the early postresuscitation period. Material and methods. Cardiac arrest was induced in mature male albino rats for 12 minutes, followed by resuscitation. The neurological state of the resuscitated animals was assessed by a scoring scale. On postresuscitation day 7, the density and composition of neuronal populations of Purkinje cells in the lateral cerebellar region and pyramidal neurons in the hippocampal CA1 sector were determined by a differential morphometric analysis. The results were statistically processed using the ANOVA method. Results. The use of GK-2 was found to accelerate neurological recovery in the resuscitated animals. On day 7 after 12-minute cardiac arrest, the resuscitated animals showed neuronal dystrophic changes and death in the neuronal populations highly susceptible to ischemia. It was shown that the systemic administration of the nerve growth factor mimetic GK-2 contributed to a reduction in the magnitude and depth of postresuscitation changes in the cerebellar Purkinje cells and prevented dystrophic changes in the pyramidal cells of the hippocampal CA1 sector. The findings suggest that GK-2 has a neuroprotective effect in the recovery period after total body ischemia. Conclusion. The results of this study indicate the efficiency of the systemic administration of the nerve growth factor mimetic GK-2 in improving the brain structural and functional state in the early postresuscitation period. This determines perspectives for the use of GK-2 to prevent and correct posthypoxic encephalopathies. Key words: the nerve growth factor mimetic GK-2, postresuscitation period, neuronal dystrophic changes and death, neurological status.

  20. Diffusion tensor imaging detects early brain microstructure changes before and after ventriculoperitoneal shunt in children with high intracranial pressure hydrocephalus

    Science.gov (United States)

    Zhao, Cailei; Li, Yongxin; Cao, Weiguo; Xiang, Kui; Zhang, Heye; Yang, Jian; Gan, Yungen

    2016-01-01

    Abstract To explore the use of diffusion tensor imaging (DTI) parameters in the quantitative assessment of early brain microstructure changes before and after ventriculoperitoneal shunt in children with high intracranial pressure hydrocephalus. Ten patients with communicating hydrocephalus (age: 2–36 months) and 14 age-/gender-matched controls (age: 2–36 months) were enrolled in this study. All patients underwent the ventriculoperitoneal shunt procedure. The imaging data were collected before and 3 months after the operation. Regions of interests (ROIs) included the white matter near the frontal horn of the lateral ventricles (FHLV), the occipital horn of the lateral ventricles (OHLV), occipital subcortical (OS) area, frontal subcortical (FS) area, and thalamus. Fractional anisotropies (FA) and apparent diffusion coefficients (ADC) of the ROIs before and after ventriculoperitoneal shunt were compared between the patients and the controls. Three months after surgery, the patients recovered from the surgery with ameliorated intracranial pressure and slight improvement of clinical intelligence scale and motor scale. Before ventriculoperitoneal shunt, the FA values (except the right FHLV) were significantly decreased and the ADC values were significantly increased in the patients with hydrocephalus, compared with the controls. After the ventriculoperitoneal shunt, the FA values in the FHLV and OHLV of the patients were similar to the controls, but the FA values in other ROIs were still significantly lower than controls. The ADC values in the FS and OS white matter areas of the patients were similar to the controls; however, the ADC values in other ROIs were still significantly higher in patients. The increase of FA and the reduction in ADC in the ROIs preceded the clinical function improvement in patients with high intracranial pressure hydrocephalus and reflected the early changes in brain tissue microstructure, such as the compression of the white matter areas in

  1. Diffusion tensor imaging detects early brain microstructure changes before and after ventriculoperitoneal shunt in children with high intracranial pressure hydrocephalus.

    Science.gov (United States)

    Zhao, Cailei; Li, Yongxin; Cao, Weiguo; Xiang, Kui; Zhang, Heye; Yang, Jian; Gan, Yungen

    2016-10-01

    To explore the use of diffusion tensor imaging (DTI) parameters in the quantitative assessment of early brain microstructure changes before and after ventriculoperitoneal shunt in children with high intracranial pressure hydrocephalus.Ten patients with communicating hydrocephalus (age: 2-36 months) and 14 age-/gender-matched controls (age: 2-36 months) were enrolled in this study. All patients underwent the ventriculoperitoneal shunt procedure. The imaging data were collected before and 3 months after the operation. Regions of interests (ROIs) included the white matter near the frontal horn of the lateral ventricles (FHLV), the occipital horn of the lateral ventricles (OHLV), occipital subcortical (OS) area, frontal subcortical (FS) area, and thalamus. Fractional anisotropies (FA) and apparent diffusion coefficients (ADC) of the ROIs before and after ventriculoperitoneal shunt were compared between the patients and the controls.Three months after surgery, the patients recovered from the surgery with ameliorated intracranial pressure and slight improvement of clinical intelligence scale and motor scale. Before ventriculoperitoneal shunt, the FA values (except the right FHLV) were significantly decreased and the ADC values were significantly increased in the patients with hydrocephalus, compared with the controls. After the ventriculoperitoneal shunt, the FA values in the FHLV and OHLV of the patients were similar to the controls, but the FA values in other ROIs were still significantly lower than controls. The ADC values in the FS and OS white matter areas of the patients were similar to the controls; however, the ADC values in other ROIs were still significantly higher in patients.The increase of FA and the reduction in ADC in the ROIs preceded the clinical function improvement in patients with high intracranial pressure hydrocephalus and reflected the early changes in brain tissue microstructure, such as the compression of the white matter areas in the ROIs.

  2. A comparison of early diagnostic utility of Alzheimer disease biomarkers in brain magnetic resonance and cerebrospinal fluid.

    Science.gov (United States)

    Monge Argilés, J A; Blanco Cantó, M A; Leiva Salinas, C; Flors, L; Muñoz Ruiz, C; Sánchez Payá, J; Gasparini Berenguer, R; Leiva Santana, C

    2014-09-01

    The goals of this study were to compare the early diagnostic utility of Alzheimer disease biomarkers in the CSF with those in brain MRI in conditions found in our clinical practice, and to ascertain the diagnostic accuracy of both techniques used together. Between 2008 and 2009, we included 30 patients with mild cognitive impairment (MCI) who were examined using 1.5 Tesla brain MRI and AD biomarker analysis in CSF. MRI studies were evaluated by 2 radiologists according to the Korf́s visual scale. CSF biomarkers were analysed using INNOTEST reagents for Aβ1-42, total-tau and phospho-tau181p. We evaluated clinical changes 2 years after inclusion. By 2 years after inclusion, 15 of the original 30 patients (50%) had developed AD (NINCDS-ADRA criteria). The predictive utility of AD biomarkers in CSF (RR 2.7; 95% CI, 1.1-6.7; P<.01) was greater than that of MRI (RR 1.5; 95% CI 95%, 0.7-3.4; P<.2); using both techniques together yielded a sensitivity and a negative predictive value of 100%. Normal results on both complementary tests ruled out progression to AD (100%) within 2 years of inclusion. Our results show that the diagnostic accuracy of biomarkers in CSF is higher than that of biomarkers in MRI. Combined use of both techniques is highly accurate for either early diagnosis or exclusion of AD in patients with MCI. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  3. Sound localization in callosal agenesis and early callosotomy subjects: brain reorganization and/or compensatory strategies.

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    Lessard, Nadia; Lepore, Franco; Villemagne, Jean; Lassonde, Maryse

    2002-05-01

    In order to evaluate the callosal involvement in sound localization, the present study examined the response accuracy of acallosal and early callosotomized subjects to monaural and binaural auditory targets presented in three-dimensional space. In these subjects, bilateral localization cues, such as interaural time and level differences, are integrated at the cortical and subcortical levels without the additional support of the callosal commissure. Because acallosal and early-callosotomized subjects have developed with this reduced source of binaural activation of cortical cells, they might have perfected their ability to use monaural sound localization cues. This hypothesis was tested by assessing localization performance under both binaural and monaural listening conditions. Five subjects with callosal agenesis, one callosotomized subject operated early in life and 19 control subjects were asked to localize broad-band noise bursts (BBNBs) of fixed intensity in the horizontal plane in an anechoic chamber. BBNBs were delivered through randomly selected loudspeakers. Two conditions were tested: (i) localization of a stationary sound source; and (ii) localization of a moving sound source. Listeners had to report the apparent stimulus location by pointing to its perceived position on a graduated perimeter. The results indicated that the acallosal subjects were less accurate than controls, but only in the binaural moving sound condition. More interestingly, in the monaural testing conditions, some of the acallosal subjects and the early-callosotomized subject performed significantly better than control subjects. This suggests that, because of the absence of the corpus callosum, these subjects compensate for their reduced access to cortically determined binaural cues by making more efficient use of monaural cues.

  4. Early Visual Word Processing Is Flexible: Evidence from Spatiotemporal Brain Dynamics.

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    Chen, Yuanyuan; Davis, Matthew H; Pulvermüller, Friedemann; Hauk, Olaf

    2015-09-01

    Visual word recognition is often described as automatic, but the functional locus of top-down effects is still a matter of debate. Do task demands modulate how information is retrieved, or only how it is used? We used EEG/MEG recordings to assess whether, when, and how task contexts modify early retrieval of specific psycholinguistic information in occipitotemporal cortex, an area likely to contribute to early stages of visual word processing. Using a parametric approach, we analyzed the spatiotemporal response patterns of occipitotemporal cortex for orthographic, lexical, and semantic variables in three psycholinguistic tasks: silent reading, lexical decision, and semantic decision. Task modulation of word frequency and imageability effects occurred simultaneously in ventral occipitotemporal regions-in the vicinity of the putative visual word form area-around 160 msec, following task effects on orthographic typicality around 100 msec. Frequency and typicality also produced task-independent effects in anterior temporal lobe regions after 200 msec. The early task modulation for several specific psycholinguistic variables indicates that occipitotemporal areas integrate perceptual input with prior knowledge in a task-dependent manner. Still, later task-independent effects in anterior temporal lobes suggest that word recognition eventually leads to retrieval of semantic information irrespective of task demands. We conclude that even a highly overlearned visual task like word recognition should be described as flexible rather than automatic.

  5. Beyond pleasure and arousal: appetitive erotic stimuli modulate electrophysiological brain correlates of early attentional processing.

    Science.gov (United States)

    Kuhr, Benjamin; Schomberg, Jessica; Gruber, Thomas; Quirin, Markus

    2013-03-27

    Previous studies investigating affective reactions to pictures that elicit a specific effect have mainly focused on the dimensions valence and arousal. Using an event-related picture-viewing paradigm in electroencephalography, we investigated whether erotica - that is appetitive, evolutionarily relevant stimuli - have effects on early stages of attentional processing that are distinct from those of other positive and arousing stimuli. Seventeen male students viewed arousing photos of erotic, nude women or pictures of extreme sport scenes, as well as control pictures of attractive, dressed women or daily activities. Erotic pictures differed from extreme sport pictures not only in late but also in early attentional processes, as indicated by event-related potentials appearing from 130 ms after stimulus onset (P1). The findings suggest (a) that the dimension of appetence should be considered in addition to valence and arousal when investigating psychophysiological reactions to affective-motivational stimuli and (b) that early attentional processing as mirrored by the P1 can be influenced by motivational systems.

  6. Brain somatostatinergic system at late pregnancy, parturition and the early postpartum period in the rat.

    Science.gov (United States)

    Barrios, V; Puebla, L; Rodriguez-Sanchez, M N; Arilla, E

    1993-11-03

    During pregnancy and postpartum rats experience a wide variety of behavioural changes. Since the somatostatinergic system has been implicated in the control of some of these changes, the present study examined somatostatin (SS) content and specific binding in the frontoparietal cortex and hippocampus of non-pregnant, pregnant (17 to 18 days), parturition and postpartum (10 and 30 days) rats as well as in ovariectomized rats which were or were not treated with estradiol valerianate. The content of somatostatin-like immunoreactivity (SSLI) was increased at 17 days of pregnancy in frontoparietal cortex and decreased at parturition and 10 days postpartum in that region and the hippocampus under study when compared with SSLI levels in non-pregnant rats. At 30 days postpartum the SSLI content returned to non-pregnant values in both brain regions. Scatchard analysis showed that the decrease in [125I]Tyr11-SS binding observed at 17 days of pregnancy in the frontoparietal cortex was due to the decrease in the number of SS receptors. In contrast, on the day of delivery the number of SS receptors in the same brain region increased. The affinity of the SS receptors was consistently unchanged in pregnant and non-pregnant rats in both regions. At 10 days postpartum the value of specific binding of the tracer to SS receptors in the frontoparietal cortex was not significantly different from that in the non-pregnant rats, although the actual number of receptors was slightly higher. Pregnancy did not change SS binding in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. A Novel Algorithm for the Assessment of Blood-Brain Barrier Permeability Suggests That Brain Topical Application of Endothelin-1 Does Not Cause Early Opening of the Barrier in Rats

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    D. Jorks

    2011-01-01

    Full Text Available There are a number of different experimental methods for ex vivo assessment of blood-brain barrier (BBB opening based on Evans blue dye extravasation. However, these methods require many different steps to prepare the brain and need special equipment for quantification. We here report a novel, simple, and fast semiquantitative algorithm to assess BBB integrity ex vivo. The method is particularly suitable for cranial window experiments, since it keeps the spatial information about where the BBB opened. We validated the algorithm using sham controls and the established model of brain topical application of the bile salt dehydrocholate for early BBB disruption. We then studied spreading depolarizations in the presence and the absence of the vasoconstrictor endothelin-1 and found no evidence of early BBB opening (three-hour time window. The algorithm can be used, for example, to assess BBB permeability ex vivo in combination with dynamic in vivo studies of BBB opening.

