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Sample records for adult primary brain

  1. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  2. Primary brain tumours in adults.

    PubMed

    Ricard, Damien; Idbaih, Ahmed; Ducray, François; Lahutte, Marion; Hoang-Xuan, Khê; Delattre, Jean-Yves

    2012-05-26

    Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas--the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials. Primary CNS lymphomas are a group of rare non-Hodgkin lymphomas. High-dose methotrexate-based regimens increase survival, but the standards of care and the place of whole-brain radiotherapy remain unclear, and are likely to depend on the age of the patient. The focus now is on the development of new polychemotherapy regimens to reduce or defer whole-brain radiotherapy and its delayed complications.

  3. Occupational and environmental risk factors of adult primary brain cancers: a systematic review.

    PubMed

    Gomes, J; Al Zayadi, A; Guzman, A

    2011-04-01

    The incidence of brain neoplasm has been progressively increasing in recent years in the industrialized countries. One of the reasons for this increased incidence could be better access to health care and improved diagnosis in the industrialized countries. It also appears that Caucasians have a higher incidence than blacks or Hispanics or Asians. A number of risk factors have been identified and described including the genetic, ethnic and age-based factors. Certain occupational and environmental factors are also believed to influence the risk of primary adult brain tumors. Potential occupational and environmental factors include exposure to diagnostic and therapeutic radiations, electromagnetic radiation from cellular phones and other wireless devices, infectious agents, air pollution and residence near landfills and high-voltage power lines and jobs as firefighters, farmers, physician, chemists and jobs in industries such as petrochemical, power generation, synthetic rubber manufacturing, agricultural chemicals manufacturing. The purpose of this systematic review is to examine occupational and environmental risk factors of brain neoplasm. A range of occupational and environmental exposures are evaluated for significance of their relationship with adult primary brain tumors. On the basis of this review we suggest a concurrent evaluation of multiple risk factors both within and beyond occupational and environmental domains. The concurrent approach needs to consider better exposure assessment techniques, lifetime occupational exposures, genotypic and phenotypic characteristics and lifestyle and dietary habits. This approach needs to be interdisciplinary with contributions from neurologists, oncologists, epidemiologists and molecular biologists. Conclusive evidence that has eluded multitude of studies with single focus and single exposure needs to multifaceted and multidisciplinary.

  4. Molecular and immunocytochemical characterization of primary neuronal cultures from adult rat brain: Differential expression of neuronal and glial protein markers.

    PubMed

    Ray, Balmiki; Bailey, Jason A; Sarkar, Sumit; Lahiri, Debomoy K

    2009-11-15

    Neurobiological studies using primary neuronal cultures commonly employ fetal-derived neurons, but much less often adult brain-derived neurons. Our goal is to perform morphological and molecular characterization of primary neuronal cultures from adult rat brain, including the relative expression of neuronal and glial cell markers at different time points. We tested the hypothesis that long-term neuronal viability is compatible with glial proliferation in adult neuron culture. We examined neuron culture from adult rat brain, which was maintained at steady state up to 24 days, and characterized them on the basis of cellular, molecular and biochemical properties at different time points of the culture. We identified neuronal and glial cells by both immunocytochemical and western immunoblotting techniques using NSE and Tau as neuronal markers and GFAP as glial protein marker, which revealed the presence of predominantly neuronal cells in the initial phase of the culture and a rise in glial cells from day 12 onwards. Notably, neuronal cells were preserved in the culture along with the glial cells even at day 24. Transfection of the cultured cells with a GFP expression vector and plasmids containing a luciferase reporter gene under the control of two different gene promoters demonstrated DNA transfectability. Taken together, these results suggest a differential expression of neuronal and glial cells at different time points and long-term neuronal viability in the presence of glial proliferation. Such adult neurons serve as a suitable system for the application of neurodegeneration models and for drug target discovery in various brain disorders including Alzheimer's disease.

  5. Primary lymphoma of the brain

    MedlinePlus

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  6. Treatment Options for Adult Primary Liver Cancer

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  7. Treatment Option Overview (Adult Primary Liver Cancer)

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  8. Stages of Adult Primary Liver Cancer

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  9. General Information about Adult Primary Liver Cancer

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  10. Left Brain/Right Brain Learning for Adult Education.

    ERIC Educational Resources Information Center

    Garvin, Barbara

    1986-01-01

    Contrasts and compares the theory and practice of adult education as it relates to the issue of right brain/left brain learning. The author stresses the need for a whole-brain approach to teaching and suggests that adult educators, given their philosophical directions, are the perfect potential users of this integrated system. (Editor/CT)

  11. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... Search Search En Español Category Cancer A-Z Brain and Spinal Cord Tumors in Adults If you have a brain or spinal cord tumor or are close to ... cope. Here you can find out all about brain and spinal cord tumors in adults, including risk ...

  12. Primary phospholipase C and brain disorders.

    PubMed

    Yang, Yong Ryoul; Kang, Du-Seock; Lee, Cheol; Seok, Heon; Follo, Matilde Y; Cocco, Lucio; Suh, Pann-Ghill

    2016-05-01

    In the brain, the primary phospholipase C (PLC) proteins, PLCβ, and PLCγ, are activated primarily by neurotransmitters, neurotrophic factors, and hormones through G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). Among the primary PLC isozymes, PLCβ1, PLCβ4, and PLCγ1 are highly expressed and differentially distributed, suggesting a specific role for each PLC subtype in different regions of the brain. Primary PLCs control neuronal activity, which is important for synapse function and development. In addition, dysregulation of primary PLC signaling is linked to several brain disorders including epilepsy, schizophrenia, bipolar disorder, Huntington's disease, depression and Alzheimer's disease. In this review, we included current knowledge regarding the roles of primary PLC isozymes in brain disorders.

  13. IT-36PHASE 1/2 STUDY OF THE COMBINATION OF INDOXIMOD AND TEMOZOLOMIDE FOR ADULT PATIENTS WITH TEMOZOLOMIDE-REFRACTORY PRIMARY MALIGNANT BRAIN TUMORS

    PubMed Central

    Zakharia, Yousef; Johnson, Theodore; Colman, Howard; Vahanian, Nicholas; Link, Charles; Kennedy, Eugene; Sadek, Ramses; Kong, Feng-Ming; Vender, John; Munn, David; Rixe, Olivier

    2014-01-01

    BACKGROUND: Indoleamine 2, 3-dioxygenase (IDO) is a key immune-modulatory enzyme that inhibits CD8+ T cells and enhances the suppressor activity of Tregs. IDO is expressed in 50 to 90% of glioblastoma (GBM) and is correlated with poor prognosis. IDO pathway inhibitors such as indoximod (1-Methyl-D-tryptophan) can improve anti-tumor T cell response slowing the tumor growth in vivo. We have demonstrated a synergistic effect of indoximod when combined with temozolomide (TMZ) and radiation in a syngeneic orthotopic brain tumor model. This phase 1 study is designed to determine maximal tolerated dose (MTD) of indoximod in combination with TMZ in GBM followed by an expansion phase 2 testing the preliminary activity of the combination in relevant situations with the addition of bevacizumab or stereotactic radiosurgery. METHODS: After progression to standard front line-therapy, patients with GBM are enrolled in a dose escalation study of indoximod (600, 1000 or 1200 mg twice daily given orally) with a standard fixed dose of TMZ. In the phase 2 part, patients are separated into 3 cohorts: cohort 2a: indoximod with TMZ, cohort 2b: indoximod with TMZ and bevacizumab (for patients who are currently on bevacizumab), cohort 2c: indoximod with TMZ and stereotactic radiosurgery. STATISTICAL ANALYSIS: The study uses a 3 + 3 dose escalation design, until reaching the MTD or the maximal specified dose. Sample size in phase 2 is based on the primary endpoint of 6 months progression free survival (PFS). CORRELATIVE STUDIES: Assessment of primary tumor samples for IDO expression, evaluation of serum for potential biomarkers of IDO pathway activity (kynurenine and tryptophan) and a pharmacokinetic analysis will be performed. RESULTS: Study is ongoing. Updates are to be presented at the meeting.

  14. Development and evaluation of information resources for patients, families, and healthcare providers addressing behavioral and cognitive sequelae among adults with a primary brain tumor.

    PubMed

    Wright, Kylie M; Simpson, Grahame K; Koh, Eng-Siew; Whiting, Diane L; Gillett, Lauren; Simpson, Teresa; Firth, Rochelle

    2015-06-01

    Behavioral and cognitive changes in patients with primary brain tumor (PBT) are common and may be distressing to patients and their family members. Healthcare professionals report a strong need for information, practical strategies, and training to assist consumers and better address management issues. A literature review by the current project found that 53% of the information resources currently available to consumers and health professionals contained minimal or no information about cognitive/behavioral changes after PBT, and 71% of the resources contained minimal or no information on associated strategies to manage these changes. This project aimed to develop an information resource for patients, carers, and health professionals addressing the behavioral and cognitive sequelae of PBT, including strategies to minimize the disabling impact of such behaviors. In consultation with staff and patient groups, 16 key information topics were identified covering cognitive and communication changes and challenging behaviors including executive impairment, behavioral disturbance, and social/emotional dysfunction. Sixteen fact sheets and 11 additional resource sheets were developed and evaluated according to established consumer communication guidelines. Preliminary data show that these resources have been positively received and well utilized. These sheets are the first of their kind addressing challenging behaviors in the neuro-oncology patient group and are a practical and useful information resource for health professionals working with these patients and their families. The new resource assists in reinforcing interventions provided to individual patients and their relatives who are experiencing difficulties in managing challenging behaviors after PBT.

  15. Primary care of adults with developmental disabilities

    PubMed Central

    Sullivan, William F.; Berg, Joseph M.; Bradley, Elspeth; Cheetham, Tom; Denton, Richard; Heng, John; Hennen, Brian; Joyce, David; Kelly, Maureen; Korossy, Marika; Lunsky, Yona; McMillan, Shirley

    2011-01-01

    Abstract Objective To update the 2006 Canadian guidelines for primary care of adults with developmental disabilities (DD) and to make practical recommendations based on current knowledge to address the particular health issues of adults with DD. Quality of evidence Knowledgeable health care providers participating in a colloquium and a subsequent working group discussed and agreed on revisions to the 2006 guidelines based on a comprehensive review of publications, feedback gained from users of the guidelines, and personal clinical experiences. Most of the available evidence in this area of care is from expert opinion or published consensus statements (level III). Main message Adults with DD have complex health issues, many of them differing from those of the general population. Good primary care identifies the particular health issues faced by adults with DD to improve their quality of life, to improve their access to health care, and to prevent suffering, morbidity, and premature death. These guidelines synthesize general, physical, behavioural, and mental health issues of adults with DD that primary care providers should be aware of, and they present recommendations for screening and management based on current knowledge that practitioners can apply. Because of interacting biologic, psychoaffective, and social factors that contribute to the health and well-being of adults with DD, these guidelines emphasize involving caregivers, adapting procedures when appropriate, and seeking input from a range of health professionals when available. Ethical care is also emphasized. The guidelines are formulated within an ethical framework that pays attention to issues such as informed consent and the assessment of health benefits in relation to risks of harm. Conclusion Implementation of the guidelines proposed here would improve the health of adults with DD and would minimize disparities in health and health care between adults with DD and those in the general population

  16. Neural repair in the adult brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury to the adult brain often results in substantial loss of neural tissue and subsequent permanent functional impairment. Over the last two decades, a number of approaches have been developed to harness the regenerative potential of neural stem cells and the existing fate plasticity of neural cells in the nervous system to prevent tissue loss or to enhance structural and functional regeneration upon injury. Here, we review recent advances of stem cell-associated neural repair in the adult brain, discuss current challenges and limitations, and suggest potential directions to foster the translation of experimental stem cell therapies into the clinic. PMID:26918167

  17. Cross-modal synaptic plasticity in adult primary sensory cortices.

    PubMed

    Lee, Hey-Kyoung; Whitt, Jessica L

    2015-12-01

    Sensory loss leads to widespread adaptation of brain circuits to allow an organism to navigate its environment with its remaining senses, which is broadly referred to as cross-modal plasticity. Such adaptation can be observed even in the primary sensory cortices, and falls into two distinct categories: recruitment of the deprived sensory cortex for processing the remaining senses, which we term 'cross-modal recruitment', and experience-dependent refinement of the spared sensory cortices referred to as 'compensatory plasticity.' Here we will review recent studies demonstrating that cortical adaptation to sensory loss involves LTP/LTD and homeostatic synaptic plasticity. Cross-modal synaptic plasticity is observed in adults, hence cross-modal sensory deprivation may be an effective way to promote plasticity in adult primary sensory cortices.

  18. Acupuncture stimulation induces neurogenesis in adult brain.

    PubMed

    Nam, Min-Ho; Ahn, Kwang Seok; Choi, Seung-Hoon

    2013-01-01

    The discovery of adult neurogenesis was a turning point in the field of neuroscience. Adult neurogenesis offers an enormous possibility to open a new therapeutic paradigm of neurodegenerative diseases and stroke. Recently, several studies suggested that acupuncture may enhance adult neurogenesis. Acupuncture has long been an important treatment for brain diseases in the East Asia. The scientific mechanisms of acupuncture treatment for the diseases, such as Alzheimer's disease, Parkinson's disease, and stroke, have not been clarified yet; however, the neurogenic effect of acupuncture can be a possible reason. Here, we have reviewed the studies on the effect of stimulation at various acupoints for neurogenesis, such as ST36 and GV20. The suggested mechanisms are also discussed including upregulation of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, basic fibroblast growth factor and neuropeptide Y, and activation of the function of primo vascular system.

  19. Life Satisfaction in Adult Survivors of Childhood Brain Tumors

    PubMed Central

    Crom, Deborah B.; Li, Zhenghong; Brinkman, Tara M.; Hudson, Melissa M.; Armstrong, Gregory T.; Neglia, Joseph; Ness, Kirsten K.

    2014-01-01

    Adult survivors of childhood brain tumors experience multiple, significant, life-long deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors’ physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggests some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population–based matched controls. Chi-square tests, t-tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors’ general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population. PMID:25027187

  20. Life satisfaction in adult survivors of childhood brain tumors.

    PubMed

    Crom, Deborah B; Li, Zhenghong; Brinkman, Tara M; Hudson, Melissa M; Armstrong, Gregory T; Neglia, Joseph; Ness, Kirsten K

    2014-01-01

    Adult survivors of childhood brain tumors experience multiple, significant, lifelong deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors' physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggest some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population-based matched controls. Chi-square tests, t tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated that life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors' general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population.

  1. Electrophysiological Recording in the Brain of Intact Adult Zebrafish

    PubMed Central

    Johnston, Lindsey; Ball, Rebecca E.; Acuff, Seth; Gaudet, John; Sornborger, Andrew; Lauderdale, James D.

    2013-01-01

    Previously, electrophysiological studies in adult zebrafish have been limited to slice preparations or to eye cup preparations and electrorentinogram recordings. This paper describes how an adult zebrafish can be immobilized, intubated, and used for in vivo electrophysiological experiments, allowing recording of neural activity. Immobilization of the adult requires a mechanism to deliver dissolved oxygen to the gills in lieu of buccal and opercular movement. With our technique, animals are immobilized and perfused with habitat water to fulfill this requirement. A craniotomy is performed under tricaine methanesulfonate (MS-222; tricaine) anesthesia to provide access to the brain. The primary electrode is then positioned within the craniotomy window to record extracellular brain activity. Through the use of a multitube perfusion system, a variety of pharmacological compounds can be administered to the adult fish and any alterations in the neural activity can be observed. The methodology not only allows for observations to be made regarding changes in neurological activity, but it also allows for comparisons to be made between larval and adult zebrafish. This gives researchers the ability to identify the alterations in neurological activity due to the introduction of various compounds at different life stages. PMID:24300281

  2. Primary carnitine deficiency in a male adult.

    PubMed

    Karmaniolas, Konstantinos; Ioannidis, Panagiotis; Liatis, Stavros; Dalamanga, Maria; Papalambros, Theoharis; Migdalis, Ilias

    2002-01-01

    The case is described of a 36 year-old man who presented with progressive proximal muscle weakness and weight loss. His serum creatine phosphokinase (CPK) levels were markedly elevated. The muscle biopsy showed lipid storage myopathy. The muscle carnitine concentration was extremely low (5.6% of normal levels), establishing the diagnosis of myopathic carnitine deficiency. The disorder was considered as primary because there were no indications of any other identifiable condition which could result in a secondary carnitine deficiency. The patient was treated with oral L-carnitine (2 g per day) and showed rapid improvement. Primary myopathic carnitine deficiency is a curable disorder and therefore it should always be considered as a potential diagnosis in cases of myopathy in young adults.

  3. Guidelines for Better Communication with Brain Impaired Adults

    MedlinePlus

    ... are here Home Guidelines for Better Communication with Brain Impaired Adults Printer-friendly version Communicating with a loved one with a brain disorder can indeed be challenging. Finding the right ...

  4. Adult human brain cell culture for neuroscience research.

    PubMed

    Gibbons, Hannah M; Dragunow, Mike

    2010-06-01

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

  5. Adult neurogenesis and its role in neuropsychiatric disease, brain repair and normal brain function.

    PubMed

    Braun, S M G; Jessberger, S

    2014-02-01

    Neural stem/progenitor cells (NSPCs) in the mammalian brain retain the ability to generate new neurones throughout life in discrete brain regions, through a process called adult neurogenesis. Adult neurogenesis, a dramatic form of adult brain circuitry plasticity, has been implicated in physiological brain function and appears to be of pivotal importance for certain forms of learning and memory. In addition, failing or altered neurogenesis has been associated with a variety of brain diseases such as major depression, epilepsy and age-related cognitive decline. Here we review recent advances in our understanding of the basic biology underlying the neurogenic process in the adult brain, focusing on mechanisms that regulate quiescence, proliferation and differentiation of NSPCs. In addition, we discuss how neurogenesis influences normal brain function, and in particular its role in memory formation, as well as its contribution to neuropsychiatric diseases. Finally, we evaluate the potential of targeting endogenous NSPCs for brain repair.

  6. Isolation and Culture of Adult Zebrafish Brain-derived Neurospheres

    PubMed Central

    Lopez-Ramirez, Miguel A.; Calvo, Charles-Félix; Ristori, Emma; Thomas, Jean-Léon; Nicoli, Stefania

    2016-01-01

    The zebrafish is a highly relevant model organism for understanding the cellular and molecular mechanisms involved in neurogenesis and brain regeneration in vertebrates. However, an in-depth analysis of the molecular mechanisms underlying zebrafish adult neurogenesis has been limited due to the lack of a reliable protocol for isolating and culturing neural adult stem/progenitor cells. Here we provide a reproducible method to examine adult neurogenesis using a neurosphere assay derived from zebrafish whole brain or from the telencephalon, tectum and cerebellum regions of the adult zebrafish brain. The protocol involves, first the microdissection of zebrafish adult brain, then single cell dissociation and isolation of self-renewing multipotent neural stem/progenitor cells. The entire procedure takes eight days. Additionally, we describe how to manipulate gene expression in zebrafish neurospheres, which will be particularly useful to test the role of specific signaling pathways during adult neural stem/progenitor cell proliferation and differentiation in zebrafish. PMID:26967835

  7. Stem Cell-Mediated Regeneration of the Adult Brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury of the adult mammalian brain is often associated with persistent functional deficits as its potential for regeneration and capacity to rebuild lost neural structures is limited. However, the discovery that neural stem cells (NSCs) persist throughout life in discrete regions of the brain, novel approaches to induce the formation of neuronal and glial cells, and recently developed strategies to generate tissue for exogenous cell replacement strategies opened novel perspectives how to regenerate the adult brain. Here, we will review recently developed approaches for brain repair and discuss future perspectives that may eventually allow for developing novel treatment strategies in acute and chronic brain injury. PMID:27781019

  8. Experience-Dependent Neural Plasticity in the Adult Damaged Brain

    ERIC Educational Resources Information Center

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

  9. Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

    ClinicalTrials.gov

    2017-03-22

    Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

  10. Morphological brain network assessed using graph theory and network filtration in deaf adults.

    PubMed

    Kim, Eunkyung; Kang, Hyejin; Lee, Hyekyoung; Lee, Hyo-Jeong; Suh, Myung-Whan; Song, Jae-Jin; Oh, Seung-Ha; Lee, Dong Soo

    2014-09-01

    Prolonged deprivation of auditory input can change brain networks in pre- and postlingual deaf adults by brain-wide reorganization. To investigate morphological changes in these brains voxel-based morphometry, voxel-wise correlation with the primary auditory cortex, and whole brain network analyses using morphological covariance were performed in eight prelingual deaf, eleven postlingual deaf, and eleven hearing adults. Network characteristics based on graph theory and network filtration based on persistent homology were examined. Gray matter density in the primary auditor cortex was preserved in prelingual deafness, while it tended to decrease in postlingual deafness. Unlike postlingual, prelingual deafness showed increased bilateral temporal connectivity of the primary auditory cortex compared to the hearing adults. Of the graph theory-based characteristics, clustering coefficient, betweenness centrality, and nodal efficiency all increased in prelingual deafness, while all the parameters of postlingual deafness were similar to the hearing adults. Patterns of connected components changing during network filtration were different between prelingual deafness and hearing adults according to the barcode, dendrogram, and single linkage matrix representations, while these were the same in postlingual deafness. Nodes in fronto-limbic and left temporal components were closely coupled, and nodes in the temporo-parietal component were loosely coupled, in prelingual deafness. Patterns of connected components changing in postlingual deafness were the same as hearing adults. We propose that the preserved density of auditory cortex associated with increased connectivity in prelingual deafness, and closer coupling between certain brain areas, represent distinctive reorganization of auditory and related cortices compared with hearing or postlingual deaf adults. The differential network reorganization in the prelingual deaf adults could be related to the absence of auditory speech

  11. Use of primary cultures of Kenyon cells from bumblebee brains to assess pesticide side effects.

    PubMed

    Wilson, Daniel E; Velarde, Rodrigo A; Fahrbach, Susan E; Mommaerts, Veerle; Smagghe, Guy

    2013-09-01

    Bumblebees are important pollinators in natural and agricultural ecosystems. The latter results in the frequent exposure of bumblebees to pesticides. We report here on a new bioassay that uses primary cultures of neurons derived from adult bumblebee workers to evaluate possible side-effects of the neonicotinoid pesticide imidacloprid. Mushroom bodies (MBs) from the brains of bumblebee workers were dissected and dissociated to produce cultures of Kenyon cells (KCs). Cultured KCs typically extend branched, dendrite-like processes called neurites, with substantial growth evident 24-48 h after culture initiation. Exposure of cultured KCs obtained from newly eclosed adult workers to 2.5 parts per billion (ppb) imidacloprid, an environmentally relevant concentration of pesticide, did not have a detectable effect on neurite outgrowth. By contrast, in cultures prepared from newly eclosed adult bumblebees, inhibitory effects of imidacloprid were evident when the medium contained 25 ppb imidacloprid, and no growth was observed at 2,500 ppb. The KCs of older workers (13-day-old nurses and foragers) appeared to be more sensitive to imidacloprid than newly eclosed adults, as strong effects on KCs obtained from older nurses and foragers were also evident at 2.5 ppb imidacloprid. In conclusion, primary cultures using KCs of bumblebee worker brains offer a tool to assess sublethal effects of neurotoxic pesticides in vitro. Such studies also have the potential to contribute to the understanding of mechanisms of plasticity in the adult bumblebee brain.

  12. Mechanisms of neuronal migration in the adult brain.

    PubMed

    Kaneko, Naoko; Sawada, Masato; Sawamoto, Kazunobu

    2017-03-02

    Adult neurogenesis was first observed nearly 60 years ago, and it has since grown into an important neurochemistry research field. Much recent research has focused on the treatment of brain diseases through neuronal regeneration with endogenously generated neurons. In the adult brain, immature neurons called neuroblasts are continuously generated in the ventricular-subventricular zone (V-SVZ). These neuroblasts migrate rapidly through the rostral migratory stream to the olfactory bulb, where they mature and are integrated into the neuronal circuitry. After brain insult, some of the neuroblasts in the V-SVZ migrate toward the lesion to repopulate the injured tissue. This notable migratory capacity of V-SVZ-derived neuroblasts is important for efficiently regenerating neurons in remote areas of the brain. As these neurons migrate for long distances through adult brain tissue, they are supported by various guidance cues and structures that act as scaffolds. Some of these mechanisms are unique to neuroblast migration in the adult brain, and are not involved in migration in the developing brain. Here, we review the latest findings on the mechanisms of neuroblast migration in the adult brain under physiological and pathological conditions, and discuss various issues that still need to be resolved. This article is protected by copyright. All rights reserved.

  13. Gamma Knife Radiosurgery for Brain Metastases From Primary Breast Cancer

    SciTech Connect

    Kased, Norbert; Binder, Devin K.; McDermott, Michael W.; Nakamura, Jean L.; Huang, Kim; Berger, Mitchel S.; Wara, William M.; Sneed, Penny K.

    2009-11-15

    Purpose: The relative roles of stereotactic radiosurgery (SRS) vs. whole brain radiotherapy (WBRT) in the treatment of patients with brain metastases from breast cancer remain undefined. In this study, we reviewed our experience with these patients. Materials and Methods: We retrospectively reviewed all patients treated between 1991 and 2005 with Gamma Knife SRS for brain metastases from breast cancer. The actuarial survival and freedom from progression endpoints were calculated using the Kaplan-Meier method. Results: Between 1991 and 2005, 176 patients underwent SRS for brain metastases from breast cancer. The median survival time was 16.0 months for 95 newly diagnosed patients and 11.7 months for 81 patients with recurrent brain metastases. In the newly diagnosed patients, omission of upfront WBRT did not significantly affect the MST (p = .20), brain freedom from progression (p = .75), or freedom from new brain metastases (p = .83). Longer survival was associated with age <50 years, Karnofsky performance score >=70, primary tumor control, estrogen receptor positivity, and Her2/neu overexpression. No association was found between the number of treated brain metastases and the survival time. Conclusion: We have described prognostic factors for breast cancer patients treated with SRS for newly diagnosed or recurrent brain metastases. Most patient subsets had a median survival time of >=11 months. Unexpectedly, upfront WBRT did not appear to improve brain freedom from progression, and a larger number of brain metastases was not associated with a shorter survival time. Breast cancer might be distinct from other primary sites in terms of prognostic factors and the roles of WBRT and SRS for brain metastases.

  14. Memory and Brain Volume in Adults Prenatally Exposed to Alcohol

    ERIC Educational Resources Information Center

    Coles, Claire D.; Goldstein, Felicia C.; Lynch, Mary Ellen; Chen, Xiangchuan; Kable, Julie A.; Johnson, Katrina C.; Hu, Xiaoping

    2011-01-01

    The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n = 26; Alcohol-related Neurodevelopmental Disorder, n = 36; and Dysmorphic, n = 30) were imaged using structural MRI with brain volume calculated for…

  15. Can deceased donor with recurrent primary brain tumor donate kidneys for transplantation?

    PubMed Central

    Kumar, Suresh; Modi, Pranjal R.; Pal, Bipin C.; Modi, Jayesh

    2016-01-01

    Kidney transplantation from deceased donors is in its infancy in India. Cadaver organ donation was accepted legally in 1994 by the “Human Organs Transplantation Act.” Marginal donors are now accepted by many centers for kidney transplantation. We report a case of procurement of both kidneys from a young deceased donor having recurrent primary brain tumor, transplanted into two adult recipients with successful outcome. PMID:26941500

  16. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

  17. Complete prevalence of malignant primary brain tumors registry data in the United States compared with other common cancers, 2010

    DOE PAGES

    Zhang, Adah S.; Ostrom, Quinn T.; Kruchko, Carol; ...

    2016-12-29

    Complete prevalence proportions illustrate the burden of disease in a population. Here, this study estimates the 2010 complete prevalence of malignant primary brain tumors overall and by Central Brain Tumor Registry of the United States (CBTRUS) histology groups, and compares the brain tumor prevalence estimates to the complete prevalence of other common cancers as determined by the Surveillance, Epidemiology, and End Results Program (SEER) by age at prevalence (2010): children (0–14 y), adolescent and young adult (AYA) (15–39 y), and adult (40+ y).

  18. Primary Care Providers' HIV Prevention Practices Among Older Adults

    PubMed Central

    Davis, Tracy; Teaster, Pamela B.; Thornton, Alice; Watkins, John F.; Alexander, Linda; Zanjani, Faika

    2016-01-01

    Purpose To explore primary care providers' HIV prevention practices for older adults. Primary care providers' perceptions and awareness were explored to understand factors that affect their provision of HIV prevention materials and HIV screening for older adults. Design and Method Data were collected through 24 semistructured interviews with primary care providers (i.e., physicians, physician assistants, and nurse practitioners) who see patients older than 50 years. Results Results reveal facilitators and barriers of HIV prevention for older adults among primary care providers and understanding of providers' HIV prevention practices and behaviors. Individual, patient, institutional, and societal factors influenced HIV prevention practices among participants, for example, provider training and work experience, lack of time, discomfort in discussing HIV/AIDS with older adults, stigma, and ageism were contributing factors. Furthermore, factors specific to primary and secondary HIV prevention were identified, for instance, the presence of sexually transmitted infections influenced providers' secondary prevention practices. Implications HIV disease, while preventable, is increasing among older adults. These findings inform future research and interventions aimed at increasing HIV prevention practices in primary care settings for patients older than 50. PMID:25736425

  19. Brain stem auditory evoked responses in human infants and adults

    NASA Technical Reports Server (NTRS)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  20. New Nerve Cells for the Adult Brain.

    ERIC Educational Resources Information Center

    Kempermann, Gerd; Gage, Fred H.

    1999-01-01

    Contrary to dogma, the human brain does produce new nerve cells in adulthood. The mature human brain spawns neurons routinely in the hippocampus, an area important to memory and learning. This research can make it possible to ease any number of disorders involving neurological damage and death. (CCM)

  1. Effects of environmental tobacco smoke on adult rat brain biochemistry.

    PubMed

    Fuller, Brian F; Gold, Mark S; Wang, Kevin K W; Ottens, Andrew K

    2010-05-01

    Environmental tobacco smoke (ETS) has been linked to deleterious health effects, particularly pulmonary and cardiac disease; yet, the general public considers ETS benign to brain function in adults. In contrast, epidemiological data have suggested that ETS impacts the brain and potentially modulates neurodegenerative disease. The present study begins to examine yet unknown biochemical effects of ETS on the adult mammalian brain. In the developed animal model, adult male rats were exposed to ETS 3 h a day for 3 weeks. Biochemical data showed altered glial fibrillary acid protein levels as a main treatment effect of ETS, suggestive of reactive astrogliosis. Yet, markers of oxidative and cell stress were unaffected by ETS exposure in the brain regions examined. Increased proteolytic degradation of alphaII-spectrin by caspase-3 and the dephosphorylation of serine(116) on PEA-15 indicated greater apoptotic cell death modulated by the extrinsic pathway in the brains of ETS-exposed animals. Further, beta-synuclein was upregulated by ETS, a neuroprotective protein previously reported to exhibit anti-apoptotic and anti-fibrillogenic properties. These findings demonstrate that ETS exposure alters the neuroproteome of the adult rat brain, and suggest modulation of inflammatory and cell death processes.

  2. Treatment of Adult Primary Alveolar Proteinosis.

    PubMed

    Rodríguez Portal, José Antonio

    2015-07-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant-like lipoproteinaceous material in the distal air spaces and terminal bronchi, which may lead to impaired gas exchange. This accumulation of surfactant is due to decreased clearance by the alveolar macrophages. Its primary, most common form, is currently considered an autoimmune disease. Better knowledge of the causes of PAP have led to the emergence of alternatives to whole lung lavage, although this is still considered the treatment of choice. Most studies are case series, often with limited patient numbers, so the level of evidence is low. Since the severity of presentation and clinical course are variable, not all patients will require treatment. Due to the low level of evidence, some objective criteria based on expert opinion have been arbitrarily proposed in an attempt to define in which patients it is best to initiate treatment.

  3. The effects of vitamin D on brain development and adult brain function.

    PubMed

    Kesby, James P; Eyles, Darryl W; Burne, Thomas H J; McGrath, John J

    2011-12-05

    A role for vitamin D in brain development and function has been gaining support over the last decade. Multiple lines of evidence suggest that this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with a host of adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. This review summarises the current state of research on the actions of vitamin D in the brain and the consequences of deficiencies in this vitamin. Furthermore, we discuss specific implications of vitamin D status on the neurotransmitter, dopamine.

  4. Refractory Adult Primary Autoimmune Neutropenia that Responded to Alemtuzumab.

    PubMed

    Neerukonda, Anu R; Lan, Fengshuo; Gabig, Theodore; Saraya, Takeshi

    2016-01-01

    Primary autoimmune neutropenia (P-AIN) is an extremely rare disease. The most effective treatment for primary P-AIN is a granulocyte colony-stimulating factor; however, no curative treatment has been reported. We herein report a case of an adult P-AIN patient with a relatively mild medical history (irrespective of the severe neutropenia) who showed a sustained hematological response over seventeen months after the initiation of treatment with subcutaneous Alemtuzumab.

  5. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  6. Lake-front property: a unique germinal niche by the lateral ventricles of the adult brain.

    PubMed

    Ihrie, Rebecca A; Alvarez-Buylla, Arturo

    2011-05-26

    New neurons and glial cells are generated in an extensive germinal niche adjacent to the walls of the lateral ventricles in the adult brain. The primary progenitors (B1 cells) have astroglial characteristics but retain important neuroepithelial properties. Recent work shows how B1 cells contact all major compartments of this niche. They share the "shoreline" on the ventricles with ependymal cells, forming a unique adult ventricular zone (VZ). In the subventricular zone (SVZ), B1 cells contact transit amplifying (type C) cells, chains of young neurons (A cells), and blood vessels. How signals from these compartments influence the behavior of B1 or C cells remains largely unknown, but recent work highlights growth factors, neurotransmitters, morphogens, and the extracellular matrix as key regulators of this niche. The integration of emerging molecular and anatomical clues forecasts an exciting new understanding of how the germ of youth is actively maintained in the adult brain.

  7. Brain abscess caused by Citrobacter koseri infection in an adult.

    PubMed

    Liu, Heng-Wei; Chang, Chih-Ju; Hsieh, Cheng-Ta

    2015-04-01

    Citrobacter koseri is a gram-negative bacillus that causes mostly meningitis and brain abscesses in neonates and infants. However, brain abscess caused by Citrobacter koseri infection in an adult is extremely rare, and only 2 cases have been described. Here, we reported a 73-year-old male presenting with a 3-week headache. A history of diabetes mellitus was noted. The images revealed a brain abscess in the left frontal lobe and pus culture confirmed the growth of Citrobacter koseri. The clinical symptoms improved completely postoperatively.

  8. Inflammation is detrimental for neurogenesis in adult brain

    NASA Astrophysics Data System (ADS)

    Ekdahl, Christine T.; Claasen, Jan-Hendrik; Bonde, Sara; Kokaia, Zaal; Lindvall, Olle

    2003-11-01

    New hippocampal neurons are continuously generated in the adult brain. Here, we demonstrate that lipopolysaccharide-induced inflammation, which gives rise to microglia activation in the area where the new neurons are born, strongly impairs basal hippocampal neurogenesis in rats. The increased neurogenesis triggered by a brain insult is also attenuated if it is associated with microglia activation caused by tissue damage or lipopolysaccharide infusion. The impaired neurogenesis in inflammation is restored by systemic administration of minocycline, which inhibits microglia activation. Our data raise the possibility that suppression of hippocampal neurogenesis by activated microglia contributes to cognitive dysfunction in aging, dementia, epilepsy, and other conditions leading to brain inflammation.

  9. FACS purification of immunolabeled cell types from adult rat brain.

    PubMed

    Guez-Barber, Danielle; Fanous, Sanya; Harvey, Brandon K; Zhang, Yongqing; Lehrmann, Elin; Becker, Kevin G; Picciotto, Marina R; Hope, Bruce T

    2012-01-15

    Molecular analysis of brain tissue is greatly complicated by having many different classes of neurons and glia interspersed throughout the brain. Fluorescence-activated cell sorting (FACS) has been used to purify selected cell types from brain tissue. However, its use has been limited to brain tissue from embryos or transgenic mice with promoter-driven reporter genes. To overcome these limitations, we developed a FACS procedure for dissociating intact cell bodies from adult wild-type rat brains and sorting them using commercially available antibodies against intracellular and extracellular proteins. As an example, we isolated neurons using a NeuN antibody and confirmed their identity using microarray and real time PCR of mRNA from the sorted cells. Our FACS procedure allows rapid, high-throughput, quantitative assays of molecular alterations in identified cell types with widespread applications in neuroscience.

  10. Neuromorphometry of primary brain tumors by magnetic resonance imaging

    PubMed Central

    Hevia-Montiel, Nidiyare; Rodriguez-Perez, Pedro I.; Lamothe-Molina, Paul J.; Arellano-Reynoso, Alfonso; Bribiesca, Ernesto; Alegria-Loyola, Marco A.

    2015-01-01

    Abstract. Magnetic resonance imaging is a technique for the diagnosis and classification of brain tumors. Discrete compactness is a morphological feature of two-dimensional and three-dimensional objects. This measure determines the compactness of a discretized object depending on the sum of the areas of the connected voxels and has been used for understanding the morphology of nonbrain tumors. We hypothesized that regarding brain tumors, we may improve the malignancy grade classification. We analyzed the values in 20 patients with different subtypes of primary brain tumors: astrocytoma, oligodendroglioma, and glioblastoma multiforme subdivided into the contrast-enhanced and the necrotic tumor regions. The preliminary results show an inverse relationship between the compactness value and the malignancy grade of gliomas. Astrocytomas exhibit a mean of 973±14, whereas oligodendrogliomas exhibit a mean of 942±21. In contrast, the contrast-enhanced region of the glioblastoma presented a mean of 919±43, and the necrotic region presented a mean of 869±66. However, the volume and area of the enclosing surface did not show a relationship with the malignancy grade of the gliomas. Discrete compactness appears to be a stable characteristic between primary brain tumors of different malignancy grades, because similar values were obtained from different patients with the same type of tumor. PMID:26158107

  11. Radiosurgery for Brain Metastases From Unknown Primary Cancers

    SciTech Connect

    Niranjan, Ajay; Kano, Hideyuki; Khan, Aftab; Kim, In-Young; Kondziolka, Douglas; Flickinger, John C.; Lunsford, L. Dade

    2010-08-01

    Purpose: We evaluated the role of Gamma Knife stereotactic radiosurgery in the multidisciplinary management of brain metastases from an undiagnosed primary cancer. Methods and Materials: Twenty-nine patients who had solitary or multiple brain metastases without a detectable primary site underwent stereotactic radiosurgery between January 1990 and March 2007 at the University of Pittsburgh. The median patient age was 61.7 years (range, 37.9-78.7 years). The median target volume was 1.0 cc (range, 0.02-23.6 cc), and the median margin radiosurgical dose was 16 Gy (range, 20-70 Gy). Results: After radiosurgery, the local tumor control rate was 88.5%. Twenty four patients died and 5 patients were living at the time of this analysis. The overall median survival was 12 months. Actuarial survival rates from stereotactic radiosurgery at 1 and 2 years were 57.2% and 36.8%, respectively. Factors associated with poor progression-free survival included large tumor volume (3 cc or more) and brainstem tumor location. Conclusions: Radiosurgery is an effective and safe minimally invasive option for patients with brain metastases from an unknown primary site.

  12. Bilateral Brain Regions Associated with Naming in Older Adults

    ERIC Educational Resources Information Center

    Obler, Loraine K.; Rykhlevskaia, Elena; Schnyer, David; Clark-Cotton, Manuella R.; Spiro, Avron, III; Hyun, JungMoon; Kim, Dae-Shik; Goral, Mira; Albert, Martin L.

    2010-01-01

    To determine structural brain correlates of naming abilities in older adults, we tested 24 individuals aged 56-79 on two confrontation-naming tests (the Boston Naming Test (BNT) and the Action Naming Test (ANT)), then collected from these individuals structural Magnetic-Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data. Overall,…

  13. Pedophilic brain potential responses to adult erotic stimuli.

    PubMed

    Knott, Verner; Impey, Danielle; Fisher, Derek; Delpero, Emily; Fedoroff, Paul

    2016-02-01

    Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults.

  14. Experience-dependent neural plasticity in the adult damaged brain

    PubMed Central

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper extremity (hand and arm) impairments. A prolonged and widespread process of repair and reorganization of surviving neural circuits is instigated by injury to the adult brain. When experience impacts these same neural circuits, it interacts with degenerative and regenerative cascades to shape neural reorganization and functional outcome. This is evident in the cortical plasticity resulting from compensatory reliance on the “good” forelimb in rats with unilateral sensorimotor cortical infarcts. Behavioral interventions (e.g., rehabilitative training) can drive functionally beneficial neural reorganization in the injured hemisphere. However, experience can have both behaviorally beneficial and detrimental effects. The interactions between experience-dependent and injury-induced neural plasticity are complex, time-dependent, and varied with age and other factors. A better understanding of these interactions is needed to understand how to optimize brain remodeling and functional outcome. Learning outcomes Readers will be able to describe (a) experience effects that are maladaptive for behavioral outcome after brain damage, (b) manipulations of experience that drive functionally beneficial neural plasticity, and (c) reasons why rehabilitative training effects can be expected to vary with age, training duration and timing. PMID:21620413

  15. Interpreting WAIS-III performance after primary brain tumor surgery.

    PubMed

    Gonçalves, Marta de A; Simões, Mário R; Castro-Caldas, Alexandre

    2017-01-01

    The literature lacks information on the performance of patients with brain tumors on the Wechsler Intelligence Scales. This study aimed to explore the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) performance profile of 23 consecutive patients with brain tumors and 23 matched controls selected from the Portuguese WAIS-III standardization sample, using the technical manual steps recommended for score interpretation. The control group was demographically matched to the tumor group regarding gender, age, education, profession, and geographic region. The technical manual steps recommended for score interpretation were applied. Patients with brain tumors had significantly lower performances on the Performance IQ, Full-Scale IQ, Perceptual Organization Index, Working Memory Index, Processing Speed Index, Arithmetic, Object Assembly, and Picture Arrangement, though all scaled scores were within the normal range according to the manual tables. Only Vocabulary and Comprehension scatter scores were statistically different between groups. No strengths or weaknesses were found for either group. The mean discrepancy scores do not appear to have clinical value for this population. In conclusion, the study results did not reveal a specific profile for patients with brain tumors on the WAIS-III.

  16. Primary care for adults on the autism spectrum.

    PubMed

    Nicolaidis, Christina; Kripke, Clarissa Calliope; Raymaker, Dora

    2014-09-01

    Autism spectrum disorder (ASD) is defined by differences in social communication and restricted, repetitive patterns of behavior, interests, or activities. Skills and challenges can change depending on environmental stimuli, supports, and stressors. Quality of life can be improved by the use of accommodations, assistive technologies, therapies to improve adaptive function or communication, caregiver training, acceptance, access, and inclusion. This article focuses on the identification of ASD in adults, referrals for services, the recognition of associated conditions, strategies and accommodations to facilitate effective primary care services, and ethical issues related to caring for autistic adults.

  17. Relationships between gene expression and brain wiring in the adult rodent brain.

    PubMed

    French, Leon; Pavlidis, Paul

    2011-01-06

    We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain "connectome" from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at http://www.chibi.ubc.ca/ABAMS.

  18. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging

    PubMed Central

    Bell, Robert D.; Winkler, Ethan A.; Sagare, Abhay P.; Singh, Itender; LaRue, Barb; Deane, Rashid; Zlokovic, Berislav V.