  8. Early-onset Infectious Complications among Penetrating and Severe Closed Traumatic Brain Injury in Active Duty Deployed during OIF and OEF, 2008-2013

    Science.gov (United States)

    2015-02-01

    trauma that manifests as cerebral contusions and bleeding that occurs inside the skull, but outside the brain. The level of injury severity (mild...the form of early in-theater cranial decompression, followed by aggressive critical care management. 8 Medical advances, in addition to improved body...with severe disability. 4 However, early medical complications, that result from the ongoing cellular effects of trauma from the primary injury

  9. Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial

    Science.gov (United States)

    Plomgaard, Anne M.; Alderliesten, Thomas; Austin, Topun; van Bel, Frank; Benders, Manon; Claris, Olivier; Dempsey, Eugene; Fumagalli, Monica; Gluud, Christian; Hagmann, Cornelia; Hyttel-Sorensen, Simon; Lemmers, Petra; van Oeveren, Wim; Pellicer, Adelina; Petersen, Tue H.; Pichler, Gerhard; Winkel, Per; Greisen, Gorm

    2017-01-01

    Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the intervention and the control group. The primary outcome was the reduction in the burden of cerebral hypo- and hyperoxia between the two groups. In this study we describe the associations between the burden of cerebral hypo- and hyperoxia, regardless of allocation to intervention or control group, and the biomarkers of brain injury from birth till term equivalent age that was collected as secondary and explorative outcomes in the SafeBoosC II trial. Methods Cerebral oxygenation was continuously monitored during the first 72h of life in 166 extremely preterm infants. Cranial ultrasound was performed at day 1,4,7,14, and 35 and at term. Electroencephalogram (EEG) was recorded at 64h. Blood-samples taken at 6 and 64 hours were analysed for the brain injury biomarkers; S100beta, brain-fatty-acid-binding-protein, and neuroketal. All analyses were conducted post hoc. Results Significantly more infants with a cerebral burden of hypoxia within the 4th quartile versus infants within quartile 1–3 were diagnosed with severe intracranial haemorrhage (11/39 versus 11/117, p = 0.003), had low burst rate on EEG (12/28 versus 21/103, p = 0.015), or died (14/41 versus 18/123, p = 0.006), whereas none of these events were significantly associated with cerebral hyperoxia. The blood biomarkers were not significantly associated with the burden of cerebral hypo- or hyperoxia. Conclusions The explorative analysis showed that early burden of cerebral hypoxia, but not hyperoxia was significantly associated with low brain electrical activity and severe intracranial haemorrhage while none of the three blood biomarkers were associated with the burden of either cerebral hypo- or hyperoxia. PMID:28328980

  10. Role of hydrogen sulfide in early blood-brain barrier disruption following transient focal cerebral ischemia.

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    Zheng Jiang

    Full Text Available We determined the role of endogenous hydrogen sulfide (H2S in cerebral vasodilation/hyperemia and early BBB disruption following ischemic stroke. A cranial window was prepared over the left frontal, parietal and temporal cortex in mice. Transient focal cerebral Ischemia was induced by directly ligating the middle cerebral artery (MCA for two hours. Regional vascular response and cerebral blood flow (CBF during ischemia and reperfusion were measured in real time. Early BBB disruption was assessed by Evans Blue (EB and sodium fluorescein (Na-F extravasation at 3 hours of reperfusion. Topical treatment with DL-propargylglycine (PAG, an inhibitor for cystathionine γ-lyase (CSE and aspartate (ASP, inhibitor for cysteine aminotransferase/3-mercaptopyruvate sulfurtransferase (CAT/3-MST, but not O-(Carboxymethylhydroxylamine hemihydrochloride (CHH, an inhibitor for cystathionine β-synthase (CBS, abolished postischemic cerebral vasodilation/hyperemia and prevented EB and Na-F extravasation. CSE knockout (CSE-/- reduced postischemic cerebral vasodilation/hyperemia but only inhibited Na-F extravasation. An upregulated CBS was found in cerebral cortex of CSE-/- mice. Topical treatment with CHH didn't further alter postischemic cerebral vasodilation/hyperemia, but prevented EB extravasation in CSE-/- mice. In addition, L-cysteine-induced hydrogen sulfide (H2S production similarly increased in ischemic side cerebral cortex of control and CSE-/- mice. Our findings suggest that endogenous production of H2S by CSE and CAT/3-MST during reperfusion may be involved in postischemic cerebral vasodilation/hyperemia and play an important role in early BBB disruption following transient focal cerebral ischemia.

  11. The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders

    Science.gov (United States)

    Duclot, Florian; Kabbaj, Mohamed

    2017-01-01

    It is now clearly established that complex interactions between genes and environment are involved in multiple aspects of neuropsychiatric disorders, from determining an individual’s vulnerability to onset, to influencing its response to therapeutic intervention. In this perspective, it appears crucial to better understand how the organism reacts to environmental stimuli and provide a coordinated and adapted response. In the central nervous system, neuronal plasticity and neurotransmission are among the major processes integrating such complex interactions between genes and environmental stimuli. In particular, immediate early genes (IEGs) are critical components of these interactions as they provide the molecular framework for a rapid and dynamic response to neuronal activity while opening the possibility for a lasting and sustained adaptation through regulation of the expression of a wide range of genes. As a result, IEGs have been tightly associated with neuronal activity as well as a variety of higher order processes within the central nervous system such as learning, memory and sensitivity to reward. The immediate early gene and transcription factor early growth response 1 (EGR1) has thus been revealed as a major mediator and regulator of synaptic plasticity and neuronal activity in both physiological and pathological conditions. In this review article, we will focus on the role of EGR1 in the central nervous system. First, we will summarize the different factors influencing its activity. Then, we will analyze the amount of data, including genome-wide, that has emerged in the recent years describing the wide variety of genes, pathways and biological functions regulated directly or indirectly by EGR1. We will thus be able to gain better insights into the mechanisms underlying EGR1’s functions in physiological neuronal activity. Finally, we will discuss and illustrate the role of EGR1 in pathological states with a particular interest in cognitive functions

  12. Pathological and incidental findings on brain MRI in a single-center study of 229 consecutive girls with early or precocious puberty.

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    Signe Sloth Mogensen

    Full Text Available UNLABELLED: Central precocious puberty may result from organic brain lesions, but is most frequently of idiopathic origin. Clinical or biochemical factors which could predict a pathological brain MRI in girls with CPP have been searched for. With the recent decline in age at pubertal onset among US and European girls, it has been suggested that only girls with CPP below 6 years of age should have brain MRI performed. OBJECTIVE: To evaluate the outcome of brain MRI in girls referred with early signs of puberty in relation to age at presentation as well as clinical and biochemical parameters. METHOD: A single-center study of 229 consecutive girls with early or precocious puberty who had brain imaging performed. We evaluated medical history, clinical and biochemical factors, and four groups were defined based on the outcome of their MRI. RESULTS: Thirteen out of 208 (6.3% girls with precocious puberty, but no other sign of CNS symptoms, had a pathological brain MRI. Importantly, all 13 girls were above 6 years of age, and 6 girls were even 8-9 years old. Twenty girls (9.6% had incidental findings on brain MRI. Furthermore, 21 girls had known CNS pathology at time of evaluation. Basal LH was significantly higher in girls with newly diagnosed CNS pathology compared to girls with a non-pathological MRI (p = 0.025; no cut of value was found as values overlapped. CONCLUSION: A high frequency of 6-8 year old girls with precocious puberty in our study had a pathological brain MRI, which could not be predicted from any clinical nor biochemical parameters. Thus, we believe that girls with precocious pubertal development of central origin before 8 years of age should continue to be examined by a brain MRI.

  13. Early life low intensity stress experience modifies acute stress effects on juvenile brain cell proliferation of European sea bass (D. Labrax).

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    Fokos, S; Pavlidis, M; Yiotis, T; Tsalafouta, A; Papandroulakis, N; Dermon, C R

    2017-01-15

    Early life adversity may be critical for the brain structural plasticity that in turn would influence juvenile behaviour. To address this, we questioned whether early life environment has an impact on stress responses latter in life, using European sea bass, Dicentrarchus labrax, as a model organism. Unpredictable chronic low intensity stress (UCLIS), using a variety of moderate intensity stressors, was applied during two early ontogenetic stages, flexion or formation all fins. At juvenile stage, fish were exposed to acute stress and plasma cortisol, brain mRNA expression of corticosteroid receptors' genes (gr1, gr2, mr) and brain cell proliferation (using BrdU immunohistochemistry) were determined in experimental and matched controls. UCLIS treatment specifically decreased brain gr1 expression in juveniles, but had no effect on the juvenile brain cell proliferation pattern within the major neurogenic zones studied of dorsal (Dm, Dld) and ventral (Vv) telencephalic, preoptic (NPO) areas, periventricular tectum gray zone (PGZ) and valvula cerebellum (VCe). In contrast, exposure to acute stress induced significant plasma cortisol rise, decreases of cerebral cell proliferation in juveniles, not previously exposed to UCLIS, but no effect detected on the expression levels of gr1, gr2 and mr in all groups of different early life history. Interestingly, juveniles with UCLIS history showed modified responses to acute stress, attenuating acute stress-induced cell proliferation decreases, indicating a long-lasting effect of early life treatment. Taken together, early life mild stress experience influences an acute stress plasticity end-point, cerebral cell proliferation, independently of the stress-axis activation, possibly leading to more effective coping styles.

  14. Long-Term Neuropsychological Profiles and Their Role as Mediators of Adaptive Functioning after Traumatic Brain Injury in Early Childhood.

    Science.gov (United States)

    Treble-Barna, Amery; Zang, Huaiyu; Zhang, Nanhua; Taylor, H Gerry; Yeates, Keith Owen; Wade, Shari

    2017-01-15

    The objectives of the study were to characterize long-term neuropsychological outcomes following traumatic brain injury (TBI) sustained during early childhood, and determine whether identified neuropsychological impairments mediated the effect of TBI on long-term adaptive functioning. Participants included 16 children with severe TBI, 42 children with moderate TBI, and 72 children with orthopedic injuries (OI) sustained between ages 3 and 7 years. Children completed neuropsychological tests and caregivers completed a structured interview of child adaptive functioning at 6.9 (±1.10) years post-injury. Profile analysis and multiple mediator modeling were employed. Children with severe TBI demonstrated poorer fluid reasoning and inhibitory control than both children with moderate TBI and OI, as well as slower processing speed than the OI group. Both fluid reasoning and processing speed were significant independent mediators of the effect of severe TBI on adaptive functioning. No neuropsychological measure significantly mediated the effect of moderate TBI on adaptive functioning. Children sustaining early severe TBI demonstrate persisting neuropsychological impairments into adolescence and young adulthood. The impact of severe TBI on children's long-term adaptive functioning is mediated in part by its effects on fluid reasoning and processing speed.

  15. Brain region specific pre-synaptic and post-synaptic degeneration are early components of neuropathology in prion disease.

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    Zuzana Šišková

    Full Text Available Synaptic abnormalities, one of the key features of prion disease pathogenesis, gives rise to functional deficits and contributes to the devastating clinical outcome. The synaptic compartment is the first to succumb in several neurodegenerative diseases linked with protein misfolding but the mechanisms underpinning this are poorly defined. In our current study we document that a focal intrahippocampal injection of the mouse-adapted 22L scrapie strain produces a complex, region-specific pathology in the brain. Our findings reveal that early synaptic changes in the stratum radiatum of the hippocampus, identical to those observed with the ME7 strain, occur when 22L strain is introduced into the hippocampus. The pathology was defined by degenerating Type I pre-synaptic elements progressively enveloped by the post-synaptic density of the dendritic spine. In contrast, the pathology in the cerebellum suggested that dendritic disintegration rather than pre-synaptic abnormalities dominate the early degenerative changes associated with the Purkinje cells. Indeed, both of the major synaptic inputs into the cerebellum, which arise from the parallel and climbing fibers, remained intact even at late stage disease. Immunolabeling with pathway selective antibodies reinforced these findings. These observations demonstrate that neuronal vulnerability to pathological protein misfolding is strongly dependent on the structure and function of the target neurons.

  16. HIV-1 tropism testing in subjects achieving undetectable HIV-1 RNA: diagnostic accuracy, viral evolution and compartmentalization.

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    Christian Pou

    Full Text Available BACKGROUND: Technically, HIV-1 tropism can be evaluated in plasma or peripheral blood mononuclear cells (PBMCs. However, only tropism testing of plasma HIV-1 has been validated as a tool to predict virological response to CCR5 antagonists in clinical trials. The preferable tropism testing strategy in subjects with undetectable HIV-1 viremia, in whom plasma tropism testing is not feasible, remains uncertain. METHODS & RESULTS: We designed a proof-of-concept study including 30 chronically HIV-1-infected individuals who achieved HIV-1 RNA <50 copies/mL during at least 2 years after first-line ART initiation. First, we determined the diagnostic accuracy of 454 and population sequencing of gp120 V3-loops in plasma and PBMCs, as well as of MT-2 assays before ART initiation. The Enhanced Sensitivity Trofile Assay (ESTA was used as the technical reference standard. 454 sequencing of plasma viruses provided the highest agreement with ESTA. The accuracy of 454 sequencing decreased in PBMCs due to reduced specificity. Population sequencing in plasma and PBMCs was slightly less accurate than plasma 454 sequencing, being less sensitive but more specific. MT-2 assays had low sensitivity but 100% specificity. Then, we used optimized 454 sequence data to investigate viral evolution in PBMCs during viremia suppression and only found evolution of R5 viruses in one subject. No de novo CXCR4-using HIV-1 production was observed over time. Finally, Slatkin-Maddison tests suggested that plasma and cell-associated V3 forms were sometimes compartmentalized. CONCLUSIONS: The absence of tropism shifts during viremia suppression suggests that, when available, testing of stored plasma samples is generally safe and informative, provided that HIV-1 suppression is maintained. Tropism testing in PBMCs may not necessarily produce equivalent biological results to plasma, because the structure of viral populations and the diagnostic performance of tropism assays may sometimes vary

  17. Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions.

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    Meaney, Michael J; Aitken, David H; Bodnoff, Shari R; Iny, Linda J; Tatarewicz, Joseph E; Sapolsky, Robert M

    2013-10-01

    Norway rat pups were either handled (H) or undisturbed (nonhandled, NH) in the period between birth and weaning on Day 21. Following weaning, half of the animals in each group were housed socially (Soc), and half were housed in isolation (Isol). At 120-150 days of age, all animals were sacrificed, and the following regions were dissected and frozen at -70 °C until the time of assay: frontal cortex, hippocampus, hypothalamus, amygdala, septum, and pituitary. [3H]Dexamethasone (3H Dex) binding in each region was examined by an in vitro, cytosol, receptor assay. 3H Dex binding was significantly higher in the hippocampus of both H-Soc and H-Isol than in NH groups. In the frontal cortex, 3H Dex binding was higher in the H-Soc animals than in the H-Isol and NH-Isol animals. There were no significant handling or housing effects found in the amygdala, hypothalamus, septum, or pituitary. Thus, early postnatal handling appears to influence the development of the glucocorticoid receptor system in the hippocampus and frontal cortex. These results are discussed as providing a possible mechanism for some of the previously reported effects of early handling on the development of the pituitary-adrenal response to stress. 2013 APA, all rights reserved

  18. Trends in brain oxygenation during mental and physical exercise measured using near-infrared spectroscopy (NIRS): potential for early detection of Alzheimer's disease

    Science.gov (United States)

    Allen, Monica S.; Allen, Jeffery W.; Mikkilineni, Shweta; Liu, Hanli

    2005-04-01

    Motivation: Early diagnosis of Alzheimer's disease (AD) is crucial because symptoms respond best to available treatments in the initial stages of the disease. Recent studies have shown that marked changes in brain oxygenation during mental and physical tasks can be used for noninvasive functional brain imaging to detect Alzheimer"s disease. The goal of our study is to explore the possibility of using near infrared spectroscopy (NIRS) and mapping (NIRM) as a diagnostic tool for AD before the onset of significant morphological changes in the brain. Methods: A 16-channel NIRS brain imager was used to noninvasively measure spatial and temporal changes in cerebral hemodynamics induced during verbal fluency task and physical activity. The experiments involved healthy subjects (n = 10) in the age range of 25+/-5 years. The NIRS signals were taken from the subjects' prefrontal cortex during the activities. Results and Conclusion: Trends of oxygenated and deoxygenated hemoglobin in the prefrontal cortex of the brain were observed. During the mental stimulation, the subjects showed significant increase in oxygenated hemoglobin [HbO2] with a simultaneous decrease in deoxygenated hemoglobin [Hb]. However, physical exercise caused a rise in levels of HbO2 with small variations in Hb. This study basically demonstrates that NIRM taken from the prefrontal cortex of the human brain is sensitive to both mental and physical tasks and holds potential to serve as a diagnostic means for early detection of Alzheimer's disease.

  19. Existence of Distinct GB Virus C/Hepatitis G Virus Variants with Different Tropism

    Science.gov (United States)

    Fogeda, Marta; López-Alcorocho, Juan Manuel; Bartolomé, Javier; Arocena, Carlos; Martín, Maria Angeles; Carreño, Vicente

    2000-01-01

    To study the existence of GB virus C/hepatitis G virus (GBV-C/HGV) variants with different tropism, we have analyzed the heterogeneity and quasispecies composition of GBV-C/HGV isolated from in vitro-infected peripheral blood mononuclear cells (PBMC) and from sera, livers, and PBMC from two chronically infected patients. For this purpose, the GBV-C/HGV 5′ noncoding region (5′NCR) was amplified by reverse transcription-PCR and the amplified products were cloned and sequenced. These analyses showed that the master 5′NCR sequences isolated from the in vitro-infected PBMC and from the PBMC isolated from the patient whose serum was used as the inoculum were identical but different from that of the inoculum. Furthermore, phylogenetic analysis revealed that all PBMC sequences grouped together into a branch which was separate from those of the inoculum. For one of the two chronically infected patients, all the sequences from the PBMC and one from the liver clustered into a single branch while the sequences from the serum and all the other liver sequences grouped together in the other branch. For the other patient, the sequences from the serum and PBMC and three sequences from the liver grouped together into one branch, while the remaining five sequences from the liver were separated in a different cluster. In conclusion, our results support the existence of different GBV-C/HGV variants with different tissue tropism. PMID:10933701

  20. IFN-alpha-induced upregulation of CCR5 leads to expanded HIV tropism in vivo.

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    Cheryl A Stoddart

    2010-02-01

    Full Text Available Chronic immune activation and inflammation (e.g., as manifest by production of type I interferons are major determinants of disease progression in primate lentivirus infections. To investigate the impact of such activation on intrathymic T-cell production, we studied infection of the human thymus implants of SCID-hu Thy/Liv mice with X4 and R5 HIV. X4 HIV was observed to infect CD3(-CD4(+CD8(-CXCR4(+CCR5(- intrathymic T-cell progenitors (ITTP and to abrogate thymopoiesis. R5 HIV, by contrast, first established a nonpathogenic infection of thymic macrophages and then, after many weeks, began to replicate in ITTP. We demonstrate here that the tropism of R5 HIV is expanded and pathogenicity enhanced by upregulation of CCR5 on these key T-cell progenitors. Such CCR5 induction was mediated by interferon-alpha (IFN-alpha in both thymic organ cultures and in SCID-hu mice, and antibody neutralization of IFN-alpha in R5 HIV-infected SCID-hu mice inhibited both CCR5 upregulation and infection of the T-cell progenitors. These observations suggest a mechanism by which IFN-alpha production may paradoxically expand the tropism of R5 HIV and, in so doing, accelerate disease progression.

  1. A unified model of shoot tropism in plants: photo-, gravi- and Propio-ception.

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    Renaud Bastien

    2015-02-01

    Full Text Available Land plants rely mainly on gravitropism and phototropism to control their posture and spatial orientation. In natural conditions, these two major tropisms act concurrently to create a photogravitropic equilibrium in the responsive organ. Recently, a parsimonious model was developed that accurately predicted the complete gravitropic and proprioceptive control over the movement of different organs in different species in response to gravitational stimuli. Here we show that the framework of this unifying graviproprioceptive model can be readily extended to include phototropism. The interaction between gravitropism and phototropism results in an alignment of the apical part of the organ toward a photogravitropic set-point angle. This angle is determined by a combination of the two directional stimuli, gravity and light, weighted by the ratio between the gravi- and photo-sensitivities of the plant organ. In the model, two dimensionless numbers, the graviproprioceptive number B and the photograviceptive number M, control the dynamics and the shapes of the movement. The extended model agrees well with two sets of detailed quantitative data on photogravitropic equilibrium in oat coleoptiles. It is demonstrated that the influence of light intensity I can be included in the model in a power-law-dependent relationship M(I. The numbers B and M and the related photograviceptive number D are all quantitative genetic traits that can be measured in a straightforward manner, opening the way to the phenotyping of molecular and mechanical aspects of shoot tropism.

  2. Endothelial cell tropism is a determinant of H5N1 pathogenesis in mammalian species.

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    Smanla Tundup

    2017-03-01

    Full Text Available The cellular and molecular mechanisms underpinning the unusually high virulence of highly pathogenic avian influenza H5N1 viruses in mammalian species remains unknown. Here, we investigated if the cell tropism of H5N1 virus is a determinant of enhanced virulence in mammalian species. We engineered H5N1 viruses with restricted cell tropism through the exploitation of cell type-specific microRNA expression by incorporating microRNA target sites into the viral genome. Restriction of H5N1 replication in endothelial cells via miR-126 ameliorated disease symptoms, prevented systemic viral spread and limited mortality, despite showing similar levels of peak viral replication in the lungs as compared to control virus-infected mice. Similarly, restriction of H5N1 replication in endothelial cells resulted in ameliorated disease symptoms and decreased viral spread in ferrets. Our studies demonstrate that H5N1 infection of endothelial cells results in excessive production of cytokines and reduces endothelial barrier integrity in the lungs, which culminates in vascular leakage and viral pneumonia. Importantly, our studies suggest a need for a combinational therapy that targets viral components, suppresses host immune responses, and improves endothelial barrier integrity for the treatment of highly pathogenic H5N1 virus infections.

  3. A gammaherpesvirus uses alternative splicing to regulate its tropism and its sensitivity to neutralization.

    Science.gov (United States)

    Machiels, Bénédicte; Stevenson, Philip G; Vanderplasschen, Alain; Gillet, Laurent

    2013-10-01

    Human gammaherpesviruses are associated with the development of lymphomas and epithelial malignancies. The heterogeneity of these tumors reflects the ability of these viruses to route infection to different cell types at various stages of their lifecycle. While the Epstein Barr virus uses gp42--human leukocyte antigen class II interaction as a switch of cell tropism, the molecular mechanism that orientates tropism of rhadinoviruses is still poorly defined. Here, we used bovine herpesvirus 4 (BoHV-4) to further elucidate how rhadinoviruses regulate their infectivity. In the absence of any gp42 homolog, BoHV-4 exploits the alternative splicing of its Bo10 gene to produce distinct viral populations that behave differently based on the originating cell. While epithelial cells produce virions with high levels of the accessory envelope protein gp180, encoded by a Bo10 spliced product, myeloid cells express reduced levels of gp180. As a consequence, virions grown in epithelial cells are hardly infectious for CD14+ circulating cells, but are relatively resistant to antibody neutralization due to the shielding property of gp180 for vulnerable entry epitopes. In contrast, myeloid virions readily infect CD14+ circulating cells but are easily neutralized. This molecular switch could therefore allow BoHV-4 to promote either, on the one hand, its dissemination into the organism, or, on the other hand, its transmission between hosts.

  4. Canine Cutaneous Leishmaniasis: Dissemination and Tissue Tropism of Genetically Distinct Leishmania (Viannia braziliensis Populations

    Directory of Open Access Journals (Sweden)

    Guilherme Marx de Oliveira

    2013-01-01

    Full Text Available Little is known regarding the internal dissemination of initial cutaneous lesions and tissue tropism of Leishmania (Viannia braziliensis populations in naturally infected dogs. The aim of this study was to investigate genetic polymorphisms of L. (V. braziliensis populations in different anatomic sites of naturally infected dogs by using polymerase chain reaction (PCR and low-stringency single specific primer-PCR (LSSP-PCR techniques. The amplified products were analyzed by LSSP-PCR to investigate the genetic variability of the parasite populations present in different anatomical sites. Twenty-three out of the 52 samples gave PCR-positive results. The existence of L. (V. braziliensis strains that remained restricted to cutaneous lesions and others showing characteristics of dissemination to internal organs and healthy skin was observed. LSSP-PCR and numerical analyses revealed that parasite populations that do not disseminate were genetically similar and belonged to a separate phenetic cluster. In contrast, populations that showed spreading to internal organs displayed a more polymorphic genetic profile. Despite the heterogeneity, L. (V. braziliensis populations with identical genetic profiles were observed in popliteal and cervical lymph nodes of the same animal. Our results indicate that infection in dogs can be manifested by dissemination and tissue tropism of genetically distinct populations of L. (V. braziliensis.