    2010-01-01

    SUMMARY Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow and cerebral blood flow responses to brain activation which ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericytes loss results in a progressive age-dependent vascular-mediated neurodegeneration. PMID:21040844

  19. Accumulation of silver nanoparticles by cultured primary brain astrocytes

    NASA Astrophysics Data System (ADS)

    Luther, Eva M.; Koehler, Yvonne; Diendorf, Joerg; Epple, Matthias; Dringen, Ralf

    2011-09-01

    Silver nanoparticles (AgNP) are components of various food industry products and are frequently used for medical equipment and materials. Although such particles enter the vertebrate brain, little is known on their biocompatibility for brain cells. To study the consequences of an AgNP exposure of brain cells we have treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated AgNP. The incubation of cultured astrocytes with micromolar concentrations of AgNP for up to 24 h resulted in a time- and concentration-dependent accumulation of silver, but did not compromise the cell viability nor lower the cellular glutathione content. In contrast, the incubation of astrocytes for 4 h with identical amounts of silver as AgNO3 already severely compromised the cell viability and completely deprived the cells of glutathione. The accumulation of AgNP by astrocytes was proportional to the concentration of AgNP applied and significantly lowered by about 30% in the presence of the endocytosis inhibitors chloroquine or amiloride. Incubation at 4 °C reduced the accumulation of AgNP by 80% compared to the values obtained for cells that had been exposed to AgNP at 37 °C. These data demonstrate that viable cultured brain astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent process that most likely involves endocytotic pathways.

  20. Accumulation of silver nanoparticles by cultured primary brain astrocytes.

    PubMed

    Luther, Eva M; Koehler, Yvonne; Diendorf, Joerg; Epple, Matthias; Dringen, Ralf

    2011-09-16

    Silver nanoparticles (AgNP) are components of various food industry products and are frequently used for medical equipment and materials. Although such particles enter the vertebrate brain, little is known on their biocompatibility for brain cells. To study the consequences of an AgNP exposure of brain cells we have treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated AgNP. The incubation of cultured astrocytes with micromolar concentrations of AgNP for up to 24 h resulted in a time- and concentration-dependent accumulation of silver, but did not compromise the cell viability nor lower the cellular glutathione content. In contrast, the incubation of astrocytes for 4 h with identical amounts of silver as AgNO(3) already severely compromised the cell viability and completely deprived the cells of glutathione. The accumulation of AgNP by astrocytes was proportional to the concentration of AgNP applied and significantly lowered by about 30% in the presence of the endocytosis inhibitors chloroquine or amiloride. Incubation at 4 °C reduced the accumulation of AgNP by 80% compared to the values obtained for cells that had been exposed to AgNP at 37 °C. These data demonstrate that viable cultured brain astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent process that most likely involves endocytotic pathways.

  1. Decreased segregation of brain systems across the healthy adult lifespan

    PubMed Central

    Chan, Micaela Y.; Park, Denise C.; Savalia, Neil K.; Petersen, Steven E.; Wig, Gagan S.

    2014-01-01

    Healthy aging has been associated with decreased specialization in brain function. This characterization has focused largely on describing age-accompanied differences in specialization at the level of neurons and brain areas. We expand this work to describe systems-level differences in specialization in a healthy adult lifespan sample (n = 210; 20–89 y). A graph-theoretic framework is used to guide analysis of functional MRI resting-state data and describe systems-level differences in connectivity of individual brain networks. Young adults’ brain systems exhibit a balance of within- and between-system correlations that is characteristic of segregated and specialized organization. Increasing age is accompanied by decreasing segregation of brain systems. Compared with systems involved in the processing of sensory input and motor output, systems mediating “associative” operations exhibit a distinct pattern of reductions in segregation across the adult lifespan. Of particular importance, the magnitude of association system segregation is predictive of long-term memory function, independent of an individual’s age. PMID:25368199

  2. Prenatal ethanol exposure increases brain cholesterol content in adult rats.

    PubMed

    Barceló-Coblijn, Gwendolyn; Wold, Loren E; Ren, Jun; Murphy, Eric J

    2013-11-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content are known to occur in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43 %, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total polyunsaturated fatty acids (PUFA), in the n-3/n-6 ratio, and in the 22:6n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of postnatal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats.

  3. Clinical review: Brain-body temperature differences in adults with severe traumatic brain injury.

    PubMed

    Childs, Charmaine; Lunn, Kueh Wern

    2013-04-22

    Surrogate or 'proxy' measures of brain temperature are used in the routine management of patients with brain damage. The prevailing view is that the brain is 'hotter' than the body. The polarity and magnitude of temperature differences between brain and body, however, remains unclear after severe traumatic brain injury (TBI). The focus of this systematic review is on the adult patient admitted to intensive/neurocritical care with a diagnosis of severe TBI (Glasgow Coma Scale score of less than 8). The review considered studies that measured brain temperature and core body temperature. Articles published in English from the years 1980 to 2012 were searched in databases, CINAHL, PubMed, Scopus, Web of Science, Science Direct, Ovid SP, Mednar and ProQuest Dissertations & Theses Database. For the review, publications of randomised controlled trials, non-randomised controlled trials, before and after studies, cohort studies, case-control studies and descriptive studies were considered for inclusion. Of 2,391 records identified via the search strategies, 37 were retrieved for detailed examination (including two via hand searching). Fifteen were reviewed and assessed for methodological quality. Eleven studies were included in the systematic review providing 15 brain-core body temperature comparisons. The direction of mean brain-body temperature differences was positive (brain higher than body temperature) and negative (brain lower than body temperature). Hypothermia is associated with large brain-body temperature differences. Brain temperature cannot be predicted reliably from core body temperature. Concurrent monitoring of brain and body temperature is recommended in patients where risk of temperature-related neuronal damage is a cause for clinical concern and when deliberate induction of below-normal body temperature is instituted.

  4. Comparative analysis of survival, treatment, cost and resource use among patients newly diagnosed with brain metastasis by initial primary cancer.

    PubMed

    Ray, Saurabh; Dacosta-Byfield, Stacey; Ganguli, Arijit; Bonthapally, Vijayveer; Teitelbaum, April

    2013-08-01

    Brain metastases are a frequent complication of many systemic cancers and portend a poor prognosis. This retrospective analysis of health claims data compared survival, treatment and health care utilization and costs in patients with brain metastasis by primary tumor site. Adult commercial and Medicare Advantage enrollees newly diagnosed with brain metastasis in 01 Jan 2004 through 30 Apr 2010 were identified. Inclusion required at least 2 claims that identified the same primary cancer site prior to diagnosis of brain metastasis and no evidence of primary brain tumors. Health care utilization rates and costs were calculated at the patient level for each month of follow-up. Differences among primary cancer site cohorts were assessed by ANOVA (continuous variables), Chi square test (proportions) and the Poisson distribution (utilization rates). The primary cancer cohorts comprised 1,031 lung cancer, 93 melanoma and 395 female breast cancer patients. During the 6 months prior to brain metastasis diagnosis, 59 % of lung cancer patients had no evidence of lymph node involvement or other metastatic disease compared to 55 and 42 % of melanoma and breast cancer patients (P < 0.001). Survival after brain metastasis diagnosis was less than 3 months for 52, 43 and 39 % for lung cancer, breast cancer and melanoma, respectively (P < 0.001). Melanoma patients had the highest rate of inpatient stays and outpatient visits (P ≤ 0.003). Total monthly all-cause costs were: melanoma, $23,426; breast cancer $19,708; lung cancer, $17,007 (P = 0.003). Health care utilization and costs after brain metastasis diagnosis were substantial and differed by primary tumor site.

  5. A meal preparation treatment protocol for adults with brain injury.

    PubMed

    Neistadt, M E

    1994-05-01

    Adults with acquired brain injury often demonstrate dysfunction in meal preparation due to deficits in component cognitive-perceptual skills. Although occupational therapy for these clients routinely includes meal preparation training, there are no protocols in the occupational therapy literature to help structure that activity to address clients' cognitive-perceptual deficits. This paper describes a meal preparation treatment protocol based on cognitive-perceptual information processing theory that has been pilot tested in a treatment outcome study with adult men with traumatic or anoxic acquired brain injury. In that study, the group of 23 subjects treated with this meal preparation protocol showed significant improvement in their meal preparation skill, as measured by the Rabideau Kitchen Evaluation-Revised (RKE-R), a test of meal preparation skill, and in their cognitive-perceptual skill, as measured by the WAIS-R Block Design Test. The treatment protocol includes descriptions of the structure, grading, and cuing methods for light meal preparation activities.

  6. Comprehensive cellular‐resolution atlas of the adult human brain

    PubMed Central

    Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  7. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  8. Characterization of brain inflammation during primary amoebic meningoencephalitis.

    PubMed

    Cervantes-Sandoval, Isaac; Serrano-Luna, José de Jesús; García-Latorre, Ethel; Tsutsumi, Víctor; Shibayama, Mineko

    2008-09-01

    Naegleria fowleri is a free-living amoeba and the etiologic agent of primary amoebic meningoencephalitis (PAM). Trophozoites reach the brain by penetrating the olfactory epithelium, and invasion of the olfactory bulbs results in an intense inflammatory reaction. The contribution of the inflammatory response to brain damage in experimental PAM has not been delineated. Using both optical and electron microscopy, we analyzed the morphologic changes in the brain parenchyma due to inflammation during experimental PAM. Several N. fowleri trophozoites were observed in the olfactory bulbs 72 h post-inoculation, and the number of amoebae increased rapidly over the next 24 h. Eosinophils and neutrophils surrounding the amoebae were then noted at later times during infection. Electron microscopic examination of the increased numbers of neutrophils and the interactions with trophozoites indicated an active attempt to eliminate the amoebae. The extent of inflammation increased over time, with a predominant neutrophil response indicating important signs of damage and necrosis of the parenchyma. These data suggest a probable role of inflammation in tissue damage. To test the former hypothesis, we used CD38-/- knockout mice with deficiencies in chemotaxis to compare the rate of mortality with the parental strain, C57BL/6J. The results showed that inflammation and mortality were delayed in the knockout mice. Based on these results, we suggest that the host inflammatory response and polymorphonuclear cell lysis contribute to a great extent to the central nervous system tissue damage.

  9. Brain network activity in monolingual and bilingual older adults.

    PubMed

    Grady, Cheryl L; Luk, Gigi; Craik, Fergus I M; Bialystok, Ellen

    2015-01-01

    Bilingual older adults typically have better performance on tasks of executive control (EC) than do their monolingual peers, but differences in brain activity due to language experience are not well understood. Based on studies showing a relation between the dynamic range of brain network activity and performance on EC tasks, we hypothesized that life-long bilingual older adults would show increased functional connectivity relative to monolinguals in networks related to EC. We assessed intrinsic functional connectivity and modulation of activity in task vs. fixation periods in two brain networks that are active when EC is engaged, the frontoparietal control network (FPC) and the salience network (SLN). We also examined the default mode network (DMN), which influences behavior through reduced activity during tasks. We found stronger intrinsic functional connectivity in the FPC and DMN in bilinguals than in monolinguals. Although there were no group differences in the modulation of activity across tasks and fixation, bilinguals showed stronger correlations than monolinguals between intrinsic connectivity in the FPC and task-related increases of activity in prefrontal and parietal regions. This bilingual difference in network connectivity suggests that language experience begun in childhood and continued throughout adulthood influences brain networks in ways that may provide benefits in later life.

  10. Brain Network Activity in Monolingual and Bilingual Older Adults

    PubMed Central

    Grady, Cheryl L.; Luk, Gigi; Craik, Fergus I.M.; Bialystok, Ellen

    2016-01-01

    Bilingual older adults typically have better performance on tasks of executive control (EC) than do their monolingual peers, but differences in brain activity due to language experience are not well understood. Based on studies showing a relation between the dynamic range of brain network activity and performance on EC tasks, we hypothesized that life-long bilingual older adults would show increased functional connectivity relative to monolinguals in networks related to EC. We assessed intrinsic functional connectivity and modulation of activity in task vs. fixation periods in two brain networks that are active when EC is engaged, the frontoparietal control network (FPC) and the salience network (SLN). We also examined the default mode network (DMN), which influences behavior through reduced activity during tasks. We found stronger intrinsic functional connectivity in the FPC and DMN in bilinguals than in monolinguals. Although there were no group differences in the modulation of activity across tasks and fixation, bilinguals showed stronger correlations than monolinguals between intrinsic connectivity in the FPC and task-related increases of activity in prefrontal and parietal regions. This bilingual difference in network connectivity suggests that language experience begun in childhood and continued throughout adulthood influences brain networks in ways that may provide benefits in later life. PMID:25445783

  11. Time Spent Caregiving and Help Received by Spouses and Adult Children of Brain-Impaired Adults.

    ERIC Educational Resources Information Center

    Enright, Robert B., Jr.

    1991-01-01

    Surveyed 233 family caregivers for brain-impaired adults. Spousal caregivers (both husbands and wives) devoted much time to caregiving. Most caregivers received little assistance from other family members and friends, but husbands received more than others. Employed spouses received more paid help than unemployed spouses; employment did not affect…

  12. Epigenetic choreographers of neurogenesis in the adult mammalian brain

    PubMed Central

    Ma, Dengke K; Marchetto, Maria Carolina; Guo, Junjie U; Ming, Guo-li; Gage, Fred H; Song, Hongjun

    2012-01-01

    Epigenetic mechanisms regulate cell differentiation during embryonic development and also serve as important interfaces between genes and the environment in adulthood. Neurogenesis in adults, which generates functional neural cell types from adult neural stem cells, is dynamically regulated by both intrinsic state-specific cell differentiation cues and extrinsic neural niche signals. Epigenetic regulation by DNA and histone modifiers, non-coding RNAs and other self-sustained mechanisms can lead to relatively long-lasting biological effects and maintain functional neurogenesis throughout life in discrete regions of the mammalian brain. Here, we review recent evidence that epigenetic mechanisms carry out diverse roles in regulating specific aspects of adult neurogenesis and highlight the implications of such epigenetic regulation for neural plasticity and disorders. PMID:20975758

  13. Brain Gray Matter Deficits in Patients with Chronic Primary Insomnia

    PubMed Central

    Joo, Eun Yeon; Noh, Hyun Jin; Kim, Jeong-Sik; Koo, Dae Lim; Kim, Daeyoung; Hwang, Kyoung Jin; Kim, Ji Young; Kim, Sung Tae; Kim, Mi Rim; Hong, Seung Bong

    2013-01-01

    Study Objective: To investigate the structural changes in patients with chronic primary insomnia and the relationships with clinical features of insomnia. Design: Statistical parametric mapping 8-based voxel-based morphometry was used to identify differences in regional gray and white matter between patients with chronic primary insomnia and normal controls. Setting: University hospital. Patients and Participants: Twenty-seven patients and 27 age/sex-matched controls. Interventions: Regional differences were compared using two-sample t-tests with age, sex, and intracranial volume as covariates. Measurements and Results: The patients were a mean age of 52.3 y and had a mean history of insomnia of 7.6 y. Patients displayed cognitive deficits in attention, frontal/executive function, and nonverbal memory. Patients also displayed significantly reduced gray matter concentrations (GMCs) in dorsolateral prefrontal and pericentral cortices, superior temporal gyrus, and cerebellum and decreased gray matter volumes in medial frontal and middle temporal gyri compared with control patients with the cluster threshold ≥ 50 voxels at the level of uncorrected P < 0.001. Negative correlations were found between GMC of the prefrontal cortex and insomnia severity and the wakefulness after sleep onset, and between GMC of pericentral cortex and sleep latencies. None of the findings continued to be significant after correction for multiple comparisons. Conclusions: We found gray matter deficits in multiple brain regions including bilateral frontal lobes in patients with psychophysiologic insomnia. Gray matter deficit of the pericentral and lateral temporal areas may be associated with the difficulties in sleep initiation and maintenance. It is still unclear whether gray matter reductions are a preexisting abnormality or a consequence of insomnia. Citation: Joo EY; Noh HJ; Kim JS; Koo DL; Kim D; Hwang KJ; Kim JY; Kim ST; Kim MR; Hong SB. Brain gray matter deficits in patients with

  14. Differential expression of sirtuin family members in the developing, adult, and aged rat brain.

    PubMed

    Sidorova-Darmos, Elena; Wither, Robert G; Shulyakova, Natalya; Fisher, Carl; Ratnam, Melanie; Aarts, Michelle; Lilge, Lothar; Monnier, Philippe P; Eubanks, James H

    2014-01-01

    The sirtuins are NAD(+)-dependent protein deacetylases and/or ADP-ribosyltransferases that play roles in metabolic homeostasis, stress response and potentially aging. This enzyme family resides in different subcellular compartments, and acts on a number of different targets in the nucleus, cytoplasm and in the mitochondria. Despite their recognized ability to regulate metabolic processes, the roles played by specific sirtuins in the brain-the most energy demanding tissue in the body-remains less well investigated and understood. In the present study, we examined the regional mRNA and protein expression patterns of individual sirtuin family members in the developing, adult, and aged rat brain. Our results show that while each sirtuin is expressed in the brain at each of these different stages, they display unique spatial and temporal expression patterns within the brain. Further, for specific members of the family, the protein expression profile did not coincide with their respective mRNA expression profile. Moreover, using primary cultures enriched for neurons and astrocytes respectively, we found that specific sirtuin members display preferential neural lineage expression. Collectively, these results provide the first composite illustration that sirtuin family members display differential expression patterns in the brain, and provide evidence that specific sirtuins could potentially be targeted to achieve cell-type selective effects within the brain.

  15. Primary Colonic Eosinophilia and Eosinophilic Colitis in Adults.

    PubMed

    Turner, Kevin O; Sinkre, Richa A; Neumann, William L; Genta, Robert M

    2017-02-01

    The normal content of eosinophils in the adult colon and the criteria for the histopathologic diagnosis of eosinophilic colitis remain undefined. This study aimed at: (1) establishing the numbers of eosinophils in the normal adult colon; and (2) proposing a clinicopathologic framework for the diagnosis of primary colonic eosinophilia and eosinophilic colitis. To accomplish these goals, we counted the eosinophils in the right, transverse, and left colon of 159 adults with normal colonic histology. Using a database of 1.2 million patients with colonic biopsies, we extracted all adults with a diagnosis of colonic eosinophilia. We reviewed the slides from all cases and captured demographic, clinical, and pathologic data, including information about eosinophilia in other organs. We then compared the clinical manifestations of the study patients (those with no identifiable cause of eosinophilia) to those of patients with other types of colitis. The normal eosinophil counts (per mm) were 55.7±23.4 in the right, 41.0±18.6 in the transverse, and 28.6±17.2 in the left colon. Of the 194 study patients (eosinophil counts 166-5050/mm), 63 were asymptomatic and had a normal colonoscopy. Diarrhea and abdominal pain were the commonest indications for colonoscopy (38% and 27%, respectively) among the 131 patients who had symptoms, endoscopic abnormalities, or both. Neither clinical manifestations nor endoscopic appearance were sufficiently characteristic to elicit the suspicion of colonic eosinophilia. In conclusion, primary colonic eosinophilia was extremely rare in this series (<1 in 6000 patients); one third of these patients were asymptomatic. Their clinical manifestations were not distinctive and could not have led clinicians to suspect this condition; one third of the patients were asymptomatic. We suggest that regularly reporting high colonic eosinophilia may result in increased opportunities for clinicopathologic studies that might lead to a better definition of this

  16. Laparoscopic Nephroureterectomy for Adult Patient with Primary Obstructive Megaureter

    PubMed Central

    Makiyama, Kazuhide; Ohtake, Shinji; Yamanaka, Hiroyuki; Sano, Futoshi; Nakaigawa, Noboru; Kubota, Yoshinobu

    2013-01-01

    A 29-year-old female with a complaint of abdominal distension was referred to our hospital. She had a history of being treated for pyelonephritis three times. By computed tomography and retrograde pyelography, she was diagnosed with adult left primary megaureter. Her left renal function was severely deteriorated. She hoped for surgical intervention before becoming pregnant. Laparoscopic nephroureterectomy for megaureters seems to be difficult due to the large size. By sucking urine from an inserted ureteral catheter and setting trocar positions, we successfully performed laparoscopic nephroureterectomy for megaureter. PMID:24455395

  17. Acute moderate exercise enhances compensatory brain activation in older adults.

    PubMed

    Hyodo, Kazuki; Dan, Ippeita; Suwabe, Kazuya; Kyutoku, Yasushi; Yamada, Yuhki; Akahori, Mitsuya; Byun, Kyeongho; Kato, Morimasa; Soya, Hideaki

    2012-11-01

    A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation.

  18. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    PubMed Central

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-01-01

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings. PMID:26229677

  19. Neuroimaging in adult penetrating brain injury: a guide for radiographers.

    PubMed

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-01

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings.

  20. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    SciTech Connect

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-15

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings.

  1. Isolation of primary murine brain microvascular endothelial cells.

    PubMed

    Ruck, Tobias; Bittner, Stefan; Epping, Lisa; Herrmann, Alexander M; Meuth, Sven G

    2014-11-14

    The blood-brain-barrier is ultrastructurally assembled by a monolayer of brain microvascular endothelial cells (BMEC) interconnected by a junctional complex of tight and adherens junctions. Together with other cell-types such as astrocytes or pericytes, they form the neurovascular unit (NVU), which specifically regulates the interchange of fluids, molecules and cells between the peripheral blood and the CNS. Through this complex and dynamic system BMECs are involved in various processes maintaining the homeostasis of the CNS. A dysfunction of the BBB is observed as an essential step in the pathogenesis of many severe CNS diseases. However, specific and targeted therapies are very limited, as the underlying mechanisms are still far from being understood. Animal and in vitro models have been extensively used to gain in-depth understanding of complex physiological and pathophysiological processes. By reduction and simplification it is possible to focus the investigation on the subject of interest and to exclude a variety of confounding factors. However, comparability and transferability are also reduced in model systems, which have to be taken into account for evaluation. The most common animal models are based on mice, among other reasons, mainly due to the constantly increasing possibilities of methodology. In vitro studies of isolated murine BMECs might enable an in-depth analysis of their properties and of the blood-brain-barrier under physiological and pathophysiological conditions. Further insights into the complex mechanisms at the BBB potentially provide the basis for new therapeutic strategies. This protocol describes a method to isolate primary murine microvascular endothelial cells by a sequence of physical and chemical purification steps. Special considerations for purity and cultivation of MBMECs as well as quality control, potential applications and limitations are discussed.

  2. Fotemustine in the treatment of brain primary tumors and metastases.

    PubMed

    Khayat, D; Giroux, B; Berille, J; Cour, V; Gerard, B; Sarkany, M; Bertrand, P; Bizzari, J P

    1994-01-01

    Fotemustine is a new chloroethylnitrosourea characterized by the grafting of a phosphonoalanine group onto a nitrosourea radical. Clinical studies using fotemustine have been conducted in malignant glioma, brain metastasis of non-small cell lung cancer, and disseminated malignant melanoma. In recurrent malignant glioma, fotemustine has been used as a single agent: assessed by computed tomography scan, after 8 weeks, the objective response rate was 26.3% among 38 evaluable patients. Median duration of response was 33 weeks. The main toxicity was hematological (thrombocytopenia and leucopenia). A trial with high-dose fotemustine and autologous bone marrow rescue in newly diagnosed glioma was conducted in 26 patients, and 6 showed a partial response. The median overall survival was approximately 11 months. Myelosuppression was noted in all patients except 1, and other toxicity reported was central nervous system toxicity and epigastric pain. Combined with radiotherapy in 55 patients, a 29% response rate was observed, and this combination was well tolerated and easily manageable on an outpatient basis. Finally, fotemustine has been used intraarterially, with 10 objective responses observed among 26 evaluable patients. In brain metastases of non-small cell lung cancer, fotemustine proved to be active with a response rate of 16.7%. Combined with cisplatinum, fotemustine is still under study, but preliminary results are promising. In cerebral metastases of disseminated malignant melanoma, fotemustine has been evaluated in a total of 140 patients in the various studies: median response rate is 24.3%, ranging from 8.3% to 60.0%. Fotemustine appears to be a good candidate in the treatment of primary brain tumors and metastases.

  3. Pallidal deep brain stimulation relieves camptocormia in primary dystonia.

    PubMed

    Hagenacker, Tim; Gerwig, Marcus; Gasser, Thomas; Miller, Dorothea; Kastrup, Oliver; Jokisch, Daniel; Sure, Ulrich; Frings, Markus

    2013-07-01

    Camptocormia, characterised by a forward flexion of the thoracolumbar spine may occur in various movement disorders, mainly in Parkinson's disease or in primary dystonia. In severe cases, patients with camptocormia are unable to walk. While treatment options are limited, deep brain stimulation (DBS) with bilateral stimulation of the subthalamic nucleus or globus pallidus internus (GPi) has been proposed as a therapeutic option in refractory cases of Parkinson's disease. Here we present two patients with severe camptocormia as an isolated form of dystonia and as part of generalised dystonia, respectively, which were both treated with bilateral stimulation of the GPi. Symptoms of dystonia were assessed using the Burke-Fahn-Marsden dystonia rating scale (BFM) before and during deep brain stimulation. In both patients there was a significant functional improvement following long-term bilateral GPi stimulation and both patients gained ability to walk. In the first patient with an isolated dystonic camptocormia the BFM motor subscore for the truncal flexion improved by 75 %. The total BFM motor score in the second patient with a camptocormia in generalised dystonia improved by 45 %, while the BFM score for truncal flexion improved by 87 %. In both patients the effect of the bilateral GPi stimulation on camptocormia was substantial, independent of generalisation of dystonia. Therefore, GPi DBS is a possible treatment option for this rare disease.

  4. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  5. Experimental induction of corpora amylacea in adult rat brain.

    PubMed

    Schipper, H M

    1998-10-01

    Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulate in astroglia and other brain cells as a function of advancing age and, to an even greater extent, in several human neurodegenerative conditions. The mechanisms responsible for their biogenesis and their subcellular origin(s) remain unclear. We previously demonstrated that the sulfhydryl agent, cysteamine (CSH), promotes the accumulation of CA-like inclusions in cultured rat astroglia. In the present study, we show that subcutaneous administration of CSH to adult rats (150 mg/kg for 6 weeks followed by a 5-week drug-washout period) elicits the accumulation of CA in many cortical and subcortical brain regions. As in the aging human brain and in CSH-treated rat astrocyte cultures, the inclusions are periodic acid-Schiff -positive and are consistently immunostained with antibodies directed against mitochondrial epitopes and ubiquitin. Our findings support our contention that mitochondria are important structural precursors of CA, and that CSH accelerates aging-like processes in rat astroglia both in vitro and in the intact brain.

  6. Testosterone affects language areas of the adult human brain.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc.

  7. Roles for oestrogen receptor β in adult brain function.

    PubMed

    Handa, R J; Ogawa, S; Wang, J M; Herbison, A E

    2012-01-01

    Oestradiol exerts a profound influence upon multiple brain circuits. For the most part, these effects are mediated by oestrogen receptor (ER)α. We review here the roles of ERβ, the other ER isoform, in mediating rodent oestradiol-regulated anxiety, aggressive and sexual behaviours, the control of gonadotrophin secretion, and adult neurogenesis. Evidence exists for: (i) ERβ located in the paraventricular nucleus underpinning the suppressive influence of oestradiol on the stress axis and anxiety-like behaviour; (ii) ERβ expressed in gonadotrophin-releasing hormone neurones contributing to oestrogen negative-feedback control of gonadotrophin secretion; (iii) ERβ controlling the offset of lordosis behaviour; (iv) ERβ suppressing aggressive behaviour in males; (v) ERβ modulating responses to social stimuli; and (vi) ERβ in controlling adult neurogenesis. This review highlights two major themes; first, ERβ and ERα are usually tightly inter-related in the oestradiol-dependent control of a particular brain function. For example, even though oestradiol feedback to control reproduction occurs principally through ERα-dependent mechanisms, modulatory roles for ERβ also exist. Second, the roles of ERα and ERβ within a particular neural network may be synergistic or antagonistic. Examples of the latter include the role of ERα to enhance, and ERβ to suppress, anxiety-like and aggressive behaviours. Splice variants such as ERβ2, acting as dominant negative receptors, are of further particular interest because their expression levels may reflect preceeding oestradiol exposure of relevance to oestradiol replacement therapy. Together, this review highlights the predominant modulatory, but nonetheless important, roles of ERβ in mediating the many effects of oestradiol upon adult brain function.

  8. Differential expression of sirtuin family members in the developing, adult, and aged rat brain

    PubMed Central

    Sidorova-Darmos, Elena; Wither, Robert G.; Shulyakova, Natalya; Fisher, Carl; Ratnam, Melanie; Aarts, Michelle; Lilge, Lothar; Monnier, Philippe P.; Eubanks, James H.

    2014-01-01

    The sirtuins are NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that play roles in metabolic homeostasis, stress response and potentially aging. This enzyme family resides in different subcellular compartments, and acts on a number of different targets in the nucleus, cytoplasm and in the mitochondria. Despite their recognized ability to regulate metabolic processes, the roles played by specific sirtuins in the brain—the most energy demanding tissue in the body—remains less well investigated and understood. In the present study, we examined the regional mRNA and protein expression patterns of individual sirtuin family members in the developing, adult, and aged rat brain. Our results show that while each sirtuin is expressed in the brain at each of these different stages, they display unique spatial and temporal expression patterns within the brain. Further, for specific members of the family, the protein expression profile did not coincide with their respective mRNA expression profile. Moreover, using primary cultures enriched for neurons and astrocytes respectively, we found that specific sirtuin members display preferential neural lineage expression. Collectively, these results provide the first composite illustration that sirtuin family members display differential expression patterns in the brain, and provide evidence that specific sirtuins could potentially be targeted to achieve cell-type selective effects within the brain. PMID:25566066

  9. Hour-Long Nap May Boost Brain Function in Older Adults

    MedlinePlus

    ... fullstory_162923.html Hour-Long Nap May Boost Brain Function in Older Adults Linked to improved memory and ... during the day had any effects on their brain function. Nearly 60 percent of the people regularly napped ...

  10. Is primary prevention with antiepileptic drugs effective in brain tumors or brain metastases?

    PubMed

    Lobos-Urbina, Diego; Kittsteiner-Manubens, Lucas; Peña, José

    2017-03-21

    Patients with brain tumors –primary or metastatic- have an increased risk of presenting seizures during the course of their disease. So, prophylactic antiepileptic drugs have been proposed. However, the effects of this intervention are not yet clear. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified 12 systematic reviews including 80 studies overall. Twelve corresponded to randomized trials, but only two answered the question of interest. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE method. We concluded primary prevention with antiepileptic drugs might not reduce the risk of seizures, and it is associated to frequent adverse effects.

  11. The evaluation of saphenofemoral insufficiency in primary adult varicocele.

    PubMed

    Koyuncu, Hakan; Ergenoglu, Mehmet; Yencilek, Faruk; Gulcan, Nilay; Tasdelen, Neslihan; Yencilek, Esin; Sarica, Kemal

    2011-01-01

    The aim of this study was to evaluate the possible relationship between varicocele and saphenofemoral insufficiency in patients diagnosed with primary varicocele. A total of 70 patients with the primary diagnosis of varicocele were included into the study. A total of 30 age-matched healthy adults were also included in the study as a control group. Varicocele was diagnosed by palpation and observation of each spermatic cord in standing position before and during a valsalva maneuver. Additionally, scrotal Doppler and lower extremity venous Doppler ultrasonography were performed. Patients who were with spermatic varicose vein larger than 3.0 mm were included in the study group as a varicocele patient. At the lower extremity venous Doppler ultrasonography, a retrograde flow lasting longer than 0.5 seconds during normal breathing or at the valsalva maneuver was considered to be meaningful for saphenofemoral junction insufficiency. Thirty-six (51.35%) patients had insufficiency in saphenofemoral junction in the study group (6 [8.5%] bilateral, 30 [42.85%] unilateral) whereas 8 (26.6%) had insufficiency in the control group (2 [6.6%] bilateral, 6 [20%] unilateral insufficiency). The patients with primary varicocele had a statistically significant (P = .02) higher rate of venous insufficiency in their saphenofemoral junctions when compared with the control group. In the present study, the rate of saphenofemoral insufficiency has been found to be statistically higher in patients with primary varicocele compared with healthy men. Depending on the common presence of valvular insufficiency, we believe that the presence of varicocele should be investigated in the young population suffering from saphenofemoral junction insufficiency.

  12. Evaluation of an automatic brain segmentation method developed for neonates on adult MR brain images

    NASA Astrophysics Data System (ADS)

    Moeskops, Pim; Viergever, Max A.; Benders, Manon J. N. L.; Išgum, Ivana

    2015-03-01

    Automatic brain tissue segmentation is of clinical relevance in images acquired at all ages. The literature presents a clear distinction between methods developed for MR images of infants, and methods developed for images of adults. The aim of this work is to evaluate a method developed for neonatal images in the segmentation of adult images. The evaluated method employs supervised voxel classification in subsequent stages, exploiting spatial and intensity information. Evaluation was performed using images available within the MRBrainS13 challenge. The obtained average Dice coefficients were 85.77% for grey matter, 88.66% for white matter, 81.08% for cerebrospinal fluid, 95.65% for cerebrum, and 96.92% for intracranial cavity, currently resulting in the best overall ranking. The possibility of applying the same method to neonatal as well as adult images can be of great value in cross-sectional studies that include a wide age range.

  13. Significant predictors of patients' uncertainty in primary brain tumors.

    PubMed

    Lin, Lin; Chien, Lung-Chang; Acquaye, Alvina A; Vera-Bolanos, Elizabeth; Gilbert, Mark R; Armstrong, Terri S

    2015-05-01

    Patients with primary brain tumors (PBT) face uncertainty related to prognosis, symptoms and treatment response and toxicity. Uncertainty is correlated to negative mood states and symptom severity and interference. This study identified predictors of uncertainty during different treatment stages (newly-diagnosed, on treatment, followed-up without active treatment). One hundred eighty six patients with PBT were accrued at various points in the illness trajectory. Data collection tools included: a clinical checklist/a demographic data sheet/the Mishel Uncertainty in Illness Scale-Brain Tumor Form. The structured additive regression model was used to identify significant demographic and clinical predictors of illness-related uncertainty. Participants were primarily white (80 %) males (53 %). They ranged in age from 19-80 (mean = 44.2 ± 12.6). Thirty-two of the 186 patients were newly-diagnosed, 64 were on treatment at the time of clinical visit with MRI evaluation, 21 were without MRI, and 69 were not on active treatment. Three subscales (ambiguity/inconsistency; unpredictability-disease prognoses; unpredictability-symptoms and other triggers) were different amongst the treatment groups (P < .01). However, patients' uncertainty during active treatment was as high as in newly-diagnosed period. Other than treatment stages, change of employment status due to the illness was the most significant predictor of illness-related uncertainty. The illness trajectory of PBT remains ambiguous, complex, and unpredictable, leading to a high incidence of uncertainty. There was variation in the subscales of uncertainty depending on treatment status. Although patients who are newly diagnosed reported the highest scores on most of the subscales, patients on treatment felt more uncertain about unpredictability of symptoms than other groups. Due to the complexity and impact of the disease, associated symptoms, and interference with functional status, comprehensive assessment of patients

  14. Doublecortin in Oligodendrocyte Precursor Cells in the Adult Mouse Brain

    PubMed Central

    Boulanger, Jenna J.; Messier, Claude

    2017-01-01

    Key Points Oligodendrocyte precursor cells express doublecortin, a microtubule-associated protein.Oligodendrocyte precursor cells express doublecortin, but at a lower level of expression than in neuronal precursor.Doublecortin is not associated with a potential immature neuronal phenotype in Oligodendrocyte precursor cells. Oligodendrocyte precursor cells (OPC) are glial cells that differentiate into myelinating oligodendrocytes during embryogenesis and early stages of post-natal life. OPCs continue to divide throughout adulthood and some eventually differentiate into oligodendrocytes in response to demyelinating lesions. There is growing evidence that OPCs are also involved in activity-driven de novo myelination of previously unmyelinated axons and myelin remodeling in adulthood. Considering these roles in the adult brain, OPCs are likely mobile cells that can migrate on some distances before they differentiate into myelinating oligodendrocytes. A number of studies have noted that OPCs express doublecortin (DCX), a microtubule-associated protein expressed in neural precursor cells and in migrating immature neurons. Here we describe the distribution of DCX in OPCs. We found that almost all OPCs express DCX, but the level of expression appears to be much lower than what is found in neural precursor. We found that DCX is downregulated when OPCs start expressing mature oligodendrocyte markers and is absent in myelinating oligodendrocytes. DCX does not appear to signal an immature neuronal phenotype in OPCs in the adult mouse brain. Rather, it could be involved either in cell migration, or as a marker of an immature oligodendroglial cell phenotype.

  15. Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain.

    PubMed

    Feliciano, David M; Bordey, Angélique; Bonfanti, Luca

    2015-09-18

    Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization.

  16. Traumatic Brain Injury Severity Affects Neurogenesis in Adult Mouse Hippocampus.

    PubMed

    Wang, Xiaoting; Gao, Xiang; Michalski, Stephanie; Zhao, Shu; Chen, Jinhui

    2016-04-15

    Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC) proliferation in the hippocampal dentate gyrus. However, various groups have reported contradictory results on whether TBI increases neurogenesis, partially due to a wide range in the severities of injuries seen with different TBI models. To address whether the severity of TBI affects neurogenesis in the injured brain, we assessed neurogenesis in mouse brains receiving different severities of controlled cortical impact (CCI) with the same injury device. The mice were subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI severity on neurogenesis were evaluated at three stages: NSC proliferation, immature neurons, and newly-generated mature neurons. The results showed that mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI promoted NSC proliferation without increasing neurogenesis. Severe TBI increased neurogenesis at all three stages. Our data suggest that the severity of injury affects adult neurogenesis in the hippocampus, and thus it may partially explain the inconsistent results of different groups regarding neurogenesis following TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide a potential approach for using endogenous NSCs to protect against neuronal loss after trauma.

  17. Optimal Treatment Decision for Brain Metastases of Unknown Primary Origin: The Role and Timing of Radiosurgery

    PubMed Central

    Han, Hyun Jin; Chang, Won Seok; Jung, Hyun Ho; Park, Yong Gou

    2016-01-01

    Background Up to 15% of all patients with brain metastases have no clearly detected primary site despite intensive evaluation, and this incidence has decreased with the use of improved imaging technology. Radiosurgery has been evaluated as one of the treatment modality for patients with limited brain metastases. In this study, we evaluated the effectiveness of radiosurgery for brain metastases from unknown primary tumors. Methods We retrospectively evaluated 540 patients who underwent gamma knife radiosurgery (GKRS) for brain metastases radiologically diagnosed between August 1992 and September 2007 in our institution. First, the brain metastases were grouped into metachronous, synchronous, and precocious presentations according to the timing of diagnosis of the brain metastases. Then, synchronous and precocious brain metastases were further grouped into 1) unknown primary; 2) delayed known primary; and 3) synchronous metastases according to the timing of diagnosis of the primary origin. We analyzed the survival time and time to new brain metastasis in each group. Results Of the 540 patients, 29 (5.4%) presented precocious or synchronous metastases (34 GKRS procedures for 174 lesions). The primary tumor was not found even after intensive and repeated systemic evaluation in 10 patients (unknown primary, 34.5%); found after 8 months in 3 patients (delayed known primary, 1.2%); and diagnosed at the same time as the brain metastases in 16 patients (synchronous metastasis, 55.2%). No statistically significant differences in survival time and time to new brain metastasis were found among the three groups. Conclusion Identification of a primary tumor before GKRS did not affect the patient outcomes. If other possible differential diagnoses were completely excluded, early GKRS can be an effective treatment option for brain metastases from unknown primary tumor. PMID:27867920

  18. Electrophysiological Properties of Subventricular Zone Cells in Adult Mouse Brain

    PubMed Central

    Lai, Bin; Mao, Xiao Ou; Xie, Lin; Chang, Su-Youne; Xiong, Zhi-Gang; Jin, Kunlin; Greenberg, David A.

    2010-01-01

    The subventricular zone (SVZ) is a principal site of adult neurogenesis and appears to participate in the brain’s response to injury. Thus, measures that enhance SVZ neurogenesis may have a role in treatment of neurological disease. To better characterize SVZ cells and identify potential targets for therapeutic intervention, we studied electrophysiological properties of SVZ cells in adult mouse brain slices using patch-clamp techniques. Electrophysiology was correlated with immunohistochemical phenotype by injecting cells with lucifer yellow and by studying transgenic mice carrying green fluorescent protein under control of the doublecortin (DCX) or glial fibrillary acidic protein (GFAP) promoter. We identified five types of cells in the adult mouse SVZ: type 1 cells, with 4-aminopyridine (4-AP)/tetraethylammonium (TEA)-sensitive and CdCl2-sensitive inward currents; type 2 cells, with Ca2+-sensitive K+ and both 4-AP/TEA-sensitive and -insensitive currents; type 3 cells, with 4-AP/TEA-sensitive and -insensitive and small Na+ currents; type 4 cells, with slowly activating, large linear outward current and sustained outward current without fast-inactivating component; and type 5 cells, with a large outward rectifying current with a fast inactivating component. Type 2 and 3 cells expressed DCX, types 4 and 5 cells expressed GFAP, and type 1 cells expressed neither. We propose that SVZ neurogenesis involves a progression of electrophysiological cell phenotypes from types 4 and 5 cells (astrocytes) to type 1 cells (neuronal progenitors) to types 2 and 3 cells (nascent neurons), and that drugs acting on. ion channels expressed during neurogenesis might promote therapeutic neurogenesis in the injured brain. PMID:20434436

  19. Doublecortin expression in the normal and epileptic adult human brain.

    PubMed

    Liu, Y W J; Curtis, M A; Gibbons, H M; Mee, E W; Bergin, P S; Teoh, H H; Connor, B; Dragunow, M; Faull, R L M

    2008-12-01

    Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy.

  20. Imaging diagnosis and fundamental knowledge of common brain tumors in adults.

    PubMed

    Tanaka, Akio

    2006-07-01

    The most common primary brain tumors in Japanese adults are meningiomas, gliomas, pituitary adenomas, and schwannomas, which together account for 84.0% of all primary brain tumors. The typical imaging findings of these tumors are well known by radiologists; therefore, the clinical and pathological issues, including terminology, genetics, and relation to hormones are discussed in this article. Other diseases important for the differential diagnoses are also mentioned. The molecular genetic analysis of brain tumors has recently become important. For instance, genetic analysis is important for differentiating oligodendroglial tumors from astrocytic tumors, and the gene mutation predicts response to chemotherapy for anaplastic oligodendrogliomas. Background factors such as hormones, history of cranial irradiation, and medications influence oncogenesis, tumor growth, and tumor appearances as seen by imaging modalities. A differential diagnosis with knowledge of the above may have some advantages over diagnoses based on imaging findings alone. Nonneoplastic diseases such as abscesses and demyelinating diseases may mimic gliomas. Pituitary adenomas may be confused with nonneoplastic conditions such as physiological hypertrophy and Rathke's cleft cyst. Such misdiagnoses would result in a treatment protocol very different from what would be suitable. Such conditions should be carefully distinguished from neoplasms.

  1. The primary brain vesicles revisited: are the three primary vesicles (forebrain/midbrain/hindbrain) universal in vertebrates?

    PubMed

    Ishikawa, Yuji; Yamamoto, Naoyuki; Yoshimoto, Masami; Ito, Hironobu

    2012-01-01

    It is widely held that three primary brain vesicles (forebrain, midbrain, and hindbrain vesicles) develop into five secondary brain vesicles in all vertebrates (von Baer's scheme). We reviewed previous studies in various vertebrates to see if this currently accepted scheme of brain morphogenesis is a rule applicable to vertebrates in general. Classical morphological studies on lamprey, shark, zebrafish, frog, chick, Chinese hamster, and human embryos provide only partial evidence to support the existence of von Baer's primary vesicles at early stages. Rather, they suggest that early brain morphogenesis is diverse among vertebrates. Gene expression and fate map studies on medaka, chick, and mouse embryos show that the fates of initial brain vesicles do not accord with von Baer's scheme, at least in medaka and chick brains. The currently accepted von Baer's scheme of brain morphogenesis, therefore, is not a universal rule throughout vertebrates. We propose here a developmental hourglass model as an alternative general rule: Brain morphogenesis is highly conserved at the five-brain vesicle stage but diverges more extensively at earlier and later stages. This hypothesis does not preclude the existence of deep similarities in molecular prepatterns at early stages.

  2. Morphology and histology of chimpanzee primary visual striate cortex indicate that brain reorganization predated brain expansion in early hominid evolution.

    PubMed

    Holloway, Ralph L; Broadfield, Douglas C; Yuan, Michael S

    2003-07-01

    Human brain evolution is characterized by an overall increase in brain size, cerebral reorganization, and cerebral lateralization. It is generally understood when brain enlargement occurred during human evolution. However, issues concerning cerebral reorganization and hemispheric lateralization are more difficult to determine from brain endocasts, and they are topics of considerable debate. One region of the cerebral cortex that may represent the earliest evidence for brain reorganization is the primary visual cortex (PVC), or area 17 of Brodmann. In nonhuman primates, this region is larger in volume (demarcated anteriorly by the lunate sulcus), and extends further rostrally than it does in modern humans. In early hominid fossil (Australopithecus) endocasts, this region appears to occupy a smaller area compared to that in nonhuman primates. Some have argued that the brain first underwent size expansion prior to reorganization, while others maintain that reorganization predated brain expansion. To help resolve this question, we provide a description of two male, common chimpanzee (Pan troglodytes) brains, YN77-111 and YN92-115, which clearly display a more posterior lunate sulcal morphology than seen in other chimpanzees. These data show that neurogenetic variability exists in chimpanzees, and that significant differences in organization (e.g., a reduced PVC) can predate brain enlargement. While the human brain has experienced numerous expansion and reorganization events throughout evolution, the data from these two chimpanzees offer significant support for the hypothesis that the neurogenetic basis for brain reorganization was present in our early fossil ancestors (i.e., the australopithecines) prior to brain enlargement.

  3. Traumatic Brain Injury among Older Adults at Level I and II Trauma Centers

    PubMed Central

    Cuthbert, Jeffrey P.; Whyte, John; Corrigan, John D.; Faul, Mark; Harrison-Felix, Cynthia

    2013-01-01

    Abstract Individuals 65 years of age and over have the highest rates of traumatic brain injury (TBI)-related hospitalizations and deaths, and older adults (defined variably across studies) have particularly poor outcomes after TBI. The factors predicting these outcomes remain poorly understood, and age-specific care guidelines for TBI do not exist. This study provides an overview of TBI in older adults using data from the National Trauma Data Bank (NTDB) gathered between 2007 and 2010, evaluates age group-specific trends in rates of TBI over time using U.S. Census data, and examines whether routinely collected information is able to predict hospital discharge status among older adults with TBI in the NTDB. Results showed a 20–25% increase in trauma center admissions for TBI among the oldest age groups (those >=75 years), relative to the general population, between 2007 and 2010. Older adults (>=65 years) with TBI tended to be white females who have incurred an injury from a fall resulting in a “severe” Abbreviated Injury Scale (AIS) score of the head. Older adults had more in-hospital procedures, such as neuroimaging and neurosurgery, tended to experience longer hospital stays, and were more likely to require continued medical care than younger adults. Older age, injury severity, and hypotension increased the odds of in-hospital death. The public health burden of TBI among older adults will likely increase as the Baby Boom generation ages. Improved primary and secondary prevention of TBI in this cohort is needed. PMID:23962046

  4. Experience with adults shapes multisensory representation of social familiarity in the brain of a songbird.

    PubMed

    George, Isabelle; Cousillas, Hugo; Richard, Jean-Pierre; Hausberger, Martine

    2012-01-01

    Social animals learn to perceive their social environment, and their social skills and preferences are thought to emerge from greater exposure to and hence familiarity with some social signals rather than others. Familiarity appears to be tightly linked to multisensory integration. The ability to differentiate and categorize familiar and unfamiliar individuals and to build a multisensory representation of known individuals emerges from successive social interactions, in particular with adult, experienced models. In different species, adults have been shown to shape the social behavior of young by promoting selective attention to multisensory cues. The question of what representation of known conspecifics adult-deprived animals may build therefore arises. Here we show that starlings raised with no experience with adults fail to develop a multisensory representation of familiar and unfamiliar starlings. Electrophysiological recordings of neuronal activity throughout the primary auditory area of these birds, while they were exposed to audio-only or audiovisual familiar and unfamiliar cues, showed that visual stimuli did, as in wild-caught starlings, modulate auditory responses but that, unlike what was observed in wild-caught birds, this modulation was not influenced by familiarity. Thus, adult-deprived starlings seem to fail to discriminate between familiar and unfamiliar individuals. This suggests that adults may shape multisensory representation of known individuals in the brain, possibly by focusing the young's attention on relevant, multisensory cues. Multisensory stimulation by experienced, adult models may thus be ubiquitously important for the development of social skills (and of the neural properties underlying such skills) in a variety of species.

  5. Brain self-protection: the role of endogenous neural progenitor cells in adult brain after cerebral cortical ischemia.

    PubMed

    Li, Bin; Piao, Chun-Shu; Liu, Xiao-Yun; Guo, Wen-Ping; Xue, Yue-Qiang; Duan, Wei-Ming; Gonzalez-Toledo, Maria E; Zhao, Li-Ru

    2010-04-23

    Convincing evidence has shown that brain ischemia causes the proliferation of neural stem cells/neural progenitor cells (NSCs/NPCs) in both the subventricular zone (SVZ) and the subgranular zone (SGZ) of adult brain. The role of brain ischemia-induced NSC/NPC proliferation, however, has remained unclear. Here we have determined whether brain ischemia-induced amplification of the NSCs/NPCs in adult brain is required for brain self-protection. The approach of intracerebroventricular (ICV) infusion of cytosine arabinoside (Ara-C), an inhibitor for cell proliferation, for the first 7days after brain ischemia was used to block ischemia-induced NSC/NPC proliferation. We observed that ICV infusion of Ara-C caused a complete blockade of NSC/NPC proliferation in the SVZ and a dramatic reduction of NSC/NPC proliferation in the SGZ. Additionally, as a result of the inhibition of ischemia-induced NSC/NPC pool amplification, the number of neurons in the hippocampal CA1 and CA3 was significantly reduced, the infarction size was significantly enlarged, and neurological deficits were significantly worsened after focal brain ischemia. We also found that an NSC/NPC-conditioned medium showed neuroprotective effects in vitro and that adult NSC/NPC-released brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) are required for NSC/NPC-conditioned medium-induced neuroprotection. These data suggest that NSC/NPC-generated trophic factors are neuroprotective and that brain ischemia-triggered NSC/NPC proliferation is crucial for brain protection. This study provides insights into the contribution of endogenous NSCs/NPCs to brain self-protection in adult brain after ischemia injury.

  6. CILIA FORMATION IN THE ADULT CAT BRAIN AFTER PARGYLINE TREATMENT

    PubMed Central

    Milhaud, Monique; Pappas, George D.

    1968-01-01

    The brains of four adult cats treated with pargyline (a nonhydrazide monoaminoxidase inhibitor) were examined at both the light and electron microscopic levels. Formation of typical mature cilia with the 9 + 2 pattern was observed in neural cells in the following areas: habenula nuclei, interpeduncular nuclei, hippocampus, mammillary bodies, thalamus, and caudate nucleus. The most marked ciliation occurs in the habenula nuclei. In general, glial cells greatly predominate in the formation of cilia. It is not clear whether ciliation in the central nervous system is the direct result of pargyline or if it occurs indirectly as a result of inhibition of monoaminoxidase. These findings are compared with the serotonin effect on ciliation in the embryogenesis of lower forms. It is suggested that pharmacological stimulation of centriolar reproduction without subsequent mitosis may lead to ciliary formation. PMID:11905194

  7. A model for genomic imprinting in the social brain: adults.

    PubMed

    Ubeda, Francisco; Gardner, Andy

    2011-02-01

    Genomic imprinting refers to genes that are silenced when inherited via sperm or via egg. The silencing of genes conditional upon their parental origin requires an evolutionary explanation. The most widely accepted theory for the evolution of genomic imprinting-the kinship theory-argues that conflict between maternally inherited and paternally inherited genes over phenotypes with asymmetric effects on matrilineal and patrilineal kin results in self-imposed silencing of one of the copies. This theory has been applied to imprinting of genes expressed in the placenta, and infant brain determining the allocation of parental resources being the source of conflict parental promiscuity. However, there is growing evidence that imprinted genes are expressed in the postinfant brain where parental promiscuity per se is no longer a source of conflict. Here, we advance the kinship theory by developing an evolutionary model of genomic imprinting in adults, driven by intragenomic conflict over allocation to parental versus communal care. We consider the role of sex differences in dispersal and variance in reproductive success as sources of conflict. We predict that, in hominids and birds, parental care will be expressed by maternally inherited genes. In nonhominid mammals, we predict more diversity, with some mammals showing the same pattern and other showing the reverse. We use the model to interpret experimental data on imprinted genes in the house mouse: specifically, paternally expressed Peg1 and Peg3 genes, underlying maternal care, and maternally expressed Gnas and paternally expressed Gnasxl genes, underlying communal care. We also use the model to relate ancestral demography to contemporary imprinting disorders of adults, in humans and other taxa.

  8. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies

    PubMed Central

    Oliva, Carolina A.; Vargas, Jessica Y.; Inestrosa, Nibaldo C.

    2013-01-01

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function. We include the most recent data in the literature showing that Wnts are constantly released in the brain to maintain the basal neural activity. Also, we review the evidences that involve components of the Wnt pathway in the development of neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include the evidences that support a neuroprotective role of Wnt proteins in Alzheimer’s disease. We postulate that deregulation in Wnt signaling might have a fundamental role in the origin of neurological diseases, by altering the synaptic function at stages where the phenotype is not yet established but when the cognitive decline starts. PMID:24348327

  9. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies.

    PubMed

    Oliva, Carolina A; Vargas, Jessica Y; Inestrosa, Nibaldo C

    2013-12-03

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function. We include the most recent data in the literature showing that Wnts are constantly released in the brain to maintain the basal neural activity. Also, we review the evidences that involve components of the Wnt pathway in the development of neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include the evidences that support a neuroprotective role of Wnt proteins in Alzheimer's disease. We postulate that deregulation in Wnt signaling might have a fundamental role in the origin of neurological diseases, by altering the synaptic function at stages where the phenotype is not yet established but when the cognitive decline starts.

  10. Effective factors on linguistic disorder during acute phase following traumatic brain injury in adults.

    PubMed

    Chabok, Shahrokh Yousefzadeh; Kapourchali, Sara Ramezani; Leili, Ehsan Kazemnezhad; Saberi, Alia; Mohtasham-Amiri, Zahra

    2012-06-01

    Traumatic brain injury (TBI) has been known to be the leading cause of breakdown and long-term disability in people under 45 years of age. This study highlights the effective factors on post-traumatic (PT) linguistic disorder and relations between linguistic and cognitive function after trauma in adults with acute TBI. A cross-sectional design was employed to study 60 post-TBI hospitalized adults aged 18-65 years. Post-traumatic (PT) linguistic disorder and cognitive deficit after TBI were respectively diagnosed using the Persian Aphasia Test (PAT) and Persian version of Mini-Mental State Examination (MMSE) at discharge. Primary post-resuscitation consciousness level was determined using the Glasgow Coma Scale (GCS). Paracilinical data was obtained by CT scan technique. Multiple logistic regression analysis illustrated that brain injury severity was the first powerful significant predictor of PT linguistic disorder after TBI and frontotemporal lesion was the second. It was also revealed that cognitive function score was significantly correlated with score of each language skill except repetition. Subsequences of TBI are more commonly language dysfunctions that demand cognitive flexibility. Moderate, severe and fronto-temporal lesion can increase the risk of processing deficit in linguistic macrostructure production and comprehension. The dissociation risk of cortical and subcortical pathways related to cognitive-linguistic processing due to intracranial lesions can augment possibility of lexical-semantic processing deficit in acute phase which probably contributes to later cognitive-communication disorder.

  11. Brain necrosis after radiotherapy for primary intracerebral tumor.

    PubMed

    Hohwieler, M L; Lo, T C; Silverman, M L; Freidberg, S R

    1986-01-01

    Radiotherapy is a standard postoperative treatment for cerebral glioma. We have observed the onset of symptoms related to brain necrosis, as opposed to recurrent tumor, in surviving patients. This has been manifest as dementia with a computed tomographic pattern of low density in the frontal lobe uninvolved with tumor, but within the field of radiotherapy. Two patients presented with mass lesions also unrelated to recurrent tumor. We question the necessity of full brain irradiation and suggest that radiotherapy techniques be altered to target the tumor and not encompass the entire brain.

  12. Prevalence and predictors of change in adult-child primary caregivers.

    PubMed

    Szinovacz, Maximiliane E; Davey, Adam

    2013-01-01

    Family caregiving research is increasingly contextual and dynamic, but few studies have examined prevalence and predictors of change in primary caregivers, those with the most frequent contact with healthcare professionals. We identified prevalence and predictors of 2-year change in primary adult-child caregivers. Data pooled from the 1992-2000 waves of the Health and Retirement Study (HRS) represent 1,068 parent-level care occasions and 3,616 child-level occasions. There is considerable 2-year stability in primary adult-child caregivers. Parents are more prone to experience a change in adult-child primary caregivers if they live by themselves and if they have more sons and daughters. As far as the adult children are concerned, daughters and children living closer to parents are more likely to remain primary caregivers. Results suggest that change in primary caregivers is more strongly associated with available alternatives and gender norms than burden and competing obligations.

  13. Priorities for young adults when accessing UK primary care: literature review.

    PubMed

    Davey, Antoinette; Carter, Mary; Campbell, John L

    2013-10-01

    This literature review focuses on what matters to young adults when they access primary care services in the United Kingdom. Patients' access to and experience of primary care services differs across age groups. Existing research has largely focused on the needs and experiences of children, adolescents, and adults. There is some evidence to suggest the views of young adults (aged 18-25 years) that may differ from the views of other age groups, and research has not previously reported specifically on the views of this group of the population. The literature was reviewed to identify the views and priorities of young UK adults regarding primary healthcare provision, and furthermore, to identify those related topics that would benefit from further research. Relevant academic publications and grey literature published from 2000 onwards was reviewed and synthesised. We identified and reported emerging themes that were of importance to young adults in respect of the UK primary care provision. A total of 19 papers met our inclusion criteria. Young adults access primary care services less frequently than other age groups; this may be because of their experience of primary care throughout childhood and adolescence. Five aspects of primary care provision emerged as being of importance to young adults--the accessibility and availability of services, the confidentiality of health-related information, issues relating to communication with healthcare professionals, continuity of care, and behaviours and attitudes expressed towards young adults by healthcare professionals. There is a lack of focus of current research on the expectations, needs, and primary healthcare experiences of young adults. Young adults may hold views that are distinct from other age groups. Further research is needed to better understand the needs of a young adult population as their needs may impact the future use of services.

  14. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention.

  15. Transcription levels of sirtuin family in neural stem cells and brain tissues of adult mice.

    PubMed

    Wang, H F; Li, Q; Feng, R L; Wen, T Q

    2012-09-10

    Neural stem cells (NSCs) has been used as a well-known model to investigate apoptosis, differentiation, maintenance of stem cells status, and therapy of neurological disease. The C17.2 NSCs line was produced after v-myc transformation of neural progenitor from mouse cerebellar cortex. Sirtuin family plays important roles involved in neuronal differentiation, genomic stability, lifespan, cell survival. However, little is known about gene expression variation of sirtuin family in C17.2 NSCs, primary NSCs, and different brain tissues in adult mice. Here, we confirmed that the mRNA expression levels of sirt2, 3, 4, 5, and 7 in E14.5 NSCs were significantly higher than in C17.2 NSCs, whereas that sirt 6 displayed an opposing mode. Moreover, a higher mRNA level of sirtuin family was observed in the adult mouse brain compared to C17.2 NSCs. In addition, histone deacetylase (HDAC) inhibitors nicotinamide and Trichostatin A (TSA) were used to explore differential changes at the transcriptional level of sirtuins. Results indicated that the expression of sirt1, sirt5 and sirt6 was significant downregulated by nicotinamide treatment. Whereas, a significant downregulation in sirt1 and sirt3 and a significant upregulation in sirt2, sirt4, sirt6, and sirt7 were observed in the treatment of TSA. Thus our studies indicate different sirtuin mRNA expression profiles between C17.2 NSCs, E14.5 NSCs and brain tissues, suggesting the transcriptional regulation of sirtuin family could be mediated by different histone acetylation.

  16. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain.

    PubMed

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2015-11-26

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur.

  17. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain

    PubMed Central

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2015-01-01

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur. DOI: http://dx.doi.org/10.7554/eLife.11290.001 PMID:26609811

  18. GABA regulates synaptic integration of newly generated neurons in the adult brain

    NASA Astrophysics Data System (ADS)

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  19. Nurse Practitioner Primary Care Competencies in Specialty Areas: Adult, Family, Gerontological, Pediatric, and Women's Health.

    ERIC Educational Resources Information Center

    Crabtree, M. Katherine; Stanley, Joan; Werner, Kathryn E.; Schmid, Emily

    This document presents the nurse practitioner primary care competencies that a national panel of representatives of nine national organizations of the five primary care nurse practitioner specialties--adult, family, gerontological, pediatric, and women's health--identified as necessary for entry-level primary care nurse practitioners. Section 1…

  20. Expression of Npas4 mRNA in Telencephalic Areas of Adult and Postnatal Mouse Brain

    PubMed Central

    Damborsky, Joanne C.; Slaton, G. Simona; Winzer-Serhan, Ursula H.

    2015-01-01

    The transcription factor neuronal PAS domain-containing protein 4 (Npas4) is an inducible immediate early gene which regulates the formation of inhibitory synapses, and could have a significant regulatory role during cortical circuit formation. However, little is known about basal Npas4 mRNA expression during postnatal development. Here, postnatal and adult mouse brain sections were processed for isotopic in situ hybridization using an Npas4 specific cRNA antisense probe. In adults, Npas4 mRNA was found in the telencephalon with very restricted or no expression in diencephalon or mesencephalon. In most telencephalic areas, including the anterior olfactory nucleus (AON), piriform cortex, neocortex, hippocampus, dorsal caudate putamen (CPu), septum and basolateral amygdala nucleus (BLA), basal Npas4 expression was detected in scattered cells which exhibited strong hybridization signal. In embryonic and neonatal brain sections, Npas4 mRNA expression signals were very low. Starting at postnatal day 5 (P5), transcripts for Npas4 were detected in the AON, CPu and piriform cortex. At P8, additional Npas4 hybridization was found in CA1 and CA3 pyramidal layer, and in primary motor cortex. By P13, robust mRNA expression was located in layers IV and VI of all sensory cortices, frontal cortex and cingulate cortex. After onset of expression, postnatal spatial mRNA distribution was similar to that in adults, with the exception of the CPu, where Npas4 transcripts became gradually restricted to the most dorsal part. In conclusion, the spatial distribution of Npas4 mRNA is mostly restricted to telencephalic areas, and the temporal expression increases with developmental age during postnatal development, which seem to correlate with the onset of activity-driven excitatory transmission. PMID:26633966

  1. Cilengitide in Treating Children With Refractory Primary Brain Tumors

    ClinicalTrials.gov

    2013-09-27

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  2. Encoding of mechanical nociception differs in the adult and infant brain

    PubMed Central

    Fabrizi, Lorenzo; Verriotis, Madeleine; Williams, Gemma; Lee, Amy; Meek, Judith; Olhede, Sofia; Fitzgerald, Maria

    2016-01-01

    Newborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0–19 days (n = 18, clinically required) and adults aged 23–48 years (n = 21). Time-frequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2–4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain. PMID:27345331

  3. Primary Blast-Induced Traumatic Brain Injury in Rats Leads to Increased Prion Protein in Plasma: A Potential Biomarker for Blast-Induced Traumatic Brain Injury

    PubMed Central

    Pham, Nam; Sawyer, Thomas W.; Wang, Yushan; Jazii, Ferdous Rastgar; Vair, Cory

    2015-01-01

    Abstract Traumatic brain injury (TBI) is deemed the “signature injury” of recent military conflicts in Afghanistan and Iraq, largely because of increased blast exposure. Injuries to the brain can often be misdiagnosed, leading to further complications in the future. Therefore, the use of protein biomarkers for the screening and diagnosis of TBI is urgently needed. In the present study, we have investigated the plasma levels of soluble cellular prion protein (PrPC) as a novel biomarker for the diagnosis of primary blast-induced TBI (bTBI). We hypothesize that the primary blast wave can disrupt the brain and dislodge extracellular localized PrPC, leading to a rise in concentration within the systemic circulation. Adult male Sprague–Dawley rats were exposed to single pulse shockwave overpressures of varying intensities (15-30 psi or 103.4–206.8 kPa] using an advanced blast simulator. Blood plasma was collected 24 h after insult, and PrPC concentration was determined with a modified commercial enzyme-linked immunosorbent assay (ELISA) specific for PrPC. We provide the first report that mean PrPC concentration in primary blast exposed rats (3.97 ng/mL±0.13 SE) is significantly increased compared with controls (2.46 ng/mL±0.14 SE; two tailed test p<0.0001). Furthermore, we report a mild positive rank correlation between PrPC concentration and increasing blast intensity (psi) reflecting a plateaued response at higher pressure magnitudes, which may have implications for all military service members exposed to blast events. In conclusion, it appears that plasma levels of PrPC may be a novel biomarker for the detection of primary bTBI. PMID:25058115

  4. Primary blast-induced traumatic brain injury in rats leads to increased prion protein in plasma: a potential biomarker for blast-induced traumatic brain injury.

    PubMed

    Pham, Nam; Sawyer, Thomas W; Wang, Yushan; Jazii, Ferdous Rastgar; Vair, Cory; Taghibiglou, Changiz

    2015-01-01

    Traumatic brain injury (TBI) is deemed the "signature injury" of recent military conflicts in Afghanistan and Iraq, largely because of increased blast exposure. Injuries to the brain can often be misdiagnosed, leading to further complications in the future. Therefore, the use of protein biomarkers for the screening and diagnosis of TBI is urgently needed. In the present study, we have investigated the plasma levels of soluble cellular prion protein (PrPC) as a novel biomarker for the diagnosis of primary blast-induced TBI (bTBI). We hypothesize that the primary blast wave can disrupt the brain and dislodge extracellular localized PrPC, leading to a rise in concentration within the systemic circulation. Adult male Sprague-Dawley rats were exposed to single pulse shockwave overpressures of varying intensities (15-30 psi or 103.4-206.8 kPa] using an advanced blast simulator. Blood plasma was collected 24 h after insult, and PrPC concentration was determined with a modified commercial enzyme-linked immunosorbent assay (ELISA) specific for PrPC. We provide the first report that mean PrPC concentration in primary blast exposed rats (3.97 ng/mL ± 0.13 SE) is significantly increased compared with controls (2.46 ng/mL ± 0.14 SE; two tailed test p < 0.0001). Furthermore, we report a mild positive rank correlation between PrPC concentration and increasing blast intensity (psi) reflecting a plateaued response at higher pressure magnitudes, which may have implications for all military service members exposed to blast events. In conclusion, it appears that plasma levels of PrPC may be a novel biomarker for the detection of primary bTBI.

  5. Trajectories of brain aging in middle-aged and older adults: regional and individual differences.

    PubMed

    Raz, Naftali; Ghisletta, Paolo; Rodrigue, Karen M; Kennedy, Kristen M; Lindenberger, Ulman

    2010-06-01

    The human brain changes with age. However, the rate and the trajectories of change vary among the brain regions and among individuals, and the reasons for these differences are unclear. In a sample of healthy middle-aged and older adults, we examined mean volume change and individual differences in the rate of change in 12 regional brain volumes over approximately 30 months. In addition to the baseline assessment, there were two follow-ups, 15 months apart. We observed significant average shrinkage of the hippocampus, entorhinal cortex, orbital-frontal cortex, and cerebellum in each of the intervals. Shrinkage of the hippocampus accelerated with time, whereas shrinkage of the caudate nucleus, prefrontal subcortical white matter, and corpus callosum emerged only at the second follow-up. Throughout both assessment intervals, the mean volumes of the lateral prefrontal and primary visual cortices, putamen, and pons did not change. Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions (medial-temporal structures, the insula, and the basal ganglia) showed significant individual variation in change during the second follow-up. No individual variability was noted in the change of orbital frontal and visual cortices. In two white matter regions, we were able to identify factors associated with individual differences in brain shrinkage. In corpus callosum, shrinkage rate was greater in persons with hypertension, and in the pons, women and carriers of the ApoEepsilon4 allele exhibited declines not noted in the whole sample.

  6. Trajectories of brain aging in middle-aged and older adults: Regional and individual differences

    PubMed Central

    Raz, Naftali; Ghisletta, Paolo; Rodrigue, Karen M.; Kennedy, Kristen M.; Lindenberger, Ulman

    2010-01-01

    The human brain changes with age. However, the rate and the trajectories of change vary among the brain regions and among individuals, and the reasons for these differences are unclear. In a sample of healthy middle-aged and older adults, we examined mean volume change and individual differences in the rate of change in 12 regional brain volumes over approximately 30 months. In addition to the baseline assessment, there were two follow-ups, 15 months apart. We observed significant average shrinkage of the hippocampus, entorhinal cortex, orbital–frontal cortex, and cerebellum in each of the intervals. Shrinkage of the hippocampus accelerated with time, whereas shrinkage of the caudate nucleus, prefrontal subcortical white matter, and corpus callosum emerged only at the second follow-up. Throughout both assessment intervals, the mean volumes of the lateral prefrontal and primary visual cortices, putamen, and pons did not change. Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions (medial–temporal structures, the insula, and the basal ganglia) showed significant individual variation in change during the second follow-up. No individual variability was noted in the change of orbital frontal and visual cortices. In two white matter regions, we were able to identify factors associated with individual differences in brain shrinkage. In corpus callosum, shrinkage rate was greater in persons with hypertension, and in the pons, women and carriers of the ApoEε4 allele exhibited declines not noted in the whole sample. PMID:20298790

  7. Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression After Whole-Brain Irradiation

    PubMed Central

    Wong-Goodrich, Sarah J.E.; Pfau, Madeline L.; Flores, Catherine T.; Fraser, Jennifer A.; Williams, Christina L.; Jones, Lee W.

    2010-01-01

    Whole-brain irradiation (WBI) therapy produces progressive learning and memory deficits in patients with primary or secondary brain tumors. Exercise enhances memory and adult hippocampal neurogenesis in the intact brain, so we hypothesized that exercise may be an effective treatment to alleviate consequences of WBI. Previous studies using animal models to address this issue have yielded mixed results and have not examined potential molecular mechanisms. We investigated the short- and long-term effects of WBI on spatial learning and memory retention, and determined whether voluntary running after WBI aids recovery of brain and cognitive function. Forty adult female C57Bl/6 mice given a single dose of 5 Gy or sham WBI were trained 2.5 weeks and up to four months after WBI in a Barnes maze. Half of the mice received daily voluntary wheel access starting one month after sham- or WBI. Daily running following WBI prevented the marked decline in spatial memory retention observed months after irradiation. Bromodeoxyuridine (BrdU) immunolabeling and ELISA indicated that this behavioral rescue was accompanied by a partial restoration of newborn BrdU+/NeuN+ neurons in the dentate gyrus and increased hippocampal expression of brain-derived vascular endothelial growth factor and insulin-like growth factor, and occurred despite irradiation-induced elevations in hippocampal pro-inflammatory cytokines. WBI in adult mice produced a progressive memory decline consistent with what has been reported in cancer patients receiving WBI therapy. Our findings show that running can abrogate this memory decline and aid recovery of adult hippocampal plasticity, thus highlighting exercise as a potential therapeutic intervention. PMID:20884629

  8. Exosomes as Tools to Suppress Primary Brain Tumor.

    PubMed

    Katakowski, Mark; Chopp, Michael

    2016-04-01

    Exosomes are small microvesicles released by cells that efficiently transfer their molecular cargo to other cells, including tumor. Exosomes may pass the blood-brain barrier and have been demonstrated to deliver RNAs contained within to brain. As they are non-viable, the risk profile of exosomes is thought to be less than that of cellular therapies. Exosomes can be manufactured at scale in culture, and exosomes can be engineered to incorporate therapeutic miRNAs, siRNAs, or chemotherapeutic molecules. As natural biological delivery vehicles, interest in the use of exosomes as therapeutic delivery agents is growing. We previously demonstrated a novel treatment whereby mesenchymal stromal cells were employed to package tumor-suppressing miR-146b into exosomes, which were then used to reduce malignant glioma growth in rat. The use of exosomes to raise the immune system against tumor is also drawing interest. Exosomes from dendritic cells which are antigen-presenting, and have been used for treatment of brain tumor may be divided into three categories: (1) exosomes for immunomodulation-based therapy, (2) exosomes as delivery vehicles for anti-tumor nucleotides, and (3) exosomes as drug delivery vehicles. Here, we will provide an overview of these three applications of exosomes to treat brain tumor, and examine their prospects on the long road to clinical use.

  9. Behavioral and magnetoencephalographic correlates of plasticity in the adult human brain

    PubMed Central

    Ramachandran, V. S.

    1993-01-01

    Recent behavioral and physiological evidence suggests that even brief sensory deprivation can lead to the rapid emergence of new and functionally effective neural connections in the adult human brain. Images Fig. 2 PMID:8248123

  10. A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors.

    PubMed

    Rubin, Joshua B; Kung, Andrew L; Klein, Robyn S; Chan, Jennifer A; Sun, YanPing; Schmidt, Karl; Kieran, Mark W; Luster, Andrew D; Segal, Rosalind A

    2003-11-11

    The vast majority of brain tumors in adults exhibit glial characteristics. Brain tumors in children are diverse: Many have neuronal characteristics, whereas others have glial features. Here we show that activation of the Gi protein-coupled receptor CXCR4 is critical for the growth of both malignant neuronal and glial tumors. Systemic administration of CXCR4 antagonist AMD 3100 inhibits growth of intracranial glioblastoma and medulloblastoma xenografts by increasing apoptosis and decreasing the proliferation of tumor cells. This reflects the ability of AMD 3100 to reduce the activation of extracellular signal-regulated kinases 1 and 2 and Akt, all of which are pathways downstream of CXCR4 that promote survival, proliferation, and migration. These studies (i) demonstrate that CXCR4 is critical to the progression of diverse brain malignances and (ii) provide a scientific rationale for clinical evaluation of AMD 3100 in treating both adults and children with malignant brain tumors.

  11. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    PubMed Central

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain tumors. PMID:27375363

  12. Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesis via the brain-derived neurotrophic factor pathway.

    PubMed

    Qian, Qi; Liu, Qiuji; Zhou, Dongming; Pan, Hongyu; Liu, Zhiwei; He, Fangping; Ji, Suying; Wang, Dongpi; Bao, Wangxiao; Liu, Xinyi; Liu, Zhaoling; Zhang, Heng; Zhang, Xiaoqin; Zhang, Ling; Wang, Mingkai; Xu, Ying; Huang, Fude; Luo, Benyan; Sun, Binggui

    2017-02-13

    Efr3 is a newly identified plasma membrane protein and plays an important role in the phosphoinositide metabolism on the plasma membrane. However, although it is highly expressed in the brain, the functional significance of Efr3 in the brain is not clear. In the present study, we generated Efr3a(f/f) mice and then crossed them with Nestin-Cre mice to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. We found that brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology. Moreover, the brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling pathway was significantly enhanced in the hippocampus of Efr3a-deficient mice, as reflected by increased expression of BDNF, TrkB, and the downstream molecules, including phospho-MAPK and phospho-Akt. Furthermore, the number of TUNEL(+) cells was decreased in the subgranular zone of dentate gyrus in Efr3a-deficient mice compared with that of control mice. Our data suggest that brain-specific deletion of Efr3a could promote adult hippocampal neurogenesis, presumably by upregulating the expression of BDNF and its receptor, TrkB, and therefore provide new insight into the roles of Efr3 in the brain.-Qian, Q., Liu, Q., Zhou, D., Pan, H., Liu, Z., He, F., Ji, S., Wang, D., Bao, W., Liu, X., Liu, Z., Zhang, H., Zhang, X., Zhang, L., Wang, M., Xu, Y., Huang, F., Luo, B., Sun B. Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesis via the brain-derived neurotrophic factor pathway.

  13. Enhancing Primary Health Care Services for Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Melville, C. A.; Finlayson, J.; Cooper, S.-A.; Allan, L.; Robinson, N.; Burns, E.; Martin, G.; Morrison, J.

    2005-01-01

    Primary health care teams have an important part to play in addressing the health inequalities and high levels of unmet health needs experienced by people with intellectual disabilities (ID). Practice nurses have an expanding role within primary health care teams. However, no previous studies have measured their attitudes, knowledge, training…

  14. Health Problems Precede Traumatic Brain Injury in Older Adults

    PubMed Central

    Dams-O’Connor, Kristen; Gibbons, Laura E; Landau, Alexandra; Larson, Eric B; Crane, Paul K.

    2016-01-01

    Objectives To evaluate whether indices of pre-injury health and functioning were associated with risk for incident traumatic brain injury (TBI) with loss of consciousness (LOC), and evaluated health-related factors associated with mortality among those with an incident TBI. Design Prospective community cohort study. Setting Group Health, Seattle Washington. Participants 3,363 individuals aged 65 and older with no self-reported prior TBI with LOC were enrolled and followed every 2 years for an average of 7.5 years (range 0–18 years). Measurements We used Weibull survival models to evaluate baseline and time-varying predictors of incident TBI with LOC, including measures of depression, activities of daily living, cerebrovascular disease, and disease comorbidity. Results In an adjusted multivariate model, baseline depression symptoms as measured by CES-D score (hazard ratio (HR) and 95% confidence interval (CI) for 4 points = 1.34 (1.13, 1.58); p<0.05) and baseline impairment in activities of daily living (ADL; HR (95% CI) = 2.37 (1.24, 4.53); p<0.01) were associated with incident TBI. In a model that included time-dependent covariates, cerebrovascular disease at the previous visit (HR (95% CI) = 2.28 (1.37, 3.78); p<0.01), CES-D score the previous visit (HR for 4 points (95% CI) = 1.23 (1.02, 1.49); p<0.05) and baseline impairment in ADL (HR (95% CI) 2.14 (1.11, 4.13); p<0.05) predicted incident TBI. Of factors considered, cerebrovascular disease and ADL impairment were associated with earlier mortality among those with an incident TBI with LOC. Conclusion Indices of health, mood, and functional status predict incident TBI with LOC in older adults. These findings may have implications for injury prevention and post-injury clinical management. PMID:26925541

  15. Monte Carlo simulation of light propagation in the adult brain

    NASA Astrophysics Data System (ADS)

    Mudra, Regina M.; Nadler, Andreas; Keller, Emanuella; Niederer, Peter

    2004-06-01

    When near infrared spectroscopy (NIRS) is applied noninvasively to the adult head for brain monitoring, extra-cerebral bone and surface tissue exert a substantial influence on the cerebral signal. Most attempts to subtract extra-cerebral contamination involve spatially resolved spectroscopy (SRS). However, inter-individual variability of anatomy restrict the reliability of SRS. We simulated the light propagation with Monte Carlo techniques on the basis of anatomical structures determined from 3D-magnetic resonance imaging (MRI) exhibiting a voxel resolution of 0.8 x 0.8 x 0.8 mm3 for three different pairs of T1/T2 values each. The MRI data were used to define the material light absorption and dispersion coefficient for each voxel. The resulting spatial matrix was applied in the Monte Carlo Simulation to determine the light propagation in the cerebral cortex and overlaying structures. The accuracy of the Monte Carlo Simulation was furthermore increased by using a constant optical path length for the photons which was less than the median optical path length of the different materials. Based on our simulations we found a differential pathlength factor (DPF) of 6.15 which is close to with the value of 5.9 found in the literature for a distance of 4.5cm between the external sensors. Furthermore, we weighted the spatial probability distribution of the photons within the different tissues with the probabilities of the relative blood volume within the tissue. The results show that 50% of the NIRS signal is determined by the grey matter of the cerebral cortex which allows us to conclude that NIRS can produce meaningful cerebral blood flow measurements providing that the necessary corrections for extracerebral contamination are included.

  16. Treatment Efficacy: Cognitive-Communicative Disorders Resulting from Traumatic Brain Injury in Adults.

    ERIC Educational Resources Information Center

    Coelho, Carl A.; And Others

    1996-01-01

    This article discusses adults with brain injuries and resulting cognitive communicative disorders. The incidence of brain injuries, the effects of cognitive-communication disorders, the role of the speech-language pathologist, the benefits of treatment, and the effects of different treatments are discussed. Charts are included that summarize…

  17. Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses.

    PubMed

    Guo, Bing-Bing; Zheng, Xiao-Lin; Lu, Zhen-Gang; Wang, Xing; Yin, Zheng-Qin; Hou, Wen-Sheng; Meng, Ming

    2015-10-01

    Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only "see" pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex (the implant area) is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine (LSVM) as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern.

  18. Risk and prognosis of adult primary immune thrombocytopenia.

    PubMed

    Frederiksen, Henrik; Christiansen, Christian Fynbo; Nørgaard, Mette

    2012-04-01

    Adult immune thrombocytopenia was previously considered a benign disease affecting young people and with a low risk of severe bleeding. This view was challenged by studies published during the past decade, as the median age of adult immune thrombocytopenia patients has been found to be 55-60 years and the incidence increases with age. Recent studies reported that mortality and morbidity are increased compared with the general population. In this review, we describe patient-specific factors associated with the outcome of disease, the clinical course of immune thrombocytopenia including the potential adverse impact of some treatments and finally the overall prognosis.

  19. Future Concerns of Adult Siblings of Persons with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Degeneffe, Charles Edmund; Olney, Marjorie F.

    2008-01-01

    This study examined future concerns conveyed by adult siblings who provided regular caregiving support to their brothers and sisters with traumatic brain injury (TBI). The authors surveyed a national sample of 280 adult siblings of persons with TBI. Using a constant comparative approach to text analysis, the authors analyzed responses to the…

  20. Correlates of Depression in Adult Siblings of Persons with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Degeneffe, Charles Edmund; Lynch, Ruth Torkelson

    2006-01-01

    Using Pearlin's stress process model, this study examined correlates of depression in 170 adult siblings of persons with traumatic brain injury (TBI). Approximately 39% of adult sibling participants evinced "Center for Epidemiologic Studies-Depression" (CES-D; Radloff, 1977) scores indicating clinically significant depressive symptoms. Background…

  1. Development of a Conceptual Model to Predict Physical Activity Participation in Adults with Brain Injuries

    ERIC Educational Resources Information Center

    Driver, Simon

    2008-01-01

    The purpose was to examine psychosocial factors that influence the physical activity behaviors of adults with brain injuries. Two differing models, based on Harter's model of self-worth, were proposed to examine the relationship between perceived competence, social support, physical self-worth, affect, and motivation. Adults numbering 384 with…

  2. The Social Environment and Neurogenesis in the Adult Mammalian Brain

    PubMed Central

    Lieberwirth, Claudia; Wang, Zuoxin

    2012-01-01

    Adult neurogenesis – the formation of new neurons in adulthood – has been shown to be modulated by a variety of endogenous (e.g., trophic factors, neurotransmitters, and hormones) as well as exogenous (e.g., physical activity and environmental complexity) factors. Research on exogenous regulators of adult neurogenesis has focused primarily on the non-social environment. More recently, however, evidence has emerged suggesting that the social environment can also affect adult neurogenesis. The present review details the effects of adult–adult (e.g., mating and chemosensory interactions) and adult–offspring (e.g., gestation, parenthood, and exposure to offspring) interactions on adult neurogenesis. In addition, the effects of a stressful social environment (e.g., lack of social support and dominant–subordinate interactions) on adult neurogenesis are reviewed. The underlying hormonal mechanisms and potential functional significance of adult-generated neurons in mediating social behaviors are also discussed. PMID:22586385

  3. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex.

    PubMed

    Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J

    2014-01-01

    Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults.

  4. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    PubMed

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  5. Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors

    PubMed Central

    Dunbar, E. M.; Coats, B. S.; Shroads, A. L.; Langaee, T.; Lew, A.; Forder, J. R.; Shuster, J. J.; Wagner, D. A.

    2015-01-01

    Summary Background Recurrent malignant brain tumors (RMBTs) carry a poor prognosis. Dichloroacetate (DCA) activates mitochondrial oxidative metabolism and has shown activity against several human cancers. Design We conducted an open-label study of oral DCA in 15 adults with recurrent WHO grade III – IV gliomas or metastases from a primary cancer outside the central nervous system. The primary objective was detection of a dose limiting toxicity for RMBTs at 4 weeks of treatment, defined as any grade 4 or 5 toxicity, or grade 3 toxicity directly attributable to DCA, based on the National Cancer Institute’s Common Toxicity Criteria for Adverse Events, version 4.0. Secondary objectives involved safety, tolerability and hypothesis-generating data on disease status. Dosing was based on haplotype variation in glutathione transferase zeta 1/maleylacetoacetate isomerase (GSTZ1/MAAI), which participates in DCA and tyrosine catabolism. Results Eight patients completed at least 1 four week cycle. During this time, no dose-limiting toxicities occurred. No patient withdrew because of lack of tolerance to DCA, although 2 subjects experienced grade 0–1 distal parasthesias that led to elective withdrawal and/or dose-adjustment. All subjects completing at least 1 four week cycle remained clinically stable during this time and remained on DCA for an average of 75.5 days (range 26–312). Conclusions Chronic, oral DCA is feasible and well-tolerated in patients with recurrent malignant gliomas and other tumors metastatic to the brain using the dose range established for metabolic diseases. The importance of genetic-based dosing is confirmed and should be incorporated into future trials of chronic DCA administration. PMID:24297161

  6. Primary Care for Adults with Down Syndrome: Adherence to Preventive Healthcare Recommendations

    ERIC Educational Resources Information Center

    Jensen, K. M.; Taylor, L. C.; Davis, M. M.

    2013-01-01

    Background: Due to significant medical improvements, persons with Down syndrome now live well into adulthood. Consequently, primary care for adults with Down syndrome needs to incorporate routine care with screening for condition-specific comorbidities. This study seeks to evaluate the adherence of primary care physicians to age- and…

  7. Efficient regeneration by activation of neurogenesis in homeostatically quiescent regions of the adult vertebrate brain.

    PubMed

    Berg, Daniel A; Kirkham, Matthew; Beljajeva, Anna; Knapp, Dunja; Habermann, Bianca; Ryge, Jesper; Tanaka, Elly M; Simon, András

    2010-12-01

    In contrast to mammals, salamanders and teleost fishes can efficiently repair the adult brain. It has been hypothesised that constitutively active neurogenic niches are a prerequisite for extensive neuronal regeneration capacity. Here, we show that the highly regenerative salamander, the red spotted newt, displays an unexpectedly similar distribution of active germinal niches with mammals under normal physiological conditions. Proliferation zones in the adult newt brain are restricted to the forebrain, whereas all other regions are essentially quiescent. However, ablation of midbrain dopamine neurons in newts induced ependymoglia cells in the normally quiescent midbrain to proliferate and to undertake full dopamine neuron regeneration. Using oligonucleotide microarrays, we have catalogued a set of differentially expressed genes in these activated ependymoglia cells. This strategy identified hedgehog signalling as a key component of adult dopamine neuron regeneration. These data show that brain regeneration can occur by activation of neurogenesis in quiescent brain regions.

  8. Age-Related Differences in the Brain Areas outside the Classical Language Areas among Adults Using Category Decision Task

    ERIC Educational Resources Information Center

    Cho, Yong Won; Song, Hui-Jin; Lee, Jae Jun; Lee, Joo Hwa; Lee, Hui Joong; Yi, Sang Doe; Chang, Hyuk Won; Berl, Madison M.; Gaillard, William D.; Chang, Yongmin

    2012-01-01

    Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that…

  9. Control of adult neurogenesis by programmed cell death in the mammalian brain.

    PubMed

    Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

    2016-04-21

    The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases.

  10. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility.

    PubMed

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28-37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found that AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility.

  11. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility

    PubMed Central

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T.