  5. Plasma HIV-1 tropism and risk of short-term clinical progression to AIDS or death

    DEFF Research Database (Denmark)

    Fontdevila, Maria Casadellà; Cozzi-Lepri, Alessandro; Phillips, Andrew;

    2014-01-01

    INTRODUCTION: It is uncertain if plasma HIV-1 tropism is an independent predictor of short-term risk of clinical progression / death, in addition to the CD4 count and HIV RNA level. We conducted a nested case-control study within EuroSIDA to assess this question amongst people with current HIV RNA...... level >1000 copies/mL, including both people on ART and those ART naïve. METHODS: People with an AIDS diagnosis or who died from any causes for whom there was a stored plasma sample with HIV-1 RNA (VL)≥1,000 copies/mL available in the time window of 3-12 months prior to the event were identified....... At least one control was selected for each case matched for age, VL and HCV status at the time of sampling. Controls were event-free after a matched duration of time from the date of sampling. Plasma HIV tropism was estimated using 454 and population sequencing (PS). Non-R5 HIV was defined as: (a) ≥2...

  6. A gammaherpesvirus uses alternative splicing to regulate its tropism and its sensitivity to neutralization.

    Directory of Open Access Journals (Sweden)

    Bénédicte Machiels

    2013-10-01

    Full Text Available Human gammaherpesviruses are associated with the development of lymphomas and epithelial malignancies. The heterogeneity of these tumors reflects the ability of these viruses to route infection to different cell types at various stages of their lifecycle. While the Epstein Barr virus uses gp42--human leukocyte antigen class II interaction as a switch of cell tropism, the molecular mechanism that orientates tropism of rhadinoviruses is still poorly defined. Here, we used bovine herpesvirus 4 (BoHV-4 to further elucidate how rhadinoviruses regulate their infectivity. In the absence of any gp42 homolog, BoHV-4 exploits the alternative splicing of its Bo10 gene to produce distinct viral populations that behave differently based on the originating cell. While epithelial cells produce virions with high levels of the accessory envelope protein gp180, encoded by a Bo10 spliced product, myeloid cells express reduced levels of gp180. As a consequence, virions grown in epithelial cells are hardly infectious for CD14+ circulating cells, but are relatively resistant to antibody neutralization due to the shielding property of gp180 for vulnerable entry epitopes. In contrast, myeloid virions readily infect CD14+ circulating cells but are easily neutralized. This molecular switch could therefore allow BoHV-4 to promote either, on the one hand, its dissemination into the organism, or, on the other hand, its transmission between hosts.

  7. Complex determinants of macrophage tropism in env of simian immunodeficiency virus.

    Science.gov (United States)

    Mori, K; Ringler, D J; Kodama, T; Desrosiers, R C

    1992-04-01

    Macrophage-tropic virus variants evolved during the course of infection of individual rhesus monkeys with cloned, non-macrophagetropic simian immunodeficiency virus. Specific changes in the envelope gene (env) were found to be primarily responsible for the dramatic increase in the ability of the virus to replicate in macrophages. Cloned viruses differing at nine amino acid positions in env exhibited a more than 100-fold difference in replicative capacity for primary cultures of rhesus monkey alveolar macrophages. At least five of the nine amino acid changes contributed to macrophage tropism. These determinants were distributed across the full length of env, including both the gp120 and gp41 products of the env gene. Furthermore, the emergence of macrophagetropic variants in vivo was associated with specific pathologic manifestations in which the macrophage is the major infected cell type. Thus, major determinants of macrophage tropism reside in env, they can be complex in nature, and the presence of macrophage-tropic virus variants in vivo can influence the disease course and disease manifestations.

  8. Narrative processing in typically developing children and children with early unilateral brain injury: seeing gesture matters.

    Science.gov (United States)

    Demir, Özlem Ece; Fisher, Joan A; Goldin-Meadow, Susan; Levine, Susan C

    2014-03-01

    Narrative skill in kindergarteners has been shown to be a reliable predictor of later reading comprehension and school achievement. However, we know little about how to scaffold children's narrative skill. Here we examine whether the quality of kindergarten children's narrative retellings depends on the kind of narrative elicitation they are given. We asked this question with respect to typically developing (TD) kindergarten children and children with pre- or perinatal unilateral brain injury (PL), a group that has been shown to have difficulty with narrative production. We compared children's skill in retelling stories originally presented to them in 4 different elicitation formats: (a) wordless cartoons, (b) stories told by a narrator through the auditory modality, (c) stories told by a narrator through the audiovisual modality without co-speech gestures, and (e) stories told by a narrator in the audiovisual modality with co-speech gestures. We found that children told better structured narratives in response to the audiovisual + gesture elicitation format than in response to the other 3 elicitation formats, consistent with findings that co-speech gestures can scaffold other aspects of language and memory. The audiovisual + gesture elicitation format was particularly beneficial for children who had the most difficulty telling a well-structured narrative, a group that included children with larger lesions associated with cerebrovascular infarcts.

  9. Preinjury resilience and mood as predictors of early outcome following mild traumatic brain injury.

    Science.gov (United States)

    McCauley, Stephen R; Wilde, Elisabeth A; Miller, Emmy R; Frisby, Melissa L; Garza, Hector M; Varghese, Reni; Levin, Harvey S; Robertson, Claudia S; McCarthy, James J

    2013-04-15

    There is significant heterogeneity in outcomes following mild traumatic brain injury (mTBI). While several host factors (age, gender, and preinjury psychiatric history) have been investigated, the influence of preinjury psychological resilience and mood status in conjunction with mild TBI remains relatively unexplored. Euthymic mood and high resilience are potentially protective against anxiety and postconcussion symptoms, but their relative contributions are currently unknown. This prospective study obtained preinjury estimates of resilience and mood measures in addition to measures of anxiety (Acute Stress Disorder Scale and PTSD-Checklist-Civilian form) and postconcussion symptom severity (Rivermead Post Concussion Symptoms Questionnaire) resilience or mood status at baseline, but differed significantly on measures of anxiety and postconcussion symptom severity at each subsequent study occasion. Multivariate linear regression analyses were conducted to determine if preinjury resilience and mood were significant contributors to anxiety and postconcussion symptoms during the first month postinjury after accounting for other known host factors (e.g., age at injury, gender, and education). Injury group and preinjury mood status were significant predictors for all three dependent variables at each study occasion (all presilience showed a positive trend only for acute stress severity at baseline, but demonstrated significant prediction of all three dependent measures at one week and one month postinjury. These results suggest that preinjury depressed mood and resilience are significant contributors to the severity of postinjury anxiety and postconcussion symptoms, even after accounting for effects of other specific host factors.

  10. Neuroimaging assessment of early and late neurobiological sequelae of traumatic brain injury: implications for CTE

    Directory of Open Access Journals (Sweden)

    Mark eSundman

    2015-09-01

    Full Text Available Traumatic brain injury (TBI has been increasingly accepted as a major external risk factor for neurodegenerative morbidity and mortality. Recent evidence indicates that the resultant chronic neurobiological sequelae following head trauma may, at least in part, contribute to a pathologically distinct disease known as Chronic Traumatic Encephalopathy (CTE. The clinical manifestation of CTE is variable, but the symptoms of this progressive disease include impaired memory and cognition, affective disorders (i.e., impulsivity, aggression, depression, suicidality, etc., and diminished motor control. Notably, mounting evidence suggests that the pathology contributing to CTE may be caused by repetitive exposure to subconcussive hits to the head, even in those with no history of a clinically evident head injury. Given the millions of athletes and military personnel with potential exposure to repetitive subconcussive insults and TBI, CTE represents an important public health issue. However, the incidence rates and pathological mechanisms are still largely unknown, primarily due to the fact that there is no in vivo diagnostic tool. The primary objective of this manuscript is to address this limitation and discuss potential neuroimaging modalities that may be capable of diagnosing CTE in vivo through the detection of tau and other known pathological features. Additionally, we will discuss the challenges of TBI research, outline the known pathology of CTE (with an emphasis on Tau, review current neuroimaging modalities to assess the potential routes for in vivo diagnosis, and discuss the future directions of CTE research.

  11. Cortical modulations increase in early sessions with brain-machine interface.

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    Miriam Zacksenhouse

    Full Text Available BACKGROUND: During planning and execution of reaching movements, the activity of cortical motor neurons is modulated by a diversity of motor, sensory, and cognitive signals. Brain-machine interfaces (BMIs extract part of these modulations to directly control artificial actuators. However, cortical modulations that emerge in the novel context of operating the BMI are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we analyzed the changes in neuronal modulations that occurred in different cortical motor areas as monkeys learned to use a BMI to control reaching movements. Using spike-train analysis methods we demonstrate that the modulations of the firing-rates of cortical neurons increased abruptly after the monkeys started operating the BMI. Regression analysis revealed that these enhanced modulations were not correlated with the kinematics of the movement. The initial enhancement in firing rate modulations declined gradually with subsequent training in parallel with the improvement in behavioral performance. CONCLUSIONS/SIGNIFICANCE: We conclude that the enhanced modulations are related to computational tasks that are significant especially in novel motor contexts. Although the function and neuronal mechanism of the enhanced cortical modulations are open for further inquiries, we discuss their potential role in processing execution errors and representing corrective or explorative activity. These representations are expected to contribute to the formation of internal models of the external actuator and their decoding may facilitate BMI improvement.

  12. Early Nutritional Interventions for Brain and Cognitive Development in Preterm Infants: A Review of the Literature

    Science.gov (United States)

    Schneider, Nora; Garcia-Rodenas, Clara L.

    2017-01-01

    Adequate nutrition is important for neurodevelopmental outcomes in preterm-born infants. In this review, we aim to summarize the current knowledge on nutritional interventions initiated during the hospital stay targeting brain and cognitive development benefits in preterm human infants. Studies can broadly be split in general dietary intervention studies and studies investigating specific nutrients or nutritional supplements. In general, mother’s breast milk was reported to be better for preterm infants’ neurodevelopment compared to infant formula. The differences in methodologies make it difficult to conclude any effects of interventions with individual nutrients. Only protein and iron level studies showed some consistent findings regarding optimal doses; however, confirmatory studies are needed. This review does not support some widely accepted associations, such as that between long-chain polyunsaturated fatty acid supplementation and visual development. Clear nutritional recommendations cannot be made based on this review. However, the type of infant nutrition (i.e., breast milk versus formula or donor milk), the timing of the nutritional intervention, and the dose of the nutrient/supplement have been found to be relevant factors in determining the success of nutritional intervention studies in preterm infants. PMID:28241501

  13. Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease.

    Science.gov (United States)

    Hacker, Mallory L; Tonascia, James; Turchan, Maxim; Currie, Amanda; Heusinkveld, Lauren; Konrad, Peter E; Davis, Thomas L; Neimat, Joseph S; Phibbs, Fenna T; Hedera, Peter; Wang, Lily; Shi, Yaping; Shade, David M; Sternberg, Alice L; Drye, Lea T; Charles, David

    2015-10-01

    The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Chagas cardiomyopathy: the potential of diastolic dysfunction and brain natriuretic peptide in the early identification of cardiac damage.

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    Ana Garcia-Alvarez

    Full Text Available INTRODUCTION: Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP in the early identification of cardiac involvement in Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-four patients divided into 3 groups--group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32, group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14, and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction 37 pg/ml were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27 ± 26 vs. 11 ± 8 pg/ml, p = 0.03. CONCLUSION/SIGNIFICANCE: In conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease.

  15. Snake pictures draw more early attention than spider pictures in non-phobic women : Evidence from event-related brain potentials

    NARCIS (Netherlands)

    Van Strien, J. W.; Eijlers, R.; Franken, I. H A; Huijding, J.

    2014-01-01

    Snakes were probably the first predators of mammals and may have been important agents of evolutionary changes in the primate visual system allowing rapid visual detection of fearful stimuli (Isbell, 2006). By means of early and late attention-related brain potentials, we examined the hypothesis tha

  16. Snake pictures draw more early attention than spider pictures in non-phobic women: Evidence from event-related brain potentials

    NARCIS (Netherlands)

    J.W. van Strien (Jan); R. Eijlers (R.); I.H.A. Franken (Ingmar); J. Huijding (Jorg)

    2014-01-01

    textabstractSnakes were probably the first predators of mammals and may have been important agents of evolutionary changes in the primate visual system allowing rapid visual detection of fearful stimuli (Isbell, 2006). By means of early and late attention-related brain potentials, we examined the hy

  17. Snake pictures draw more early attention than spider pictures in non-phobic women : Evidence from event-related brain potentials

    NARCIS (Netherlands)

    Van Strien, J. W.; Eijlers, R.; Franken, I. H A; Huijding, J.