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28–37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility. PMID:24275185

  12. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export

    PubMed Central

    Legati, Andrea; Giovannini, Donatella; Nicolas, Gaël; López-Sánchez, Uriel; Quintáns, Beatriz; Oliveira, João; Sears, Renee L.; Marisa Ramos, Eliana; Spiteri, Elizabeth; Sobrido, María-Jesús; Carracedo, Ángel; Castro-Fernández, Cristina; Cubizolle, Stéphanie; Fogel, Brent L.; Goizet, Cyril; Jen, Joanna C.; Kirdlarp, Suppachok; Lang, Anthony E.; Miedzybrodzka, Zosia; Mitarnun, Witoon; Paucar, Martin; Paulson, Henry; Pariente, Jérémie; Richard, Anne-Claire; Salins, Naomi S.; Simpson, Sheila A.; Striano, Pasquale; Svenningsson, Per; Tison, François; Unni, Vivek K.; Vanakker, Olivier; Wessels, Marja W.; Wetchaphanphesat, Suppachok; Yang, Michele; Boller, Francois; Campion, Dominique; Hannequin, Didier; Sitbon, Marc; Geschwind, Daniel H.; Battini, Jean-Luc; Coppola, Giovanni

    2015-01-01

    Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions, thus far associated with SLC20A2, PDGFB, or PDGFRB mutations. We identified in multiple PFBC families mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, providing a direct evidence of an impact of XPR1 and phosphate homeostasis in PFBC. PMID:25938945

  13. Intracerebral transplants of primary muscle cells: a potential 'platform' for transgene expression in the brain

    NASA Technical Reports Server (NTRS)

    Jiao, S.; Schultz, E.; Wolff, J. A.

    1992-01-01

    After the transplantation of rat primary muscle cells into the caudate or cortex of recipient rats, the muscle cells were able to persist for at least 6 months. Muscle cells transfected with expression plasmids prior to transplantation were able to express reporter genes in the brains for at least 2 months. These results suggest that muscle cells might be a useful 'platform' for transgene expression in the brain.

  14. Guideline for primary care management of headache in adults

    PubMed Central

    Becker, Werner J.; Findlay, Ted; Moga, Carmen; Scott, N. Ann; Harstall, Christa; Taenzer, Paul

    2015-01-01

    Abstract Objective To increase the use of evidence-informed approaches to diagnosis, investigation, and treatment of headache for patients in primary care. Quality of evidence A comprehensive search was conducted for relevant guidelines and systematic reviews published between January 2000 and May 2011. The guidelines were critically appraised using the AGREE (Appraisal of Guidelines for Research and Evaluation) tool, and the 6 highest-quality guidelines were used as seed guidelines for the guideline adaptation process. Main message A multidisciplinary guideline development group of primary care providers and other specialists crafted 91 specific recommendations using a consensus process. The recommendations cover diagnosis, investigation, and management of migraine, tension-type, medication-overuse, and cluster headache. Conclusion A clinical practice guideline for the Canadian health care context was created using a guideline adaptation process to assist multidisciplinary primary care practitioners in providing evidence-informed care for patients with headache. PMID:26273080

  15. PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain.

    PubMed

    Henriksson, Richard; Bäckman, Cristina M; Harvey, Brandon K; Kadyrova, Helena; Bazov, Igor; Shippenberg, Toni S; Bakalkin, Georgy

    2014-11-01

    The dynorphin κ-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders.

  16. Not(ch) just development: Notch signalling in the adult brain

    PubMed Central

    Ables, Jessica L.; Breunig, Joshua J.; Eisch, Amelia J.; Rakic, Pasko

    2011-01-01

    The Notch pathway is often regarded as a developmental pathway, but components of Notch signalling are expressed and active in the adult brain. With the advent of more sophisticated genetic manipulations, evidence has emerged that suggests both conserved and novel roles for Notch signalling in the adult brain. Not surprisingly, Notch is a key regulator of adult neural stem cells, but it is increasingly clear that Notch signalling also has roles in the regulation of migration, morphology, synaptic plasticity and survival of immature and mature neurons. Understanding the many functions of Notch signalling in the adult brain, and its dysfunction in neurodegenerative disease and malignancy, is crucial to the development of new therapeutics that are centred around this pathway. PMID:21505516

  17. Primary Afferent Synapses on Developing and Adult Renshaw Cells

    PubMed Central

    Mentis, George Z.; Siembab, Valerie C.; Zerda, Ricardo; O’Donovan, Michael J.; Alvarez, Francisco J.

    2010-01-01

    The mechanisms that diversify adult interneurons from a few pools of embryonic neurons are unknown. Renshaw cells, Ia inhibitory interneurons (IaINs), and possibly other types of mammalian spinal interneurons have common embryonic origins within the V1 group. However, in contrast to IaINs and other V1-derived interneurons, adult Renshaw cells receive motor axon synapses and lack proprioceptive inputs. Here, we investigated how this specific pattern of connectivity emerges during the development of Renshaw cells. Tract tracing and immunocytochemical markers [parvalbumin and vesicular glutamate transporter 1 (VGLUT1)] showed that most embryonic (embryonic day 18) Renshaw cells lack dorsal root inputs, but more than half received dorsal root synapses by postnatal day 0 (P0) and this input spread to all Renshaw cells by P10–P15. Electrophysiological recordings in neonates indicated that this input is functional and evokes Renshaw cell firing. VGLUT1-IR bouton density on Renshaw cells increased until P15 but thereafter decreased because of limited synapse proliferation coupled with the enlargement of Renshaw cell dendrites. In parallel, Renshaw cell postsynaptic densities apposed to VGLUT1-IR synapses became smaller in adult compared with P15. In contrast, vesicular acetylcholine transporter-IR motor axon synapses contact embryonic Renshaw cells and proliferate postnatally matching Renshaw cell growth. Like other V1 neurons, Renshaw cells are thus competent to receive sensory synapses. However, after P15, these sensory inputs appear deselected through arrested proliferation and synapse weakening. Thus, Renshaw cells shift from integrating sensory and motor inputs in neonates to predominantly motor inputs in adult. Similar synaptic weight shifts on interneurons may be involved in the maturation of motor reflexes and locomotor circuitry. PMID:17182780

  18. Primary afferent synapses on developing and adult Renshaw cells.

    PubMed

    Mentis, George Z; Siembab, Valerie C; Zerda, Ricardo; O'Donovan, Michael J; Alvarez, Francisco J

    2006-12-20

    The mechanisms that diversify adult interneurons from a few pools of embryonic neurons are unknown. Renshaw cells, Ia inhibitory interneurons (IaINs), and possibly other types of mammalian spinal interneurons have common embryonic origins within the V1 group. However, in contrast to IaINs and other V1-derived interneurons, adult Renshaw cells receive motor axon synapses and lack proprioceptive inputs. Here, we investigated how this specific pattern of connectivity emerges during the development of Renshaw cells. Tract tracing and immunocytochemical markers [parvalbumin and vesicular glutamate transporter 1 (VGLUT1)] showed that most embryonic (embryonic day 18) Renshaw cells lack dorsal root inputs, but more than half received dorsal root synapses by postnatal day 0 (P0) and this input spread to all Renshaw cells by P10-P15. Electrophysiological recordings in neonates indicated that this input is functional and evokes Renshaw cell firing. VGLUT1-IR bouton density on Renshaw cells increased until P15 but thereafter decreased because of limited synapse proliferation coupled with the enlargement of Renshaw cell dendrites. In parallel, Renshaw cell postsynaptic densities apposed to VGLUT1-IR synapses became smaller in adult compared with P15. In contrast, vesicular acetylcholine transporter-IR motor axon synapses contact embryonic Renshaw cells and proliferate postnatally matching Renshaw cell growth. Like other V1 neurons, Renshaw cells are thus competent to receive sensory synapses. However, after P15, these sensory inputs appear deselected through arrested proliferation and synapse weakening. Thus, Renshaw cells shift from integrating sensory and motor inputs in neonates to predominantly motor inputs in adult. Similar synaptic weight shifts on interneurons may be involved in the maturation of motor reflexes and locomotor circuitry.

  19. Improving nutritional support for adults in primary and secondary care.

    PubMed

    Cartwright, Andrea

    There has been serious concern about the nutritional care provided in some secondary and primary care settings. As a result, best practice, benchmarking initiatives and nutritional guidance have been issued by government and non-government agencies. This article helps nurses to synthesise these initiatives and improve their knowledge of nutritional care.

  20. Early Activation of Primary Brain Microvascular Endothelial Cells by Nipah Virus Glycoprotein-Containing Particles

    PubMed Central

    Freitag, Tanja C.

    2015-01-01

    Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes pronounced infection of brain endothelia and central nervous system (CNS) inflammation. Using primary porcine brain microvascular endothelial cells, we showed that upregulation of E-selectin precedes cytokine induction and is induced not only by infectious NiV but also by NiV-glycoprotein-containing virus-like particles. This demonstrates that very early events in NiV brain endothelial infection do not depend on NiV replication but can be triggered by the NiV glycoproteins alone. PMID:26676791

  1. Primary primitive neuroectodermal tumour of the kidney in adults.

    PubMed

    Verma, Ritu; Singhal, Mitali; Pandey, Rakesh

    2013-03-04

    Primitive neuroectodermal tumour (PNET) is a neural crest tumour derived from neuroectoderm. Renal PNET is a very rare tumour occurring during childhood or adolescence. We report two cases of PNET involving kidney in adults. Presenting signs and symptoms include abdominal/flank pain and/or haematuria. Microscopy reveals the tumour consisted of small round cells with round nuclei and scant cytoplasm. Diagnosis was confirmed by immunohistochemistry with diffuse membranous positivity of tumour cells with CD99. As these tumours have an aggressive clinical course with rapid death in many reported cases, it is important to differentiate them from other small round-cell tumours.

  2. Sex, stress and the brain: interactive actions of hormones on the developing and adult brain.

    PubMed

    McEwen, B S

    2014-12-01

    The brain is a target of steroid hormone actions that affect brain architecture, molecular and neurochemical processes, behavior and neuroprotection via both genomic and non-genomic actions. Estrogens have such effects throughout the brain and this article provides an historical and current view of how this new view has come about and how it has affected the study of sex differences, as well as other areas of neuroscience, including the effects of stress on the brain.

  3. BDNF Expression in Larval and Adult Zebrafish Brain: Distribution and Cell Identification

    PubMed Central

    Cacialli, Pietro; Gueguen, Marie-Madeleine; Coumailleau, Pascal; D’Angelo, Livia; Kah, Olivier; Lucini, Carla; Pellegrini, Elisabeth

    2016-01-01

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has emerged as an active mediator in many essential functions in the central nervous system of mammals. BDNF plays significant roles in neurogenesis, neuronal maturation and/or synaptic plasticity and is involved in cognitive functions such as learning and memory. Despite the vast literature present in mammals, studies devoted to BDNF in the brain of other animal models are scarse. Zebrafish is a teleost fish widely known for developmental genetic studies and is emerging as model for translational neuroscience research. In addition, its brain shows many sites of adult neurogenesis allowing higher regenerative properties after traumatic injuries. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the distribution of bdnf mRNAs in the larval and adult zebrafish brain and to characterize the phenotype of cells expressing bdnf mRNAs by means of double staining studies. Our results showed that bdnf mRNAs were widely expressed in the brain of 7 days old larvae and throughout the whole brain of mature female and male zebrafish. In adults, bdnf mRNAs were mainly observed in the dorsal telencephalon, preoptic area, dorsal thalamus, posterior tuberculum, hypothalamus, synencephalon, optic tectum and medulla oblongata. By combining immunohistochemistry with in situ hybridization, we showed that bdnf mRNAs were never expressed by radial glial cells or proliferating cells. By contrast, bdnf transcripts were expressed in cells with neuronal phenotype in all brain regions investigated. Our results provide the first demonstration that the brain of zebrafish expresses bdnf mRNAs in neurons and open new fields of research on the role of the BDNF factor in brain mechanisms in normal and brain repairs situations. PMID:27336917

  4. Clonal development and organization of the adult Drosophila central brain

    PubMed Central

    Yu, Hung-Hsiang; Awasaki, Takeshi; Schroeder, Mark David; Long, Fuhui; Yang, Jacob S.; He, Yisheng; Ding, Peng; Kao, Jui-Chun; Wu, Gloria Yueh-Yi; Peng, Hanchuan; Myers, Gene; Lee, Tzumin

    2013-01-01

    Summary Background The insect brain can be divided into neuropils that are formed by neurites of both local and remote origin. The complexity of the interconnections obscures how these neuropils are established and interconnected through development. The Drosophila central brain develops from a fixed number of neuroblasts (NBs) that deposit neurons in regional clusters. Results By determining individual NB clones and pursuing their projections into specific neuropils we unravel the regional development of the brain neural network. Exhaustive clonal analysis revealed 95 stereotyped neuronal lineages with characteristic cell body locations and neurite trajectories. Most clones show complex projection patterns, but despite the complexity, neighboring clones often co-innervate the same local neuropil(s) and further target a restricted set of distant neuropils. Conclusions These observations argue for regional clonal development of both neuropils and neuropil connectivity throughout the Drosophila central brain. PMID:23541733

  5. Environmental factors associated with primary care access among urban older adults.

    PubMed

    Ryvicker, Miriam; Gallo, William T; Fahs, Marianne C

    2012-09-01

    Disparities in primary care access and quality impede optimal chronic illness prevention and management for older adults. Although research has shown associations between neighborhood attributes and health, little is known about how these factors - in particular, the primary care infrastructure - inform older adults' primary care use. Using geographic data on primary care physician supply and surveys from 1260 senior center attendees in New York City, we examined factors that facilitate and hinder primary care use for individuals living in service areas with different supply levels. Supply quartiles varied in primary care use (visit within the past 12 months), racial and socio-economic composition, and perceived neighborhood safety and social cohesion. Primary care use did not differ significantly after controlling for compositional factors. Individuals who used a community clinic or hospital outpatient department for most of their care were less likely to have had a primary care visit than those who used a private doctor's office. Stratified multivariate models showed that within the lowest-supply quartile, public transit users had a higher odds of primary care use than non-transit users. Moreover, a higher score on the perceived neighborhood social cohesion scale was associated with a higher odds of primary care use. Within the second-lowest quartile, nonwhites had a lower odds of primary care use compared to whites. Different patterns of disadvantage in primary care access exist that may be associated with - but not fully explained by - local primary care supply. In lower-supply areas, racial disparities and inadequate primary care infrastructure hinder access to care. However, accessibility and elder-friendliness of public transit, as well as efforts to improve social cohesion and support, may facilitate primary care access for individuals living in low-supply areas.

  6. Event-related brain potentials - Comparison between children and adults

    NASA Technical Reports Server (NTRS)

    Courchesne, E.

    1977-01-01

    The reported investigation shows that nontarget stimuli which are infrequently presented and deviate from the background elicit Nc and Pc waves in children. The same stimuli elicit P3 waves in adults. The scalp distribution of P3 waves in adults appears to vary with the ease of stimulus recognition or the degree of stimulus novelty. However, the Nc and Pc distributions in children do not seem to vary with these factors. The differences between children and adults in event-related potentials suggest corresponding differences in the mode of processing employed by each when rare, deviant stimuli are encountered

  7. [Interdisciplinary neuro-oncology: part 2: systemic therapy of primary brain tumors].

    PubMed

    Tabatabai, G; Hattingen, E; Schlegel, J; Stummer, W; Schlegel, U

    2014-08-01

    By combining the expertise of clinical neuroscience, the aim of neuro-oncology is to optimize diagnostic planning and therapy of primary brain tumors in an interdisciplinary setting together with radio-oncology and medical oncology. High-end imaging frequently allows brain tumors to be diagnosed preoperatively with respect to tumor entity and even tumor malignancy grade. Moreover, neuroimaging is indispensable for guidance of biopsy resection and monitoring of therapy. Surgical resection of intracranial lesions with preservation of neurological function has become dramatically more extensive. Tools to achieve this goal are, for example neuronavigation, functional magnetic resonance imaging (fMRI), tractography, intraoperative cortical stimulation and precise intraoperative definition of tumor margins by virtue of various techniques. In addition to classical histopathological diagnosis and tumor classification, modern neuropathology is supplemented by molecular characterization of brain tumors in order to provide clinicians with prognostic and predictive (of therapy) markers, such as codeletion of chromosomes 1p and 19q in anaplastic gliomas and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas. Although this is not yet individualized tumor therapy, the increasingly more detailed analysis of the molecular pathogenesis of an individual glioma will eventually lead to specific pharmacological blockade of disturbed intracellular pathways in individual patients. This article gives an overview of the state of the art of interdisciplinary neuro-oncology whereby part 1 deals with the diagnostics and surgical therapy of primary brain tumors and part 2 describes the medical therapy of primary brain tumors.

  8. [Interdisciplinary neuro-oncology: part 1: diagnostics and operative therapy of primary brain tumors].

    PubMed

    Tabatabai, G; Hattingen, E; Schlegel, J; Stummer, W; Schlegel, U

    2014-08-01

    By combining the expertise of clinical neuroscience, the aim of neuro-oncology is to optimize diagnostic planning and therapy of primary brain tumors in an interdisciplinary setting together with radio-oncology and medical oncology. High-end imaging frequently allows brain tumors to be diagnosed preoperatively with respect to tumor entity and even tumor malignancy grade. Moreover, neuroimaging is indispensable for guidance of biopsy resection and monitoring of therapy. Surgical resection of intracranial lesions with preservation of neurological function is increasingly feasible. Tools to achieve this goal are, for example neuronavigation, functional magnetic resonance imaging (fMRI), tractography, intraoperative cortical stimulation and precise intraoperative definition of tumor margins by virtue of various techniques. In addition to classical histopathological diagnosis and tumor classification, modern neuropathology is supplemented by molecular characterization of brain tumors in order to provide clinicians with prognostic and predictive (of therapy) markers, such as codeletion of chromosomes 1p and 19q in anaplastic gliomas and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas. Although this is not yet individualized tumor therapy, the increasingly more detailed analysis of the molecular pathogenesis of an individual glioma will eventually lead to specific pharmacological blockade of disturbed intracellular pathways in individual patients. This article gives an overview of the state of the art of interdisciplinary neuro-oncology whereby part 1 deals with the diagnostics and surgical therapy of primary brain tumors and part 2 describes the medical therapy of primary brain tumors.

  9. Bimanual Motor Coordination in Older Adults Is Associated with Increased Functional Brain Connectivity – A Graph-Theoretical Analysis

    PubMed Central

    Heitger, Marcus H.; Goble, Daniel J.; Dhollander, Thijs; Dupont, Patrick; Caeyenberghs, Karen; Leemans, Alexander; Sunaert, Stefan; Swinnen, Stephan P.

    2013-01-01

    In bimanual coordination, older and younger adults activate a common cerebral network but the elderly also have additional activation in a secondary network of brain areas to master task performance. It remains unclear whether the functional connectivity within these primary and secondary motor networks differs between the old and the young and whether task difficulty modulates connectivity. We applied graph-theoretical network analysis (GTNA) to task-driven fMRI data in 16 elderly and 16 young participants using a bimanual coordination task including in-phase and anti-phase flexion/extension wrist movements. Network nodes for the GTNA comprised task-relevant brain areas as defined by fMRI activation foci. The elderly matched the motor performance of the young but showed an increased functional connectivity in both networks across a wide range of connectivity metrics, i.e., higher mean connectivity degree, connection strength, network density and efficiency, together with shorter mean communication path length between the network nodes and also a lower betweenness centrality. More difficult movements showed an increased connectivity in both groups. The network connectivity of both groups had “small world” character. The present findings indicate (a) that bimanual coordination in the aging brain is associated with a higher functional connectivity even between areas also activated in young adults, independently from task difficulty, and (b) that adequate motor coordination in the context of task-driven bimanual control in older adults may not be solely due to additional neural recruitment but also to aging-related changes of functional relationships between brain regions. PMID:23637982

  10. aBEAT: A Toolbox for Consistent Analysis of Longitudinal Adult Brain MRI

    PubMed Central

    Dai, Yakang; Wang, Yaping; Wang, Li; Wu, Guorong; Shi, Feng; Shen, Dinggang

    2013-01-01

    Longitudinal brain image analysis is critical for revealing subtle but complex structural and functional changes of brain during aging or in neurodevelopmental disease. However, even with the rapid increase of clinical research and trials, a software toolbox dedicated for longitudinal image analysis is still lacking publicly. To cater for this increasing need, we have developed a dedicated 4D Adult Brain Extraction and Analysis Toolbox (aBEAT) to provide robust and accurate analysis of the longitudinal adult brain MR images. Specially, a group of image processing tools were integrated into aBEAT, including 4D brain extraction, 4D tissue segmentation, and 4D brain labeling. First, a 4D deformable-surface-based brain extraction algorithm, which can deform serial brain surfaces simultaneously under temporal smoothness constraint, was developed for consistent brain extraction. Second, a level-sets-based 4D tissue segmentation algorithm that incorporates local intensity distribution, spatial cortical-thickness constraint, and temporal cortical-thickness consistency was also included in aBEAT for consistent brain tissue segmentation. Third, a longitudinal groupwise image registration framework was further integrated into aBEAT for consistent ROI labeling by simultaneously warping a pre-labeled brain atlas to the longitudinal brain images. The performance of aBEAT has been extensively evaluated on a large number of longitudinal MR T1 images which include normal and dementia subjects, achieving very promising results. A Linux-based standalone package of aBEAT is now freely available at http://www.nitrc.org/projects/abeat. PMID:23577105

  11. Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents.

    PubMed

    Zhou, June; Keenan, Michael J; Fernandez-Kim, Sun Ok; Pistell, Paul J; Ingram, Donald K; Li, Bing; Raggio, Anne M; Shen, Li; Zhang, Hanjie; McCutcheon, Kathleen L; Tulley, Richard T; Blackman, Marc R; Keller, Jeffrey N; Martin, Roy J

    2013-11-01

    Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (i) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (ii) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (iii) a higher serum active glucagon-like peptide-1 (GLP-1). Then, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (i) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and (ii) GLP-1 is important in the optimal feeding response to a fast.

  12. Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

    SciTech Connect

    Miyoshi, Ko; Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato

    2009-10-30

    The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li{sub 2}CO{sub 3} were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

  13. Highly efficient transduction of primary adult CNS and PNS neurons

    PubMed Central

    Levin, Evgeny; Diekmann, Heike; Fischer, Dietmar

    2016-01-01

    Delivery and expression of recombinant genes, a key methodology for many applications in biological research, remains a challenge especially for mature neurons. Here, we report easy, highly efficient and well tolerated transduction of adult peripheral and central neuronal populations of diverse species in culture using VSV-G pseudo-typed, recombinant baculovirus (BacMam). Transduction rates of up to 80% were reliably achieved at high multiplicity of infection without apparent neuro-cytopathic effects. Neurons could be transduced either shortly after plating or after several days in culture. Co-incubation with two different baculoviruses attained near complete co-localization of fluorescent protein expression, indicating multigene delivery. Finally, evidence for functional protein expression is provided by means of cre-mediated genetic recombination and neurite outgrowth assays. Recombinant protein was already detected within hours after transduction, thereby enabling functional readouts even in relatively short-lived neuronal cultures. Altogether, these results substantiate the usefulness of baculovirus-mediated transduction of mature neurons for future research in neuroscience. PMID:27958330

  14. Delineating multiple functions of VEGF-A in the adult brain.

    PubMed

    Licht, Tamar; Keshet, Eli

    2013-05-01

    Vascular endothelial growth factor-A (abbreviated throughout this review as VEGF) is mostly known for its angiogenic activity, for its activity as a vascular permeability factor, and for its vascular survival activity [1]. There is a growing body of evidence, however, that VEGF fulfills additional less 'traditional' functions in multiple organs, both during development, as well as homeostatic functions in fully developed organs. This review focuses on the multiple roles of VEGF in the adult brain and is less concerned with the roles played by VEGF during brain development, functions described elsewhere in this review series. Most functions of VEGF that are essential for proper brain development are, in fact, dispensable in the adult brain as was clearly demonstrated using a conditional brain-specific VEGF loss-of-function (LOF) approach. Thus, in contrast to VEGF LOF in the developing brain, a process which is detrimental for the growth and survival of blood vessels and leads to massive neuronal apoptosis [2-4], continued signaling by VEGF in the mature brain is no longer required for maintaining already established cerebral vasculature and its inhibition does not cause appreciable vessel regression, hypoxia or apoptosis [4-7]. Yet, VEGF continues to be expressed in the adult brain in a constitutive manner. Moreover, VEGF is expressed in the adult brain in a region-specific manner and in distinctive spatial patterns incompatible with an angiogenic role (see below), strongly suggesting angiogenesis-independent and possibly also perfusion-independent functions. Here we review current knowledge on some of these 'non-traditional', often unexpected homeostatic VEGF functions, including those unrelated to its effects on the brain vasculature. These effects could be mediated directly (on non-vascular cells expressing cognate VEGF receptors) or indirectly (via the endothelium). Experimental approaches aimed at distinguishing between these possibilities for each particular

  15. Cranial irradiation induces bone marrow-derived microglia in adult mouse brain tissue.

    PubMed

    Okonogi, Noriyuki; Nakamura, Kazuhiro; Suzuki, Yoshiyuki; Suto, Nana; Suzue, Kazutomo; Kaminuma, Takuya; Nakano, Takashi; Hirai, Hirokazu

    2014-07-01

    Postnatal hematopoietic progenitor cells do not contribute to microglial homeostasis in adult mice under normal conditions. However, previous studies using whole-body irradiation and bone marrow (BM) transplantation models have shown that adult BM cells migrate into the brain tissue and differentiate into microglia (BM-derived microglia; BMDM). Here, we investigated whether cranial irradiation alone was sufficient to induce the generation of BMDM in the adult mouse brain. Transgenic mice that express green fluorescent protein (GFP) under the control of a murine stem cell virus (MSCV) promoter (MSCV-GFP mice) were used. MSCV-GFP mice express GFP in BM cells but not in the resident microglia in the brain. Therefore, these mice allowed us to detect BM-derived cells in the brain without BM reconstitution. MSCV-GFP mice, aged 8-12 weeks, received 13.0 Gy irradiation only to the cranium, and BM-derived cells in the brain were quantified at 3 and 8 weeks after irradiation. No BM-derived cells were detected in control non-irradiated MSCV-GFP mouse brains, but numerous GFP-labeled BM-derived cells were present in the brain stem, basal ganglia and cerebral cortex of the irradiated MSCV-GFP mice. These BM-derived cells were positive for Iba1, a marker for microglia, indicating that GFP-positive BM-derived cells were microglial in nature. The population of BMDM was significantly greater at 8 weeks post-irradiation than at 3 weeks post-irradiation in all brain regions examined. Our results clearly show that cranial irradiation alone is sufficient to induce the generation of BMDM in the adult mouse.

  16. Receptor protein tyrosine phosphatase σ binds to neurons in the adult mouse brain

    PubMed Central

    Yi, Jae-Hyuk; Katagiri, Yasuhiro; Yu, Panpan; Lourie, Jacob; Bangayan, Nathanael J.; Symes, Aviva J.; Geller, Herbert M.

    2014-01-01

    The role of type IIA receptor protein tyrosine phosphatases (RPTPs), which includes LAR, RPTPσ and RPTPδ, in the nervous system is becoming increasingly recognized. Evidence supports a significant role for these RPTPs during the development of the nervous system as well as after injury, and mutations in RPTPs are associated with human disease. However, a major open question is the nature of the ligands that interact with type IIA RPTPs in the adult brain. Candidates include several different proteins as well as the glycosaminoglycan chains of proteoglycans. In order to investigate this problem, we used a receptor affinity probe assay with RPTPσ-AP fusion proteins on sections of adult mouse brain and to cultured neurons. Our results demonstrate that the major binding sites for RPTPσ in adult mouse brain are on neurons and are not proteoglycan GAG chains, as RPTPσ binding overlaps with the neuronal marker NeuN and was not significantly altered by treatments which eliminate chondroitin sulfate, heparan sulfate, or both. We also demonstrate no overlap of binding of RPTPσ with perineuronal nets, and a unique modulation of RPTPσ binding to brain by divalent cations. Our data therefore point to neuronal proteins, rather than CSPGs, as being the ligands for RPTPσ in the adult, uninjured brain. PMID:24530640

  17. Using network science to evaluate exercise-associated brain changes in older adults.

    PubMed

    Burdette, Jonathan H; Laurienti, Paul J; Espeland, Mark A; Morgan, Ashley; Telesford, Qawi; Vechlekar, Crystal D; Hayasaka, Satoru; Jennings, Janine M; Katula, Jeffrey A; Kraft, Robert A; Rejeski, W Jack

    2010-01-01

    Literature has shown that exercise is beneficial for cognitive function in older adults and that aerobic fitness is associated with increased hippocampal tissue and blood volumes. The current study used novel network science methods to shed light on the neurophysiological implications of exercise-induced changes in the hippocampus of older adults. Participants represented a volunteer subgroup of older adults that were part of either the exercise training (ET) or healthy aging educational control (HAC) treatment arms from the Seniors Health and Activity Research Program Pilot (SHARP-P) trial. Following the 4-month interventions, MRI measures of resting brain blood flow and connectivity were performed. The ET group's hippocampal cerebral blood flow (CBF) exhibited statistically significant increases compared to the HAC group. Novel whole-brain network connectivity analyses showed greater connectivity in the hippocampi of the ET participants compared to HAC. Furthermore, the hippocampus was consistently shown to be within the same network neighborhood (module) as the anterior cingulate cortex only within the ET group. Thus, within the ET group, the hippocampus and anterior cingulate were highly interconnected and localized to the same network neighborhood. This project shows the power of network science to investigate potential mechanisms for exercise-induced benefits to the brain in older adults. We show a link between neurological network features and CBF, and it is possible that this alteration of functional brain networks may lead to the known improvement in cognitive function among older adults following exercise.

  18. Modular Brain Network Organization Predicts Response to Cognitive Training in Older Adults

    PubMed Central

    Gallen, Courtney L.; Baniqued, Pauline L.; Chapman, Sandra B.; Aslan, Sina; Keebler, Molly; Didehbani, Nyaz; D’Esposito, Mark

    2016-01-01

    Cognitive training interventions are a promising approach to mitigate cognitive deficits common in aging and, ultimately, to improve functioning in older adults. Baseline neural factors, such as properties of brain networks, may predict training outcomes and can be used to improve the effectiveness of interventions. Here, we investigated the relationship between baseline brain network modularity, a measure of the segregation of brain sub-networks, and training-related gains in cognition in older adults. We found that older adults with more segregated brain sub-networks (i.e., more modular networks) at baseline exhibited greater training improvements in the ability to synthesize complex information. Further, the relationship between modularity and training-related gains was more pronounced in sub-networks mediating “associative” functions compared with those involved in sensory-motor processing. These results suggest that assessments of brain networks can be used as a biomarker to guide the implementation of cognitive interventions and improve outcomes across individuals. More broadly, these findings also suggest that properties of brain networks may capture individual differences in learning and neuroplasticity. Trail Registration: ClinicalTrials.gov, NCT#00977418 PMID:28006029

  19. Transformation of adult rat cardiac myocytes in primary culture.

    PubMed

    Banyasz, Tamas; Lozinskiy, Ilya; Payne, Charles E; Edelmann, Stephanie; Norton, Byron; Chen, Biyi; Chen-Izu, Ye; Izu, Leighton T; Balke, C William

    2008-03-01

    We characterized the morphological, electrical and mechanical alterations of cardiomyocytes in long-term cell culture. Morphometric parameters, sarcomere length, T-tubule density, cell capacitance, L-type calcium current (I(Ca,L)), inward rectifier potassium current (I(K1)), cytosolic calcium transients, action potential and contractile parameters of adult rat ventricular myocytes were determined on each day of 5 days in culture. We also analysed the health of the myocytes using an apoptotic/necrotic viability assay. The data show that myocytes undergo profound morphological and functional changes during culture. We observed a progressive reduction in the cell area (from 2502 +/- 70 microm(2) on day 0 to 1432 +/- 50 microm(2) on day 5), T-tubule density, systolic shortening (from 0.11 +/- 0.02 to 0.05 +/- 0.01 microm) and amplitude of calcium transients (from 1.54 +/- 0.19 to 0.67 +/- 0.19) over 5 days of culture. The negative force-frequency relationship, characteristic of rat myocardium, was maintained during the first 2 days but diminished thereafter. Cell capacitance (from 156 +/- 8 to 105 +/- 11 pF) and membrane currents were also reduced (I(Ca,L), from 3.98 +/- 0.39 to 2.12 +/- 0.37 pA pF; and I(K1), from 34.34p +/- 2.31 to 18.00 +/- 5.97 pA pF(-1)). We observed progressive depolarization of the resting membrane potential during culture (from 77.3 +/- 2.5 to 34.2 +/- 5.9 mV) and, consequently, action potential morphology was profoundly altered as well. The results of the viability assays indicate that these alterations could not be attributed to either apoptosis or necrosis but are rather an adaptation to the culture conditions over time.

  20. Primary cutaneous smoldering adult T-cell leukemia/ lymphoma.

    PubMed

    Gittler, Julia; Martires, Kathryn; Terushkin, Vitaly; Brinster, Nooshin; Ramsay, David

    2016-12-15

    HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration. Histopathologic examinationwas suggestive of mycosis fungoides, laboratoryresults showed HTLV-I and II, and the patient wasdiagnosed with primary cutaneous ATLL. We reviewthe literature on HTLV-1 and ATLL and specifically theprognosis of cutaneous ATLL. The literature suggeststhat a diagnosis of ATLL should be considered amongpatients of Caribbean origin or other endemicareas with skin lesions that suggest a cutaneousT-cell lymphoma, with clinicopathologic features ofmycosis fungoides. Differentiation between ATLLand cutaneous T-cell lymphoma is imperative as theyhave different prognoses and treatment approaches.

  1. Brain function differences in language processing in children and adults with autism.

    PubMed

    Williams, Diane L; Cherkassky, Vladimir L; Mason, Robert A; Keller, Timothy A; Minshew, Nancy J; Just, Marcel Adam

    2013-08-01

    Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience.

  2. ABAEnrichment: an R package to test for gene set expression enrichment in the adult and developing human brain.

    PubMed

    Grote, Steffi; Prüfer, Kay; Kelso, Janet; Dannemann, Michael

    2016-10-15

    We present ABAEnrichment, an R package that tests for expression enrichment in specific brain regions at different developmental stages using expression information gathered from multiple regions of the adult and developing human brain, together with ontologically organized structural information about the brain, both provided by the Allen Brain Atlas. We validate ABAEnrichment by successfully recovering the origin of gene sets identified in specific brain cell-types and developmental stages.

  3. Hypotonic hyponatremia by primary polydipsia caused brain death in a 10-year-old boy

    PubMed Central

    Ko, A Ra; Kim, Soo Jung; Jung, Mo Kyung; Kim, Ki Eun; Chae, Hyun Wook; Kim, Duk Hee; Kim, Ho-Seong

    2015-01-01

    Hypotonic hyponatremia by primary polydipsia can cause severe neurologic complications due to cerebral edema. A 10-year-and-4-month-old boy with a psychiatric history of intellectual disability and behavioral disorders who presented with chief complaints of seizure and mental change showed severe hypotonic hyponatremia with low urine osmolality (serum sodium, 101 mmol/L; serum osmolality, 215 mOsm/kg; urine osmolality, 108 mOsm/kg). The patient had been polydipsic for a few months prior, and this had been worse in the previous few days. A diagnosis of hypotonic hyponatremia caused by primary polydipsia was made. The patient was in a coma, and developed respiratory arrest and became brain death shortly after admission, despite the treatment. The initial brain magnetic resonance imaging showed severe brain swelling with tonsillar and uncal herniation, and the patient was declared as brain death. It has been reported that antidiuretic hormone suppression is inadequate in patients with chronic polydipsia, and that this inadequate suppression of antidiuretic hormone is aggravated in patients with acute psychosis. Therefore, hyponatremia by primary polydipsia, although it is rare, can cause serious and life-threatening neurologic complications. PMID:26512354

  4. The effects of sleep deprivation on brain functioning in older adults.

    PubMed

    Almklov, Erin L; Drummond, Sean P A; Orff, Henry; Alhassoon, Omar M

    2015-01-01

    Few studies have examined the effects of total sleep deprivation (TSD) on cognitive performance and brain activation using functional MRI (fMRI) in older adults. The current study examines blood oxygen level-dependent (BOLD) activation in older adults and younger adults during the sustained attention (GO) and response inhibition (NOGO) portions of a GO-NOGO cognitive task following 36 hr of total sleep deprivation. No significant performance differences were observed between the groups on the behavioral outcome measures of total hits and false alarms. Neuroimaging results, however, revealed a significant interaction between age-group and sleep-deprivation status. Specifically, older adults showed greater BOLD activation as compared to younger adults after 36 hours total sleep deprivation in brain regions typically associated with attention and inhibitory processes. These results suggest in order for older adults to perform the GO-NOGO task effectively after sleep deprivation, they rely on compensatory recruitment of brain regions that aide in the maintenance of cognitive performance.

  5. Educating the adult brain: How the neuroscience of learning can inform educational policy

    NASA Astrophysics Data System (ADS)

    Knowland, Victoria C. P.; Thomas, Michael S. C.

    2014-05-01

    The acquisition of new skills in adulthood can positively affect an individual's quality of life, including their earning potential. In some cases, such as the learning of literacy in developing countries, it can provide an avenue to escape from poverty. In developed countries, job retraining in adulthood contributes to the flexibility of labour markets. For all adults, learning opportunities increase participation in society and family life. However, the popular view is that adults are less able to learn for an intrinsic reason: their brains are less plastic than in childhood. This article reviews what is currently known from neuroscientific research about how brain plasticity changes with age, with a particular focus on the ability to acquire new skills in adulthood. Anchoring their review in the examples of the adult acquisition of literacy and new motor skills, the authors address five specific questions: (1) Are sensitive periods in brain development relevant to learning complex educational skills like literacy? (2) Can adults become proficient in a new skill? (3) Can everyone learn equally effectively in adulthood? (4) What is the role of the learning environment? (5) Does adult education cost too much? They identify areas where further research is needed and conclude with a summary of principles for enhancing adult learning now established on a neuroscience foundation.

  6. Primary brain calcification in patients undergoing treatment with the biphosphanate alendronate.

    PubMed

    Oliveira, J R M; Oliveira, M F

    2016-03-15

    Brain calcification might be associated with various metabolic, infectious or vascular conditions. Clinically, brain calcification can include symptoms such as migraine, parkinsonism, psychosis or dementia. The term Primary Brain Calcification was recently used for those patients without an obvious cause (formerly idiopathic) while Primary Familial Brain Calcifications was left for the cases with autosomal dominant inheritance. Recent studies found mutations in four genes (SLC20A2, PDGFRB, PDGFB and XPR1). However, these gene represent only 60% of all familial cases suggesting other genes remain to be elucidated. Studies evaluating treatments for such a devastating disease are scattered, usually appearing as single case reports. In the present study, we describe a case series of 7 patients treated with Alendronate, a widely prescribed biphosphanate. We observed good tolerance and evidence of improvements and stability by some patients. No side effects were reported and no specific symptoms related to medication. Younger patients and one individual continuing a prescription (prior to study commencement) appeared to respond more positively with some referred improvements in symptoms. Biphosphanates may represent an excellent prospect for the treatment of brain calcifications due to their being well tolerated and easily available. Conversely, prospective and controlled studies should promptly address weaknesses found in the present analysis.

  7. The effects of acetaldehyde on nicotine-induced transmitter levels in young and adult brain areas.

    PubMed

    Sershen, H; Shearman, E; Fallon, S; Chakraborty, G; Smiley, J; Lajtha, A

    2009-08-14

    The aim of the present study was to examine the effect of acetaldehyde administration on neurotransmitters in the presence of nicotine in brain areas associated with cognition and reward. We assayed these effects via microdialysis in conscious freely moving male Sprague-Dawley rats. It was reported that low doses of acetaldehyde enhance nicotine self-administration in young, but not in adult rats. Since nicotine enhances reward and learning, while acetaldehyde is reported to enhance reward but inhibit learning, acetaldehyde thus would be likely to stimulate reward without stimulating learning. We hoped that examining the effects of acetaldehyde (on nicotine-mediated neurotransmitter changes) would help to distinguish reward mechanisms less influenced by learning mechanisms. To avoid the aversive effect of acetaldehyde, we used a low dose of acetaldehyde (0.16 mg/kg) administered after nicotine (0.3mg/kg). We analyzed six brain regions: nucleus accumbens shell (NAccS), ventral tegmental area (VTA), ventral and dorsal hippocampus (VH and DH), and prefrontal and medial temporal cortex (PFC, MTC), assaying dopamine (DA), norepinephrine (NE) and serotonin (5-HT) and their metabolites in young and adult rats. The effect of acetaldehyde on nicotine-induced transmitter changes was different in young as compared to adult rat brain regions. In the NAccS of the young, DA was not affected while NE and 5-HT were increased. In the adult in this area DA and NE were decreased, while 5-HT was not altered. In other areas also in many cases, the effect of acetaldehyde in the young and in the adult was different. As an example, acetaldehyde administration increased NE in young and decreased NE in adult DH. We found stimulation of nicotine-induced changes by acetaldehyde in seven instances - six of these were observed in areas in young brain, NE in four areas (NAccS, DH, VH, and PFC), and 5-HT in two (NAccS and DH). Only one increase was noted in adult brain (DA in VTA). Inhibition of

  8. Brain Metastases from Different Primary Carcinomas: an Evaluation of DSC MRI Measurements.

    PubMed

    Zhang, H; Zhang, G; Oudkerk, M

    2012-03-01

    This study evaluated the roles of different dynamic susceptibility contrast magnetic imaging (DSC MRI) measurements in discriminating between brain metastases derived from four common primary carcinomas. Thirty-seven patients with brain metastases were enrolled. Relative cerebral blood volume (rCBV), cerebral blood flow (rCBF) and relative mean transit time (rMTT) in both tumor and peritumoral edema were measured. Metastases were grouped by their primary tumor (lung, gastrointestinal, breast and renal cell carcinoma). DSC MRI measurements were compared between groups. Mean rCBV, rCBF, rMTT in tumor and peritumoral edema of all brain metastases (n=37) were 2.79 ± 1.73, 2.56 ± 2.11, 1.21 ± 0.48 and 1.05 ± 0.53, 0.86 ± 0.40, 1.99 ± 0.41, respectively. The tumoral rCBV (5.26 ± 1.89) and rCBF (5.32 ± 3.28) of renal metastases were greater than those of the other three metastases (P<0.05). The tumoral rMTT (1.58 ± 0.77) of breast metastases was statistically greater than that (0.96 ± 0.31) of gastrointestinal metastases (P=0.013). No statistical difference was found between peritumoral rCBV, rCBF and rMTT (P>0.05). Evaluating various DSC MRI measurements can provide complementary hemodynamic information on brain metastases. The tumoral rCBV, rCBF and likely rMTT can help discriminate between brain metastases originating from different primary carcinomas. The peritumoral DSC MRI measurements had limited value in discriminating between brain metastases.

  9. Fetal Alcohol Exposure Reduces Adult Brain Plasticity. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief summarizes the findings and implications of "Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice" (I. Y. Choi; A. M. Allan; and L. A. Cunningham). Observations of mice…

  10. A miRNA-based signature detected in primary melanoma tissue predicts development of brain metastasis

    PubMed Central

    Hanniford, Doug; Zhong, Judy; Koetz, Lisa; Gaziel-Sovran, Avital; Lackaye, Daniel J.; Shang, Shulian; Pavlick, Anna; Shapiro, Richard; Berman, Russell; Darvishian, Farbod; Shao, Yongzhao; Osman, Iman; Hernando, Eva

    2015-01-01

    Purpose Brain metastasis is the major cause of mortality among melanoma patients. A molecular prognostic test that can reliably stratify patients at initial melanoma diagnosis by risk of developing brain metastasis may inform the clinical management of these patients. Experimental Design We performed a retrospective, cohort-based study analyzing genome-wide and targeted microRNA expression profiling of primary melanoma tumors of three patient cohorts (n= 92, n= 119, n= 45) with extensive clinical follow up. We used Cox regression analysis to establish a microRNA-based signature that improves the ability of the current clinicopathologic staging system to predict the development of brain metastasis. Results Our analyses identified a 4-microRNA (miR-150–5p, miR-15b-5p, miR-16–5p, and miR-374b-3p) prognostic signature that, in combination with stage, distinguished primary melanomas that metastasized to the brain from non-recurrent and non-brain-metastatic primary tumors (training cohort: C-index=81.4%, validation cohort: C-index=67.4%, independent cohort: C-index=76.9%). Corresponding Kaplan-Meier curves of high- vs. low-risk patients displayed a clear separation in brain-metastasis-free and overall survival (training: p<0.001, p<0.001, validation: p=0.033, p=0.007, independent: p=0.021, p=0.022, respectively). Finally, of the microRNA in the prognostic model, we found that the expression of a key lymphocyte miRNA, miR-150–5p, which is less abundant in primary melanomas metastatic to brain, correlated with presence of CD45+ tumor infiltrating lymphocytes. Conclusions A prognostic assay based on the described miRNA expression signature combined with the currently used staging criteria may improve accuracy of primary melanoma patient prognoses and aid clinical management of patients, including selection for adjuvant treatment or clinical trials of adjuvant therapies. PMID:26089374

  11. Discrimination of Different Brain Metastases and Primary CNS Lymphomas Using Morphologic Criteria and Diffusion Tensor Imaging.

    PubMed

    Bette, S; Wiestler, B; Delbridge, C; Huber, T; Boeckh-Behrens, T; Meyer, B; Zimmer, C; Gempt, J; Kirschke, J

    2016-12-01

    Purpose: Brain metastases are a common complication of cancer and occur in about 15 - 40 % of patients with malignancies. The aim of this retrospective study was to differentiate between metastases from different primary tumors/CNS lymphyomas using morphologic criteria, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Materials and Methods: Morphologic criteria such as hemorrhage, cysts, pattern of contrast enhancement and location were reported in 200 consecutive patients with brain metastases/primary CNS lymphomas. FA and ADC values were measured in regions of interest (ROIs) placed in the contrast-enhancing tumor part, the necrosis and the non-enhancing peritumoral region (NEPTR). Differences between histopathological subtypes of metastases were analyzed using non-parametric tests, decision trees and hierarchical clustering analysis. Results: Significant differences were found in morphologic criteria such as hemorrhage or pattern of contrast enhancement. In diffusion measurements, significant differences between the different tumor entities were only found in ADC analyzed in the contrast-enhancing tumor part. Among single tumor entities, primary CNS lymphomas showed significantly lower median ADC values in the contrast-enhancing tumor part (ADClymphoma 0.92 [0.83 - 1.07] vs. ADCno_lymphoma 1.35 [1.10 - 1.64] P = 0.001). Further differentiation between types of metastases was not possible using FA and ADC. Conclusion: There were morphologic differences among the main subtypes of brain metastases/CNS lymphomas. However, due to a high variability of common types of metastases and low specificity, prospective differentiation remained challenging. DTI including FA and ADC was not a reliable tool for differentiation between different histopathological subtypes of brain metastases except for CNS lymphomas showing lower ADC values. Biopsy, surgery and staging remain essential for diagnosis. Key Points:

  12. Executive control function, brain activation and white matter hyperintensities in older adults

    PubMed Central

    Venkatraman, Vijay K.; Aizenstein, Howard; Guralnik, Jack; Newman, Anne B.; Glynn, Nancy W.; Taylor, Christopher; Studenski, Stephanie; Launer, Lenore; Pahor, Marco; Williamson, Jeff; Rosano, Caterina

    2009-01-01

    Context Older adults responding to executive control function (ECF) tasks show greater brain activation on functional MRI (fMRI). It is not clear whether greater fMRI activation indicates a strategy to compensate for underlying brain structural abnormalities while maintaining higher performance. Objective To identify the patterns of fMRI activation in relationship with ECF performance and with brain structural abnormalities. Design Cross-sectional analysis. Main variables of interest: fMRI activation, accuracy while performing an ECF task (Digit Symbol Substitution Test), volume of white matter hyperintensities and of total brain atrophy. Setting Cohort of community-dwelling older adults. Participants Data were obtained on 25 older adults (20 women, 81 years mean age). Outcome Measure Accuracy (number of correct response / total number of responses) while performing the Digit Symbol Substitution Test. Results Greater accuracy was significantly associated with greater peak fMRI activation, from ECF regions, including left middle frontal gyrus and right posterior parietal cortex. Greater WMH was associated with lower activation within accuracy-related regions. The interaction of accuracy by white matter hyperintensities volume was significant within the left posterior parietal region. Specifically, the correlation of white matter hyperintensities volume with fMRI activation varied as a function of accuracy and it was positive for greater accuracy. Associations with brain atrophy were not significant. Conclusions Recruitment of additional areas and overall greater brain activation in older adults is associated with higher performance. Posterior parietal activation may be particularly important to maintain higher accuracy in the presence of underlying brain connectivity structural abnormalities. PMID:19922803

  13. Neuroanatomical distribution of galectin-3 in the adult rat brain.

    PubMed

    Yoo, Hong-Il; Kim, Eu-Gene; Lee, Eun-Jin; Hong, Sung-Young; Yoon, Chi-Sun; Hong, Min-Ju; Park, Sang-Jin; Woo, Ran-Sook; Baik, Tai-Kyoung; Song, Dae-Yong

    2017-04-01

    Galectin-3 is a member of the lectin subfamily that enables the specific binding of β-galactosides. It is expressed in a broad spectrum of species and organs, and is known to have various functions related to cell adhesion, signal transduction, and proinflammatory responses. Although, expression of galectin-3 in some activated neuroglia under neuroinflammation has been well documented in the central nervous system, little is known about the neuronal expression and distribution of galectin-3 in normal brain. To describe the cellular and neuroanatomical expression map of galectin-3, we performed galectin-3 immunohistochemistry on the entire normal rat brain and subsequently analyzed the neuronal distribution. Galectin-3 expression was observed not only in some neuroglia but also in neurons. Neuronal expression of galectin-3 was observed in many functional parts of the cerebral cortex and various other subcortical nuclei in the hypothalamus and brainstem. Neuroanatomical analysis revealed that robust galectin-3 immuno-signals were present in many hypothalamic nuclei related to a variety of physiological functions responsible for mediating anxiety responses, energy balance, and neuroendocrine regulation. In addition, the regions highly connected with these hypothalamic nuclei also showed intense galectin-3 expression. Moreover, multiple key regions involved in regulating autonomic functions exhibited high levels of galectin-3 expression. In contrast, the subcortical nuclei responsible for the control of voluntary motor functions and limbic system exhibited no galectin-3 immunoreactivity. These observations suggest that galectin-3 expression in the rat brain seems to be regulated by developmental cascades, and that functionally and neuroanatomically related brain nuclei constitutively express galectin-3 in adulthood.

  14. Brain tissue pressure measurements in perinatal and adult rabbits.

    PubMed

    Hornig, G W; Lorenzo, A V; Zavala, L M; Welch, K

    1987-12-01

    Brain tissue pressure (BTP) in pre- and post-natal anesthetized rabbits, held in a stereotactic head holder, was measured with a fluid filled 23 gauge open-ended cannula connected distally to a pressure transducer. By advancing the cannula step wise through a hole in the cranium it was possible to sequentially measure pressure from the cranial subarachnoid space, cortex, ventricle and basal ganglia. Separate cannulas and transducers were used to measure CSFP from the cisterna magna and arterial and/or venous pressure. Pressure recordings obtained when the tip of the BTP cannula was located in the cranial subarachnoid space or ventricle exhibited respiratory and blood pressure pulsations equivalent to and in phase with CSF pulsations recorded from the cisterna magna. When the tip was advanced into brain parenchymal sites such pulsations were suppressed or non-detectable unless communication with a CSF compartment had been established inadvertently. Although CSF pressures in the three spinal fluid compartments were equivalent, in most animals BTP was higher than CSFP. However, after momentary venting of the system BTP equilibrated at a pressure below that of CSFP. We speculate that venting of the low compliance system (1.20 x 10(-5) ml/mmHg) relieves the isometric pressure build-up due to insertion of the cannula into brain parenchyma. Under these conditions, and at all ages examined, BTP in the rabbit is consistently lower than CSFP and, as with CSFP, it increases as the animal matures.

  15. Canonical Genetic Signatures of the Adult Human Brain

    PubMed Central

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  16. Proliferation zones in the brain of adult fish Austrolebias (Cyprinodontiform: Rivulidae): a comparative study.

    PubMed

    Fernández, A S; Rosillo, J C; Casanova, G; Olivera-Bravo, S

    2011-08-25

    In contrast with mammals, adult fish brains exhibit an enormous potential to produce new cells. Proliferation zones, however, have been described in only a few species, hindering comparisons among genuses and orders. Here we analyzed brain cell proliferation in annual teleostean fishes Austrolebias (Cyprinodontiform: Rivulidae). Immunocytochemistry against 5-bromo-2'-deoxyuridine (BrdU) was quantitated and mapped 24 h after injection in three species with different phylogenetic positions or habitats. All species had similar brain anatomy and total volume, but olfactory bulbs, torus longitudinalis and cerebellum were of different sizes in different species. Cell proliferation was found throughout the brain. Three-D reconstructions provided evidence for contiguity along the rostro-caudal axis and concentration in the vicinity of the ventricles. Brain regions analyzed exhibited high mitotic activity, and the torus longitudinalis had the highest volume-normalized proliferation index. A. affinis exhibited the highest normalized proliferation indexes in visual regions but the lowest in olfactory bulb. A. reicherti showed an inverse pattern, suggesting that these species have a different hierarchy of sensorial modalities that could be related to phylogeny or habitat. Double immunostaining against BrdU and cell-type specific markers was performed to determine the fate of proliferating cells. A widespread gliogenesis was evidenced. Few cells positive for both BrdU and the neuronal marker HuC/D were found in the brain of the three species, demonstrating neurogenesis in the adult Austrolebias brain. Summarizing, adult members of the three species showed similar brain anatomy and cell proliferation patterns. Among species, volume-normalized proliferation indexes varied in regions involved in different sensory modalities. To our knowledge, this is the first report showing proliferating cells with neuronal markers as earlier as 24 h after BrdU injection.

  17. A Comparison of Intralesional Triamcinolone Acetonide Injection for Primary Chalazion in Children and Adults

    PubMed Central

    Lee, Jacky W. Y.; Yau, Gordon S. K.; Wong, Michelle Y. Y.; Yuen, Can Y. F.

    2014-01-01

    Purpose. To investigate outcome differences of intralesional triamcinolone acetonide (TA) injection for primary chalazia in children versus adults. Methods. A retrospective review of consecutive subjects with primary chalazion who received intralesional TA injection was conducted. A single investigator injected 0.05–0.15 mL of TA (40 mg/mL) intralesionally. Patients were stratified into the pediatric (<18 years old) and adult (≥18 years old) group. In both groups, the correlation of resolution time with chalazion size and TA dose was performed. Results. 17 children and 24 adults were enrolled, with a mean age of 7.4 ± 5.5 and 39.3 ± 16.7 years, respectively. Both groups had statistically similar baseline characteristics. There was no significant difference between the resolution time in the pediatric (18.2 ± 11.4 days) and adult (16.5 ± 11.0 days) group (P = 0.7). There were no significant complications from the TA injection. There was no significant correlation of resolution time to chalazion size (P = 0.7) nor TA dose (P = 0.3) in both groups. Conclusion. TA for the treatment of primary chalazion was equally effective in children and adults, without any significant complications, and the rate of clinical response did not appear to be dose-dependent. PMID:25386597

  18. Campylobacter fetus bacteremia with purulent pleurisy in a young adult with primary hypogammaglobulinemia.

    PubMed

    Yamagami, Keiko; Miyashita, Tomoko; Nakamura, Tomoyuki; Shirano, Michinori; Nakamura, Tadahiro; Kameda, Kazuaki; Nishijima, Masayoshi; Imanishi, Masahiro; Yang, Xi; Kanegane, Hirokazu

    2014-01-01

    A 24-year-old man presented with fever and pleural effusion predominantly containing lymphocytes. Cultures of the pleural effusion and blood revealed Campylobacter fetus, and laboratory studies showed a low serum level of immunoglobulin. The patient was diagnosed with C. fetus pleuritis, bacteremia and primary hypogammaglobulinemia, and subsequent treatment with meropenem and immunoglobulin improved his condition. Although the underlying cause of the primary hypogammaglobulinemia remains unclear, the patient's status improved under immunoglobulin replacement therapy. C. fetus pleuritis is a rare infectious disease usually observed in immunocompromised hosts. We herein describe the first report of C. fetus pleuritis in a young adult with primary hypogammaglobulinemia.

  19. Adult Antisocial Behavior and Affect Regulation among Primary Crack/Cocaine-Using Women

    ERIC Educational Resources Information Center

    Litt, Lisa Caren; Hien, Denise A.; Levin, Deborah

    2003-01-01

    The relationship between deficits in affect regulation and Adult Antisocial Behavior (ASB) in primary crack/cocaine-using women was explored in a sample of 80 inner-city women. Narrative early memories were coded for two components of affect regulation, Affect Tolerance and Affect Expression, using the Epigenetic Assessment Rating Scale (EARS;…

  20. A Meta-Analysis of Adult-Rated Child Personality and Academic Performance in Primary Education

    ERIC Educational Resources Information Center

    Poropat, Arthur E.

    2014-01-01

    Background: Personality is reliably associated with academic performance, but personality measurement in primary education can be problematic. Young children find it difficult to accurately self-rate personality, and dominant models of adult personality may be inappropriate for children. Aims: This meta-analysis was conducted to determine the…

  1. Physician Perspectives on Providing Primary Medical Care to Adults with Autism Spectrum Disorders (ASD)

    ERIC Educational Resources Information Center

    Warfield, Marji Erickson; Crossman, Morgan K.; Delahaye, Jennifer; Der Weerd, Emma; Kuhlthau, Karen A.

    2015-01-01

    We conducted in-depth case studies of 10 health care professionals who actively provide primary medical care to adults with autism spectrum disorders. The study sought to understand their experiences in providing this care, the training they had received, the training they lack and their suggestions for encouraging more physicians to provide this…

  2. Prevalence of Epilepsy in Adults with Mental Retardation and Related Disabilities in Primary Care

    ERIC Educational Resources Information Center

    McDermott, Suzanne; Moran, Robert; Platt, Tan; Wood, Hope; Isaac, Terri; Dasari, Srikanth

    2005-01-01

    Two primary care practices were used to recruit adults with and without disability. Disability groups included autism, Down syndrome, cerebral palsy, and mental retardation. The patients without disability had an epilepsy prevalence rate of 1%. The prevalence of epilepsy within the disability groups was 13% for cerebral palsy, 13.6% for Down…

  3. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Cancer.gov

    Adults with low-grade gliomas, a form of brain tumor, who received chemotherapy following completion of radiation therapy lived longer than patients who received radiation therapy alone, according to long-term follow-up results from a NIH-supported random

  4. Humor, Rapport, and Uncomfortable Moments in Interactions with Adults with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Kovarsky, Dana; Schiemer, Christine; Murray, Allison

    2011-01-01

    We examined uncomfortable moments that damaged rapport during group interactions between college students in training to become speech-language pathologists and adults with traumatic brain injury. The students worked as staff in a community-based program affiliated with a university training program that functioned as a recreational gathering…

  5. Brain Blood Flow Related to Acoustic Laryngeal Reaction Time in Adult Developmental Stutterers.

    ERIC Educational Resources Information Center

    Watson, Ben C.; And Others

    1992-01-01

    This study sought to identify patterns of impaired acoustic laryngeal reaction time as a function of response complexity parallel to metabolic measures of brain function. Findings indicated that the disruption in speech motor control for 16 adult male developmental stutterers was systematically related to metabolic asymmetry in left superior and…

  6. Neural Underpinnings of Working Memory in Adult Survivors of Childhood Brain Tumors.

    PubMed

    King, Tricia Z; Na, Sabrina; Mao, Hui

    2015-08-01

    Adult survivors of childhood brain tumors are at risk for cognitive performance deficits that require the core cognitive skill of working memory. Our goal was to examine the neural mechanisms underlying working memory performance in survivors. We studied the working memory of adult survivors of pediatric posterior fossa brain tumors using a letter n-back paradigm with varying cognitive workload (0-, 1-, 2-, and 3-back) and functional magnetic resonance imaging as well as neuropsychological measures. Survivors of childhood brain tumors evidenced lower working memory performance than demographically matched healthy controls. Whole-brain analyses revealed significantly greater blood-oxygen level dependent (BOLD) activation in the left superior / middle frontal gyri and left parietal lobe during working memory (2-back versus 0-back contrast) in survivors. Left frontal BOLD response negatively correlated with 2- and 3-back working memory performance, Auditory Consonant Trigrams (ACT), and Digit Span Backwards. In contrast, parietal lobe BOLD response negatively correlated with 0-back (vigilance task) and ACT. The results revealed that adult survivors of childhood posterior fossa brain tumors recruited additional cognitive control resources in the prefrontal lobe during increased working memory demands. This increased prefrontal activation is associated with lower working memory performance and is consistent with the allocation of latent resources theory.

  7. Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

    PubMed Central

    Zheng, Zhiwei; Zhu, Xinyi; Yin, Shufei; Wang, Baoxi; Niu, Yanan; Huang, Xin; Li, Rui; Li, Juan

    2015-01-01

    Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age. PMID:25810927

  8. Uptake and utilization of CDP-choline in primary brain cell cultures from fetal brain.

    PubMed

    Vecchini, A; Binaglia, L; Floridi, A; Palmerini, C A; Procellati, G

    1983-03-01

    The utilization of double-labeled CDP-choline by cultured brain cells has been studied. CDP-choline is demonstrated to be rapidly hydrolysed into CMP and choline phosphate. The fragments, or their hydrolysis products, penetrate into the cells and are utilized for lipid synthesis. At short times after the isotope administration a rapid labeling of phosphatidylcholine was detected, when cells were incubated with CDP-choline. The same was not seen when cells were incubated with labeled choline. From these observations it can be inferred that either CDP- choline can penetrate the cell membrane or that some mechanism involving CDP-choline and leading to phospholipid synthesis can work at the external surface of the plasma membranes.

  9. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche

    PubMed Central

    Chang, Eun Hyuk; Adorjan, Istvan; Mundim, Mayara V.; Sun, Bin; Dizon, Maria L. V.; Szele, Francis G.

    2016-01-01

    Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI. PMID:27531972

  10. [Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain].

    PubMed

    Respondek, Michalina; Buszman, Ewa

    2015-12-31

    Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

  11. Transcriptional profiling of adult neural stem-like cells from the human brain.

    PubMed

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  12. Primary pediatric mid-brain lymphoma: Report of a rare pediatric tumor in a rare location

    PubMed Central

    Benson, Rony; Mallick, Supriya; Purkait, Suvendu; Suri, Vaishali; Haresh, K P; Gupta, Subhash; Sharma, Dayanand; Julka, Pramod Kumar; Rath, Goura Kishore

    2016-01-01

    Primary central nervous system lymphoma (PCNSL) is a rare disease in pediatric age group. A thirteen-year-old male child presented with complaints of headache for six months, vomiting and diplopia for three days. Magnetic resonance imaging of the brain showed a single lesion of 1.7 cm × 1.6 cm × 1.6 cm in the mid brain and tectum. He underwent a gross total resection of the tumor. The histopathological evaluation revealed B cell high grade non Hodgkin lymphoma. The patient was treated with High dose methotrexate and cranio spinal radiation. The patient was alive without disease 12 mo after completion of treatment. This case highlights importance of keeping PCNSL as differential in brain stem lesions of pediatric patients also. Radiation and chemotherapy remains the most important treatment for such patients. PMID:28035316

  13. New neurons clear the path of astrocytic processes for their rapid migration in the adult brain.

    PubMed

    Kaneko, Naoko; Marín, Oscar; Koike, Masato; Hirota, Yuki; Uchiyama, Yasuo; Wu, Jane Y; Lu, Qiang; Tessier-Lavigne, Marc; Alvarez-Buylla, Arturo; Okano, Hideyuki; Rubenstein, John L R; Sawamoto, Kazunobu

    2010-07-29

    In the long-range neuronal migration of adult mammals, young neurons travel from the subventricular zone to the olfactory bulb, a long journey (millimeters to centimeters, depending on the species). How can these neurons migrate through the dense meshwork of neuronal and glial processes of the adult brain parenchyma? Previous studies indicate that young neurons achieve this by migrating in chains through astrocytic tunnels. Here, we report that young migrating neurons actively control the formation and maintenance of their own migration route. New neurons secrete the diffusible protein Slit1, whose receptor, Robo, is expressed on astrocytes. We show that the Slit-Robo pathway is required for morphologic and organizational changes in astrocytes that result in the formation and maintenance of the astrocytic tunnels. Through this neuron-glia interaction, the new neurons regulate the formation of the astrocytic meshwork that is needed to enable their rapid and directional migration in adult brain.

  14. Removing brakes on adult brain plasticity: from molecular to behavioral interventions

    PubMed Central

    Bavelier, D.; Levi, D.M.; Li, R.W.; Dan, Y.; Hensch, T.K.

    2010-01-01

    Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these “brakes” are structural, such as peri-neuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects. PMID:21068299

  15. Rapid and efficient gene delivery into the adult mouse brain via focal electroporation

    PubMed Central

    Nomura, Tadashi; Nishimura, Yusuke; Gotoh, Hitoshi; Ono, Katsuhiko

    2016-01-01

    In vivo gene delivery is required for studying the cellular and molecular mechanisms of various biological events. Virus-mediated gene transfer or generation of transgenic animals is widely used; however, these methods are time-consuming and expensive. Here we show an improved electroporation technique for acute gene delivery into the adult mouse brain. Using a syringe-based microelectrode, local DNA injection and the application of electric current can be performed simultaneously; this allows rapid and efficient gene transduction of adult non-neuronal cells. Combining this technique with various expression vectors that carry specific promoters resulted in targeted gene expression in astrocytic cells. Our results constitute a powerful strategy for the genetic manipulation of adult brains in a spatio-temporally controlled manner. PMID:27430903

  16. Oxytocin enhances inter-brain synchrony during social coordination in male adults.

    PubMed

    Mu, Yan; Guo, Chunyan; Han, Shihui

    2016-12-01

    Recent brain imaging research has revealed oxytocin (OT) effects on an individual's brain activity during social interaction but tells little about whether and how OT modulates the coherence of inter-brain activity related to two individuals' coordination behavior. We developed a new real-time coordination game that required two individuals of a dyad to synchronize with a partner (coordination task) or with a computer (control task) by counting in mind rhythmically. Electroencephalography (EEG) was recorded simultaneously from a dyad to examine OT effects on inter-brain synchrony of neural activity during interpersonal coordination. Experiment 1 found that dyads showed smaller interpersonal time lags of counting and greater inter-brain synchrony of alpha-band neural oscillations during the coordination (vs control) task and these effects were reliably observed in female but not male dyads. Moreover, the increased alpha-band inter-brain synchrony predicted better interpersonal behavioral synchrony across all participants. Experiment 2, using a double blind, placebo-controlled between-subjects design, revealed that intranasal OT vs placebo administration in male dyads improved interpersonal behavioral synchrony in both the coordination and control tasks but specifically enhanced alpha-band inter-brain neural oscillations during the coordination task. Our findings provide first evidence that OT enhances inter-brain synchrony in male adults to facilitate social coordination.

  17. Developmental and cell type-specific expression of thyroid hormone transporters in the mouse brain and in primary brain cells.

    PubMed

    Braun, Doreen; Kinne, Anita; Bräuer, Anja U; Sapin, Remy; Klein, Marc O; Köhrle, Josef; Wirth, Eva K; Schweizer, Ulrich

    2011-03-01

    Cellular thyroid hormone uptake and efflux are mediated by transmembrane transport proteins. One of these, monocarboxylate transporter 8 (MCT8) is mutated in Allan-Herndon-Dudley syndrome, a severe mental retardation associated with abnormal thyroid hormone constellations. Since mice deficient in Mct8 exhibit a milder neurological phenotype than patients, we hypothesized that alternative thyroid hormone transporters may compensate in murine brain cells for the lack of Mct8. Using qPCR, Western Blot, and immunocytochemistry, we investigated the expression of three different thyroid hormone transporters, i.e., Mct8 and L-type amino acid transporters Lat1 and Lat2, in mouse brain. All three thyroid hormone transporters are expressed from corticogenesis and peak around birth. Primary cultures of neurons and astrocytes express Mct8, Lat1, and Lat2. Microglia specifically expresses Mct10 and Slco4a1 in addition to high levels of Lat2 mRNA and protein. As in vivo, a brain microvascular endothelial cell line expressed Mct8 and Lat1. 158N, an oligodendroglial cell line expressed Mct8 protein, consistent with delayed myelination in MCT8-deficient patients. Functional T(3)- and T(4)-transport assays into primary astrocytes showed K(M) values of 4.2 and 3.7 μM for T(3) and T(4). Pharmacological inhibition of L-type amino acid transporters by BCH and genetic inactivation of Lat2 reduced astrocytic T(3) uptake to the same extent. BSP, a broad spectrum inhibitor, including Mct8, reduced T(3) uptake further suggesting the cooperative activity of several T(3) transporters in astrocytes.

  18. Combined Effects of Primary and Tertiary Blast on Rat Brain: Characterization of a Model of Blast-induced Mild Traumatic Brain Injury

    DTIC Science & Technology

    2014-03-01

    combat are exposed to a brain insult resulting from a combination of both a shock wave and biomechanical perturbation related to rapid acceleration...blast waves affect the brain along with diagnosing mbTBI are still a matter of considerable debate. The abovementioned caveats underline the...AD Award Number: W81XWH-11-2-0127 TITLE: Combined Effects of Primary and Tertiary Blast on Rat Brain : Characterization of a Model of

  19. Epidemiology of primary brain tumors: current concepts and review of the literature.

    PubMed Central

    Wrensch, Margaret; Minn, Yuriko; Chew, Terri; Bondy, Melissa; Berger, Mitchel S.

    2002-01-01

    The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines. PMID:12356358

  20. Regional differences in actomyosin contraction shape the primary vesicles in the embryonic chicken brain

    NASA Astrophysics Data System (ADS)

    Filas, Benjamen A.; Oltean, Alina; Majidi, Shabnam; Bayly, Philip V.; Beebe, David C.; Taber, Larry A.

    2012-12-01

    In the early embryo, the brain initially forms as a relatively straight, cylindrical epithelial tube composed of neural stem cells. The brain tube then divides into three primary vesicles (forebrain, midbrain, hindbrain), as well as a series of bulges (rhombomeres) in the hindbrain. The boundaries between these subdivisions have been well studied as regions of differential gene expression, but the morphogenetic mechanisms that generate these constrictions are not well understood. Here, we show that regional variations in actomyosin-based contractility play a major role in vesicle formation in the embryonic chicken brain. In particular, boundaries did not form in brains exposed to the nonmuscle myosin II inhibitor blebbistatin, whereas increasing contractile force using calyculin or ATP deepened boundaries considerably. Tissue staining showed that contraction likely occurs at the inner part of the wall, as F-actin and phosphorylated myosin are concentrated at the apical side. However, relatively little actin and myosin was found in rhombomere boundaries. To determine the specific physical mechanisms that drive vesicle formation, we developed a finite-element model for the brain tube. Regional apical contraction was simulated in the model, with contractile anisotropy and strength estimated from contractile protein distributions and measurements of cell shapes. The model shows that a combination of circumferential contraction in the boundary regions and relatively isotropic contraction between boundaries can generate realistic morphologies for the primary vesicles. In contrast, rhombomere formation likely involves longitudinal contraction between boundaries. Further simulations suggest that these different mechanisms are dictated by regional differences in initial morphology and the need to withstand cerebrospinal fluid pressure. This study provides a new understanding of early brain morphogenesis.

  1. Differentiating histologic malignancy of primary brain tumors: Pentavalent Technetium-99m-DMSA

    SciTech Connect

    Hirano, Tsuneo; Otake, Hidenori; Shibasaki, Takashi

    1997-01-01

    This study assessed pentavalent {sup 99m}Tc-DMSA uptake in primary brain tumors and evaluated the relationship between retention and histologic malignancy. SPECT images of the brain were obtained at 30 min and 3 hr after intravenous administration of approximately 555 MBq {sup 99m}Tc(V)-DMSA in patients with brain tumors. Sixty studies were performed in 57 patients and 63 lesions were demonstrated: 11 glioblastomas, 13 anaplastic astrocytomas (Grade 3), 11 astrocytomas (Grade 2), 18 meningiomas and 10 schwannomas. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade. Approximately 95% of both benign and malignant primary brain tumors were demonstrated by {sup 99m}Tc(V)-DMSA SPECT images. False negative was noted in three cases. The early uptake ratios were closely related to the tumor vascularity but had no statistically significant difference in the tumor vascularity but had no statistically significant difference in the tumor histology or histologic malignancy. 16 refs., 6 figs., 2 tabs.

  2. Brain-specific tropomyosins TMBr-1 and TMBr-3 have distinct patterns of expression during development and in adult brain.

    PubMed Central

    Stamm, S; Casper, D; Lees-Miller, J P; Helfman, D M

    1993-01-01

    In this study we report on the developmental and regional expression of two brain-specific isoforms of tropomyosin, TMBr-1 and TMBr-3, that are generated from the rat alpha-tropomyosin gene via the use of alternative promoters and alternative RNA splicing. Western blot analysis using an exon-specific peptide polyclonal antibody revealed that the two isoforms are differentially expressed in development with TMBr-3 appearing in the embryonic brain at 16 days of gestation, followed by the expression of TMBr-1 at 20 days after birth. TMBr-3 was detected in all brain regions examined, whereas TMBr-1 was detected predominantly in brain areas that derived from the prosencephalon. Immunocytochemical studies on mixed primary cultures made from rat embryonic midbrain indicate that expression of the brain-specific epitope is restricted to neurons. The developmental pattern and neuronal localization of these forms of tropomyosin suggest that these isoforms have a specialized role in the development and plasticity of the nervous system. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7694294

  3. Are preoperative sex-related differences of affective symptoms in primary brain tumor patients associated with postoperative histopathological grading?

    PubMed

    Richter, Andre; Jenewein, J; Krayenbühl, N; Woernle, C; Bellut, D

    2016-01-01

    Our objective was to explore the impact of the histopathological tumor type on affective symptoms before surgery among male and female patients with supratentorial primary brain tumors. A total of 44 adult patients were included in the study. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory. Additionally, clinical interviews, including the Hamilton Depression Rating Scale (HDRS), were conducted. The general function of patients was measured with the Karnofsky Performance Status scale (KPS). All measures were obtained before surgery and therefore before the final histopathological diagnosis. All self-rating questionnaires but not the HDRS, showed significantly higher scores in female patients. The functional status assessed with the KPS was lower in female patients and correlated to the somatic part of the BDI. We further found a tendency for higher HDRS scores in male patients with a WHO grade 4 tumor stage compared to female patients. This finding was supported by positive correlations between HDRS scores and WHO grade in male and negative correlations between HDRS scores and WHO grade in female patients. In conclusion the preoperative evaluation of affective symptoms with self-rating questionnaires in patients with brain tumors may be invalidated by the patient’s functional status. Depression should be explored with clinical interviews in these patients. Sex differences of affective symptoms in this patient group may also be related to the malignancy of the tumor, but further studies are needed to disentangle this relationship.

  4. A systematic review of the risk factors associated with the onset and progression of primary brain tumours.

    PubMed

    Quach, Pauline; El Sherif, Reem; Gomes, James; Krewksi, Daniel

    2016-05-17

    The overall aim of this systematic review was to identify risk factors for onset and natural progression, which were shown to increase, decrease, or have a null association with risk of primary brain tumour. For onset, the project was separated into two phases. The first phase consisted of a systematic search of existing systematic reviews and meta-analyses. Moderate to high methodological quality reviews were incorporated and summarized with relevant observational studies published since 2010, identified from a systematic search performed in phase 2. For natural progression, only the first phase was conducted. Standard systematic review methodology was utilized. Based on this review, various genetic variants, pesticide exposures, occupational farming/hairdressing, cured meat consumption and personal hair dye use appear to be associated with increased risk of onset amongst adults. The specific EGF polymorphsm 61-A allele within Caucasian populations and having a history of allergy was associated with a decreased risk. For progression, M1B-1 antigen was shown to increase the risk. High birth weight, pesticide exposure (childhood exposure, and parental occupational exposure) and maternal consumption of cured meat during pregnancy may also increase the risk of onset of childhood brain tumours. Conversely, maternal intake of pre-natal supplements (folic acid) appeared to decrease risk. Children with neurofibromatosis 2 were considered to have worse overall and relapse free survival compared to neurofibromatosis 1, as were those children who had grade III tumours compared to lesser grades.

  5. Inflammation regulates functional integration of neurons born in adult brain.

    PubMed

    Jakubs, Katherine; Bonde, Sara; Iosif, Robert E; Ekdahl, Christine T; Kokaia, Zaal; Kokaia, Merab; Lindvall, Olle

    2008-11-19

    Inflammation influences several steps of adult neurogenesis, but whether it regulates the functional integration of the new neurons is unknown. Here, we explored, using confocal microscopy and whole-cell patch-clamp recordings, whether a chronic inflammatory environment affects the morphological and electrophysiological properties of new dentate gyrus granule cells, labeled with a retroviral vector encoding green fluorescent protein. Rats were exposed to intrahippocampal injection of lipopolysaccharide, which gave rise to long-lasting microglia activation. Inflammation caused no changes in intrinsic membrane properties, location, dendritic arborization, or spine density and morphology of the new cells. Excitatory synaptic drive increased to the same extent in new and mature cells in the inflammatory environment, suggesting increased network activity in hippocampal neural circuitries of lipopolysaccharide-treated animals. In contrast, inhibitory synaptic drive was more enhanced by inflammation in the new cells. Also, larger clusters of the postsynaptic GABA(A) receptor scaffolding protein gephyrin were found on dendrites of new cells born in the inflammatory environment. We demonstrate for the first time that inflammation influences the functional integration of adult-born hippocampal neurons. Our data indicate a high degree of synaptic plasticity of the new neurons in the inflammatory environment, which enables them to respond to the increase in excitatory input with a compensatory upregulation of activity and efficacy at their afferent inhibitory synapses.

  6. Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

    ClinicalTrials.gov

    2016-09-07

    Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

  7. Neuronal Organization of Deep Brain Opsin Photoreceptors in Adult Teleosts

    PubMed Central

    Hang, Chong Yee; Kitahashi, Takashi; Parhar, Ishwar S.

    2016-01-01

    Biological impacts of light beyond vision, i.e., non-visual functions of light, signify the need to better understand light detection (or photoreception) systems in vertebrates. Photopigments, which comprise light-absorbing chromophores bound to a variety of G-protein coupled receptor opsins, are responsible for visual and non-visual photoreception. Non-visual opsin photopigments in the retina of mammals and extra-retinal tissues of non-mammals play an important role in non-image-forming functions of light, e.g., biological rhythms and seasonal reproduction. This review highlights the role of opsin photoreceptors in the deep brain, which could involve conserved neurochemical systems that control different time- and light-dependent physiologies in in non-mammalian vertebrates including teleost fish. PMID:27199680

  8. Sleep and synaptic plasticity in the developing and adult brain.

    PubMed

    Frank, Marcos G

    2015-01-01

    Sleep is hypothesized to play an integral role in brain plasticity. This has traditionally been investigated using behavioral assays. In the last 10-15 years, studies combining sleep measurements with in vitro and in vivo models of synaptic plasticity have provided exciting new insights into how sleep alters synaptic strength. In addition, new theories have been proposed that integrate older ideas about sleep function and recent discoveries in the field of synaptic plasticity. There remain, however, important challenges and unanswered questions. For example, sleep does not appear to have a single effect on synaptic strength. An unbiased review of the literature indicates that the effects of sleep vary widely depending on ontogenetic stage, the type of waking experience (or stimulation protocols) that precede sleep and the type of neuronal synapse under examination. In this review, I discuss these key findings in the context of current theories that posit different roles for sleep in synaptic plasticity.

  9. Evaluation of a Reading Comprehension Strategy Package to Improve Reading Comprehension of Adult College Students with Acquired Brain Injuries

    ERIC Educational Resources Information Center

    Griffiths, Gina G.

    2013-01-01

    Adults with mild to moderate acquired brain injury (ABI) often pursue post-secondary or professional education after their injuries in order to enter or re-enter the job market. An increasing number of these adults report problems with reading-to-learn. The problem is particularly concerning given the growing population of adult survivors of ABI.…

  10. Noninvasive imaging of brain oxygen metabolism in children with primary nocturnal enuresis during natural sleep.

    PubMed

    Yu, Bing; Huang, Mingzhu; Zhang, Xu; Ma, Hongwei; Peng, Miao; Guo, Qiyong

    2017-02-14

    A series of studies have revealed that nocturnal enuresis is closely related to hypoxia in children with primary nocturnal enuresis (PNE). However, brain oxygen metabolism of PNE children has not been investigated before. The purpose of this study was to investigate changes in whole-brain cerebral metabolic rate of oxygen (CMRO2 ), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) in children suffering from PNE. We used the newly developed T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging technique. Neurological evaluation, structural imaging, phase-contrast, and the TRUST imaging method were applied in children with PNE (n = 37) and healthy age- and sex-matched control volunteers (n = 39) during natural sleep to assess whole-brain CMRO2 , CBF, OEF, and arousal from sleep scores. Results showed that whole-brain CMRO2 and OEF values of PNE children were higher in controls, while there was no significant difference in CBF. Consequently, OEF levels of PNE children were increased to maintain oxygen supply. The elevation of OEF was positively correlated with the difficulty of arousal. Our results provide the first evidence that high oxygen consumption and high OEF values could make PNE children more susceptible to hypoxia, which may induce cumulative arousal deficits and make them more prone to nocturnal enuresis. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  11. Homeostasis of Microglia in the Adult Brain: Review of Novel Microglia Depletion Systems.

    PubMed

    Waisman, Ari; Ginhoux, Florent; Greter, Melanie; Bruttger, Julia

    2015-10-01

    Microglia are brain macrophages that emerge from early erythro-myeloid precursors in the embryonic yolk sac and migrate to the brain mesenchyme before the blood brain barrier is formed. They seed the brain, and proliferate until they have formed a grid-like distribution in the central nervous system that is maintained throughout lifespan. The mechanisms through which these embryonic-derived cells contribute to microglia homoeostasis at steady state and upon inflammation are still not entirely clear. Here we review recent studies that provided insight into the contribution of embryonically-derived microglia and of adult 'microglia-like' cells derived from monocytes during inflammation. We examine different microglia depletion models, and discuss the origin of their rapid repopulation after depletion and outline important areas of future research.

  12. Large-scale identification of coregulated enhancer networks in the adult human brain.

    PubMed

    Vermunt, Marit W; Reinink, Peter; Korving, Jeroen; de Bruijn, Ewart; Creyghton, Paul M; Basak, Onur; Geeven, Geert; Toonen, Pim W; Lansu, Nico; Meunier, Charles; van Heesch, Sebastiaan; Clevers, Hans; de Laat, Wouter; Cuppen, Edwin; Creyghton, Menno P

    2014-10-23

    Understanding the complexity of the human brain and its functional diversity remain a major challenge. Distinct anatomical regions are involved in an array of processes, including organismal homeostasis, cognitive functions, and susceptibility to neurological pathologies, many of which define our species. Distal enhancers have emerged as key regulatory elements that acquire histone modifications in a cell- and species-specific manner, thus enforcing specific gene expression programs. Here, we survey the epigenomic landscape of promoters and cis-regulatory elements in 136 regions of the adult human brain. We identify a total of 83,553 promoter-distal H3K27ac-enriched regions showing global characteristics of brain enhancers. We use coregulation of enhancer elements across many distinct regions of the brain to uncover functionally distinct networks at high resolution and link these networks to specific neuroglial functions. Furthermore, we use these data to understand the relevance of noncoding genomic variations previously linked to Parkinson's disease incidence.

  13. Phosphorylated retinoblastoma protein (p-Rb) is involved in neuronal apoptosis after traumatic brain injury in adult rats.

    PubMed

    Liu, Wei; Liu, Xiaojuan; Yang, Huilin; Zhu, Xinhui; Yi, Hong; Zhu, Xuesong; Zhang, Jie

    2013-04-01

    Phosphorylated retinoblastoma protein (p-Rb), a well identified cell cycle related protein, is involved in regulating the biological functions of various cell types including neurons. One attractive biological function of p-Rb is releasing E2F transcription factor to induce S-phase entry and cellular proliferation of mitotic cells. However, some studies point out that the role of p-Rb in post-mitotic cells such as mature neurons is unique; it may induce cellular apoptosis rather than proliferation via regulating cell cycle reactivation. Up to now, the knowledge of p-Rb function in CNS is still limited. To investigate whether p-Rb is involved in CNS injury and repair, we performed a traumatic brain injury model in adult rats. Up-regulation of p-Rb was observed in the injured brain cortex by western blot analysis and immunohistochemistry staining. Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) staining suggested that p-Rb was relevant to neuronal apoptosis after brain injury. In addition, glutamate excitotoxic model of primary cortex neurons was introduced to further investigate the role of p-Rb in neuronal apoptosis; the result implied p-Rb was associated with cell cycle activation in the apoptotic neurons. Based on our data, we suggested that p-Rb might play an important role in neuronal apoptosis after traumatic brain injury in rat; which might also provide a basis for the further study on its role in regulating cell cycle re-entry in apoptotic neurons, and might gain a novel strategy for the clinical therapy for traumatic brain injury.

  14. Frog Virus 3 dissemination in the brain of tadpoles, but not in adult Xenopus, involves blood brain barrier dysfunction

    PubMed Central

    De Jesús Andino, Francisco; Jones, Letitia; Maggirwar, Sanjay B.; Robert, Jacques

    2016-01-01

    While increasing evidence points to a key role of monocytes in amphibian host defenses, monocytes are also thought to be important in the dissemination and persistent infection caused by ranavirus. However, little is known about the fate of infected macrophages or if ranavirus exploits immune privileged organs, such as the brain, in order to establish a reservoir. The amphibian Xenopus laevis and Frog Virus 3 (FV3) were established as an experimental platform for investigating in vivo whether ranavirus could disseminate to the brain. Our data show that the FV3 infection alters the BBB integrity, possibly mediated by an inflammatory response, which leads to viral dissemination into the central nervous system in X. laevis tadpole but not adult. Furthermore, our data suggest that the macrophages play a major role in viral dissemination by carrying the virus into the neural tissues. PMID:26931458

  15. Vertex-wise examination of depressive symptom dimensions and brain volumes in older adults.

    PubMed

    McLaren, Molly E; Szymkowicz, Sarah M; O'Shea, Andrew; Woods, Adam J; Anton, Stephen D; Dotson, Vonetta M

    2017-02-28

    Differences in brain volumes have commonly been reported in older adults with both subthreshold and major depression. Few studies have examined the association between specific symptom dimensions of depression and brain volumes. This study used vertex-wise analyses to examine the association between specific symptom dimensions of depression and brain volumes in older adults with subthreshold levels of depressive symptoms. Forty-three community-dwelling adults between the ages of 55 and 81 years underwent a structural Magnetic Resonance Imaging scan and completed the Center for Epidemiologic Studies Depression Scale (CES-D). Vertex-wise analyses were conducted using Freesurfer Imaging Suite to examine the relationship between CES-D subscale scores and gray matter volumes while controlling for sex, age, and education. We found distinct associations between depressed mood, somatic symptoms, and lack of positive affect subscales with regional volumes, including primarily positive relationships in temporal regions and a negative association with the lingual gyrus. The relationship between higher depressed mood subscale scores and larger volumes in the left inferior temporal lobe withstood Monte-Carlo correction for multiple comparisons. Results from this preliminary study highlight the importance of examining depression on a symptom dimension level and identify brain regions that may be important in larger studies of depression.