    2014-01-01

    Snakes were probably the first predators of mammals and may have been important agents of evolutionary changes in the primate visual system allowing rapid visual detection of fearful stimuli (Isbell, 2006). By means of early and late attention-related brain potentials, we examined the hypothesis tha

  18. Snake pictures draw more early attention than spider pictures in non-phobic women: Evidence from event-related brain potentials

    NARCIS (Netherlands)

    J.W. van Strien (Jan); R. Eijlers (R.); I.H.A. Franken (Ingmar); J. Huijding (Jorg)

    2014-01-01

    textabstractSnakes were probably the first predators of mammals and may have been important agents of evolutionary changes in the primate visual system allowing rapid visual detection of fearful stimuli (Isbell, 2006). By means of early and late attention-related brain potentials, we examined the hy

  19. Patterns of exposure to infectious diseases and social contacts in early life and risk of brain tumours in children and adolescents

    DEFF Research Database (Denmark)

    Andersen, T V; Schmidt, L S; Poulsen, A H;

    2013-01-01

    BACKGROUND: Infectious diseases and social contacts in early life have been proposed to modulate brain tumour risk during late childhood and adolescence. METHODS: CEFALO is an interview-based case-control study in Denmark, Norway, Sweden and Switzerland, including children and adolescents aged 7-...... tumour may reflect involvement of immune functions, recall bias or inverse causality and deserve further attention.......BACKGROUND: Infectious diseases and social contacts in early life have been proposed to modulate brain tumour risk during late childhood and adolescence. METHODS: CEFALO is an interview-based case-control study in Denmark, Norway, Sweden and Switzerland, including children and adolescents aged 7......-19 years with primary intracranial brain tumours diagnosed between 2004 and 2008 and matched population controls. RESULTS: The study included 352 cases (participation rate: 83%) and 646 controls (71%). There was no association with various measures of social contacts: daycare attendance, number...

  20. Phonemic versus allophonic status modulates early brain responses to language sounds: an MEG/ERF study

    DEFF Research Database (Denmark)

    Nielsen, Andreas Højlund; Gebauer, Line; Mcgregor, William

    Objective: An early component of the auditory event-related potential (ERP), the mismatch negativity (MMN/MMNm), has been shown to be sensitive to native versus non-native language sounds (Brandmeyer et al., 2012; Kazanina et al., 2006; Näätänen et al., 1997); i.e. sensitive to phonemic versus...... allophonic sound contrasts. So far this has only been attested between languages. In the present study we wished to investigate this effect within the same language: Does the same sound contrast that is phonemic in one environment, but allophonic in another, elicit different MMNm responses in native......] thus as deviants, respectively. Data were preprocessed using Elekta’s MaxFilter software and SPM8, all statistical analyses were conducted in sensor-space using SPM8. Results: Focusing on the 150-300 ms time period after stimulus onset (typical MMNm time range for language sound contrasts), only...

  1. Early Iron Deficiency Has Brain and Behavior Effects Consistent with Dopaminergic Dysfunction123

    Science.gov (United States)

    Lozoff, Betsy

    2011-01-01

    To honor the late John Beard’s many contributions regarding iron and dopamine biology, this review focuses on recent human studies that test specific hypotheses about effects of early iron deficiency on dopamine system functioning. Short- and long-term alterations associated with iron deficiency in infancy can be related to major dopamine pathways (mesocortical, mesolimbic, nigrostriatal, tuberohypophyseal). Children and young adults who had iron deficiency anemia in infancy show poorer inhibitory control and executive functioning as assessed by neurocognitive tasks where pharmacologic and neuroimaging studies implicate frontal-striatal circuits and the mesocortical dopamine pathway. Alterations in the mesolimbic pathway, where dopamine plays a major role in behavioral activation and inhibition, positive affect, and inherent reward, may help explain altered social-emotional behavior in iron-deficient infants, specifically wariness and hesitance, lack of positive affect, diminished social engagement, etc. Poorer motor sequencing and bimanual coordination and lower spontaneous eye blink rate in iron-deficient anemic infants are consistent with impaired function in the nigrostriatal pathway. Short- and long-term changes in serum prolactin point to dopamine dysfunction in the tuberohypophyseal pathway. These hypothesis-driven findings support the adverse effects of early iron deficiency on dopamine biology. Iron deficiency also has other effects, specifically on other neurotransmitters, myelination, dendritogenesis, neurometabolism in hippocampus and striatum, gene and protein profiles, and associated behaviors. The persistence of poorer cognitive, motor, affective, and sensory system functioning highlights the need to prevent iron deficiency in infancy and to find interventions that lessen the long-term effects of this widespread nutrient disorder. PMID:21346104

  2. Rapid Changes in Cortical and Subcortical Brain Regions after Early Bilateral Enucleation in the Mouse.

    Directory of Open Access Journals (Sweden)

    Olga O Kozanian

    Full Text Available Functional sensory and motor areas in the developing mammalian neocortex are formed through a complex interaction of cortically intrinsic mechanisms, such as gene expression, and cortically extrinsic mechanisms such as those mediated by thalamic input from the senses. Both intrinsic and extrinsic mechanisms are believed to be involved in cortical patterning and the establishment of areal boundaries in early development; however, the nature of the interaction between intrinsic and extrinsic processes is not well understood. In a previous study, we used a perinatal bilateral enucleation mouse model to test some aspects of this interaction by reweighting sensory input to the developing cortex. Visual deprivation at birth resulted in a shift of intraneocortical connections (INCs that aligned with ectopic ephrin A5 expression in the same location ten days later at postnatal day (P 10. A prevailing question remained: Does visual deprivation first induce a change in gene expression, followed by a shift in INCs, or vice versa? In the present study, we address this question by investigating the neuroanatomy and patterns of gene expression in post-natal day (P 1 and 4 mice following bilateral enucleation at birth. Our results demonstrate a rapid reduction in dorsal lateral geniculate nucleus (dLGN size and ephrin A5 gene expression 24-hours post-enucleation, with more profound effects apparent at P4. The reduced nuclear size and diminished gene expression mirrors subtle changes in ephrin A5 expression evident in P1 and P4 enucleated neocortex, 11 and 8 days prior to natural eye opening, respectively. Somatosensory and visual INCs were indistinguishable between P1 and P4 mice bilaterally enucleated at birth, indicating that perinatal bilateral enucleation initiates a rapid change in gene expression (within one day followed by an alteration of sensory INCs later on (second postnatal week. With these results, we gain a deeper understanding of how gene

  3. Early deep brain stimulation in patients with myoclonus-dystonia syndrome.

    Science.gov (United States)

    Rocha, Helena; Linhares, Paulo; Chamadoira, Clara; Rosas, Maria José; Vaz, Rui

    2016-05-01

    Myoclonus-dystonia (MD) is a rare movement disorder which is disabling and frequently refractory to medical treatment. Deep brain stimulation (DBS) of the globus pallidus interna (GPi) has been used to treat some patients. Although there is significant motor improvement with DBS, the impact on disability and on quality of life has been infrequently reported. Also, the benefit of the procedure is not established in patients without ε-sarcoglycan gene (SGCE) mutations. We present two patients with severe MD treated with GPi-DBS, one of the patients without a SGCE mutation. Motor improvements (rest/action/total subscores of the Unified Myoclonus Rating Scale and movement subscore of the Burke-Fahn-Marsden Dystonia Rating Scale [BFMRS]) and disability (BFMRS disability subscore) were carefully evaluated preoperatively and at 6 and 12months after surgery. Quality of life (addressed using the Portuguese version of the Medical Outcomes Study 36-item Short-Form General Health Survey, version 2.0 [SF-36v2]) was tested preoperatively and 12months after DBS. At 12-month follow-up, myoclonus improved 78.6% in Patient 1 and 80.7% in Patient 2, while dystonia improved 37% and 86.7%, respectively. Improvements in disability ranged from 71.4% to 75%. With regard to quality of life, all parameters addressed by the SF-36v2 improved or stabilized in both patients. No major adverse effects were noticed. Improvements in motor symptoms are consistent with reports in the literature and were obtained regardless of the identification of a SGCE gene mutation. There were also significant benefits on disability and quality of life. DBS should be considered for MD.

  4. Early detection of brain death using the Bispectral Index (BIS) in patients treated by extracorporeal cardiopulmonary resuscitation (E-CPR) for refractory cardiac arrest.

    Science.gov (United States)

    Jouffroy, Romain; Lamhaut, Lionel; Guyard, Alexandra; Philippe, Pascal; An, Kim; Spaulding, Christian; Baud, Frédéric; Carli, Pierre; Vivien, Benoît

    2017-08-24

    Despite increasing use of extracorporeal cardiopulmonary resuscitation (E-CPR) for treatment of refractory cardiac arrest patients, prognosis remains dismal, often resulting in brain-death. However, clinical assessment of brain-death occurence is difficult in post-cardiac arrest patients, sedated, paralyzed, under mild therapeutic hypothermia (MTH). Our objective was to assess the usefulness of Bispectral-Index (BIS) monitoring at bedside for an early detection of brain-death occurrence in refractory cardiac arrest patients treated by E-CPR. This prospective study was performed in an intensive care unit of an university hospital. Forty-six patients suffering from refractory cardiac arrest treated by E-CPR were included. BIS was continuously recorded during ICU hospitalization. Clinical brain-death was confirmed when appropriate by EEG and/or cerebral CT angiography. Twenty-nine patients evolved into brain-death and had average BIS values under MTH and after rewarming (temperature ≥35°C) of 4 (0-47) and 0 (0-82), respectively. Among these, 11 (38%) entered into a procedure of organs donation. Among the 17 non-brain-dead patients, the average BIS values at admission and after rewarming were 39 (0-65) and 59 (22-82), respectively. Two patients had on admission a BIS value equal to zero and evolved to a poor prognostic (CPC 4) and died after care limitations. BIS values were significantly different between patients who developed brain death and those who did not. In both groups, no differences were observed between the AUCs of ROC curves for BIS values under MTH and after rewarming (respectively 0.86 vs 0.83, NS). Initial values of BIS could be used as an assessment tool for early detection of brain-death in refractory cardiac arrest patients treated by mild therapeutic hypothermia and E-CPR. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Directory of Open Access Journals (Sweden)

    Jennifer H Campbell

    2014-12-01

    Full Text Available Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab once a week for three weeks beginning on 28 days post-infection (late. Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS, and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+ in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  6. A mathematical theory of shape and neuro-fuzzy methodology-based diagnostic analysis: a comparative study on early detection and treatment planning of brain cancer.

    Science.gov (United States)

    Kar, Subrata; Majumder, D Dutta

    2017-08-01

    Investigation of brain cancer can detect the abnormal growth of tissue in the brain using computed tomography (CT) scans and magnetic resonance (MR) images of patients. The proposed method classifies brain cancer on shape-based feature extraction as either benign or malignant. The authors used input variables such as shape distance (SD) and shape similarity measure (SSM) in fuzzy tools, and used fuzzy rules to evaluate the risk status as an output variable. We presented a classifier neural network system (NNS), namely Levenberg-Marquardt (LM), which is a feed-forward back-propagation learning algorithm used to train the NN for the status of brain cancer, if any, and which achieved satisfactory performance with 100% accuracy. The proposed methodology is divided into three phases. First, we find the region of interest (ROI) in the brain to detect the tumors using CT and MR images. Second, we extract the shape-based features, like SD and SSM, and grade the brain tumors as benign or malignant with the concept of SD function and SSM as shape-based parameters. Third, we classify the brain cancers using neuro-fuzzy tools. In this experiment, we used a 16-sample database with SSM (μ) values and classified the benignancy or malignancy of the brain tumor lesions using the neuro-fuzzy system (NFS). We have developed a fuzzy expert system (FES) and NFS for early detection of brain cancer from CT and MR images. In this experiment, shape-based features, such as SD and SSM, were extracted from the ROI of brain tumor lesions. These shape-based features were considered as input variables and, using fuzzy rules, we were able to evaluate brain cancer risk values for each case. We used an NNS with LM, a feed-forward back-propagation learning algorithm, as a classifier for the diagnosis of brain cancer and achieved satisfactory performance with 100% accuracy. The proposed network was trained with MR image datasets of 16 cases. The 16 cases were fed to the ANN with 2 input neurons, one

  7. Atypical Bilateral Brain Synchronization in the Early Stage of Human Voice Auditory Processing in Young Children with Autism

    Science.gov (United States)