  16. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

    PubMed

    Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M

    2017-04-03

    Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

  17. Network Structure among Brain Systems in Adult ADHD is Uniquely Modified by Stimulant Administration.

    PubMed

    Cary, Robert P; Ray, Siddharth; Grayson, David S; Painter, Julia; Carpenter, Samuel; Maron, Leeza; Sporns, Olaf; Stevens, Alexander A; Nigg, Joel T; Fair, Damien A

    2016-07-14

    Current research in connectomics highlights that self-organized functional networks or "communities" of cortical areas can be detected in the adult brain. This perspective may provide clues to mechanisms of treatment response in psychiatric conditions. Here we examine functional brain community topology based on resting-state fMRI in adult Attention-Deficit/Hyperactivity Disorder (ADHD; n = 22) and controls (n = 31). We sought to evaluate ADHD patterns in adulthood and their modification by short term stimulants administration. Participants with ADHD were scanned one or two weeks apart, once with medication and once without; comparison participants were scanned at one time-point. Functional connectivity was estimated from these scans and community detection applied to determine cortical network topology. Measures of change in connectivity profile were calculated via a graph measure, termed the Node Dissociation Index (NDI). Compared to controls, several cortical networks had atypical connectivity in adults with ADHD when withholding stimulants, as measured by NDI. In most networks stimulants significantly reduced, but did not eliminate, differences in the distribution of connections between key brain systems relative to the control sample. These findings provide an enriched model of connectivity in ADHD and demonstrate how stimulants may exert functional effects by altering connectivity profiles in the brain.

  18. Localization and regulation of PML bodies in the adult mouse brain.

    PubMed

    Hall, Małgorzata H; Magalska, Adriana; Malinowska, Monika; Ruszczycki, Błażej; Czaban, Iwona; Patel, Satyam; Ambrożek-Latecka, Magdalena; Zołocińska, Ewa; Broszkiewicz, Hanna; Parobczak, Kamil; Nair, Rajeevkumar R; Rylski, Marcin; Pawlak, Robert; Bramham, Clive R; Wilczyński, Grzegorz M

    2016-06-01

    PML is a tumor suppressor protein involved in the pathogenesis of promyelocytic leukemia. In non-neuronal cells, PML is a principal component of characteristic nuclear bodies. In the brain, PML has been implicated in the control of embryonic neurogenesis, and in certain physiological and pathological phenomena in the adult brain. Yet, the cellular and subcellular localization of the PML protein in the brain, including its presence in the nuclear bodies, has not been investigated comprehensively. Because the formation of PML bodies appears to be a key aspect in the function of the PML protein, we investigated the presence of these structures and their anatomical distribution, throughout the adult mouse brain. We found that PML is broadly expressed across the gray matter, with the highest levels in the cerebral and cerebellar cortices. In the cerebral cortex PML is present exclusively in neurons, in which it forms well-defined nuclear inclusions containing SUMO-1, SUMO 2/3, but not Daxx. At the ultrastructural level, the appearance of neuronal PML bodies differs from the classic one, i.e., the solitary structure with more or less distinctive capsule. Rather, neuronal PML bodies have the form of small PML protein aggregates located in the close vicinity of chromatin threads. The number, size, and signal intensity of neuronal PML bodies are dynamically influenced by immobilization stress and seizures. Our study indicates that PML bodies are broadly involved in activity-dependent nuclear phenomena in adult neurons.

  19. The functional organisation of glia in the adult brain of Drosophila and other insects

    PubMed Central

    Edwards, Tara N.; Meinertzhagen, Ian A.

    2010-01-01

    This review annotates and categorises the glia of adult Drosophila and other model insects and describes the developmental origins of these in the Drosophila optic lobe. The functions of glia in the adult vary depending upon their sub-type and location in the brain. The task of annotating glia is essentially complete only for the glia of the fly's lamina, which comprise: two types of surface glia - the pseudocartridge and fenestrated glia; two types of cortex glia - the distal and proximal satellite glia; and two types of neuropile glia - the epithelial and marginal glia. We advocate that the term subretinal glia, as used to refer to both pseudocartridge and fenestrated glia, be abandoned. Other neuropiles contain similar glial subtypes, but other than the antennal lobes these have not been described in detail. Surface glia form the blood brain barrier, regulating the flow of substances into and out of the nervous system, both for the brain as a whole and the optic neuropiles in particular. Cortex glia provide a second level of barrier, wrapping axon fascicles and isolating neuronal cell bodies both from neighbouring brain regions and from their underlying neuropiles. Neuropile glia can be generated in the adult and a subtype, ensheathing glia, are responsible for cleaning up cellular debris during Wallerian degeneration. Both the neuropile ensheathing and astrocyte-like glia may be involved in clearing neurotransmitters from the extracellular space, thus modifying the levels of histamine, glutamate and possibly dopamine at the synapse to ultimately affect behaviour. PMID:20109517

  20. Urolithiasis in an Adult with Primary Obstructive Megaureter: A Case Report

    PubMed Central

    Al-Marhoon, Mohammed S.; Venkiteswaran, Khrishna P.; Shareef, Omar W.

    2013-01-01

    This is a rare case of adult primary obstructive megaureter complicated by combined uric acid-oxalate lithiasis of the ureter and renal stones. A 24-year-old male patient presented with frank hematuria on exercise of 4 years duration. The patient had an open surgery in the form of excision of stenotic segment of ureter and left ureteric re-implantation with removal of ureteric and renal stones. Congenital megaureter is a diagnosis that urologists and radiologists need to consider in the setting of isolated distal ureteral dilation, as the diagnosis of adult megaureter may require more involved surgical measures to prevent recurrence of adverse symptoms. PMID:24044065

  1. Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats

    PubMed Central

    Sántha, Petra; Veszelka, Szilvia; Hoyk, Zsófia; Mészáros, Mária; Walter, Fruzsina R.; Tóth, Andrea E.; Kiss, Lóránd; Kincses, András; Oláh, Zita; Seprényi, György; Rákhely, Gábor; Dér, András; Pákáski, Magdolna; Kálmán, János; Kittel, Ágnes; Deli, Mária A.

    2016-01-01

    Stress is well-known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognized in the development of neurodegenerative disorders, such as Alzheimer's disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3, and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occluding, and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, 1-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5, and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and

  2. Nuclear receptors of the honey bee: annotation and expression in the adult brain.

    PubMed

    Velarde, Rodrigo A; Robinson, Gene E; Fahrbach, Susan E

    2006-10-01

    The Drosophila genome encodes 18 canonical nuclear receptors. All of the Drosophila nuclear receptors are here shown to be present in the genome of the honey bee (Apis mellifera). Given that the time since divergence of the Drosophila and Apis lineages is measured in hundreds of millions of years, the identification of matched orthologous nuclear receptors in the two genomes reveals the fundamental set of nuclear receptors required to 'make' an endopterygote insect. The single novelty is the presence in the A. mellifera genome of a third insect gene similar to vertebrate photoreceptor-specific nuclear receptor (PNR). Phylogenetic analysis indicates that this novel gene, which we have named AmPNR-like, is a new member of the NR2 subfamily not found in the Drosophila or human genomes. This gene is expressed in the developing compound eye of the honey bee. Like their vertebrate counterparts, arthropod nuclear receptors play key roles in embryonic and postembryonic development. Studies in Drosophila have focused primarily on the role of these transcription factors in embryogenesis and metamorphosis. Examination of an expressed sequence tag library developed from the adult bee brain and analysis of transcript expression in brain using in situ hybridization and quantitative RT-PCR revealed that several members of the nuclear receptor family (AmSVP, AmUSP, AmERR, AmHr46, AmFtz-F1, and AmHnf-4) are expressed in the brain of the adult bee. Further analysis of the expression of AmUSP and AmSVP in the mushroom bodies, the major insect brain centre for learning and memory, revealed changes in transcript abundance and, in the case of AmUSP, changes in transcript localization, during the development of foraging behaviour in the adult. Study of the honey bee therefore provides a model for understanding nuclear receptor function in the adult brain.

  3. Increased juvenile predation is not associated with evolved differences in adult brain size in Trinidadian killifish (Rivulus hartii).

    PubMed

    Beston, Shannon M; Broyles, Whitnee; Walsh, Matthew R

    2017-02-01

    Vertebrates exhibit extensive variation in brain size. The long-standing assumption is that this variation is driven by ecologically mediated selection. Recent work has shown that an increase in predator-induced mortality is associated with evolved increases and decreases in brain size. Thus, the manner in which predators induce shifts in brain size remains unclear. Increased predation early in life is a key driver of many adult traits, including life-history and behavioral traits. Such results foreshadow a connection between age-specific mortality and selection on adult brain size. Trinidadian killifish, Rivulus hartii, are found in sites with and without guppies, Poecilia reticulata. The densities of Rivulus drop dramatically in sites with guppies because guppies prey upon juvenile Rivulus. Previous work has shown that guppy predation is associated with the evolution of adult life-history traits in Rivulus. In this study, we compared second-generation laboratory-born Rivulus from sites with and without guppies for differences in brain size and associated trade-offs between brain size and other components of fitness. Despite the large amount of existing research on the importance of early-life events on the evolution of adult traits, and the role of predation on both behavior and brain size, we did not find an association between the presence of guppies and evolutionary shifts in Rivulus brain size. Such results argue that increased rates of juvenile mortality may not alter selection on adult brain size.

  4. Primary brain tumor patients' supportive care needs and multidisciplinary rehabilitation, community and psychosocial support services: awareness, referral and utilization.

    PubMed

    Langbecker, Danette; Yates, Patsy

    2016-03-01

    Primary brain tumors are associated with significant physical, cognitive and psychosocial changes. Although treatment guidelines recommend offering multidisciplinary rehabilitation and support services to address patients' residual deficits, the extent to which patients access such services is unclear. This study aimed to assess patients' supportive care needs early after diagnosis, and quantify service awareness, referral and utilization. A population-based sample of 40 adults recently diagnosed with primary brain tumors was recruited through the Queensland Cancer Registry, representing 18.9 % of the eligible population of 203 patients. Patients or carer proxies completed surveys of supportive care needs at baseline (approximately 3 months after diagnosis) and 3 months later. Descriptive statistics summarized needs and service utilization, and linear regression identified predictors of service use. Unmet supportive care needs were highest at baseline for all domains, and highest for the physical and psychological needs domains at each time point. At follow-up, participants reported awareness of, referral to, and use of 32 informational, support, health professional or practical services. All or almost all participants were aware of at least one informational (100 %), health professional (100 %), support (97 %) or practical service (94 %). Participants were most commonly aware of speech therapists (97 %), physiotherapists (94 %) and diagnostic information from the internet (88 %). Clinician referrals were most commonly made to physiotherapists (53 %), speech therapists (50 %) and diagnostic information booklets (44 %), and accordingly, participants most commonly used physiotherapists (56 %), diagnostic information booklets (47 %), diagnostic information from the internet (47 %), and speech therapists (43 %). Comparatively low referral to and use of psychosocial services may limit patients' abilities to cope with their condition and the changes they

  5. Immunohistochemical and ultrastructural changes in the brain in probable adult glycogenosis type IV: adult polyglucosan body disease.

    PubMed

    Wierzba-Bobrowicz, Teresa; Lewandowska, Eliza; Stepień, Tomasz; Modzelewska, Joanna

    2008-01-01

    Glycogenosis type IV is caused by a deficiency of glycogen branching enzyme (alpha-1,4 glucan 6-transglucosylase). Adult polyglucosan body disease (APBD) may represent a neuropathological hallmark of the adult form of this storage disease of the central nervous system. We analysed a case of a 45-year-old unconscious woman who died three days after admission to the hospital. Neuropathological examination revealed massive accumulation of polyglucosan bodies (PBs) in the cortex and white matter of the whole brain. PBs were located in the processes of neurons, astrocytes and microglial cells. The storage material in the cytoplasm of neurons and glial cells was visible as fine granules. Ultrastructurally, PBs consisted of non-membrane-bound deposits of branched and densely packed filaments, measuring about 7-10 nm in diameter, typical of polyglucosan bodies. APBD patients develop upper and lower neuron disease and dementia, probably secondary to the disruption of neuron and astrocyte functions.

  6. An Update of the Mayo Clinic Cohort of Patients With Adult Primary Central Nervous System Vasculitis

    PubMed Central

    Salvarani, Carlo; Brown, Robert D.; Christianson, Teresa; Miller, Dylan V.; Giannini, Caterina; Huston, John; Hunder, Gene G.

    2015-01-01

    Abstract Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with

  7. Spatiotemporal expression patterns of Pax6 in the brain of embryonic, newborn, and adult mice.

    PubMed

    Duan, Deyi; Fu, Yuhong; Paxinos, George; Watson, Charles

    2013-03-01

    The transcription factor Pax6 has been reported to specify neural progenitor cell fates during development and maintain neuronal commitments in the adult. The spatiotemporal patterns of Pax6 expression were examined in sagittal and horizontal sections of the embryonic, postnatal, and adult brains using immunohistochemistry and double immunolabeling. The proportion of Pax6-immunopositive cells in various parts of the adult brain was estimated using the isotropic fractionator methodology. It was shown that at embryonic day 11 (E11) Pax6 was robustly expressed in the proliferative neuroepithelia of the ventricular zone in the forebrain and hindbrain, and in the floor and the mesencephalic reticular formation (mRt) in the midbrain. At E12, its expression emerged in the nucleus of the lateral lemniscus in the rhombencephalon and disappeared from the floor of the midbrain. As neurodevelopment proceeds, the expression pattern of Pax6 changes from the mitotic germinal zone in the ventricular zone to become extensively distributed in cell groups in the forebrain and hindbrain, and the expression persisted in the mRt. The majority of Pax6-positive cell groups were maintained until adult life, but the intensity of Pax6 expression became much weaker. Pax6 expression was maintained in the mitotic subventricular zone in the adult brain, but not in the germinal region dentate gyrus in the adult hippocampus. There was no obvious colocalization of Pax6 and NeuN during embryonic development, suggesting Pax6 is found primarily in developing progenitor cells. In the adult brain, however, Pax6 maintains neuronal features of some subtypes of neurons, as indicated by 97.1% of Pax6-positive cells co-expressing NeuN in the cerebellum, 40.7% in the olfactory bulb, 38.3% in the cerebrum, and 73.9% in the remaining brain except the hippocampus. Differentiated tyrosine hydroxylase (TH) neurons were observed in the floor of the E11 midbrain where Pax6 was also expressed, but no obvious

  8. [Autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in adults: report of three cases].

    PubMed

    Santos, Oscar Mauricio; Muñoz Ortiz, Edison; Pérez, Camilo; Restrepo, Juan Carlos

    2012-04-01

    Overlap syndromes are cases of liver diseases that share clinical, serological, histological and radiological criteria of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). No definitions have been fully established and therefore there is no solid evidence on the diagnosis and treatment. This article presents the cases of three adult patients with overlapping features of AIH and PSC. Orthotopic liver transplantation was considered the best therapeutic alternative due to advanced disease progression in one patient, while medical treatment was provided in the remaining two patients.

  9. A Rare Case of Primary Anterior Mediastinal Yolk Sac Tumor in an Elderly Adult Male

    PubMed Central

    Nakhla, Sammy G.; Sundararajan, Srinath

    2016-01-01

    Mediastinal germ cell tumors are extragonadal germ cell tumors (EGGCTs) commonly seen in children and young adults. They are more common in men. Clinically they are classified as teratomas, seminomas, and nonseminomatous germ cell tumors. Primary mediastinal yolk sac neoplasm is an extremely rare tumor. We present here a very rare case of primary yolk sac tumor of the anterior mediastinum in a 73-year-old male. Mediastinal germ cell tumors have a worse prognosis than gonadal germ cell tumors. Chemotherapy followed by adjuvant surgery improves overall response in EGGCTs. However, comorbidities can render treatment with chemotherapy and surgery challenging in elderly patients. PMID:27144043

  10. Initial manifestation of primary hyperoxaluria type I in adults-- recognition, diagnosis, and management.

    PubMed Central

    Kuiper, J J

    1996-01-01

    Primary hyperoxaluria type I may initially manifest as urolithiasis, renal insufficiency, or symptoms of systemic oxalosis. This hereditary disorder was fatal until effective therapies evolved during the past two decades. Difficulty in recognizing and diagnosing this disorder in adults is illustrated in a report of a patient eventually restored to good health by high-flux dialysis and combined renal and hepatic transplantation. I explore the molecular processes of the genetic defect and discuss clinical indicators of primary hyperoxaluria type I, manifestations of oxalosis, the pathogenesis of chronic oxalate nephropathy, and the diagnosis and management of this disease. Images Figure 2. Figure 3. Figure 4. PMID:8779202

  11. Adult Brain Serotonin Deficiency Causes Hyperactivity, Circadian Disruption, and Elimination of Siestas

    PubMed Central

    Whitney, Meredith Sorenson; Shemery, Ashley M.; Yaw, Alexandra M.; Donovan, Lauren J.; Glass, J. David

    2016-01-01

    Serotonin (5-HT) is a crucial neuromodulator linked to many psychiatric disorders. However, after more than 60 years of study, its role in behavior remains poorly understood, in part because of a lack of methods to target 5-HT synthesis specifically in the adult brain. Here, we have developed a genetic approach that reproducibly achieves near-complete elimination of 5-HT synthesis from the adult ascending 5-HT system by stereotaxic injection of an adeno-associated virus expressing Cre recombinase (AAV-Cre) into the midbrain/pons of mice carrying a loxP-conditional tryptophan hydroxylase 2 (Tph2) allele. We investigated the behavioral effects of deficient brain 5-HT synthesis and discovered a unique composite phenotype. Surprisingly, adult 5-HT deficiency did not affect anxiety-like behavior, but resulted in a robust hyperactivity phenotype in novel and home cage environments. Moreover, loss of 5-HT led to an altered pattern of circadian behavior characterized by an advance in the onset and a delay in the offset of daily activity, thus revealing a requirement for adult 5-HT in the control of daily activity patterns. Notably, after normalizing for hyperactivity, we found that the normal prolonged break in nocturnal activity (siesta), a period of rapid eye movement (REM) and non-REM sleep, was absent in all animals in which 5-HT deficiency was verified. Our findings identify adult 5-HT as a requirement for siestas, implicate adult 5-HT in sleep–wake homeostasis, and highlight the importance of our adult-specific 5-HT-synthesis-targeting approach in understanding 5-HT's role in controlling behavior. SIGNIFICANCE STATEMENT Serotonin (5-HT) is a crucial neuromodulator, yet its role in behavior remains poorly understood, in part because of a lack of methods to target specifically adult brain 5-HT synthesis. We developed an approach that reproducibly achieves near-complete elimination of 5-HT synthesis from the adult ascending 5-HT system. Using this technique, we

  12. Primary Blast Traumatic Brain Injury in the Rat: Relating Diffusion Tensor Imaging and Behavior

    PubMed Central

    Budde, Matthew D.; Shah, Alok; McCrea, Michael; Cullinan, William E.; Pintar, Frank A.; Stemper, Brian D.

    2013-01-01

    The incidence of traumatic brain injury (TBI) among military personnel is at its highest point in U.S. history. Experimental animal models of blast have provided a wealth of insight into blast injury. The mechanisms of neurotrauma caused by blast, however, are still under debate. Specifically, it is unclear whether the blast shockwave in the absence of head motion is sufficient to induce brain trauma. In this study, the consequences of blast injury were investigated in a rat model of primary blast TBI. Animals were exposed to blast shockwaves with peak reflected overpressures of either 100 or 450 kPa (39 and 110 kPa incident pressure, respectively) and subsequently underwent a battery of behavioral tests. Diffusion tensor imaging (DTI), a promising method to detect blast injury in humans, was performed on fixed brains to detect and visualize the spatial dependence of blast injury. Blast TBI caused significant deficits in memory function as evidenced by the Morris Water Maze, but limited emotional deficits as evidenced by the Open Field Test and Elevated Plus Maze. Fractional anisotropy, a metric derived from DTI, revealed significant brain abnormalities in blast-exposed animals. A significant relationship between memory deficits and brain microstructure was evident in the hippocampus, consistent with its role in memory function. The results provide fundamental insight into the neurological consequences of blast TBI, including the evolution of injury during the sub-acute phase and the spatially dependent pattern of injury. The relationship between memory dysfunction and microstructural brain abnormalities may provide insight into the persistent cognitive difficulties experienced by soldiers exposed to blast neurotrauma and may be important to guide therapeutic and rehabilitative efforts. PMID:24133481

  13. The brain and the braincase: a spatial analysis on the midsagittal profile in adult humans.

    PubMed

    Bruner, Emiliano; Amano, Hideki; de la Cuétara, José Manuel; Ogihara, Naomichi

    2015-09-01

    The spatial relationships between brain and braincase represent a major topic in surgery and evolutionary neuroanatomy. In paleoneurology, neurocranial landmarks are often used as references for brain areas. In this study, we analyze the variation and covariation of midsagittal brain and skull coordinates in a sample of adult modern humans in order to demonstrate spatial associations between hard and soft tissues. The correlation between parietal lobe size and parietal bone size is very low, and there is a marked individual variation. The distances between lobes and bones are partially influenced by the dimensions of the parietal lobes. The main pattern of morphological variability among individuals, associated with the size of the precuneus, apparently does not influence the position of the neurocranial sutures. Therefore, variations in precuneal size modify the distance between the paracentral lobule and bregma, and between the parietal lobe and lambda. Hence, the relative position of the cranial and cerebral landmarks can change as a function of the parietal dimensions. The slight correlation and covariation among these elements suggests a limited degree of spatial integration between soft and hard tissues. Therefore, although the brain influences the cranial size and shape during morphogenesis, the specific position of the cerebral components is sensitive to multiple effects and local factors, without a strict correspondence with the bone landmarks. This absence of correspondent change between brain and skull boundaries suggests caution when making inferences about the brain areas from the position of the cranial sutures. The fact that spatial relationships between cranial and brain areas may vary according to brain proportions must be considered in paleoneurology, when brain anatomy is inferred from cranial evidence.

  14. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q

    SciTech Connect

    Wirtz, M.K.; Samples, J.R.; Kramer, P.L.

    1997-02-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-on-set primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. 57 refs., 3 figs., 3 tabs.

  15. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q.

    PubMed Central

    Wirtz, M K; Samples, J R; Kramer, P L; Rust, K; Topinka, J R; Yount, J; Koler, R D; Acott, T S

    1997-01-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-onset primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. PMID:9012402

  16. Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain

    PubMed Central

    Sun, Gerald J.; Zhou, Yi; Stadel, Ryan P.; Moss, Jonathan; Yong, Jing Hui A.; Ito, Shiori; Kawasaki, Nicholas K.; Phan, Alexander T.; Oh, Justin H.; Modak, Nikhil; Reed, Randall R.; Toni, Nicolas; Song, Hongjun; Ming, Guo-li

    2015-01-01

    In a classic model of mammalian brain formation, precursors of principal glutamatergic neurons migrate radially along radial glia fibers whereas GABAergic interneuron precursors migrate tangentially. These migration modes have significant implications for brain function. Here we used clonal lineage tracing of active radial glia-like neural stem cells in the adult mouse dentate gyrus and made the surprising discovery that proliferating neuronal precursors of glutamatergic granule neurons exhibit significant tangential migration along blood vessels, followed by limited radial migration. Genetic birthdating and morphological and molecular analyses pinpointed the neuroblast stage as the main developmental window when tangential migration occurs. We also developed a partial “whole-mount” dentate gyrus preparation and observed a dense plexus of capillaries, with which only neuroblasts, among the entire population of progenitors, are directly associated. Together, these results provide insight into neuronal migration in the adult mammalian nervous system. PMID:26170290

  17. Neuronal sources of hedgehog modulate neurogenesis in the adult planarian brain.

    PubMed

    Currie, Ko W; Molinaro, Alyssa M; Pearson, Bret J

    2016-11-19

    The asexual freshwater planarian is a constitutive adult, whose central nervous system (CNS) is in a state of constant homeostatic neurogenesis. However, very little is known about the extrinsic signals that act on planarian stem cells to modulate rates of neurogenesis. We have identified two planarian homeobox transcription factors, Smed-nkx2.1 and Smed-arx, which are required for the maintenance of cholinergic, GABAergic, and octopaminergic neurons in the planarian CNS. These very same neurons also produce the planarian hedgehog ligand (Smed-hh), which appears to communicate with brain-adjacent stem cells to promote normal levels of neurogenesis. Planarian stem cells nearby the brain express core hh signal transduction genes, and consistent hh signaling levels are required to maintain normal production of neural progenitor cells and new mature cholinergic neurons, revealing an important mitogenic role for the planarian hh signaling molecule in the adult CNS.

  18. Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain.

    PubMed

    Barbosa, Joana S; Sanchez-Gonzalez, Rosario; Di Giaimo, Rossella; Baumgart, Emily Violette; Theis, Fabian J; Götz, Magdalena; Ninkovic, Jovica

    2015-05-15

    Adult neural stem cells are the source for restoring injured brain tissue. We used repetitive imaging to follow single stem cells in the intact and injured adult zebrafish telencephalon in vivo and found that neurons are generated by both direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. We observed an imbalance of direct conversion consuming the stem cells and asymmetric and symmetric self-renewing divisions, leading to depletion of stem cells over time. After brain injury, neuronal progenitors are recruited to the injury site. These progenitors are generated by symmetric divisions that deplete the pool of stem cells, a mode of neurogenesis absent in the intact telencephalon. Our analysis revealed changes in the behavior of stem cells underlying generation of additional neurons during regeneration.

  19. Brain volume and cognitive function in adult survivors of childhood acute lymphoblastic leukemia.

    PubMed

    Edelmann, Michelle N; Krull, Kevin R

    2013-10-01

    The survival rate for childhood acute lymphoblastic leukemia (ALL) is greater than 80%. However, many of these survivors develop long-term chronic health conditions, with a relatively common late effect being neurocognitive dysfunction. Although neurocognitive impairments have decreased in frequency and severity as treatment has evolved, there is a subset of survivors in the current treatment era that are especially vulnerable to the neurotoxic effects of ALL and its treatment. Additionally, little is known about long-term brain development as survivors mature into adulthood. A recent study by Zeller et al. compared neurocognitive function and brain volume in 130 adult survivors of childhood ALL to 130 healthy adults matched on age and sex. They identified the caudate as particularly sensitive to the neurotoxic effects of chemotherapy. We discuss the implications and limitations of this study, including how their findings support the concept of individual vulnerability to ALL and its treatment.

  20. [Screening for attention deficit hyperactivity disorder in adult patients in primary care].

    PubMed

    Aragonès, Enric; Cañisá, Anna; Caballero, Antònia; Piñol-Moreso, Josep Lluís

    2013-05-01

    AIMS. To estimate the proportion of adult patients in primary care with a positive screening test for attention deficit hyper-activity disorder (ADHD) and to analyse their characteristics. PATIENTS AND METHODS. A cross-sectional descriptive study was performed in nine primary care clinics in the province of Tarragona. The sample consisted of 432 consecutive patients in primary care who visited for any reason, with ages ranging from 18 to 55 years. Screening for ADHD was carried out by means of the Adult ADHD Self-Report Scale (ASRS). Data about functional impact (Sheehan Disability Inventory) were obtained and a review of the patient records provided data concerning psychiatric comorbidity and the consumption of psychopharmaceuticals. RESULTS. The percentage of positive results in the screening tests was 19.9% (95% CI = 16.4-23.9%). Taking into account the sensitivity and specificity of the ASRS, the 'real' prevalence was estimated to be 12.5% (95% CI = 8.2-16.8%). None of these patients were diagnosed or treated for ADHD. Positive screening tests are associated with occupational, social and familial dysfunction, and greater perceived stress. There is also a higher level of comorbidity with affective disorders and substance abuse, as well as greater use of psychopharmaceuticals. CONCLUSIONS. Screening for ADHD in adult patients in primary care gives rise to a notably high proportion of positive screening test results, which suggests that there could be a significant prevalence of patients with ADHD. These data contrast with the absence of this diagnosis in the patient records. Further research is needed to determine the usefulness of the diagnosis of ADHD and the possible role that must be played by primary care.

  1. Associations among executive function, cardiorespiratory fitness, and brain network properties in older adults

    PubMed Central

    Kawagoe, Toshikazu; Onoda, Keiichi; Yamaguchi, Shuhei

    2017-01-01

    Aging is associated with deterioration in a number of cognitive functions. Previous reports have demonstrated the beneficial effect of physical fitness on cognitive function, especially executive function (EF). The graph theoretical approach models the brain as a complex network represented graphically as nodes and edges. We analyzed several measures of EF, an index of physical fitness, and resting-state functional magnetic resonance imaging data from healthy older volunteers to elucidate the associations among EF, cardiorespiratory fitness, and brain network properties. The topological neural properties were significantly related to the level of EF and/or physical fitness. Global efficiency, which represents how well the whole brain is integrated, was positively related, whereas local efficiency, which represents how well the brain is functionally segregated, was negatively related, to the level of EF and fitness. The associations among EF, physical fitness and topological resting-state functional network property appear related to compensation and dedifferentiation in older age. A mediation analysis showed that high-fit older adults gain higher global efficiency of the brain at the expense of lower local efficiency. The results suggest that physical fitness may be beneficial in maintaining EF in healthy aging by enhancing the efficiency of the global brain network. PMID:28054664

  2. Applications of hybrid diffuse optics for clinical management of adults after brain injury

    NASA Astrophysics Data System (ADS)

    Kim, Meeri Nam

    Information about cerebral blood flow (CBF) is valuable for clinical management of patients after severe brain injury. Unfortunately, current modalities for monitoring brain are often limited by hurdles that include high cost, low throughput, exposure to ionizing radiation, probe invasiveness, and increased risk to critically ill patients when transportation out of their room or unit is required. A further limitation of current technologies is an inability to provide continuous bedside measurements that are often desirable for unstable patients. Here we explore the clinical utility of diffuse correlation spectroscopy (DCS) as an alternative approach for bedside CBF monitoring. DCS uses the rapid intensity fluctuations of near-infrared light to derive a continuous measure of changes in blood flow without ionizing radiation or invasive probing. Concurrently, we employ another optical technique, called diffuse optical spectroscopy (DOS), to derive changes in cerebral oxyhemoglobin ( HbO2) and deoxyhemoglobin (Hb) concentrations. Our clinical studies integrate DCS with DOS into a single hybrid instrument that simultaneously monitors CBF and HbO2/Hb in the injured adult brain. The first parts of this dissertation present the motivations for monitoring blood flow in injured brain, as well as the theory underlying diffuse optics technology. The next section elaborates on details of the hybrid instrumentation. The final chapters describe four human subject studies carried out with these methods. Each of these studies investigates an aspect of the potential of the hybrid monitor in clinical applications involving adult brain. The studies include: (1) validation of DCS-measured CBF against xenon-enhanced computed tomography in brain-injured adults; (2) a study of the effects of age and gender on posture-change-induced CBF variation in healthy subjects; (3) a study of the efficacy of DCS/DOS for monitoring neurocritical care patients during various medical interventions such

  3. Biomaterial microenvironments to support the generation of new neurons in the adult brain.

    PubMed

    Conway, Anthony; Schaffer, David V

    2014-05-01

    Neural stem cells (NSC) in two regions of the adult mammalian brain--the subventricular zone (SVZ) and hippocampus--continuously generate new neurons, enabled by a complex repertoire of factors that precisely regulate the activation, proliferation, differentiation, and integration of the newborn cells. A growing number of studies also report low-level neurogenesis in regions of the adult brain outside these established neurogenic niches--potentially via NSC recruitment or activation of local, quiescent NSCs--under perturbations such as ischemia, cell death, or viral gene delivery of proneural growth factors. We have explored whether implantation of engineered biomaterials can stimulate neurogenesis in normally quiescent regions of the brain. Specifically, recombinant versions of factors found within the NSC microenvironment, Sonic hedgehog, and ephrin-B2 were conjugated to long polymers, thereby creating highly bioactive, multivalent ligands that begin to emulate components of the neurogenic niche. In this engineered biomaterial microenvironment, new neuron formation was observed in normally non-neurogenic regions of the brain, the striatum, and the cortex, and combining these multivalent biomaterials with stromal cell-derived factor-1α increased neuronal commitment of newly divided cells seven- to eightfold in these regions. Additionally, the decreased hippocampal neurogenesis of geriatric rodents was partially rescued toward levels of young animals. We thus demonstrate for the first time de novo neurogenesis in both the cortex and striatum of adult rodents stimulated solely by delivery of synthetic biomaterial forms of proteins naturally found within adult neurogenic niches, offering the potential to replace neurons lost in neurodegenerative disease or injury as an alternative to cell implantation.

  4. Central artery stiffness, baroreflex sensitivity, and brain white matter neuronal fiber integrity in older adults.

    PubMed

    Tarumi, Takashi; de Jong, Daan L K; Zhu, David C; Tseng, Benjamin Y; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B; Kerwin, Diana R; Lu, Hanzhang; Munro Cullum, C; Zhang, Rong

    2015-04-15

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65 ± 6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults.

  5. Oatp-associated uptake and toxicity of microcystins in primary murine whole brain cells

    SciTech Connect

    Feurstein, D.; Holst, K.; Fischer, A.; Dietrich, D.R.

    2009-01-15

    Microcystins (MCs) are naturally occurring cyclic heptapeptides that exhibit hepato-, nephro- and possibly neurotoxic effects in mammals. Organic anion transporting polypeptides (rodent Oatp/human OATP) appear to be specifically required for active uptake of MCs into hepatocytes and kidney epithelial cells. Based on symptoms of neurotoxicity in MC-intoxicated patients and the presence of Oatp/OATP at the blood-brain-barrier (BBB) and blood-cerebrospinal-fluid-barrier (BCFB) it is hypothesized that MCs can be transported across the BBB/BCFB in an Oatp/OATP-dependent manner and can induce toxicity in brain cells via inhibition of protein phosphatase (PP). To test these hypotheses, the presence of murine Oatp (mOatp) in primary murine whole brain cells (mWBC) was investigated at the mRNA and protein level. MC transport was tested by exposing mWBCs to three different MC-congeners (MC-LR, -LW, -LF) with/without co-incubation with the OATP/Oatp-substrates taurocholate (TC) and bromosulfophthalein (BSP). Uptake of MCs and cytotoxicity was demonstrated via MC-Western blot analysis, immunocytochemistry, cell viability and PP inhibition assays. All MC congeners bound covalently and inhibited mWBC PP. MC-LF was the most cytotoxic congener followed by -LW and -LR. The lowest toxin concentration significantly reducing mWBC viability after 48 h exposure was 400 nM (MC-LF). Uptake of MCs into mWBCs was inhibited via co-incubation with excess TC (50 and 500 {mu}M) and BSP (50 {mu}M). MC-Western blot analysis demonstrated a concentration-dependent accumulation of MCs. In conclusion, the in vitro data support the assumed MC-congener-dependent uptake in a mOatp-associated manner and cytotoxicity of MCs in primary murine whole brain cells.

  6. Radiotherapy and death from cerebrovascular disease in patients with primary brain tumors.

    PubMed

    Aizer, Ayal A; Du, Rose; Wen, Patrick Y; Arvold, Nils D

    2015-09-01

    Radiotherapy is often used in the management of primary brain tumors, but late cerebrovascular risks remain incompletely characterized. We examined the relationship between radiotherapy and the risk of death from cerebrovascular disease (CVD) in this population. We used the Surveillance, Epidemiology, and End Results Program to identify 19,565 patients of any age diagnosed with a primary brain tumor between 1983-2002. Multivariable competing risks analysis and an interaction model were used to determine whether receipt of radiotherapy was associated with an increased risk of CVD-specific death, adjusting for tumor proximity to central arterial circulations of the brain. The median follow up in surviving patients was 12.75 years. Baseline characteristics were similar in patients who did and did not receive radiotherapy. Ten-year CVD-specific mortality in patients with tumors near central arterial circulations who did and did not receive radiotherapy were 0.64 % (95 % CI 0.42-0.93 %) versus 0.16 % (95 % CI 0.055-0.40 %), p = 0.01. After adjustment for demographic, tumor-related, and treatment-related covariates, patients with tumors near central arterial circulations were significantly more likely to experience CVD-specific mortality after radiotherapy (HR 2.81; 95 % CI 1.25-6.31; p = 0.01); no association was observed among patients with more distant tumors (HR 0.77; 95 % CI 0.50-1.16; p = 0.21). The interaction model showed that tumor location was a key predictor of the risk of radiotherapy-associated, CVD-specific mortality (p-interaction = 0.004). Patients receiving radiotherapy for tumors near but not distant from the central vasculature of the brain are at increased risk for death secondary to CVD, which should be considered when counseling patients.

  7. Hippocampal Brain Volume Is Associated with Faster Facial Emotion Identification in Older Adults: Preliminary Results

    PubMed Central

    Szymkowicz, Sarah M.; Persson, Jonas; Lin, Tian; Fischer, Håkan; Ebner, Natalie C.

    2016-01-01

    Quick correct identification of facial emotions is highly relevant for successful social interactions. Research suggests that older, compared to young, adults experience increased difficulty with face and emotion processing skills. While functional neuroimaging studies suggest age differences in neural processing of faces and emotions, evidence about age-associated structural brain changes and their involvement in face and emotion processing is scarce. Using structural magnetic resonance imaging (MRI), this study investigated the extent to which volumes of frontal and temporal brain structures were related to reaction time in accurate identification of facial emotions in 30 young and 30 older adults. Volumetric segmentation was performed using FreeSurfer and gray matter volumes from frontal and temporal regions were extracted. Analysis of covariances (ANCOVAs) models with response time (RT) as the dependent variable and age group and regional volume, and their interaction, as independent variables were conducted, controlling for total intracranial volume (ICV). Results indicated that, in older adults, larger hippocampal volumes were associated with faster correct facial emotion identification. These preliminary observations suggest that greater volume in brain regions associated with face and emotion processing contributes to improved facial emotion identification performance in aging. PMID:27610082

  8. Differential regulation of laminin b1 transgene expression in the neonatal and adult mouse brain.

    PubMed

    Sharif, K A; Baker, H; Gudas, L J

    2004-01-01

    Laminins are the major glycoproteins present in basement membrane, a type of extracellular matrix. We showed that the LAMB1 gene, which encodes the laminin beta1 subunit, is transcriptionally activated by retinoic acid in embryonic stem cells. However, little information is available concerning LAMB1 developmental regulation and spatial expression in the adult mouse brain. In this study we used transgenic mice expressing different lengths of LAMB1 promoter driving beta-galactosidase to investigate developmental and adult transcriptional regulation in the regions of the brain in which the laminin beta1 protein is expressed. CNS expression was not observed in transgenic mice carrying a 1.4LAMB1betagal construct. Mice carrying a 2.5LAMB1betagal construct expressed the LAMB1 transgene, as assayed by X-gal staining, only in the molecular layer of the neonatal cerebellum. In contrast, a 3.9LAMB1betagal transgene showed broad regional expression in the adult mouse brain, including the hippocampus, entorhinal cortex, colliculi, striatum, and substantia nigra. Similar expression patterns were observed for the endogenous laminin beta1 protein and for the 3.9LAMB1betagal transgene, analyzed with an antibody against the beta-galactosidase protein. The 3.9LAMB1betagal transgene expression in the hippocampal tri-synaptic circuit suggests a role for the LAMB1 gene in learning and memory.

  9. Netrin-5 is highly expressed in neurogenic regions of the adult brain.

    PubMed

    Yamagishi, Satoru; Yamada, Kohei; Sawada, Masato; Nakano, Suguru; Mori, Norio; Sawamoto, Kazunobu; Sato, Kohji

    2015-01-01

    Mammalian netrin family proteins are involved in targeting of axons, neuronal migration, and angiogenesis and act as repulsive and attractive guidance molecules. Netrin-5 is a new member of the netrin family with homology to the C345C domain of netrin-1. Unlike other netrin proteins, murine netrin-5 consists of two EGF motifs of the laminin V domain (LE) and the C345C domain, but lacks the N-terminal laminin VI domain and one of the three LE motifs. We generated a specific antibody against netrin-5 to investigate its expression pattern in the rodent adult brain. Strong netrin-5 expression was observed in the olfactory bulb (OB), rostral migrate stream (RMS), the subventricular zone (SVZ), and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, where neurogenesis occurs in the adult brain. In the SVZ and RMS, netrin-5 expression was observed in Mash1-positive transit-amplifying cells and in Doublecortin (DCX)-positive neuroblasts, but not in GFAP-positive astrocytes. In the OB, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons. In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells. These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain.

  10. Eating disorder psychopathology, brain structure, neuropsychological correlates and risk mechanisms in very preterm young adults.

    PubMed

    Micali, Nadia; Kothari, Radha; Nam, Kie Woo; Gioroukou, Elena; Walshe, Muriel; Allin, Matthew; Rifkin, Larry; Murray, Robin M; Nosarti, Chiara

    2015-03-01

    This study investigates the prevalence of eating disorder (ED) psychopathology, neuropsychological function, structural brain correlates and risk mechanisms in a prospective cohort of very preterm (VPT) young adults. We assessed ED psychopathology and neuropsychological correlates in 143 cohort individuals born at <33 weeks of gestation. Structural brain correlates and risk factors at birth, in childhood and adolescence, were investigated using prospectively collected data throughout childhood/adolescence. VPT-born individuals had high levels of ED psychopathology at age 21 years. Executive function did not correlate with ED symptomatology. VPT adults presenting with ED psychopathology had smaller grey matter volume at age 14/15 years in the left posterior cerebellum and smaller white matter volume in the fusiform gyrus bilaterally, compared with VPT adults with no ED psychopathology. Caesarean delivery predicted engaging in compensatory behaviours, and severe eating difficulty at age 14 years predicted ED symptomatology in young adulthood. VPT individuals are at risk for ED symptomatology, with evidence of associated structural alterations in posterior brain regions. Further prospective studies are needed to clarify the pathways that lead from perinatal/obstetric complications to ED and relevant neurobiological mechanisms. © 2015 The Authors. European Eating Disorders Review published by John Wiley &Sons, Ltd.

  11. Neuronal Organization of the Brain in the Adult Amphioxus (Branchiostoma lanceolatum): A Study With Acetylated Tubulin Immunohistochemistry.

    PubMed

    Castro, Antonio; Becerra, Manuela; Manso, María Jesús; Anadón, Ramón

    2015-10-15

    Amphioxus (Cephalochordata) belongs to the most basal extant chordates, and knowledge of their brain organization appears to be key to deciphering the early stages of evolution of vertebrate brains. Most comprehensive studies of the organization of the central nervous system of adult amphioxus have investigated the spinal cord. Some brain populations have been characterized via neurochemistry and electron microscopy, and the overall cytoarchitecture of the brain was studied by Ekhart et al. (2003; J. Comp. Neurol. 466:319-330) with general staining methods and retrograde transport from the spinal cord. Here, the cytoarchitecture of the brain of adult amphioxus Branchiostoma lanceolatum was reinvestigated by using acetylated tubulin immunohistochemistry, which specifically stains neurons and fibers, in combination with some ancillary methods. This method allowed reproducible staining and mapping of types of neuron, mostly in brain regions caudal to the entrance level of nerve 2, and its comparison with spinal cord populations. The brain populations studied and discussed in detail were the Retzius bipolar cells, lamellate cells, Joseph cells, various types of translumenal cells, somatic motoneurons, Rohde nucleus cells, small ventral multipolar neurons, and Edinger cells. These observations expand our knowledge of the distribution of cell types and provide additional data on the number of cells and the axonal tracts and commissural regions of the adult amphioxus brain. The results of this comprehensive study provide a framework for comparison of complex adult populations with the early brain neuronal populations revealed in developmental studies of the amphioxus.

  12. Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults.

    PubMed

    DeLario, Melissa R; Sheehan, Andrea M; Ataya, Ramona; Bertuch, Alison A; Vega, Carlos; Webb, C Renee; Lopez-Terrada, Dolores; Venkateswaran, Lakshmi

    2012-05-01

    Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients.

  13. Neurocognitive and Family Functioning and Quality of Life Among Young Adult Survivors of Childhood Brain Tumors

    PubMed Central

    Hocking, Matthew C.; Hobbie, Wendy L.; Deatrick, Janet A.; Lucas, Matthew S.; Szabo, Margo M.; Volpe, Ellen M.; Barakat, Lamia P.

    2012-01-01

    Many childhood brain tumor survivors experience significant neurocognitive late effects across multiple domains that negatively affect quality of life. A theoretical model of survivorship suggests that family functioning and survivor neurocognitive functioning interact to affect survivor and family outcomes. This paper reviews the types of neurocognitive late effects experienced by survivors of pediatric brain tumors. Quantitative and qualitative data from three case reports of young adult survivors and their mothers are analyzed according to the theoretical model and presented in this paper to illustrate the importance of key factors presented in the model. The influence of age at brain tumor diagnosis, family functioning, and family adaptation to illness on survivor quality of life and family outcomes are highlighted. Future directions for research and clinical care for this vulnerable group of survivors are discussed. PMID:21722062

  14. Spatial distribution and cellular composition of adult brain proliferative zones in the teleost, Gymnotus omarorum

    PubMed Central

    Olivera-Pasilio, Valentina; Peterson, Daniel A.; Castelló, María E.

    2014-01-01

    Proliferation of stem/progenitor cells during development provides for the generation of mature cell types in the CNS. While adult brain proliferation is highly restricted in the mammals, it is widespread in teleosts. The extent of adult neural proliferation in the weakly electric fish, Gymnotus omarorum has not yet been described. To address this, we used double thymidine analog pulse-chase labeling of proliferating cells to identify brain proliferation zones, characterize their cellular composition, and analyze the fate of newborn cells in adult G. omarorum. Short thymidine analog chase periods revealed the ubiquitous distribution of adult brain proliferation, similar to other teleosts, particularly Apteronotus leptorhynchus. Proliferating cells were abundant at the ventricular-subventricular lining of the ventricular-cisternal system, adjacent to the telencephalic subpallium, the diencephalic preoptic region and hypothalamus, and the mesencephalic tectum opticum and torus semicircularis. Extraventricular proliferation zones, located distant from the ventricular-cisternal system surface, were found in all divisions of the rombencephalic cerebellum. We also report a new adult proliferation zone at the caudal-lateral border of the electrosensory lateral line lobe. All proliferation zones showed a heterogeneous cellular composition. The use of short (24 h) and long (30 day) chase periods revealed abundant fast cycling cells (potentially intermediate amplifiers), sparse slow cycling (potentially stem) cells, cells that appear to have entered a quiescent state, and cells that might correspond to migrating newborn neural cells. Their abundance and migration distance differed among proliferation zones: greater numbers and longer range and/or pace of migrating cells were associated with subpallial and cerebellar proliferation zones. PMID:25249943

  15. IGF-I redirects doublecortin-positive cell migration in the normal adult rat brain.

    PubMed

    Maucksch, C; McGregor, A L; Yang, M; Gordon, R J; Yang, M; Connor, B

    2013-06-25

    The migration of subventricular zone (SVZ)-derived neural precursor cells through the rostral migratory stream (RMS) to the olfactory bulb is tightly regulated by local micro-environmental cues. Insulin-like Growth Factor-I (IGF-I) can stimulate the migration of several neuronal cell types and acts as a 'departure' factor in the avian SVZ. To establish whether IGF-I can also act as a migratory factor for adult neuronal precursor cells in vivo, in addition to its well established role in precursor cell proliferation and differentiation, we used AAV2-mediated gene transfer to produce ectopic expression of IGF-I in the normal adult rat striatum. We then assessed whether the expression of IGF-I would recruit SVZ-derived neuronal precursor cells from the RMS into the striatum. Ectopic expression of IGF-I in the normal adult rat brain significantly increased the number of doublecortin (Dcx)-positive cells and the extent of their migration into the striatum 4 and 8 weeks after AAV2-IGF-I injection but did not promote neuronal differentiation. In vitro migration assays confirmed that IGF-I is an inducer of migration and directs SVZ-derived adult neuronal precursor cell migration by both chemotaxis and chemokinesis. These results demonstrate that overexpression of IGF-I in the normal adult rat brain can override the normal cues directing precursor cell migration along the RMS and can redirect precursor cell migration into a non-neurogenic region. Enhanced expression of IGF-I following brain injury may therefore act as a diffusible factor mediating precursor cell migration to areas of neuronal cell damage.

  16. Brain-expressed imprinted genes and adult behaviour: the example of Nesp and Grb10.

    PubMed

    Dent, Claire L; Isles, Anthony R

    2014-02-01

    Imprinted genes are defined by their parent-of-origin-specific monoallelic expression. Although the epigenetic mechanisms regulating imprinted gene expression have been widely studied, their functional importance is still unclear. Imprinted genes are associated with a number of physiologies, including placental function and foetal growth, energy homeostasis, and brain and behaviour. This review focuses on genomic imprinting in the brain and on two imprinted genes in particular, Nesp and paternal Grb10, which, when manipulated in animals, have been shown to influence adult behaviour. These two genes are of particular interest as they are expressed in discrete and overlapping neural regions, recognised as key "imprinting hot spots" in the brain. Furthermore, these two genes do not appear to influence placental function and/or maternal provisioning of offspring. Consequently, by understanding their behavioural function we may begin to shed light on the evolutionary significance of imprinted genes in the adult brain, independent of the recognised role in maternal care. In addition, we discuss the potential future directions of research investigating the function of these two genes and the behavioural role of imprinted genes more generally.

  17. Arginine vasotocin neuronal development and its projection in the adult brain of the medaka.

    PubMed

    Kagawa, Nao; Honda, Akira; Zenno, Akiko; Omoto, Ryosuke; Imanaka, Saya; Takehana, Yusuke; Naruse, Kiyoshi

    2016-02-02

    The neurohypophysial peptide arginine vasotocin (AVT) and its mammalian ortholog arginine vasopressin function in a wide range of physiological and behavioral events. Here, we generated a new line of transgenic medaka (Oryzias latipes), which allowed us to monitor AVT neurons by enhanced green fluorescent protein (EGFP) and demonstrate AVT neuronal development in the embryo and the projection of AVT neurons in the adult brain of avt-egfp transgenic medaka. The onset of AVT expression manifested at 2 days postfertilization (dpf) as a pair of signals in the telencephalon of the brain. The telencephalic AVT neurons migrated and converged on the preoptic area (POA) by 4dpf. At the same stage, another onset of AVT expression manifested in the central optic tectum (OT), and they migrated to the ventral part of the hypothalamus (VH) by 6dpf. In the adult brain, the AVT somata with EGFP signals existed in the gigantocellular POA (gPOA), magnocellular POA (mPOA), and parvocellular POA (pPOA) and in the VH. Whereas the major projection of AVT fibers was found from the pPOA and VH to the posterior pituitary, it was also found that AVT neurons in the three POAs send their fibers into wide regions of the brain such as the telencephalon, mesencephalon and diencephalon. This study suggests that the avt-egfp transgenic medaka is a useful model to explore AVT neuronal development and function.

  18. Midsagittal brain variation and MRI shape analysis of the precuneus in adult individuals.

    PubMed

    Bruner, Emiliano; Rangel de Lázaro, Gizéh; de la Cuétara, José Manuel; Martín-Loeches, Manuel; Colom, Roberto; Jacobs, Heidi I L

    2014-04-01

    Recent analyses indicate that the precuneus is one of the main centres of integration in terms of functional and structural processes within the human brain. This neuroanatomical element is formed by different subregions, involved in visuo-spatial integration, memory and self-awareness. We analysed the midsagittal brain shape in a sample of adult humans (n = 90) to evidence the patterns of variability and geometrical organization of this area. Interestingly, the major brain covariance pattern within adult humans is strictly associated with the relative proportions of the precuneus. Its morphology displays a marked individual variation, both in terms of geometry (mostly in its longitudinal dimensions) and anatomy (patterns of convolution). No patent differences are evident between males and females, and the allometric effect of size is minimal. However, in terms of morphology, the precuneus does not represent an individual module, being influenced by different neighbouring structures. Taking into consideration the apparent involvement of the precuneus in higher-order human brain functions and evolution, its wide variation further stresses the important role of these deep parietal areas in modern neuroanatomical organization.

  19. Extremely low frequency electromagnetic fields (EMF) and brain cancer in adults and children: review and comment.

    PubMed Central

    Gurney, J. G.; van Wijngaarden, E.

    1999-01-01

    Epidemiologic and experimental research on the potential carcinogenic effects of extremely low frequency electromagnetic fields (EMF) has now been conducted for over two decades. Cancer epidemiology studies in relation to EMF have focused primarily on brain cancer and leukemia, both from residential sources of exposure in children and adults and from occupational exposure in adult men. Because genotoxic effects of EMF have not been shown, most recent laboratory research has attempted to show biological effects that could be related to cancer promotion. In this report, we briefly review residential and occupational EMF studies on brain cancer. We also provide a general review of experimental studies as they relate both to the biological plausibility of an EMF-brain cancer relation and to the insufficiency of such research to help guide exposure assessment in epidemiologic studies. We conclude from our review that no recent research, either epidemiologic or experimental, has emerged to provide reasonable support for a causal role of EMF on brain cancer. PMID:11550314

  20. The distinction between juvenile and adult-onset primary open-angle glaucoma

    SciTech Connect

    Wiggs, J.L.; Haines, J.L.; Damji, K.F.

    1996-01-01

    Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light of the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.

  1. Genus Distichopora (Cnidaria, Hydrozoa): from primary cyclosystem to adult pore organisation

    NASA Astrophysics Data System (ADS)

    Puce, S.; Pica, D.; Brun, F.; Mancini, L.; Bavestrello, G.

    2012-09-01

    This investigation provides the first detailed description of the growth stages of two Distichopora species showing the formation of a primary cyclosystem and explaining the growth process leading from primary cyclosystem to adult pore organisation. The earliest observed stage is an oval calcareous disc from which, at a later stage, a primary cyclosystem raises up. Then, the addition of new gastropores and dactylopores leads to the pore rows typical of the genus. Using X-ray computed microtomography, we are able to visualise the dense canal network that permeates the coenosteum and envelops the gastropores and the dactylopores in all the observed growth stages. In both species, the thin canals surrounding the gastropores are responsible for the formation of the new gastropores that originate between the old ones, while the thin canals placed on the external side of the dactylopore rows produce the new dactylopores.

  2. Effects of heavy ion to the primary culture of mouse brain cells

    NASA Technical Reports Server (NTRS)

    Nojima, Kumie; Nakadai, Taeko; Kohno, Yukio; Vazquez, Marcelo E.; Yasuda, Nakahiro; Nagaoka, Shunji

    2004-01-01

    To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions by HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05 Gy up to 2.0 Gy. The subsequent biological effects were evaluated by an induction of apoptosis and neuron survival focusing on the dependencies of the animal strains, SCID, B6, B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to particle radiation as evaluated by 10% apoptotic criterion. The LET dependency was compared with using SCID and B6 cells exposing to different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency was observed in the high LET (55-200 keV/micrometers) and low dose (<0.5 Gy) regions. The survivability profiles of the neurons were different in the mouse strains and ions. In this report, a result of memory and learning function to adult mice after whole-body and brain local irradiation at carbon ion and iron ion.

  3. Brain white matter structure and COMT gene are linked to second-language learning in adults.

    PubMed

    Mamiya, Ping C; Richards, Todd L; Coe, Bradley P; Eichler, Evan E; Kuhl, Patricia K

    2016-06-28

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype.

  4. Brain white matter structure and COMT gene are linked to second-language learning in adults

    PubMed Central

    Mamiya, Ping C.; Richards, Todd L.; Coe, Bradley P.; Eichler, Evan E.; Kuhl, Patricia K.

    2016-01-01

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects’ grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype. PMID:27298360

  5. Sustained increase in adult neurogenesis in the rat hippocampal dentate gyrus after transient brain ischemia.

    PubMed

    Wang, Congmin; Zhang, Mingguang; Sun, Chifei; Cai, Yuqun; You, Yan; Huang, Liping; Liu, Fang

    2011-01-13

    It is known that the number of newly generated neurons is increased in the young and adult rodent subventricular zone (SVZ) and dentate gyrus (DG) after transient brain ischemia. However, it remains unclear whether increase in neurogenesis in the adult DG induced by ischemic stroke is transient or sustained. We here reported that from 2 weeks to 6 months after transient middle cerebral artery occlusion (MCAO), there were more doublecortin positive (DCX+) cells in the ipsilateral compared to the sham-control and contralateral DG of the adult rat. After the S-phase marker 5-bromo-2'-deoxyuridine (BrdU) was injected 2 days after MCAO to label newly generated cells, a large number of BrdU-labeled neuroblasts differentiated into mature granular neurons. These BrdU-labeled neurons survived for at least 6 months. When BrdU was injected 6 weeks after injury, there were still more newly generated neuroblasts differentiated into mature neurons in the ipsilateral DG. Altogether, our data indicate that transient brain ischemia initiates a prolonged increase in neurogenesis and promotes the normal development of the newly generated neurons in the adult DG.

  6. Abundant Production of Brain-Derived Neurotrophic Factor by Adult Visceral Epithelia

    PubMed Central

    Lommatzsch, Marek; Braun, Armin; Mannsfeldt, Anne; Botchkarev, Vladimir A.; Botchkareva, Natalia V.; Paus, Ralf; Fischer, Axel; Lewin, Gary R.; Renz, Harald

    1999-01-01

    Brain-derived neurotrophic factor (BDNF) plays a crucial role for the survival of visceral sensory neurons during development. However, the physiological sources and the function of BDNF in the adult viscera are poorly described. We have investigated the cellular sources and the potential role of BDNF in adult murine viscera. We found markedly different amounts of BDNF protein in different organs. Surprisingly, BDNF levels in the urinary bladder, lung, and colon were higher than those found in the brain or skin. In situ hybridization experiments revealed that BDNF mRNA was made by visceral epithelial cells, several types of smooth muscle, and neurons of the myenteric plexus. Epithelia that expressed BDNF lacked both the high- and low-affinity receptors for BDNF, trkB and p75NTR. In contrast, both receptors were present on neurons of the peripheral nervous system. Studies with BDNF−/−mice demonstrated that epithelial and smooth muscle cells developed normally in the absence of BDNF. These data provide evidence that visceral epithelia are a major source, but not a target, of BDNF in the adult viscera. The abundance of BDNF protein in certain internal organs suggests that this neurotrophin may regulate the function of adult visceral sensory and motor neurons. PMID:10514401

  7. PET imaging of neurogenic activity in the adult brain: Toward in vivo imaging of human neurogenesis.

    PubMed

    Tamura, Yasuhisa; Kataoka, Yosky

    2017-01-01

    Neural stem cells are present in 2 neurogenic regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), and continue to generate new neurons throughout life. Adult hippocampal neurogenesis is linked to a variety of psychiatric disorders such as depression and anxiety, and to the therapeutic effects of antidepressants, as well as learning and memory. In vivo imaging for hippocampal neurogenic activity may be used to diagnose psychiatric disorders and evaluate the therapeutic efficacy of antidepressants. However, these imaging techniques remain to be established until now. Recently, we established a quantitative positron emission tomography (PET) imaging technique for neurogenic activity in the adult brain with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT) and probenecid, a drug transporter inhibitor in blood-brain barrier. Moreover, we showed that this PET imaging technique can monitor alterations in neurogenic activity in the hippocampus of adult rats with depression and following treatment with an antidepressant. This PET imaging method may assist in diagnosing depression and in monitoring the therapeutic efficacy of antidepressants. In this commentary, we discuss the possibility of in vivo PET imaging for neurogenic activity in adult non-human primates and humans.

  8. Prion diseases and adult neurogenesis: how do prions counteract the brain's endogenous repair machinery?

    PubMed

    Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

    2014-01-01

    Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process, however it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies.

  9. Prion diseases and adult neurogenesis: How do prions counteract the brain's endogenous repair machinery?

    PubMed Central

    Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

    2014-01-01

    Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process; however, it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies. PMID:24831876

  10. Brain activation during interference resolution in young and older adults: an fMRI study.

    PubMed

    Zhu, David C; Zacks, Rose T; Slade, Jill M

    2010-04-01

    A rapid event-related fMRI arrow flanker task was used to study aging-associated decline in executive functions related to interference resolution. Older adults had more difficulty responding to Incongruent cues during the flanker task compared to the young adults; the response time difference between the Incongruent and Congruent conditions in the older group was over 50% longer compared to the young adults. In the frontal regions, differential activation ("Incongruent-Congruent" conditions) was observed in the inferior and middle frontal gyri in within-group analyses for both groups. However, the cluster was smaller in the older group and the centroid location was shifted by 19.7 mm. The left superior and medial frontal gyri also appeared to be specifically recruited by older adults during interference resolution, partially driven by errors. The frontal right lateralization found in the young adults was maintained in the older adults during successful trials. Interestingly, bilateral activation was observed when error trials were combined with successful trials highlighting the influence of brain activation associated with errors during cognitive processing. In conclusion, aging appears to result in modified functional regions that may contribute to reduced interference resolution. In addition, error processing should be considered and accounted for when studying age-related cognitive changes as errors may confound the interpretation of task specific age-related activation differences.

  11. Language of the aging brain: Event-related potential studies of comprehension in older adults

    PubMed Central

    Wlotko, Edward W.; Lee, Chia-Lin; Federmeier, Kara D.

    2010-01-01

    Normal aging brings increased richness in knowledge and experience as well as declines in cognitive abilities. Event-related brain potential (ERP) studies of language comprehension corroborate findings showing that the structure and organization of semantic knowledge remains relatively stable with age. Highlighting the advantages of the temporal and functional specificity of ERPs, this survey focuses on age-related changes in higher-level processes required for the successful comprehension of meaning representations built from multiple words. Older adults rely on different neural pathways and cognitive processes during normal, everyday comprehension, including a shift away from the predictive use of sentential context, differential recruitment of neural resources, and reduced engagement of controlled processing. Within age groups, however, there are important individual differences that, for example, differentiate a subset of older adults whose processing patterns more closely resemble that of young adults, providing a window into cognitive skills and abilities that may mediate or moderate age-related declines. PMID:20823949

  12. Radiosurgical treatment of previously irradiated primary brain tumors and brain metastiasis: Final report of Radiation Therapy Oncology Group (RTOG) protocol 90-05

    SciTech Connect

    Shaw, E.; Dinapoli, R.; Kline, R.

    1995-12-31

    The objective of this program was to determine the maximum single radiosurgical dose that can be given to patients (pts) with recurrent primary brain tumors (1{degree}BT) or brain metastasis (BM) who had received prior fractionated external beam radiation therapy (FEBRT). The treated tumor had to be {ge}40 mm in maximum diameter. Dose was prescribed to the periphery of the tumor (without margin) based on diameter, to the 50% to 90% isodose line.

  13. EEG to Primary Rewards: Predictive Utility and Malleability by Brain Stimulation

    PubMed Central

    Prause, Nicole; Siegle, Greg J.; Deblieck, Choi; Wu, Allan; Iacoboni, Marco

    2016-01-01

    Theta burst stimulation (TBS) is thought to affect reward processing mechanisms, which may increase and decrease reward sensitivity. To test the ability of TBS to modulate response to strong primary rewards, participants hypersensitive to primary rewards were recruited. Twenty men and women with at least two opposite-sex, sexual partners in the last year received two forms of TBS. Stimulations were randomized to avoid order effects and separated by 2 hours to reduce carryover. The two TBS forms have been demonstrated to inhibit (continuous) or excite (intermittent) the left dorsolateral prefrontal cortex using different pulse patterns, which links to brain areas associated with reward conditioning. After each TBS, participants completed tasks assessing their reward responsiveness to monetary and sexual rewards. Electroencephalography (EEG) was recorded. They also reported their number of orgasms in the weekend following stimulation. This signal was malleable by TBS, where excitatory TBS resulted in lower EEG alpha relative to inhibitory TBS to primary rewards. EEG responses to sexual rewards in the lab (following both forms of TBS) predicted the number of orgasms experienced over the forthcoming weekend. TBS may be useful in modifying hypersensitivity or hyposensitivity to primary rewards that predict sexual behaviors. Since TBS altered the anticipation of a sexual reward, TBS may offer a novel treatment for sexual desire problems. PMID:27902711

  14. The whole-brain N-acetylaspartate correlates with education in normal adults.

    PubMed

    Glodzik, Lidia; Wu, William E; Babb, James S; Achtnichts, Lutz; Amann, Michael; Sollberger, Marc; Monsch, Andreas U; Gass, Achim; Gonen, Oded

    2012-10-30

    N-acetylaspartate (NAA) is an index of neuronal integrity. We hypothesized that in healthy subjects its whole brain concentration (WBNAA) may be related to formal educational attainment, a common proxy for cognitive reserve. To test this hypothesis, 97 middle aged to elderly subjects (51-89 years old, 38% women) underwent brain magnetic resonance imaging and non-localizing proton spectroscopy. Their WBNAA was obtained by dividing their whole-head NAA amount by the brain volume. Intracranial volume and fractional brain volume, a metric of brain atrophy, were also determined. Each subject's educational attainment was the sum of his/her years of formal education. In the entire group higher education was associated with larger intracranial volume. The relationship between WBNAA and education was observed only in younger (51-70 years old) participants. In this group, education explained 21% of the variance in WBNAA. More WBNAA was related to more years of formal education in adults and younger elders. Prospective studies can determine whether this relationship reflects a true advantage from years of training versus innate characteristics predisposing a subject to higher achievements later in life. We propose that late-life WBNAA may be more affected by other factors acting at midlife and later.

  15. Differential Distribution of Major Brain Gangliosides in the Adult Mouse Central Nervous System

    PubMed Central

    Vajn, Katarina; Viljetić, Barbara; Degmečić, Ivan Večeslav; Schnaar, Ronald L.; Heffer, Marija

    2013-01-01

    Gangliosides - sialic acid-bearing glycolipids - are major cell surface determinants on neurons and axons. The same four closely related structures, GM1, GD1a, GD1b and GT1b, comprise the majority of total brain gangliosides in mammals and birds. Gangliosides regulate the activities of proteins in the membranes in which they reside, and also act as cell-cell recognition receptors. Understanding the functions of major brain gangliosides requires knowledge of their tissue distribution, which has been accomplished in the past using biochemical and immunohistochemical methods. Armed with new knowledge about the stability and accessibility of gangliosides in tissues and new IgG-class specific monoclonal antibodies, we investigated the detailed tissue distribution of gangliosides in the adult mouse brain. Gangliosides GD1b and GT1b are widely expressed in gray and white matter. In contrast, GM1 is predominately found in white matter and GD1a is specifically expressed in certain brain nuclei/tracts. These findings are considered in relationship to the hypothesis that gangliosides GD1a and GT1b act as receptors for an important axon-myelin recognition protein, myelin-associated glycoprotein (MAG). Mediating axon-myelin interactions is but one potential function of the major brain gangliosides, and more detailed knowledge of their distribution may help direct future functional studies. PMID:24098718

  16. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults.

    PubMed

    Chapman, Sandra B; Aslan, Sina; Spence, Jeffrey S; Keebler, Molly W; DeFina, Laura F; Didehbani, Nyaz; Perez, Alison M; Lu, Hanzhang; D'Esposito, Mark

    2016-01-01

    Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56-75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health.

  17. Resting state fMRI entropy probes complexity of brain activity in adults with ADHD.

    PubMed

    Sokunbi, Moses O; Fung, Wilson; Sawlani, Vijay; Choppin, Sabine; Linden, David E J; Thome, Johannes

    2013-12-30

    In patients with attention deficit hyperactivity disorder (ADHD), quantitative neuroimaging techniques have revealed abnormalities in various brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Nonlinear signal processing techniques such as sample entropy have been used to probe the regularity of brain magnetoencephalography signals in patients with ADHD. In the present study, we extend this technique to analyse the complex output patterns of the 4 dimensional resting state functional magnetic resonance imaging signals in adult patients with ADHD. After adjusting for the effect of age, we found whole brain entropy differences (P=0.002) between groups and negative correlation (r=-0.45) between symptom scores and mean whole brain entropy values, indicating lower complexity in patients. In the regional analysis, patients showed reduced entropy in frontal and occipital regions bilaterally and a significant negative correlation between the symptom scores and the entropy maps at a family-wise error corrected cluster level of P<0.05 (P=0.001, initial threshold). Our findings support the hypothesis of abnormal frontal-striatal-cerebellar circuits in ADHD and the suggestion that sample entropy is a useful tool in revealing abnormalities in the brain dynamics of patients with psychiatric disorders.

  18. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults

    PubMed Central

    Chapman, Sandra B.; Aslan, Sina; Spence, Jeffrey S.; Keebler, Molly W.; DeFina, Laura F.; Didehbani, Nyaz; Perez, Alison M.; Lu, Hanzhang; D'Esposito, Mark

    2016-01-01

    Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56–75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health. PMID:27462210

  19. Arthroscopic Treatment for Primary Septic Arthritis of the Hip in Adults

    PubMed Central

    2016-01-01

    Purpose. Primary septic arthritis is a rare differential diagnosis of acute hip pain in adults. Inspired by the success of all-arthroscopic treatment in pediatric patients, we developed a diagnostic and surgical pathway for our adult patients. Methods. Seven patients, average age 44 ± 13.7 years with acute hip pain since 4.4 ± 2.9 days in the average, were included. Septic arthritis was confirmed by joint aspiration and dissemination was excluded by MRI and standard radiographs. Surgical treatment consisted of immediate arthroscopic lavage using 4 portals for debridement, high-volume irrigation, partial synovectomy, and drainage. Results. Patients were treated in hospital for 12.4 ± 3.1 days (range 7–16 days). WBC and CRP returned to physiological levels. During the mean follow-up of 26.4 ± 19.4 months (range 13–66 months) no patient showed recurrence of infection. The 5 patients with an unimpaired hip joint prior to the infection had a mean modified Harris Hip Score of 94 ± 5.6 points (range 91–100) at final follow-up. Conclusions. Arthroscopic therapy using a minimally invasive approach with low perioperative morbidity for the treatment of primary septic arthritis of the adult hip is able to restore normal hip function in acute cases without dissemination of the infection. Level of Evidence. IV. PMID:27800188

  20. A Case of Primary Central Nervous System Lymphoma Located at Brain Stem in a Child

    PubMed Central

    Kim, Jinho

    2016-01-01

    Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's lymphoma that is confined to the brain, eyes, and/or leptomeninges without evidence of a systemic primary tumor. Although the tumor can affect all age groups, it is rare in childhood; thus, its incidence and prognosis in children have not been well defined and the best treatment strategy remains unclear. A nine-year old presented at our department with complaints of diplopia, dizziness, dysarthria, and right side hemiparesis. Magnetic resonance image suggested a diffuse brain stem glioma with infiltration into the right cerebellar peduncle. The patient was surgically treated by craniotomy and frameless stereotactic-guided biopsy, and unexpectedly, the histopathology of the mass was consistent with diffuse large B cell lymphoma, and immunohistochemical staining revealed positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for systemic lymphoma, but no evidence of lymphoma elsewhere in the body was obtained. In addition, she had a negative serologic finding for human immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL. She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis. PMID:27867930

  1. Hypothalamus-Related Resting Brain Network Underlying Short-Term Acupuncture Treatment in Primary Hypertension

    PubMed Central

    Chen, Hongyan; Zhang, Xiaozhe; Wang, Kai; Huang, Shuhua; Cao, Qingtian; Wang, Hong; Liang, Yuhong; Shi, Chuanying; Li, Mengyuan; Ha, Tingting; Ai, Lin; Li, Shaowu; Ma, Jun; Wei, Wenjuan; You, Youbo; Liu, Zhenyu; Tian, Jie; Bai, Lijun

    2013-01-01

    The present study attempted to explore modulated hypothalamus-seeded resting brain network underlying the cardiovascular system in primary hypertensive patients after short-term acupuncture treatment. Thirty right-handed patients (14 male) were divided randomly into acupuncture and control groups. The acupuncture group received a continuous five-day acupuncture treatment and undertook three resting-state fMRI scans and 24-hour ambulatory blood pressure monitoring (ABPM) as well as SF-36 questionnaires before, after, and one month after acupuncture treatment. The control group undertook fMRI scans and 24-hour ABPM. For verum acupuncture, average blood pressure (BP) and heart rate (HR) decreased after treatment but showed no statistical differences. There were no significant differences in BP and HR between the acupuncture and control groups. Notably, SF-36 indicated that bodily pain (P = 0.005) decreased and vitality (P = 0.036) increased after acupuncture compared to the baseline. The hypothalamus-related brain network showed increased functional connectivity with the medulla, brainstem, cerebellum, limbic system, thalamus, and frontal lobes. In conclusion, short-term acupuncture did not decrease BP significantly but appeared to improve body pain and vitality. Acupuncture may regulate the cardiovascular system through a complicated brain network from the cortical level, the hypothalamus, and the brainstem. PMID:23781269

  2. Primary Hydatid Cyst of the Brain in a Child: A Case Report

    PubMed Central

    Imperato, Alessia; Consales, Alessandro; Ravegnani, Marcello; Castagnola, Elio; Bandettini, Roberto; Rossi, Andrea

    2016-01-01

    Summary Background Primary intracranial hydatid cyst is a rare location of human echinococcosis whose spontaneous, traumatic or even iatrogenic rupture, as in case of misdiagnosis, may cause anaphylactic reactions and dissemination. Case Report We discuss the management of a 9-year-old boy who was admitted to our Emergency Department with an intracranial hypertension syndrome. Head CT scan and brain MRI showed a huge intra-axial right temporo-parieto-occipital cyst with a marginal calcification, associated with left ventricular uncompensated hydrocephalus. DTI showed displacement of the ipsilateral corticospinal tract, whereas MR spectroscopy showed absence of normal brain metabolites and presence of succinate and lactate within the cyst. A diagnosis of hydatid cyst was then presumed on the basis of the neuroradiological findings. Empiric chemotherapy with albendazole was instituted and surgical en bloc removal of the cyst was obtained, allowing the patient to recover without complications. Diagnosis of brain echinococcosis was confirmed by laboratory tests. Conclusions HE is still an endemic manifestation in some rural areas of the world, and it should be included in the differential diagnosis of children living in or coming from an endemic country who present with an intracerebral cyst. Early diagnosis and complete surgical removal of the intact cyst are the main factors that determine a favourable outcome. PMID:27994696

  3. Brain activation during visual working memory correlates with behavioral mobility performance in older adults.

    PubMed

    Kawagoe, Toshikazu; Suzuki, Maki; Nishiguchi, Shu; Abe, Nobuhito; Otsuka, Yuki; Nakai, Ryusuke; Yamada, Minoru; Yoshikawa, Sakiko; Sekiyama, Kaoru

    2015-01-01

    Functional mobility and cognitive function often decline with age. We previously found that functional mobility as measured by the Timed Up and Go Test (TUG) was associated with cognitive performance for visually-encoded (i.e., for location and face) working memory (WM) in older adults. This suggests a common neural basis between TUG and visual WM. To elucidate this relationship further, the present study aimed to examine the neural basis for the WM-mobility association. In accordance with the well-known neural compensation model in aging, we hypothesized that "attentional" brain activation for easy WM would increase in participants with lower mobility. The data from 32 healthy older adults were analyzed, including brain activation during easy WM tasks via functional Magnetic Resonance Imaging (fMRI) and mobility performance via both TUG and a simple walking test. WM performance was significantly correlated with TUG but not with simple walking. Some prefrontal brain activations during WM were negatively correlated with TUG performance, while positive correlations were found in subcortical structures including the thalamus, putamen and cerebellum. Moreover, activation of the subcortical regions was significantly correlated with WM performance, with less activation for lower WM performers. These results indicate that older adults with lower mobility used more cortical (frontal) and fewer subcortical resources for easy WM tasks. To date, the frontal compensation has been proposed separately in the motor and cognitive domains, which have been assumed to compensate for dysfunction of the other brain areas; however, such dysfunction was less clear in previous studies. The present study observed such dysfunction as degraded activation associated with lower performance, which was found in the subcortical regions. We conclude that a common dysfunction-compensation activation pattern is likely the neural basis for the association between visual WM and functional mobility.

  4. Brain activation during visual working memory correlates with behavioral mobility performance in older adults

    PubMed Central

    Kawagoe, Toshikazu; Suzuki, Maki; Nishiguchi, Shu; Abe, Nobuhito; Otsuka, Yuki; Nakai, Ryusuke; Yamada, Minoru; Yoshikawa, Sakiko; Sekiyama, Kaoru

    2015-01-01

    Functional mobility and cognitive function often decline with age. We previously found that functional mobility as measured by the Timed Up and Go Test (TUG) was associated with cognitive performance for visually-encoded (i.e., for location and face) working memory (WM) in older adults. This suggests a common neural basis between TUG and visual WM. To elucidate this relationship further, the present study aimed to examine the neural basis for the WM-mobility association. In accordance with the well-known neural compensation model in aging, we hypothesized that “attentional” brain activation for easy WM would increase in participants with lower mobility. The data from 32 healthy older adults were analyzed, including brain activation during easy WM tasks via functional Magnetic Resonance Imaging (fMRI) and mobility performance via both TUG and a simple walking test. WM performance was significantly correlated with TUG but not with simple walking. Some prefrontal brain activations during WM were negatively correlated with TUG performance, while positive correlations were found in subcortical structures including the thalamus, putamen and cerebellum. Moreover, activation of the subcortical regions was significantly correlated with WM performance, with less activation for lower WM performers. These results indicate that older adults with lower mobility used more cortical (frontal) and fewer subcortical resources for easy WM tasks. To date, the frontal compensation has been proposed separately in the motor and cognitive domains, which have been assumed to compensate for dysfunction of the other brain areas; however, such dysfunction was less clear in previous studies. The present study observed such dysfunction as degraded activation associated with lower performance, which was found in the subcortical regions. We conclude that a common dysfunction—compensation activation pattern is likely the neural basis for the association between visual WM and functional

  5. Saccadic Eye Movement Characteristics in Adult Niemann-Pick Type C Disease: Relationships with Disease Severity and Brain Structural Measures

    PubMed Central

    Abel, Larry A.; Bowman, Elizabeth A.; Velakoulis, Dennis; Fahey, Michael C.; Desmond, Patricia; Macfarlane, Matthew D.; Looi, Jeffrey Chee Leong; Adamson, Christopher L.; Walterfang, Mark

    2012-01-01

    Niemann-Pick Type C disease (NPC) is a rare genetic disorder of lipid metabolism. A parameter related to horizontal saccadic peak velocity was one of the primary outcome measures in the clinical trial assessing miglustat as a treatment for NPC. Neuropathology is widespread in NPC, however, and could be expected to affect other saccadic parameters. We compared horizontal saccadic velocity, latency, gain, antisaccade error percentage and self-paced saccade generation in 9 adult NPC patients to data from 10 age-matched controls. These saccadic measures were correlated with appropriate MRI-derived brain structural measures (e.g., dorsolateral prefrontal cortex, frontal eye fields, supplemental eye fields, parietal eye fields, pons, midbrain and cerebellar vermis) and with measures of disease severity and duration. The best discriminators between groups were reflexive saccade gain and the two volitional saccade measures. Gain was also the strongest correlate with disease severity and duration. Most of the saccadic measures showed strongly significant correlations with neurophysiologically appropriate brain regions. While our patient sample is small, the apparent specificity of these relationships suggests that as new diagnostic methods and treatments become available for NPC, a broader range of saccadic measures may be useful tools for the assessment of disease progression and treatment efficacy. PMID:23226429

  6. The effect of elevated plasma phenylalanine levels on protein synthesis rates in adult rat brain.

    PubMed Central

    Dunlop, D S; Yang, X R; Lajtha, A

    1994-01-01

    Increasing the plasma phenylalanine concentration to levels as high as 0.560-0.870 mM (over ten times normal levels) had no detectable effect on the rate of brain protein synthesis in adult rats. The average rates for 7-week-old rats were: valine, 0.58 +/- 0.05%/h, phenylalanine, 0.59 +/- 0.06%/h, and tyrosine, 0.60 +/- 0.09%/h, or 0.59 +/- 0.06%/h overall. Synthesis rates calculated on the basis of the specific activity of the tRNA-bound amino acid were slightly lower (4% lower for phenylalanine) than those based on the brain free amino acid pool. Similarly, the specific activities of valine and phenylalanine in microdialysis fluid from striatum were practically the same as those in the brain free amino acid pool. Thus the specific activities of the valine and phenylalanine brain free pools are good measures of the precursor specific activity for protein synthesis. In any event, synthesis rates, whether based on the specific activities of the amino acids in the brain free pool or those bound to tRNA, were unaffected by elevated levels of plasma phenylalanine. Brain protein synthesis rates measured after the administration of quite large doses of phenylalanine (> 1.5 mumol/g) or valine (15 mumol/g) were in agreement (0.62 +/- 0.01 and 0.65 +/- 0.01%/h respectively) with the rates determined with infusions of trace amounts of amino acids. Thus the technique of stabilizing precursor-specific activity, and pushing values in the brain close to those of the plasma, by the administration of large quantities of precursor, appears to be valid. PMID:8093014

  7. Progressive Gender Differences of Structural Brain Networks in Healthy Adults: A Longitudinal, Diffusion Tensor Imaging Study

    PubMed Central

    Sun, Yu; Lee, Renick; Chen, Yu; Collinson, Simon; Thakor, Nitish; Bezerianos, Anastasios; Sim, Kang

    2015-01-01

    Sexual dimorphism in the brain maturation during childhood and adolescence has been repeatedly documented, which may underlie the differences in behaviors and cognitive performance. However, our understanding of how gender modulates the development of structural connectome in healthy adults is still not entirely clear. Here we utilized graph theoretical analysis of longitudinal diffusion tensor imaging data over a five-year period to investigate the progressive gender differences of brain network topology. The brain networks of both genders showed prominent economical “small-world” architecture (high local clustering and short paths between nodes). Additional analysis revealed a more economical “small-world” architecture in females as well as a greater global efficiency in males regardless of scan time point. At the regional level, both increased and decreased efficiency were found across the cerebral cortex for both males and females, indicating a compensation mechanism of cortical network reorganization over time. Furthermore, we found that weighted clustering coefficient exhibited significant gender-time interactions, implying different development trends between males and females. Moreover, several specific brain regions (e.g., insula, superior temporal gyrus, cuneus, putamen, and parahippocampal gyrus) exhibited different development trajectories between males and females. Our findings further prove the presence of sexual dimorphism in brain structures that may underlie gender differences in behavioral and cognitive functioning. The sex-specific progress trajectories in brain connectome revealed in this work provide an important foundation to delineate the gender related pathophysiological mechanisms in various neuropsychiatric disorders, which may potentially guide the development of sex-specific treatments for these devastating brain disorders. PMID:25742013

  8. A different story on "Theory of Mind" deficit in adults with right hemisphere brain damage.

    PubMed

    Tompkins, Connie A; Scharp, Victoria L; Fassbinder, Wiltrud; Meigh, Kimberly M; Armstrong, Elizabeth M

    2008-01-01

    BACKGROUND: Difficulties in social cognition and interaction can characterise adults with unilateral right hemisphere brain damage (RHD). Some pertinent evidence involves their apparently poor reasoning from a "Theory of Mind" perspective, which requires a capacity to attribute thoughts, beliefs, and intentions in order to understand other people's behaviour. Theory of Mind is typically assessed with tasks that induce conflicting mental representations. Prior research with a commonly used text task reported that adults with RHD were less accurate in drawing causal inferences about mental states than at making non-mental-state causal inferences from control texts. However, the Theory of Mind and control texts differed in the number and nature of competing discourse entity representations. This stimulus discrepancy, together with the explicit measure of causal inferencing, likely put the adults with RHD at a disadvantage on the Theory of Mind texts. AIMS: This study revisited the question of Theory of Mind deficit in adults with RHD. The aforementioned Theory of Mind texts were used but new control texts were written to address stimulus discrepancies, and causal inferencing was assessed relatively implicitly. Adults with RHD were hypothesised not to display a Theory of Mind deficit under these conditions. METHODS #ENTITYSTARTX00026; PROCEDURES: The participants were 22 adults with unilateral RHD from cerebrovascular accident, and 38 adults without brain damage. Participants listened to spoken texts that targeted either mental-state or non-mental-state causal inferences. Each text was followed by spoken True/False probe sentences, to gauge target inference comprehension. Both accuracy and RT data were recorded. Data were analysed with mixed, two-way Analyses of Variance (Group by Text Type). OUTCOMES #ENTITYSTARTX00026; RESULTS: There was a main effect of Text Type in both accuracy and RT analyses, with a performance advantage for the Theory of Mind

  9. Outcomes of low-molecular-weight heparin treatment for venous thromboembolism in patients with primary and metastatic brain tumours.

    PubMed

    Chai-Adisaksopha, Chatree; Linkins, Lori-Ann; ALKindi, Said Y; Cheah, Matthew; Crowther, Mark A; Iorio, Alfonso

    2017-02-28

    Venous thromboembolism (VTE) is one of the most common complications in patients with brain tumours. There is limited data available in the literature on VTE treatment in these patients. We conducted a matched retrospective cohort study of patients with primary or metastatic brain cancer who were diagnosed with cancer-associated VTE. Patients were selected after a retrospective chart review of consecutive patients who were diagnosed with cancer-associated VTE between January 2010 and January 2014 at the Juravinski Thrombosis Clinic, Hamilton, Canada. Controls were age- and gender-matched patients with cancer-associated VTE from the same cohort, but without known brain tumours. A total of 364 patients with cancer-associated VTE were included (182 with primary or metastatic brain tumours and 182 controls). The median follow-up duration was 6.7 (interquartile range 2.5-15.8) months. The incidence rate of recurrent VTE was 11.0 per 100 patient-years (95 % CI; 6.7-17.9) in patients with brain tumours and 13.5 per 100 patient-years (95 % CI; 9.3-19.7) in non-brain tumour group. The incidence of major bleeding was 8.6 per 100 (95 % CI; 4.8-14.7) patient-years in patients with brain tumours versus 5.0 per 100 patient-years (95 % CI; 2.8-9.2) in controls. Rate of intracranial bleeding was higher in brain tumour patients (4.4 % vs 0 %, p-value=0.004). In summary, rates of recurrent VTE and major bleeding were not significantly different in patients with cancer-associated VTE in the setting of primary or metastatic brain tumours compared those without known brain tumours. However, greater numbers of intracranial bleeds were observed in patients with brain tumours.

  10. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    PubMed

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic

  11. Expression of connexin36 in the adult and developing rat brain.

    PubMed

    Belluardo, N; Mudò, G; Trovato-Salinaro, A; Le Gurun, S; Charollais, A; Serre-Beinier, V; Amato, G; Haefliger, J A; Meda, P; Condorelli, D F

    2000-05-19

    The distribution of connexin36 (Cx36) in the adult rat brain and retina has been analysed at the protein (immunofluorescence) and mRNA (in situ hybridization) level. Cx36 immunoreactivity, consisting primarily of round or elongated puncta, is highly enriched in specific brain regions (inferior olive and the olfactory bulb), in the retina, in the anterior pituitary and in the pineal gland, in agreement with the high levels of Cx36 mRNA in the same regions. A lower density of immunoreactive puncta can be observed in several brain regions, where only scattered subpopulations of cells express Cx36 mRNA. By combining in situ hybridization for Cx36 mRNA with immunohistochemistry for a general neuronal marker (NeuN), we found that neuronal cells are responsible for the expression of Cx36 mRNA in inferior olive, cerebellum, striatum, hippocampus and cerebral cortex. Cx36 mRNA was also demonstrated in parvalbumin-containing GABAergic interneurons of cerebral cortex, striatum, hippocampus and cerebellar cortex. Analysis of developing brain further revealed that Cx36 reaches a peak of expression in the first two weeks of postnatal life, and decreases sharply during the third week. Moreover, in these early stages of postnatal development Cx36 is detectable in neuronal populations that are devoid of Cx36 mRNA at the adult stage. The developmental changes of Cx36 expression suggest a participation of this connexin in the extensive interneuronal coupling which takes place in several regions of the early postnatal brain.

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

    PubMed

    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 < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc.