    Kurita, Toshiharu; Kikuchi, Mitsuru; Yoshimura, Yuko; Hiraishi, Hirotoshi; Hasegawa, Chiaki; Takahashi, Tetsuya; Hirosawa, Tetsu; Furutani, Naoki; Higashida, Haruhiro; Ikeda, Takashi; Mutou, Kouhei; Asada, Minoru; Minabe, Yoshio

    2016-01-01

    Autism spectrum disorder (ASD) has been postulated to involve impaired neuronal cooperation in large-scale neural networks, including cortico-cortical interhemispheric circuitry. In the context of ASD, alterations in both peripheral and central auditory processes have also attracted a great deal of interest because these changes appear to represent pathophysiological processes; therefore, many prior studies have focused on atypical auditory responses in ASD. The auditory evoked field (AEF), recorded by magnetoencephalography, and the synchronization of these processes between right and left hemispheres was recently suggested to reflect various cognitive abilities in children. However, to date, no previous study has focused on AEF synchronization in ASD subjects. To assess global coordination across spatially distributed brain regions, the analysis of Omega complexity from multichannel neurophysiological data was proposed. Using Omega complexity analysis, we investigated the global coordination of AEFs in 3–8-year-old typically developing (TD) children (n = 50) and children with ASD (n = 50) in 50-ms time-windows. Children with ASD displayed significantly higher Omega complexities compared with TD children in the time-window of 0–50 ms, suggesting lower whole brain synchronization in the early stage of the P1m component. When we analyzed the left and right hemispheres separately, no significant differences in any time-windows were observed. These results suggest lower right-left hemispheric synchronization in children with ASD compared with TD children. Our study provides new evidence of aberrant neural synchronization in young children with ASD by investigating auditory evoked neural responses to the human voice. PMID:27074011

  8. Sex differences in structural brain asymmetry predict overt aggression in early adolescents.

    Science.gov (United States)

    Visser, Troy A W; Ohan, Jeneva L; Whittle, Sarah; Yücel, Murat; Simmons, Julian G; Allen, Nicholas B

    2014-04-01

    The devastating social, emotional and economic consequences of human aggression are laid bare nightly on newscasts around the world. Aggression is principally mediated by neural circuitry comprising multiple areas of the prefrontal cortex and limbic system, including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), amygdala and hippocampus. A striking characteristic of these regions is their structural asymmetry about the midline (i.e. left vs right hemisphere). Variations in these asymmetries have been linked to clinical disorders characterized by aggression and the rate of aggressive behavior in psychiatric patients. Here, we show for the first time that structural asymmetries in prefrontal cortical areas are also linked to aggression in a normal population of early adolescents. Our findings indicate a relationship between parent reports of aggressive behavior in adolescents and structural asymmetries in the limbic and paralimbic ACC and OFC, and moreover, that this relationship varies by sex. Furthermore, while there was no relationship between aggression and structural asymmetries in the amygdala or hippocampus, hippocampal volumes did predict aggression in females. Taken together, the results suggest that structural asymmetries in the prefrontal cortex may influence human aggression, and that the anatomical basis of aggression varies substantially by sex.

  9. Context-dependent impact of presuppositions on early magnetic brain responses during speech perception.

    Science.gov (United States)

    Hertrich, Ingo; Kirsten, Mareike; Tiemann, Sonja; Beck, Sigrid; Wühle, Anja; Ackermann, Hermann; Rolke, Bettina

    2015-10-01

    Discourse structure enables us to generate expectations based upon linguistic material that has already been introduced. The present magnetoencephalography (MEG) study addresses auditory perception of test sentences in which discourse coherence was manipulated by using presuppositions (PSP) that either correspond or fail to correspond to items in preceding context sentences with respect to uniqueness and existence. Context violations yielded delayed auditory M50 and enhanced auditory M200 cross-correlation responses to syllable onsets within an analysis window of 1.5s following the PSP trigger words. Furthermore, discourse incoherence yielded suppression of spectral power within an expanded alpha band ranging from 6 to 16Hz. This effect showed a bimodal temporal distribution, being significant in an early time window of 0.0-0.5s following the PSP trigger and a late interval of 2.0-2.5s. These findings indicate anticipatory top-down mechanisms interacting with various aspects of bottom-up processing during speech perception.

  10. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors: A Nationwide, Multicenter Study.

    Science.gov (United States)

    Clement, Sarah C; Schouten-van Meeteren, Antoinette Y N; Boot, Annemieke M; Claahsen-van der Grinten, Hedy L; Granzen, Bernd; Sen Han, K; Janssens, Geert O; Michiels, Erna M; van Trotsenburg, A S Paul; Vandertop, W Peter; van Vuurden, Dannis G; Kremer, Leontien C M; Caron, Hubert N; van Santen, Hanneke M

    2016-12-20

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients with craniopharyngeoma or a pituitary gland tumor were excluded. Results of all endocrine investigations, which were performed at diagnosis and during follow-up, were collected from patient charts. Multivariable logistic regression was used to study associations between demographic and tumor- and treatment-related variables and the prevalence of early endocrine disorders. Results After a median follow-up of 6.6 years, 178 CBTS (24.8%) were diagnosed with an endocrine disorder. A total of 159 CBTS (22.1%) presented with at least one endocrine disorder within the first 5 years after diagnosis. The most common endocrine disorders were growth hormone deficiency (12.5%), precocious puberty (12.2%), thyroid-stimulating hormone deficiency (9.2%), and thyroidal hypothyroidism (5.8%). The risk of hypothalamic-pituitary dysfunction (n = 138) was associated with radiotherapy (odds ratio [OR], 15.74; 95% CI, 8.72 to 28.42), younger age at diagnosis (OR, 1.09; 95% CI, 1.04 to 1.14), advanced follow-up time (OR, 1.10; 95% CI, 1.02 to 1.18), hydrocephalus at diagnosis (OR, 1.77; 95% CI, 1.09 to 2.88), and suprasellar (OR, 34.18; 95% CI, 14.74 to 79.29) and infratentorial (OR, 2.65; 95% CI, 1.48 to 4.74) tumor site. Conclusion The prevalence of early endocrine disorders among CBTS is high. The observation that 22.1% of CBTS developed at least one endocrine disorder within the first 5 years after diagnosis stresses the importance of early and regular assessment of endocrine function in CBTS who are at risk for endocrine damage.

  11. Early (N170/M170 face-sensitivity despite right lateral occipital brain damage in acquired prosopagnosia

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    Esther eAlonso Prieto

    2011-12-01

    Full Text Available Compared to objects, pictures of faces elicit a larger early electromagnetic response at occipito-temporal sites on the human scalp, with an onset of 130 ms and a peak at about 170 ms. This N170 face effect is larger in the right than the left hemisphere and has been associated with the early categorization of the stimulus as a face. Here we tested whether this effect can be observed in the absence of some of the visual areas showing a preferential response to faces as typically identified in neuroimaging. Event related potentials were recorded in response to faces, cars and their phase-scrambled versions in a well-known brain-damaged case of prosopagnosia (PS. Despite the patient’s right inferior occipital gyrus lesion encompassing the most posterior cortical area showing preferential response to faces (occipital face area, OFA, we identified an early face-sensitive component over the right occipito-temporal hemisphere of the patient that was identified as the N170. A second experiment supported this conclusion, showing the typical N170 increase of latency and amplitude in response to inverted faces. In contrast, there was no N170 in the left hemisphere, where PS has a lesion to the middle fusiform gyrus and shows no evidence of face-preferential response in neuroimaging (no left fusiform face area, or lFFA. These results were replicated by a magneto-encephalographic (MEG investigation of the patient, disclosing a M170 component only in the right hemisphere. These observations indicate that face preferential activation in the inferior occipital cortex is not necessary to elicit early visual responses associated with face perception (N170/M170 on the human scalp. These results further suggest that when the right inferior occipital cortex is damaged, the integrity of the middle fusiform gyrus and/or the superior temporal sulcus – two areas showing face preferential responses in the patient’s right hemisphere - might be necessary to generate

  12. Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia.

    Science.gov (United States)

    Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita

    2017-01-01

    Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison

  13. Co-receptor tropism prediction among 1045 Indian HIV-1 subtype C sequences: Therapeutic implications for India

    Directory of Open Access Journals (Sweden)

    Kuttiatt Vijesh S

    2010-07-01

    Full Text Available Abstract Background Understanding co-receptor tropism of HIV-1 strains circulating in India will provide key analytical leverage for assessing the potential usefulness of newer antiretroviral drugs such as chemokine co-receptor antagonists among Indian HIV-infected populations. The objective of this study was to determine using in silico methods, HIV-1 tropism among a large number of Indian isolates both from primary clinical isolates as well as from database-derived sequences. Results R5-tropism was seen in 96.8% of a total of 1045 HIV-1 subtype C Indian sequences. Co-receptor prediction of 15 primary clinical isolates detected two X4-tropic strains using the C-PSSM matrix. R5-tropic HIV-1 subtype C V3 sequences were conserved to a greater extent than X4-tropic strains. X4-tropic strains were obtained from subjects who had a significantly longer time since HIV diagnosis (96.5 months compared to R5-tropic strains (20.5 months. Conclusions High prevalence of R5 tropism and greater homogeneity of the V3 sequence among HIV-1 subtype C strains in India suggests the potential benefit of CCR5 antagonists as a therapeutic option in India.

  14. Tissue tropism in the chicken embryo of non-virulent and virulent Newcastle diseases strains that express green fluorescence protein

    NARCIS (Netherlands)

    Al-Garib, S.O.; Gielkens, A.L.J.; Gruys, E.; Peeters, B.P.H.; Koch, G.

    2003-01-01

    The tissue tropism of non-virulent and virulent Newcastle disease virus (NDV) was investigated using 8-day-old and 14-day-old embryonating chicken eggs (ECE), inoculated with an infectious clone of the non-virulent La Sota strain (NDFL-GFP) or its virulent derivative (NDFLtag-GFP). Both strains expr

  15. Vocabulary, syntax, and narrative development in typically developing children and children with early unilateral brain injury: early parental talk about the "there-and-then" matters.

    Science.gov (United States)

    Demir, Özlem Ece; Rowe, Meredith L; Heller, Gabriella; Goldin-Meadow, Susan; Levine, Susan C

    2015-02-01

    This study examines the role of a particular kind of linguistic input--talk about the past and future, pretend, and explanations, that is, talk that is decontextualized--in the development of vocabulary, syntax, and narrative skill in typically developing (TD) children and children with pre- or perinatal brain injury (BI). Decontextualized talk has been shown to be particularly effective in predicting children's language skills, but it is not clear why. We first explored the nature of parent decontextualized talk and found it to be linguistically richer than contextualized talk in parents of both TD and BI children. We then found, again for both groups, that parent decontextualized talk at child age 30 months was a significant predictor of child vocabulary, syntax, and narrative performance at kindergarten, above and beyond the child's own early language skills, parent contextualized talk and demographic factors. Decontextualized talk played a larger role in predicting kindergarten syntax and narrative outcomes for children with lower syntax and narrative skill at age 30 months, and also a larger role in predicting kindergarten narrative outcomes for children with BI than for TD children. The difference between the 2 groups stemmed primarily from the fact that children with BI had lower narrative (but not vocabulary or syntax) scores than TD children. When the 2 groups were matched in terms of narrative skill at kindergarten, the impact that decontextualized talk had on narrative skill did not differ for children with BI and for TD children. Decontextualized talk is thus a strong predictor of later language skill for all children, but may be particularly potent for children at the lower-end of the distribution for language skill. The findings also suggest that variability in the language development of children with BI is influenced not only by the biological characteristics of their lesions, but also by the language input they receive.

  16. Brain-derived neurotrophic factor expression is higher in brain tissue from patients with refractory epilepsy than in normal controls

    Institute of Scientific and Technical Information of China (English)

    Yudan Lv; Jiqing Qiu; Zan Wang; Li Cui; Hongmei Meng; Weihong Lin

    2011-01-01

    The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with refractory epilepsy are associated with brain-derived neurotrophic factor expression alterations.

  17. Brain development in male rats subjected to early weaning and treated with diet containing flour or flaxseed oil after 21 days until 60 days.

    Science.gov (United States)

    Pessanha, C R; da Camara Boueri, B Ferolla; da Costa, L Rodrigues; Ferreira, M Rocha; Melo, H Saldanha; de Abreu, M Duque Coutinho; Pessoa, L Rozeno; da Silva, P C Alves; Pereira, A D'Avila; Ribeiro, D Cavalcante; de Meneses, J Azevedo; da Costa, C A Soares; Boaventura, G T

    2015-08-01

    The precocious interruption of lactation is a prime factor for developmental plasticity. Here we analyzed whether flour or flaxseed oil treatment contributes to body and brain mass in male rats subjected to early weaning. Pups were weaned for separation from their mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, some of the pups were evaluated (C21 v. EW21). After 21 days, control pups (C60) were fed a control diet. EW pups were divided into those fed a control diet (EWC60), those given flaxseed flour (EWFF60), and those given flaxseed oil (EWFO60) until 60 days. EW21 showed lower body and absolute brain mass and higher relative brain mass. At 60 days, EWC60 and EWFO60 had lower body mass. With regard to relative brain mass, EWC60 was heavier; EWFO60 had lower values compared with EWC60 and higher values compared with C60 and EWFF60. These results indicated that flaxseed flour, in comparison with flaxseed oil, contributes to brain development after EW.

  18. Role of nitric oxide synthases in early blood-brain barrier disruption following transient focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Zheng Jiang

    Full Text Available The role of nitric oxide synthases (NOSs in early blood-brain barrier (BBB disruption was determined using a new mouse model of transient focal cerebral ischemia. Ischemia was induced by ligating the middle cerebral artery (MCA at its M2 segment and reperfusion was induced by releasing the ligation. The diameter alteration of the MCA, arterial anastomoses and collateral arteries were imaged and measured in real time. BBB disruption was assessed by Evans Blue (EB and sodium fluorescein (Na-F extravasation at 3 hours of reperfusion. The reperfusion produced an extensive vasodilation and a sustained hyperemia. Although expression of NOSs was not altered at 3 hours of reperfusion, L-NAME (a non-specific NOS inhibitor abolished reperfusion-induced vasodilation/hyperemia and significantly reduced EB and Na-F extravasation. L-NIO (an endothelial NOS (eNOS inhibitor significantly attenuated cerebral vasodilation but not BBB disruption, whereas L-NPA and 7-NI (neuronal NOS (nNOS inhibitors significantly reduced BBB disruption but not cerebral vasodilation. In contrast, aminoguanidine (AG (an inducible NOS (iNOS inhibitor had less effect on either cerebral vasodilation or BBB disruption. On the other hand, papaverine (PV not only increased the vasodilation/hyperemia but also significantly reduced BBB disruption. Combined treatment with L-NAME and PV preserved the vasodilation/hyperemia and significantly reduced BBB disruption. Our findings suggest that nNOS may play a major role in early BBB disruption following transient focal cerebral ischemia via a hyperemia-independent mechanism.

  19. Long-term classroom functioning and its association with neuropsychological and academic performance following traumatic brain injury during early childhood.

    Science.gov (United States)

    Treble-Barna, Amery; Schultz, Hanna; Minich, Nori; Taylor, H Gerry; Yeates, Keith Owen; Stancin, Terry; Wade, Shari L

    2017-07-01

    The present study utilized ecobehavioral assessment to examine classroom functioning several years following early childhood traumatic brain injury (TBI) or orthopedic injury (OI) and its association with injury factors, neuropsychological abilities, and academic performance. Participants included 39 children with moderate to severe TBI and 51 children with OI sustained between ages 3 and 7 years. At 7.2 (± 1.3) years post injury, ecobehavioral assessment was used to examine classroom functioning. Additional outcomes included neuropsychological tests, parent and teacher ratings of dysexecutive behavior, and teacher ratings of academic performance. Groups were compared on measures controlling for demographic characteristics, and associations among outcomes were examined using linear regression. Children with TBI showed lower academic engagement relative to children with OI, as well as more frequent individual teacher attention for children with more severe injuries. For children with TBI, difficulties in classroom functioning were associated with lower cognitive flexibility and higher parent and teacher ratings of dysexecutive behavior. Lower scores on a test of fluid reasoning and a greater frequency of individual teacher attention were also associated with lower academic performance in children with TBI. Difficulties in classroom functioning are evident several years after early childhood TBI and were associated with greater injury severity, neuropsychological weaknesses, and poorer academic performance. Children with impaired cognitive flexibility and fluid reasoning skills were at greatest risk for these difficulties and associated weaknesses in academic performance. Instructional interactions may be a potential target for intervention to promote academic progress in at-risk children. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Early excision and late excision of heterotopic ossification after traumatic brain injury are equivalent: a systematic review of the literature.

    Science.gov (United States)

    Chalidis, Byron; Stengel, Dirk; Giannoudis, Peter V

    2007-11-01

    Heterotopic ossification (HO) is a common complication in patients with coma after brain injury. As the optimal timing of surgical resection is still controversial and unclear, a review of the literature was performed in order to determine the impact of early operation on recurrence rate and joint mobility. We identified all types of studies dealing with surgical excision of HO in patients after head injury in major medical and publishers' databases. Publication bias and statistical heterogeneity were assessed by funnel-plot asymmetry and Galbraith regression. We abstracted demographic and outcome information from manuscripts that tabulated individual patient data (IPD) to build univariate logistic and linear regression models. Means and proportions for random-effects meta-regression analysis were also obtained. Of 318 studies originally identified, 16 observational studies enrolling 255 patients (212 men, 329 affected joints, mean age of 30.6 [+/-SEM of 1.4] years) were included in the analysis. The reported overall recurrence rate in eleven studies was 38/192 (19.8%). Both IPD and meta-regression analysis failed to show a marked impact of the interval to resection on the probability of recurrence (odds ratio 1.00, 95% CI 0.98-1.03). The predicted probability of recurrence after 13, 21, and 30 months of waiting was 9%, 14%, and 19%, respectively. The length of coma period and patient's neurologic deficit were statistically significant negative predictors for both recurrence rate and functional outcome. Although no conclusive inferences can be drawn from the identified studies, the available data do not support the concept that early excision triggers later recurrence.

  1. Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice.

    Science.gov (United States)

    Meyer, Urs; Nyffeler, Myriel; Yee, Benjamin K; Knuesel, Irene; Feldon, Joram

    2008-05-01

    Maternal infection during pregnancy increases the risk for neurodevelopmental disorders such as schizophrenia and autism in the offspring. This association appears to be critically dependent on the precise prenatal timing. However, the extent to which distinct adult psychopathological and neuropathological traits may be sensitive to the precise times of prenatal immune activation remains to be further characterized. Here, we evaluated in a mouse model of prenatal immune challenge by the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyIC), whether prenatal immune activation in early/middle and late gestation may influence the susceptibility to some of the critical cognitive, pharmacological, and neuroanatomical dysfunctions implicated in schizophrenia and autism. We revealed that PolyIC-induced prenatal immune challenge on gestation day (GD) 9 but not GD17 significantly impaired sensorimotor gating and reduced prefrontal dopamine D1 receptors in adulthood, whereas prenatal immune activation specifically in late gestation impaired working memory, potentiated the locomotor reaction to the NMDA-receptor antagonist dizocilpine, and reduced hippocampal NMDA-receptor subunit 1 expression. On the other hand, potentiation of the locomotor reaction to the dopamine-receptor agonist amphetamine and reduction in Reelin- and Parvalbumin-expressing prefrontal neurons emerged independently of the precise times of prenatal immune challenge. Our findings thus highlight that prenatal immune challenge during early/middle and late fetal development in mice leads to distinct brain and behavioral pathological symptom clusters in adulthood. Further examination and evaluation of in utero immune challenge at different times of gestation may provide important new insight into the neuroimmunological and neuropathological mechanisms underlying the segregation of different symptom clusters in heterogeneous neuropsychiatric disorders such as schizophrenia and autism.

  2. Early outcome and blood-brain barrier integrity after co-administered thrombolysis and hyperbaric oxygenation in experimental stroke

    Directory of Open Access Journals (Sweden)

    Michalski Dominik

    2011-06-01

    Full Text Available Abstract Background After promising results in experimental stroke, normobaric (NBO or hyperbaric oxygenation (HBO have recently been discussed as co-medication with tissue plasminogen activator (tPA for improving outcome. This study assessed the interactions of hyperoxia and tPA, focusing on survival, early functional outcome and blood-brain barrier (BBB integrity following experimental stroke. Methods Rats (n = 109 underwent embolic middle cerebral artery occlusion or sham surgery. Animals were assigned to: Control, NBO (60-minute pure oxygen, HBO (60-minute pure oxygen at 2.4 absolute atmospheres, tPA, or HBO+tPA. Functional impairment was assessed at 4 and 24 hours using Menzies score, followed by intravenous application of FITC-albumin as a BBB permeability marker, which was allowed to circulate for 1 hour. Further, blood sampling was performed at 5 and 25 hours for MMP-2, MMP-9, TIMP-1 and TIMP-2 concentration. Results Mortality rates did not differ significantly between groups, whereas functional improvement was found for NBO, tPA and HBO+tPA. NBO and HBO tended to stabilize BBB and to reduce MMP-2. tPA tended to increase BBB permeability with corresponding MMP and TIMP elevation. Co-administered HBO failed to attenuate these early deleterious effects, independent of functional improvement. Conclusions The long-term consequences of simultaneously applied tPA and both NBO and HBO need to be addressed by further studies to identify therapeutic potencies in acute stroke, and to avoid unfavorable courses following combined treatment.

  3. A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus.

    Science.gov (United States)

    Coleman, Stewart; Choi, K Yeon; Root, Matthew; McGregor, Alistair

    2016-07-01

    In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107-179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model.

  4. Blood constituents trigger brain swelling, tissue death, and reduction of glucose metabolism early after acute subdural hematoma in rats.

    Science.gov (United States)

    Baechli, Heidi; Behzad, Melika; Schreckenberger, Matthias; Buchholz, Hans-Georg; Heimann, Axel; Kempski, Oliver; Alessandri, Beat

    2010-03-01

    Outcome from acute subdural hematoma is often worse than would be expected from the pure increase of intracranial volume by bleeding. The aim was to test whether volume-independent pathomechanisms aggravate damage by comparing the effects of blood infusion with those of an inert fluid, paraffin oil, on intracranial pressure (ICP), cerebral perfusion pressure (CPP), local cerebral blood flow (CBF), edema formation, glucose metabolism ([18F]-deoxyglucose, MicroPET ), and histological outcome. Rats were injured by subdural infusion of 300 muL venous blood or paraffin. ICP, CPP, and CBF changes, assessed during the first 30 mins after injury, were not different between the injury groups at most time points (n=8 per group). Already at 2 h after injury, blood caused a significantly more pronounced decrease in glucose metabolism in the injured cortex when compared with paraffin (P<0.001, n=5 per group). Ipsilateral brain edema did not differ between groups at 2 h, but was significantly more pronounced in the blood-treated groups at 24 and 48 h after injury (n=8 per group). These changes caused a 56.2% larger lesion after blood when compared with paraffin (48.1+/-23.0 versus 21.1+/-11.8 mm(3); P<0.02). Blood constituent-triggered pathomechanisms aggravate the immediate effects due to ICP, CPP, and CBF during hemorrhage and lead to early reduction of glucose metabolism followed by more severe edema and histological damage.

  5. Does linguistic input play the same role in language learning for children with and without early brain injury?

    Science.gov (United States)

    Rowe, Meredith L; Levine, Susan C; Fisher, Joan A; Goldin-Meadow, Susan

    2009-01-01

    Children with unilateral pre- or perinatal brain injury (BI) show remarkable plasticity for language learning. Previous work highlights the important role that lesion characteristics play in explaining individual variation in plasticity in the language development of children with BI. The current study examines whether the linguistic input that children with BI receive from their caregivers also contributes to this early plasticity, and whether linguistic input plays a similar role in children with BI as it does in typically developing (TD) children. Growth in vocabulary and syntactic production is modeled for 80 children (53 TD, 27 BI) between 14 and 46 months. Findings indicate that caregiver input is an equally potent predictor of vocabulary growth in children with BI and in TD children. In contrast, input is a more potent predictor of syntactic growth for children with BI than for TD children. Controlling for input, lesion characteristics (lesion size, type, seizure history) also affect the language trajectories of children with BI. Thus, findings illustrate how both variability in the environment (linguistic input) and variability in the organism (lesion characteristics) work together to contribute to plasticity in language learning.

  6. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner.

    Science.gov (United States)

    Clarke, G; Grenham, S; Scully, P; Fitzgerald, P; Moloney, R D; Shanahan, F; Dinan, T G; Cryan, J F

    2013-06-01

    Bacterial colonisation of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signalling. Regulation of the microbiome-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. However, there is a paucity of data pertaining to the influence of microbiome on the serotonergic system. Germ-free (GF) animals represent an effective preclinical tool to investigate such phenomena. Here we show that male GF animals have a significant elevation in the hippocampal concentration of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, its main metabolite, compared with conventionally colonised control animals. Moreover, this alteration is sex specific in contrast with the immunological and neuroendocrine effects which are evident in both sexes. Concentrations of tryptophan, the precursor of serotonin, are increased in the plasma of male GF animals, suggesting a humoral route through which the microbiota can influence CNS serotonergic neurotransmission. Interestingly, colonisation of the GF animals post weaning is insufficient to reverse the CNS neurochemical consequences in adulthood of an absent microbiota in early life despite the peripheral availability of tryptophan being restored to baseline values. In addition, reduced anxiety in GF animals is also normalised following restoration of the intestinal microbiota. These results demonstrate that CNS neurotransmission can be profoundly disturbed by the absence of a normal gut microbiota and that this aberrant neurochemical, but not behavioural, profile is resistant to restoration of a normal gut flora in later life.

  7. Memory timeline: Brain ERP C250 (not P300) is an early biomarker of short-term storage.

    Science.gov (United States)

    Chapman, Robert M; Gardner, Margaret N; Mapstone, Mark; Dupree, Haley M; Antonsdottir, Inga M

    2015-04-16

    Brain event-related potentials (ERPs) offer a quantitative link between neurophysiological activity and cognitive performance. ERPs were measured while young adults performed a task that required storing a relevant stimulus in short-term memory. Using principal components analysis, ERP component C250 (maximum at 250 ms post-stimulus) was extracted from a set of ERPs that were separately averaged for various task conditions, including stimulus relevancy and stimulus sequence within a trial. C250 was more positive in response to task-specific stimuli that were successfully stored in short-term memory. This relationship between C250 and short-term memory storage of a stimulus was confirmed by a memory probe recall test where the behavioral recall of a stimulus was highly correlated with its C250 amplitude. ERP component P300 (and its subcomponents of P3a and P3b, which are commonly thought to represent memory operations) did not show a pattern of activation reflective of storing task-relevant stimuli. C250 precedes the P300, indicating that initial short-term memory storage may occur earlier than previously believed. Additionally, because C250 is so strongly predictive of a stimulus being stored in short-term memory, C250 may provide a strong index of early memory operations. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. The reproductive biology and early life ecology of a common Caribbean brain coral, Diploria labyrinthiformis (Scleractinia: Faviinae)

    Science.gov (United States)

    Chamberland, Valérie F.; Snowden, Skylar; Marhaver, Kristen L.; Petersen, Dirk; Vermeij, Mark J. A.

    2017-03-01

    Despite the fact that most of the severe demographic bottlenecks in coral populations occur during their earliest life stages, information on the reproductive biology and early life history traits of many coral species is limited and often inferred from adult traits only. This study reports on several atypical aspects of the reproductive biology and early life ecology of the grooved brain coral, Diploria labyrinthiformis (Linnaeus, 1758), a conspicuous reef-building species on Caribbean reefs. The timing of gamete release of D. labyrinthiformis was monitored in Curaçao over eight consecutive months, and embryogenesis, planulae behavior, and settlement rates were observed and quantified. We further studied growth and symbiont acquisition in juvenile D. labyrinthiformis for 3.5 yr and compared settler survival under ambient and nutrient-enriched conditions in situ. Notably, D. labyrinthiformis reproduced during daylight hours in six consecutive monthly spawning events between May and September 2013, with a peak in June. This is the largest number of reproductive events per year ever observed in a broadcast-spawning Caribbean coral species. In settlement experiments, D. labyrinthiformis planulae swam to the bottom of culture containers 13 h after spawning and rapidly settled when provided with settlement cues (42% within 14 h). After 5 months, the survival and growth rates of settled juveniles were 3.7 and 1.9 times higher, respectively, for settlers that acquired zooxanthellae within 1 month after settlement, compared to those that acquired symbionts later on. Nutrient enrichment increased settler survival fourfold, but only for settlers that had acquired symbionts within 1 month after settlement. With at least six reproductive events per year, a short planktonic larval phase, high settlement rates, and a positive response to nutrient enrichment, the broadcast-spawning species D. labyrinthiformis displays a range of reproductive and early life-history traits that

  9. Adeno-associated virus serotype rh.10 displays strong muscle tropism following intraperitoneal delivery.

    Science.gov (United States)

    Ai, Jianzhong; Li, Jia; Gessler, Dominic J; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

    2017-01-09

    Recombinant adeno-associated virus (rAAV) is an attractive tool for basic science and translational medicine including gene therapy, due to the versatility in its cell and organ transduction. Previous work indicates that rAAV transduction patterns are highly dependent on route of administration. Based on this relationship, we hypothesized that intraperitoneal (IP) administration of rAAV produces unique patterns of tissue tropism. To test this hypothesis, we investigated the transduction efficiency of 12 rAAV serotypes carrying an enhanced green fluorescent protein (EGFP) reporter gene in a panel of 12 organs after IP injection. Our data suggest that IP administration emphasizes transduction patterns that are different from previously reported intravascular delivery methods. Using this approach, rAAV efficiently transduces the liver, pancreas, skeletal muscle, heart and diaphragm without causing significant histopathological changes. Of note, rAAVrh.10 showed excellent muscle transduction following IP administration, highlighting its potential as a new muscle-targeting vector.

  10. Replication-competent chimeric lenti-oncovirus with expanded host cell tropism.

    Science.gov (United States)

    Reiprich, S; Gundlach, B R; Fleckenstein, B; Uberla, K

    1997-04-01

    Baboon bone marrow was grafted into human immunodeficiency virus type 1-infected patients in the course of recent trials for AIDS treatment. Since the baboon genome harbors multiple copies of an endogenous oncovirus, chimeric lenti-oncoviruses could emerge in the xenotransplant recipient. To analyze the potential replication competence of hybrid viruses between different genera of retroviruses, we replaced most of the env gene of simian immunodeficiency virus with the env gene of an amphotropic murine leukemia virus. The hybrid virus could be propagated in human T-cell lines, in peripheral blood mononuclear cells of rhesus macaques, and in CD4- B-cell lines. Because of the expanded cell tropism, the hybrid virus might have a selective advantage in comparison to parental viruses. Therefore, emerging chimeric viruses may be considered a serious risk of xenotransplantation. A note of caution is also suggested for the use of pseudotyped lentiviral vectors for human gene therapy.

  11. Neural Processing of Auditory Signals and Modular Neural Control for Sound Tropism of Walking Machines

    Directory of Open Access Journals (Sweden)

    Hubert Roth

    2008-11-01

    Full Text Available The specialized hairs and slit sensillae of spiders (Cupiennius salei can sense the airflow and auditory signals in a low-frequency range. They provide the sensor information for reactive behavior, like e.g. capturing a prey. In analogy, in this paper a setup is described where two microphones and a neural preprocessing system together with a modular neural controller are used to generate a sound tropism of a four-legged walking machine. The neural preprocessing network is acting as a low-pass filter and it is followed by a network which discerns between signals coming from the left or the right. The parameters of these networks are optimized by an evolutionary algorithm. In addition, a simple modular neural controller then generates the desired different walking patterns such that the machine walks straight, then turns towards a switched-on sound source, and then stops near to it.

  12. Neural processing of auditory signals and modular neural control for sound tropism of walking machines

    DEFF Research Database (Denmark)

    Manoonpong, Poramate; Pasemann, Frank; Fischer, Joern

    2005-01-01

    The specialized hairs and slit sensillae of spiders (Cupiennius salei) can sense the airflow and auditory signals in a low-frequency range. They provide the sensor information for reactive behavior, like e.g. capturing a prey. In analogy, in this paper a setup is described where two microphones...... and a neural preprocessing system together with a modular neural controller are used to generate a sound tropism of a four-legged walking machine. The neural preprocessing network is acting as a low-pass filter and it is followed by a network which discerns between signals coming from the left or the right....... The parameters of these networks are optimized by an evolutionary algorithm. In addition, a simple modular neural controller then generates the desired different walking patterns such that the machine walks straight, then turns towards a switched-on sound source, and then stops near to it....

  13. Blast-induced moderate neurotrauma (BINT) elicits early complement activation and tumor necrosis factor α (TNFα) release in a rat brain.

    Science.gov (United States)

    Dalle Lucca, Jurandir J; Chavko, Mikulas; Dubick, Michael A; Adeeb, Saleena; Falabella, Michael J; Slack, Jessica L; McCarron, Richard; Li, Yansong

    2012-07-15

    Blast-induced neurotrauma (BINT) is a major medical concern yet its etiology is largely undefined. Complement activation may play a role in the development of secondary injury following traumatic brain injury; however, its role in BINT is still undefined. The present study was designed to characterize the complement system and adaptive immune-inflammatory responses in a rat model of moderate BINT. Anesthetized rats were exposed to a moderate blast (120 kPa) using an air-driven shock tube. Brain tissue injury, systemic and local complement, cerebral edema, inflammatory cell infiltration, and pro-inflammatory cytokine production were measured at 0.5, 3, 48, 72, 120, and 168 h. Injury to brain tissue was evaluated by histological evaluation. Systemic complement was measured via ELSIA. The remaining measurements were determined by immunohistoflourescent staining. Moderate blast triggers moderate brain injuries, elevated levels of local brain C3/C5b-9 and systemic C5b-9, increased leukocyte infiltration, unregulated tumor necrosis factor alpha (TNFα), and aquaporin-4 in rat brain cortex at 3- and 48-hour post blast. Early immune-inflammatory response to BINT involves complement and TNFα, which correlates with hippocampus and cerebral cortex damage. Complement and TNFα activation may be a novel therapeutic target for reducing the damaging effects of BINT inflammation.

  14. Genotypic tropism testing by massively parallel sequencing: qualitative and quantitative analysis

    Directory of Open Access Journals (Sweden)

    Thiele Bernhard

    2011-05-01

    Full Text Available Abstract Background Inferring viral tropism from genotype is a fast and inexpensive alternative to phenotypic testing. While being highly predictive when performed on clonal samples, sensitivity of predicting CXCR4-using (X4 variants drops substantially in clinical isolates. This is mainly attributed to minor variants not detected by standard bulk-sequencing. Massively parallel sequencing (MPS detects single clones thereby being much more sensitive. Using this technology we wanted to improve genotypic prediction of coreceptor usage. Methods Plasma samples from 55 antiretroviral-treated patients tested for coreceptor usage with the Monogram Trofile Assay were sequenced with standard population-based approaches. Fourteen of these samples were selected for further analysis with MPS. Tropism was predicted from each sequence with geno2pheno[coreceptor]. Results Prediction based on bulk-sequencing yielded 59.1% sensitivity and 90.9% specificity compared to the trofile assay. With MPS, 7600 reads were generated on average per isolate. Minorities of sequences with high confidence in CXCR4-usage were found in all samples, irrespective of phenotype. When using the default false-positive-rate of geno2pheno[coreceptor] (10%, and defining a minority cutoff of 5%, the results were concordant in all but one isolate. Conclusions The combination of MPS and coreceptor usage prediction results in a fast and accurate alternative to phenotypic assays. The detection of X4-viruses in all isolates suggests that coreceptor usage as well as fitness of minorities is important for therapy outcome. The high sensitivity of this technology in combination with a quantitative description of the viral population may allow implementing meaningful cutoffs for predicting response to CCR5-antagonists in the presence of X4-minorities.

  15. Identification of site-specific adaptations conferring increased neural cell tropism during human enterovirus 71 infection.

    Directory of Open Access Journals (Sweden)

    Samuel Cordey

    Full Text Available Enterovirus 71 (EV71 is one of the most virulent enteroviruses, but the specific molecular features that enhance its ability to disseminate in humans remain unknown. We analyzed the genomic features of EV71 in an immunocompromised host with disseminated disease according to the different sites of infection. Comparison of five full-length genomes sequenced directly from respiratory, gastrointestinal, nervous system, and blood specimens revealed three nucleotide changes that occurred within a five-day period: a non-conservative amino acid change in VP1 located within the BC loop (L97R, a region considered as an immunogenic site and possibly important in poliovirus host adaptation; a conservative amino acid substitution in protein 2B (A38V; and a silent mutation in protein 3D (L175. Infectious clones were constructed using both BrCr (lineage A and the clinical strain (lineage C backgrounds containing either one or both non-synonymous mutations. In vitro cell tropism and competition assays revealed that the VP1₉₇ Leu to Arg substitution within the BC loop conferred a replicative advantage in SH-SY5Y cells of neuroblastoma origin. Interestingly, this mutation was frequently associated in vitro with a second non-conservative mutation (E167G or E167A in the VP1 EF loop in neuroblastoma cells. Comparative models of these EV71 VP1 variants were built to determine how the substitutions might affect VP1 structure and/or interactions with host cells and suggest that, while no significant structural changes were observed, the substitutions may alter interactions with host cell receptors. Taken together, our results show that the VP1 BC loop region of EV71 plays a critical role in cell tropism independent of EV71 lineage and, thus, may have contributed to dissemination and neurotropism in the immunocompromised patient.

  16. Brain Basics

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    Full Text Available ... Some people who develop a mental illness may recover completely; others may have repeated episodes of illness ... in early detection, more tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything ...

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  3. Different early effect of irradiation in brain and small cell lung cancer examined by in vivo 31P-magnetic resonance spectroscopy