  13. Enhanced task related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation.

    PubMed

    Bowtell, Joanna L; Aboo-Bakkar, Zainie; Conway, Myra; Adlam, Anna-Lynne R; Fulford, Jonathan

    2017-03-01

    Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties. High flavonoid intakes attenuate age-related cognitive decline, but data from human intervention studies are sparse. We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion, task-related activation and cognitive function in healthy older adults. Participants were randomised to consume either 30 ml blueberry concentrate providing 387 mg anthocyanidins (5 female, 7 male; age 67.5±3.0 y; BMI, 25.9±3.3 kg.m-2) or isoenergetic placebo (8 female, 6 male; age 69.0 ±3.3 y; BMI, 27.1±.4.0 kg.m-2). Pre- and post-supplementation, participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5T MRI scanner while functional magnetic resonance images (fMRI) were continuously acquired. Quantitative resting brain perfusion was determined using an arterial spin labelling (ASL) technique, and blood biomarkers of inflammation and oxidative stress were measured. Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/21/40/44/45, precuneus, anterior cingulate, and insula/thalamus (p<0.001), as well as significant improvements in grey matter perfusion in the parietal (5.0±1.8 vs -2.9±2.4 %, p=0.013) and occipital (8.0±2.6 vs -0.7±3.2 %, p=0.031) lobes. There was also evidence suggesting improvement in working memory (two back test) after blueberry versus placebo supplementation (p=0.05). Supplementation with an anthocyanin rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.

  14. Adult depression screening in Saudi primary care: prevalence, instrument and cost

    PubMed Central

    2014-01-01

    Background By the year 2020 depression would be the second major cause of disability adjusted life years lost, as reported by the World Health Organization. Depression is a mental illness which causes persistent low mood, a sense of despair, and has multiple risk factors. Its prevalence in primary care varies between 15.3-22%, with global prevalence up to 13% and between 17-46% in Saudi Arabia. Despite several studies that have shown benefit of early diagnosis and cost-savings of up to 80%, physicians in primary care setting continue to miss out on 30-50% of depressed patients in their practices. Methods A cross sectional study was conducted at three large primary care centers in Riyadh, Saudi Arabia aiming at estimating point prevalence of depression and screening cost among primary care adult patients, and comparing Patient Health Questionnaires PHQ-2 with PHQ-9. Adult individuals were screened using Arabic version of PHQ-2 and PHQ-9. PHQ-2 scores were correlated with PHQ-9 scores using linear regression. A limited cost-analysis and cost saving estimates of depression screening was done using the Human Capital approach. Results Patients included in the survey analysis were 477, of whom 66.2% were females, 77.4% were married, and nearly 20% were illiterate. Patients exhibiting depressive symptoms on the basis of PHQ9 were 49.9%, of which 31% were mild, 13.4% moderate, 4.4% moderate-severe and 1.0% severe cases. Depression scores were significantly associated with female gender (p-value 0.049), and higher educational level (p-value 0.002). Regression analysis showed that PHQ-2 & PHQ-9 were strongly correlated R = 0.79, and R2 = 0.62. The cost-analysis showed savings of up to 500 SAR ($133) per adult patient screened once a year. Conclusion The point prevalence of screened depression is high in primary care visitors in Saudi Arabia. Gender and higher level of education were found to be significantly associated with screened depression. Majority of cases were mild to

  15. Associations between adult attachment characteristics, medical burden, and life satisfaction among older primary care patients.

    PubMed

    Kirchmann, Helmut; Nolte, Tobias; Runkewitz, Kristin; Bayerle, Lisa; Becker, Simone; Blasczyk, Verena; Lindloh, Julia; Strauss, Bernhard

    2013-12-01

    We investigated whether attachment security, measured by the Adult Attachment Prototype Rating (AAPR), was correlated with life satisfaction, independent of sociodemographic characteristics, medical burden, and age-related coping strategies in a sample of 81 patients (69-73 years) recruited from the register of a general primary care practice. Furthermore, we examined whether patients classified as AAPR-secure reported better adjustment to medical burden in terms of higher life satisfaction than did insecure patients. Attachment security was independently related to life satisfaction. Moreover, the association between medical burden and lower life satisfaction was significantly stronger for insecure than for secure participants. Our findings indicate that interventions to improve attachment security or coping processes related to attachment could help older adults retain life satisfaction.

  16. A brain-specific gene cluster isolated from the region of the mouse obesity locus is expressed in the adult hypothalamus and during mouse development

    SciTech Connect

    Laig-Webster, M.; Lim, M.E.; Chehab, F.F.

    1994-09-01

    The molecular defect underlying an autosomal recessive form of genetic obesity in a classical mouse model C57 BL/6J-ob/ob has not yet been elucidated. Whereas metabolic and physiological disturbances such as diabetes and hypertension are associated with obesity, the site of expression and the nature of the primary lesion responsible for this cascade of events remains elusive. Our efforts aimed at the positional cloning of the ob gene by YAC contig mapping and gene identification have resulted in the cloning of a brain-specific gene cluster from the ob critical region. The expression of this gene cluster is remarkably complex owing to the multitude of brain-specific mRNA transcripts detected on Northern blots. cDNA cloning of these transcripts suggests that they are expressed from different genes as well as by alternate splicing mechanisms. Furthermore, the genomic organization of the cluster appears to consist of at least two identical promoters displaying CpG islands characteristic of housekeeping genes, yet clearly involving tissue-specific expression. Sense and anti-sense synthetic RNA probes were derived from a common DNA sequence on 3 cDNA clones and hybridized to 8-16 days mouse embryonic stages and mouse adult brain sections. Expression in development was noticeable as of the 11th day of gestation and confined to the central nervous system mainly in the telencephalon and spinal cord. Coronal and sagittal sections of the adult mouse brain showed expression only in 3 different regions of the brain stem. In situ hybridization to mouse hypothalamus sections revealed the presence of a localized and specialized group of cells expressing high levels of mRNA, suggesting that this gene cluster may also be involved in the regulation of hypothalamic activities. The hypothalamus has long been hypothesized as a primary candidate tissue for the expression of the obesity gene mainly because of its well-established role in the regulation of energy metabolism and food intake.

  17. Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells.

    PubMed

    Cox, Charles S; Hetz, Robert A; Liao, George P; Aertker, Benjamin M; Ewing-Cobbs, Linda; Juranek, Jenifer; Savitz, Sean I; Jackson, Margaret L; Romanowska-Pawliczek, Anna M; Triolo, Fabio; Dash, Pramod K; Pedroza, Claudia; Lee, Dean A; Worth, Laura; Aisiku, Imoigele P; Choi, Huimahn A; Holcomb, John B; Kitagawa, Ryan S

    2017-04-01

    Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood-brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design. Adults with severe traumatic brain injury (Glasgow Coma Scale 5-8) and without signs of irreversible brain injury were evaluated for entry into the trial. A dose escalation format was performed in 25 patients: 5 controls, followed 5 patients in each dosing cohort (6, 9, 12 ×10(6) cells/kg body weight), then 5 more controls. Bone marrow harvest, cell processing to isolate the mononuclear fraction, and re-infusion occurred within 48 hours after injury. Patients were monitored for harvest-related hemodynamic changes, infusional toxicity, and adverse events. Outcome measures included magnetic resonance imaging-based measurements of supratentorial and corpus callosal volumes as well as diffusion tensor imaging-based measurements of fractional anisotropy and mean diffusivity of the corpus callosum and the corticospinal tract at the level of the brainstem at 1 month and 6 months postinjury. Functional and neurocognitive outcomes were measured and correlated with imaging data. Inflammatory cytokine arrays were measured in the plasma pretreatment, posttreatment, and at 1 and 6 month follow-up. There were no serious adverse events. There was a mild pulmonary toxicity of the highest dose that was not clinically significant. Despite the treatment group having greater injury severity, there was structural preservation of critical regions of interest

  18. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    SciTech Connect

    Schindler, Matthew K. Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-03-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

  19. Activin in the Brain Modulates Anxiety-Related Behavior and Adult Neurogenesis

    PubMed Central

    Ageta, Hiroshi; Murayama, Akiko; Migishima, Rika; Kida, Satoshi; Tsuchida, Kunihiro; Yokoyama, Minesuke; Inokuchi, Kaoru

    2008-01-01

    Activin, a member of the transforming growth factor-β superfamily, is an endocrine hormone that regulates differentiation and proliferation of a wide variety of cells. In the brain, activin protects neurons from ischemic damage. In this study, we demonstrate that activin modulates anxiety-related behavior by analyzing ACM4 and FSM transgenic mice in which activin and follistatin (which antagonizes the activin signal), respectively, were overexpressed in a forebrain-specific manner under the control of the αCaMKII promoter. Behavioral analyses revealed that FSM mice exhibited enhanced anxiety compared to wild-type littermates, while ACM4 mice showed reduced anxiety. Importantly, survival of newly formed neurons in the subgranular zone of adult hippocampus was significantly decreased in FSM mice, which was partially rescued in ACM4/FSM double transgenic mice. Our findings demonstrate that the level of activin in the adult brain bi-directionally influences anxiety-related behavior. These results further suggest that decreases in postnatal neurogenesis caused by activin inhibition affect an anxiety-related behavior in adulthood. Activin and its signaling pathway may represent novel therapeutic targets for anxiety disorder as well as ischemic brain injury. PMID:18382659

  20. Acquisition of Visual Perception in Blind Adults Using the BrainPort Artificial Vision Device

    PubMed Central

    Pintar, Christine; Arnoldussen, Aimee; Fisher, Christopher

    2015-01-01

    OBJECTIVE. We sought to determine whether intensive low vision rehabilitation would confer any functional improvement in a sample of blind adults using the BrainPort artificial vision device. METHOD. Eighteen adults ages 28–69 yr (n = 10 men and n = 8 women) who had light perception only or worse vision bilaterally spent up to 6 hr per day for 1 wk undergoing structured rehabilitation interventions. The functional outcomes of object identification and word recognition were tested at baseline and after rehabilitation training. RESULTS. At baseline, participants were unable to complete the two functional assessments. After participation in the 1-wk training protocol, participants were able to use the BrainPort device to complete the two tasks with moderate success. CONCLUSION. Without training, participants were not able to perform above chance level using the BrainPort device. As artificial vision technologies become available, occupational therapy practitioners can play a key role in clients’ success or failure in using these devices. PMID:25553750

  1. Brain activation changes during locomotion in middle-aged to older adults with multiple sclerosis.

    PubMed

    Hernandez, Manuel E; Holtzer, Roee; Chaparro, Gioella; Jean, Kharine; Balto, Julia M; Sandroff, Brian M; Izzetoglu, Meltem; Motl, Robert W

    2016-11-15

    Mobility and cognitive impairments are common in persons with multiple sclerosis (MS), and are expected to worsen with increasing age. However, no studies, to date, in part due to limitations of conventional neuroimaging methods, have examined changes in brain activation patterns during active locomotion in older patients with MS. This study used functional Near Infrared Spectroscopy (fNIRS) to evaluate real-time neural activation differences in the pre-frontal cortex (PFC) between middle-aged to older adults with MS and healthy controls during single (Normal Walk; NW) and dual-task (Walking While Talking; WWT) locomotion tasks. Eight middle-aged to older adults with MS and eight healthy controls underwent fNIRS recording while performing the NW and WWT tasks with an fNIRS cap consisting of 16 optodes positioned over the forehead. The MS group had greater elevations in PFC oxygenation levels during WWT compared to NW than healthy controls. There was no walking performance difference between groups during locomotion. These findings suggest that middle-aged to older individuals with MS might be able to achieve similar levels of performance through the use of increased brain activation. This study is the first to investigate brain activation changes during the performance of simple and divided-attention locomotion tasks in MS using fNIRS.

  2. Epigenetic gene regulation in the adult mammalian brain: multiple roles in memory formation.

    PubMed

    Lubin, Farah D

    2011-07-01

    Brain-derived neurotrophic factor (bdnf) is one of numerous gene products necessary for long-term memory formation and dysregulation of bdnf has been implicated in the pathogenesis of cognitive and mental disorders. Recent work indicates that epigenetic-regulatory mechanisms including the markings of histone proteins and associated DNA remain labile throughout the life-span and represent an attractive molecular process contributing to gene regulation in the brain. In this review, important information will be discussed on epigenetics as a set of newly identified dynamic transcriptional mechanisms serving to regulate gene expression changes in the adult brain with particular emphasis on bdnf transcriptional readout in learning and memory formation. This review will also highlight evidence for the role of epigenetics in aberrant bdnf gene regulation in the pathogenesis of cognitive dysfunction associated with seizure disorders, Rett syndrome, Schizophrenia, and Alzheimer's disease. Such research offers novel concepts for understanding epigenetic transcriptional mechanisms subserving adult cognition and mental health, and furthermore promises novel avenues for therapeutic approach in the clinic.

  3. The association of brain structure with gait velocity in older adults: a quantitative volumetric analysis of brain MRI

    PubMed Central

    Katz, Mindy J.; Lipton, Michael L.; Lipton, Richard B.; Verghese, Joe

    2015-01-01

    Introduction While cortical processes play an important role in controlling locomotion, the underlying structural brain changes associated with slowing of gait in aging are not yet fully established. Our study aimed to examine the relationship between cortical gray matter volume (GM), white matter volume (WM), ventricular volume (VV), hippocampal and hippocampal subfield volumes, and gait velocity in older adults free of dementia. Methods Gait and cognitive performance was tested in 112 community-residing adults, age 70 years and over, participating in the Einstein Aging Study. Gait velocity (cm/s) was obtained using an instrumented walkway. Volumetric MRI measures were estimated using a FreeSurfer software. We examined the cross-sectional relationship of GM, WM, VV, and hippocampal total and subfield volumes and gait velocity using linear regression models. In complementary models, the effect of memory performance on the relationship between gait velocity and regional volumes was evaluated. Results Slower gait velocity was associated with smaller cortical GM and total hippocampal volumes. There was no association between gait velocity and WM or VV. Among hippocampal subfields, only smaller presubiculum volume was significantly associated with decrease in gait velocity. Addition of the memory performance to the models attenuated the association between gait velocity and all volumetric measures. Conclusions Our findings indicate that total GM and hippocampal volumes as well as specific hippocampal subfield volumes are inversely associated with locomotor function. These associations are probably affected by cognitive status of study population. PMID:25921321

  4. Adult onset primary focal dystonia of the foot: an orthopaedic intervention.

    PubMed

    Logan, Loretta; Resseque, Barbara; Dontamsetti, Monica Sakshi

    2016-03-30

    A 54-year-old woman presented to a foot centre with a chief symptom of cramping in her toes, which, she believed, was of a secondary cause originating from a bunion. She was treated conservatively; however, she returned a month later as the symptoms had progressed to painful cramping of toes, toe-curling and instability while walking, due to involuntary movement of her toes. It was believed that the patient presented with a rare case of primary adult onset focal foot dystonia. This case report explains dystonia further in detail and delves into the different treatment and management options available today, including the unique orthopaedic intervention provided for this patient.

  5. Changes in the contralateral eye in uncomplicated persistent hyperplastic primary vitreous in adults.

    PubMed

    Awan, K J; Humayun, M

    1985-02-15

    In two adults (a 62-year-old man and a 71-year-old woman) uncomplicated full-blown unilateral persistent hyperplastic primary vitreous was diagnosed on the basis of characteristic clinical features and ultrasonography. In the contralateral uninvolved eyes, we found open-angle glaucoma, anomalous blood vessels along the entire circumference of the anterior chamber angle, band keratopathy, and heterochromia iridis. The axial length of one involved eye was about 0.85 mm larger than that of the uninvolved eye.

  6. Organization of the histaminergic system in adult zebrafish (Danio rerio) brain: neuron number, location, and cotransmitters.

    PubMed

    Sundvik, Maria; Panula, Pertti

    2012-12-01

    Histamine is an essential factor in the ascending arousal system (AAS) during motivated behaviors. Histamine and hypocretin/orexin (hcrt) are proposed to be responsible for different aspects of arousal and wakefulness, histamine mainly for cognitive and motivated behaviors. In this study we visualized the entire histaminergic neuron population in adult male and female zebrafish brain and quantified the histaminergic neuron numbers. There were 40-45 histaminergic neurons in both male and female zebrafish brain. Further, we identified cotransmitters of histaminergic neurons in the ventrocaudal hypothalamus, i.e., around the posterior recess (PR) in adult zebrafish. Galanin, γ-aminobutyric acid (GABA), and thyrotropin-releasing hormone (TRH) were colocalized with histamine in some but not all neurons, a result that was verified by intracerebroventricular injections of colchicine into adult zebrafish. Fibers immunoreactive (ir) for galanin, GABA, TRH, or methionine-enkephalin (mENK) were dense in the ventrocaudal hypothalamus around the histaminergic neurons. In histamine-ir fibers TRH and galanin immunoreactivities were also detected in the ventral telencephalon. All these neurotransmitters are involved in maintaining the equilibrium of the sleep-wake state. Our results are in accordance with results from rats, further supporting the use of zebrafish as a tool to study molecular mechanisms underlying complex behaviors.

  7. Micromanipulation of gene expression in the adult zebrafish brain using cerebroventricular microinjection of morpholino oligonucleotides.

    PubMed

    Kizil, Caghan; Iltzsche, Anne; Kaslin, Jan; Brand, Michael

    2013-05-23

    Manipulation of gene expression in tissues is required to perform functional studies. In this paper, we demonstrate the cerebroventricular microinjection (CVMI) technique as a means to modulate gene expression in the adult zebrafish brain. By using CVMI, substances can be administered into the cerebroventricular fluid and be thoroughly distributed along the rostrocaudal axis of the brain. We particularly focus on the use of antisense morpholino oligonucleotides, which are potent tools for knocking down gene expression in vivo. In our method, when applied, morpholino molecules are taken up by the cells lining the ventricular surface. These cells include the radial glial cells, which act as neurogenic progenitors. Therefore, knocking down gene expression in the radial glial cells is of utmost importance to analyze the widespread neurogenesis response in zebrafish, and also would provide insight into how vertebrates could sustain adult neurogenesis response. Such an understanding would also help the efforts for clinical applications in human neurodegenerative disorders and central nervous system regeneration. Thus, we present the cerebroventricular microinjection method as a quick and efficient way to alter gene expression and neurogenesis response in the adult zebrafish forebrain. We also provide troubleshooting tips and other useful information on how to carry out the CVMI procedure.

  8. Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

    PubMed

    Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

    2014-09-01

    The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.

  9. Differences in Brain Structure and Function in Older Adults with Self-Reported Disabling and Non-Disabling Chronic Low Back Pain

    PubMed Central

    Buckalew, Neilly; Haut, Marc W.; Aizenstein, Howard; Morrow, Lisa; Perera, Subashan; Kuwabara, Hiroto; Weiner, Debra K.

    2010-01-01

    Objective The primary aim of this pilot study was to identify structural and functional brain differences in older adults with self-reported disabling chronic low back pain (CLBP) compared with those who reported non-disabling CLBP. Design Cross-sectional. Participants Sixteen cognitively intact older adults, eight with disabling CLBP and eight with non-disabling. Exclusions were psychiatric or neurological disorders, substance abuse, opioid use, or diabetes mellitus. Methods Participants underwent: structural and functional brain MRI; neuropsychological assessment using the Repeatable Battery for the Assessment of Neuropsychological Status, Trail Making Tests A and B; and physical performance assessment using the Short Physical Performance Battery. Results In the disabled group there was significantly lower white matter (WM) integrity (P < 0.05) of the splenium of the corpus callosum. This group also demonstrated activation of the right medial prefrontal cortex at rest whereas the non-disabled demonstrated activation of the left lateral prefrontal cortex. Combined groups analysis revealed a strong positive correlation (rs = 0.80, P < 0.0002) between WM integrity of the left centrum semiovale with gait-speed. Secondary analysis revealed a strong negative correlation between total months of CLBP and WM integrity of the SCC (rs = −0.59, P < 0.02). Conclusions Brain structure and function is different in older adults with disabling CLBP compared to those with non-disabling CLBP. Deficits in brain morphology combining groups are associated with pain duration and poor physical function. Our findings suggest brain structure and function may play a key role in chronic-pain-related-disability and may be important treatment targets. PMID:20609128

  10. Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome.

    PubMed

    Hartley, Sigan L; Handen, Benjamin L; Devenny, Darlynne A; Hardison, Regina; Mihaila, Iulia; Price, Julie C; Cohen, Annie D; Klunk, William E; Mailick, Marsha R; Johnson, Sterling C; Christian, Bradley T

    2014-09-01

    Nearly all adults with Down syndrome show neuropathology of Alzheimer's disease, including amyloid-β deposition, by their fifth decade of life. In the current study, we examined the association between brain amyloid-β deposition, assessed via in vivo assessments of neocortical Pittsburgh compound B, and scores on an extensive neuropsychological battery of measures of cognitive functioning in 63 adults (31 male, 32 female) with Down syndrome aged 30-53 years who did not exhibit symptoms of dementia. Twenty-two of the adults with Down syndrome were identified as having elevated neocortical Pittsburgh compound B retention levels. There was a significant positive correlation (r = 0.62, P < 0.0001) between age and neocortical Pittsburgh compound B retention. This robust association makes it difficult to discriminate normative age-related decline in cognitive functioning from any potential effects of amyloid-β deposition. When controlling for chronological age in addition to mental age, there were no significant differences between the adults with Down syndrome who had elevated neocortical Pittsburgh compound B retention levels and those who did not on any of the neuropsychological measures. Similarly, when examining Pittsburgh compound B as a continuous variable, after controlling for mental age and chronological age, only the Rivermead Picture Recognition score was significantly negatively associated with neocortical Pittsburgh compound B retention. Our findings indicate that many adults with Down syndrome can tolerate amyloid-β deposition without deleterious effects on cognitive functioning. However, we may have obscured true effects of amyloid-β deposition by controlling for chronological age in our analyses. Moreover, our sample included adults with Down syndrome who were most 'resistant' to the effects of amyloid-β deposition, as adults already exhibiting clinical symptoms of dementia symptoms were excluded from the study.

  11. Splenomegaly as a Primary Manifestation of Gaucher Disease in a Young Adult Woman

    PubMed Central

    Merra, Giuseppe; Lago, Antonio Dal; Ricci, Roberta; Antuzzi, Daniela; Gasbarrini, Giovanni; Gasbarrini, Antonio; Ghirlanda, Giovanni

    2008-01-01

    Gaucher disease is the most common lysosomal storage disease. It is caused by the defective activity of acid β-glucosidase, which results in the accumulation of lipid glucocerebroside in macrophages throughout the body. In this case report we describe the case of a young adult woman with splenomegaly as the primary manifestation of this pathology. This is a case of type 1 Gaucher disease because there is a lack of primary neurological involvement but we have, instead, an age-independent involvement of the visceral organs. It is very important to classify or characterize these patients in a precise manner and to make a complete diagnosis with the help of the many diagnostic resources now at our disposal, especially with genetics, radiology and new techniques of advanced microscopy, also because Gaucher disease requires a long and complex management from early life to adulthood. PMID:21897802

  12. The adverse effects of reduced cerebral perfusion on cognition and brain structure in older adults with cardiovascular disease

    PubMed Central

    Alosco, Michael L; Gunstad, John; Jerskey, Beth A; Xu, Xiaomeng; Clark, Uraina S; Hassenstab, Jason; Cote, Denise M; Walsh, Edward G; Labbe, Donald R; Hoge, Richard; Cohen, Ronald A; Sweet, Lawrence H

    2013-01-01

    Background It is well established that aging and vascular processes interact to disrupt cerebral hemodynamics in older adults. However, the independent effects of cerebral perfusion on neurocognitive function among older adults remain poorly understood. We examined the associations among cerebral perfusion, cognitive function, and brain structure in older adults with varying degrees of vascular disease using perfusion magnetic resonance imaging (MRI) arterial spin labeling (ASL). Materials and methods 52 older adults underwent neuroimaging and were administered the Mini Mental State Examination (MMSE), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and measures of attention/executive function. ASL and T1-weighted MRI were used to quantify total brain perfusion, total brain volume (TBV), and cortical thickness. Results Regression analyses showed reduced total brain perfusion was associated with poorer performance on the MMSE, RBANS total index, immediate and delayed memory composites, and Trail Making Test B. Reduced frontal lobe perfusion was associated with worse executive and memory function. A similar pattern emerged between temporal lobe perfusion and immediate memory. Regression analyses revealed that decreased total brain perfusion was associated with smaller TBV and mean cortical thickness. Regional effects of reduced total cerebral perfusion were found on temporal and parietal lobe volumes and frontal and temporal cortical thickness. Discussion Reduced cerebral perfusion is independently associated with poorer cognition, smaller TBV, and reduced cortical thickness in older adults. Conclusion Prospective studies are needed to clarify patterns of cognitive decline and brain atrophy associated with cerebral hypoperfusion. PMID:24363966

  13. Origin of germ cells and formation of new primary follicles in adult human ovaries

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Upadhyaya, Nirmala B

    2004-01-01

    sophisticated adaptive mechanism created during the evolution of female reproduction. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. An essential mission of such follicular turnover might be elimination of spontaneous or environmentally induced genetic alterations of oocytes in resting primary follicles. PMID:15115550

  14. Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women

    PubMed Central

    Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

    2016-01-01

    Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects’ Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and

  15. Raising awareness of bronchiectasis in primary care: overview of diagnosis and management strategies in adults.

    PubMed

    Chalmers, James D; Sethi, Sanjay

    2017-12-01

    Bronchiectasis is a chronic lung disease characterised by recurrent infection, inflammation, persistent cough and sputum production. The disease is increasing in prevalence, requiring a greater awareness of the disease across primary and secondary care. Mild and moderate cases of bronchiectasis in adults can often be managed by primary care clinicians. Initial assessments and long-term treatment plans that include both pharmacological and non-pharmacological treatments, however, should be undertaken in collaboration with a secondary care team that includes physiotherapists and specialists in respiratory medicine. Bronchiectasis is often identified in patients with other lung diseases, such as chronic obstructive pulmonary disease, asthma, and in a lesser but not insignificant number of patients with other inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Overall goals of therapy are to prevent exacerbations, improve symptoms, improve quality of life and preserve lung function. Prompt treatment of exacerbations with antibiotic therapy is important to limit the impact of exacerbations on quality of life and lung function decline. Patient education and cooperation with health-care providers to implement treatment plans are key to successful disease management. It is important for the primary care provider to work with secondary care providers to develop an individualised treatment plan to optimise care with the goal to delay disease progression. Here, we review the diagnosis and treatment of bronchiectasis with a focus on practical considerations that will be useful to primary care.

  16. The effect of increased primary schooling on adult women's HIV status in Malawi and Uganda: Universal Primary Education as a natural experiment.

    PubMed

    Behrman, Julia Andrea

    2015-02-01

    This paper explores the causal relationship between primary schooling and adult HIV status in Malawi and Uganda, two East African countries with some of the highest HIV infection rates in the world. Using data from the 2010 Malawi Demographic Health Survey and the 2011 Uganda AIDS Indicator Survey, the paper takes advantage of a natural experiment, the implementation of Universal Primary Education policies in the mid 1990s. An instrumented regression discontinuity approach is used to model the relationship between increased primary schooling and adult women's HIV status. Results indicate that a one-year increase in schooling decreases the probability of an adult woman testing positive for HIV by 0.06 (p < 0.01) in Malawi and by 0.03 (p < 0.05) in Uganda. These results are robust to a variety of model specifications. In a series of supplementary analyses a number of potential pathways through which such effects may occur are explored. Findings indicate increased primary schooling positively affects women's literacy and spousal schooling attainment in Malawi and age of marriage and current household wealth in Uganda. However primary schooling has no effect on recent (adult) sexual behavior.

  17. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    PubMed

    Zhang, Kuan; Zhou, Yanzhao; Zhao, Tong; Wu, Liying; Huang, Xin; Wu, Kuiwu; Xu, Lun; Li, Dahu; Liu, Shuhong; Zhao, Yongqi; Fan, Ming; Zhu, Lingling

    2015-01-01

    Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  18. Methylmercury Induced Neurotoxicity and the Influence of Selenium in the Brains of Adult Zebrafish (Danio rerio).

    PubMed

    Rasinger, Josef Daniel; Lundebye, Anne-Katrine; Penglase, Samuel James; Ellingsen, Ståle; Amlund, Heidi

    2017-03-29

    The neurotoxicity of methylmercury (MeHg) is well characterised, and the ameliorating effects of selenium have been described. However, little is known about the molecular mechanisms behind this contaminant-nutrient interaction. We investigated the influence of selenium (as selenomethionine, SeMet) and MeHg on mercury accumulation and protein expression in the brain of adult zebrafish (Danio rerio). Fish were fed diets containing elevated levels of MeHg and/or SeMet in a 2 × 2 full factorial design for eight weeks. Mercury concentrations were highest in the brain tissue of MeHg-exposed fish compared to the controls, whereas lower levels of mercury were found in the brain of zebrafish fed both MeHg and SeMet compared with the fish fed MeHg alone. The expression levels of proteins associated with gap junction signalling, oxidative phosphorylation, and mitochondrial dysfunction were significantly (p < 0.05) altered in the brain of zebrafish after exposure to MeHg and SeMet alone or in combination. Analysis of upstream regulators indicated that these changes were linked to the mammalian target of rapamycin (mTOR) pathways, which were activated by MeHg and inhibited by SeMet, possibly through a reactive oxygen species mediated differential activation of RICTOR, the rapamycin-insensitive binding partner of mTOR.

  19. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

    PubMed

    Kizil, Caghan; Iltzsche, Anne; Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

    2015-01-01

    Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

  20. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides

    PubMed Central

    Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

    2015-01-01

    Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two– polyR and Trans – that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael’s addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues. PMID:25894337

  1. Adolescent and young adult survivors of childhood brain tumors: Life after treatment in their own words

    PubMed Central

    Hobbie, Wendy L.; Ogle, Sue; Reilly, Maureen; Barakat, Lamia; Lucas, Matthew S.; Ginsberg, Jill P.; Fisher, Michael J.; Volpe, Ellen M.; Deatrick, Janet A.

    2015-01-01

    Background To date there are few studies that examine the perspectives of older survivors of childhood brain tumors who are living with their families in terms of their sense of self and their role in their families. Objective To describe how adolescent and young adult survivors (AYA) of childhood brain tumors describe their HRQOL, that is their physical, emotional, and social functioning. Methods This qualitative descriptive study included a purposive sample of 41 AYA survivors of a childhood brain tumor who live with their families. Home interviews were conducted using a semi-structured interview guide. Directed content analytic techniques were used to analyze data using HRQOL as a framework. Results This group of brain tumor survivors described their everyday lives in terms of their physical health, neurocognitive functioning, emotional health, social functioning, and self-care abilities. Overall, survivors struggle for normalcy in the face of changed functioning due to their cancer and the (late) effects of their treatment. Conclusions Neurocognitive issues seemed most compelling in the narratives. The importance of families went beyond the resources, structure, and support for functioning. Their families provided the recognition that they were important beings and their existence mattered to someone. Implications for Practice The value and complexity of care coordination was highlighted by the multifaceted needs of the survivors. Advocacy for appropriate and timely educational, vocational, and social support is critical as part of comprehensive cancer survivorship care. PMID:25950583

  2. Adult attachment predicts maternal brain and oxytocin response to infant cues

    PubMed Central

    Strathearn, Lane; Fonagy, Peter; Amico, Janet; Montague, P. Read

    2010-01-01

    Infant cues, such as smiling or crying facial expressions, are powerful motivators of human maternal behavior, activating dopamine-associated brain reward circuits. Oxytocin, a neurohormone of attachment, promotes maternal care in animals, although its role in human maternal behavior is unclear. We examined 30 first-time new mothers to test whether differences in attachment, based on the Adult Attachment Interview, were related to brain reward and peripheral oxytocin response to infant cues. On viewing their own infant’s smiling and crying faces during functional MRI scanning, mothers with secure attachment showed greater activation of brain reward regions, including the ventral striatum, and the oxytocin-associated hypothalamus/pituitary region. Peripheral oxytocin response to infant contact at 7 months was also significantly higher in secure mothers, and was positively correlated with brain activation in both regions. Insecure/dismissing mothers showed greater insular activation in response to their own infant’s sad faces. These results suggest that individual differences in maternal attachment may be linked with development of the dopaminergic and oxytocinergic neuroendocrine systems. PMID:19710635

  3. Dopamine from the brain promotes spinal motor neuron generation during development and adult regeneration.

    PubMed

    Reimer, Michell M; Norris, Anneliese; Ohnmacht, Jochen; Patani, Rickie; Zhong, Zhen; Dias, Tatyana B; Kuscha, Veronika; Scott, Angela L; Chen, Yu-Chia; Rozov, Stanislav; Frazer, Sarah L; Wyatt, Cameron; Higashijima, Shin-ichi; Patton, E Elizabeth; Panula, Pertti; Chandran, Siddharthan; Becker, Thomas; Becker, Catherina G

    2013-06-10

    Coordinated development of brain stem and spinal target neurons is pivotal for the emergence of a precisely functioning locomotor system. Signals that match the development of these far-apart regions of the central nervous system may be redeployed during spinal cord regeneration. Here we show that descending dopaminergic projections from the brain promote motor neuron generation at the expense of V2 interneurons in the developing zebrafish spinal cord by activating the D4a receptor, which acts on the hedgehog pathway. Inhibiting this essential signal during early neurogenesis leads to a long-lasting reduction of motor neuron numbers and impaired motor responses of free-swimming larvae. Importantly, during successful spinal cord regeneration in adult zebrafish, endogenous dopamine promotes generation of spinal motor neurons, and dopamine agonists augment this process. Hence, we describe a supraspinal control mechanism for the development and regeneration of specific spinal cell types that uses dopamine as a signal.

  4. Biochemical effect of a ketogenic diet on the brains of obese adult rats.

    PubMed

    Mohamed, Hoda E; El-Swefy, Sahar E; Rashed, Leila A; Abd El-Latif, Sally K

    2010-07-01

    Excess weight, particularly abdominal obesity, can cause or exacerbate cardiovascular and metabolic disease. Obesity is also a proven risk factor for Alzheimer's disease (AD). Various studies have demonstrated the beneficial effects of a ketogenic diet (KD) in weight reduction and in modifying the disease activity of neurodegenerative disorders, including AD. Therefore, in this study we examined the metabolic and neurodegenerative changes associated with obesity and the possible neuroprotective effects of a KD in obese adult rats. Compared with obese rats fed a control diet, obese rats fed a KD showed significant weight loss, improvement in lipid profiles and insulin resistance, and upregulation of adiponectin mRNA expression in adipose tissue. In addition, the KD triggered significant downregulation of brain amyloid protein precursor, apolipoprotein E and caspase-3 mRNA expression, and improvement of brain oxidative stress responses. These findings suggest that a KD has anti-obesity and neuroprotective effects.

  5. Regional brain activity change predicts responsiveness to treatment for stuttering in adults.

    PubMed

    Ingham, Roger J; Wang, Yuedong; Ingham, Janis C; Bothe, Anne K; Grafton, Scott T

    2013-12-01

    Developmental stuttering is known to be associated with aberrant brain activity, but there is no evidence that this knowledge has benefited stuttering treatment. This study investigated whether brain activity could predict progress during stuttering treatment for 21 dextral adults who stutter (AWS). They received one of two treatment programs that included periodic H2(15)O PET scanning (during oral reading, monologue, and eyes-closed rest conditions). All participants successfully completed an initial treatment phase and then entered a phase designed to transfer treatment gains; 9/21 failed to complete this latter phase. The 12 pass and 9 fail participants were similar on speech and neural system variables before treatment, and similar in speech performance after the initial phase of their treatment. At the end of the initial treatment phase, however, decreased activation within a single region, L. putamen, in all 3 scanning conditions was highly predictive of successful treatment progress.

  6. Primary and Specialty Medical Care Among Ethnically Diverse, Older Rural Adults With Type 2 Diabetes: The ELDER Diabetes Study

    ERIC Educational Resources Information Center

    Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

    2005-01-01

    Purpose: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes.…

  7. Primary and Specialty Medical Care among Ethnically Diverse, Older Rural Adults with Type 2 Diabetes: The ELDER Diabetes Study

    ERIC Educational Resources Information Center

    Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

    2005-01-01

    Purpose: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes.…

  8. Expression of cyclin E in postmitotic neurons during development and in the adult mouse brain.

    PubMed

    Ikeda, Yayoi; Matsunaga, Yuko; Takiguchi, Masahito; Ikeda, Masa-Aki

    2011-01-01

    Cyclin E, a member of the G1 cyclins, is essential for the G1/S transition of the cell cycle in cultured cells, but its roles in vivo are not fully defined. The present study characterized the spatiotemporal expression profile of cyclin E in two representative brain regions in the mouse, the cerebral and cerebellar cortices. Western blotting showed that the levels of cyclin E increased towards adulthood. In situ hybridization and immunohistochemistry showed the distributions of cyclin E mRNA and protein were comparable in the cerebral cortex and the cerebellum. Immunohistochemistry for the proliferating cell marker, proliferating cell nuclear antigen (PCNA) revealed that cyclin E was expressed by both proliferating and non-proliferating cells in the cerebral cortex at embryonic day 12.5 (E12.5) and in the cerebellum at postnatal day 1 (P1). Subcellular localization in neurons was examined using immunofluorescence and western blotting. Cyclin E expression was nuclear in proliferating neuronal precursor cells but cytoplasmic in postmitotic neurons during embryonic development. Nuclear cyclin E expression in neurons remained faint in newborns, increased during postnatal development and was markedly decreased in adults. In various adult brain regions, cyclin E staining was more intense in the cytoplasm than in the nucleus in most neurons. These data suggest a role for cyclin E in the development and function of the mammalian central nervous system and that its subcellular localization in neurons is important. Our report presents the first detailed analysis of cyclin E expression in postmitotic neurons during development and in the adult mouse brain.

  9. The long-term side effects of radiation therapy for benign brain tumors in adults

    SciTech Connect

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. )

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  10. Netrin-5 is highly expressed in neurogenic regions of the adult brain

    PubMed Central

    Yamagishi, Satoru; Yamada, Kohei; Sawada, Masato; Nakano, Suguru; Mori, Norio; Sawamoto, Kazunobu; Sato, Kohji

    2015-01-01

    Mammalian netrin family proteins are involved in targeting of axons, neuronal migration, and angiogenesis and act as repulsive and attractive guidance molecules. Netrin-5 is a new member of the netrin family with homology to the C345C domain of netrin-1. Unlike other netrin proteins, murine netrin-5 consists of two EGF motifs of the laminin V domain (LE) and the C345C domain, but lacks the N-terminal laminin VI domain and one of the three LE motifs. We generated a specific antibody against netrin-5 to investigate its expression pattern in the rodent adult brain. Strong netrin-5 expression was observed in the olfactory bulb (OB), rostral migrate stream (RMS), the subventricular zone (SVZ), and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, where neurogenesis occurs in the adult brain. In the SVZ and RMS, netrin-5 expression was observed in Mash1-positive transit-amplifying cells and in Doublecortin (DCX)-positive neuroblasts, but not in GFAP-positive astrocytes. In the OB, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons. In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells. These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain. PMID:25941474

  11. In vivo brain anatomy of adult males with Fragile X syndrome: an MRI study.

    PubMed

    Hallahan, Brian P; Craig, Michael C; Toal, Fiona; Daly, Eileen M; Moore, Caroline J; Ambikapathy, Anita; Robertson, Dene; Murphy, Kieran C; Murphy, Declan G M

    2011-01-01

    Fragile X Syndrome (FraX) is caused by the expansion of a single trinucleotide gene sequence (CGG) on the X chromosome, and is a leading cause of learning disability (mental retardation) worldwide. Relatively few studies, however, have examined the neuroanatomical abnormalities associated with FraX. Of those that are available many included mixed gender populations, combined FraX children and adults into one sample, and employed manual tracing techniques which measures bulk volume of particular regions. Hence, there is relatively little information on differences in grey and white matter content across whole brain. We employed magnetic resonance imaging to investigate brain anatomy in 17 adult males with FraX and 18 healthy controls that did not differ significantly in age. Data were analysed using stereology and VBM to compare (respectively) regional brain bulk volume, and localised grey/white matter content. Using stereology we found that FraX males had a significant increase in bulk volume bilaterally of the caudate nucleus and parietal lobes and of the right brainstem, but a significant decrease in volume of the left frontal lobe. Our complimentary VBM analysis revealed an increased volume of grey matter in fronto-striatal regions (including bilaterally in the caudate nucleus), and increased white matter in regions extending from the brainstem to the parahippocampal gyrus, and from the left cingulate cortex extending into the corpus callosum. People with FraX have regionally specific differences in brain anatomy from healthy controls with enlargement of the caudate nuclei that persists into adulthood.

  12. Distinct expression of Cbln family mRNAs in developing and adult mouse brains.

    PubMed

    Miura, Eriko; Iijima, Takatoshi; Yuzaki, Michisuke; Watanabe, Masahiko

    2006-08-01

    Cbln1 belongs to the C1q and tumour necrosis factor superfamily, and plays crucial roles as a cerebellar granule cell-derived transneuronal regulator for synapse integrity and plasticity in Purkinje cells. Although Cbln2-Cbln4 are also expressed in the brain and could form heteromeric complexes with Cbln1, their precise expressions remain unclear. Here, we investigated gene expression of the Cbln family in developing and adult C57BL mouse brains by reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blot, and high-resolution in situ hybridization (ISH) analyses. In the adult brain, spatial patterns of mRNA expression were highly differential depending on Cbln subtypes. Notably, particularly high levels of Cbln mRNAs were expressed in some nuclei and neurons, whereas their postsynaptic targets often lacked or were low for any Cbln mRNAs, as seen for cerebellar granule cells/Purkinje cells, entorhinal cortex/hippocampus, intralaminar group of thalamic nuclei/caudate-putamen, and dorsal nucleus of the lateral lemniscus/central nucleus of the inferior colliculus. In the developing brain, Cbln1, 2, and 4 mRNAs appeared as early as embryonic day 10-13, and exhibited transient up-regulation during the late embryonic and neonatal periods. For example, Cbln2 mRNA was expressed in the cortical plate of the developing neocortex, displaying a high rostromedial to low caudolateral gradient. In contrast, Cbln3 mRNA was selective to cerebellar granule cells throughout development, and its onset was as late as postnatal day 7-10. These results will provide a molecular-anatomical basis for future studies that characterize roles played by the Cbln family.

  13. Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains

    PubMed Central

    Weimann, James M.; Charlton, Carol A.; Brazelton, Timothy R.; Hackman, Robert C.; Blau, Helen M.

    2003-01-01

    We show here that cells within human adult bone marrow can contribute to cells in the adult human brain. Cerebellar tissues from female patients with hematologic malignancies, who had received chemotherapy, radiation, and a bone marrow transplant, were analyzed. Brain samples were obtained at autopsy from female patients who received male (sex-mismatched) or female (sex-matched, control) bone marrow transplants. Cerebella were evaluated in 10-μm-thick, formaldehyde-fixed, paraffin-embedded sections that encompassed up to ≈50% of a human Purkinje nucleus. A total of 5,860 Purkinje cells from sex-mismatched females and 3,202 Purkinje cells from sex-matched females were screened for Y chromosomes by epifluorescence. Confocal laser scanning microscopy allowed definitive identification of the sex chromosomes within the morphologically distinct Purkinje cells. In the brains of females who received male bone marrow, four Purkinje neurons were found that contained an X and a Y chromosome and two other Purkinje neurons contained more than a diploid number of sex chromosomes. No Y chromosomes were detected in the brains of sex-matched controls. The total frequency of male bone marrow contribution to female Purkinje cells approximated 0.1%. This study demonstrates that although during human development Purkinje neurons are no longer generated after birth, cells within the bone marrow can contribute to these CNS neurons even in adulthood. The underlying mechanism may be caused either by generation de novo of Purkinje neurons from bone marrow-derived cells or by fusion of marrow-derived cells with existing recipient Purkinje neurons. PMID:12576546

  14. APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults

    PubMed Central

    Su, Yun Yan; Liang, Xue; Schoepf, U. Joseph; Varga-Szemes, Akos; West, Henry C.; Qi, Rongfeng; Kong, Xiang; Chen, Hui Juan; Lu, Guang Ming; Zhang, Long Jiang

    2015-01-01

    Abstract To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging. Seventy-six healthy adults (34 men, 23.7 ± 2.8 y; 31 APOE ε4/ε3 carriers, 31 ε3/ε3 carriers, and 14 ε2/ε3 carriers) were included. For resting-state functional MRI data, default mode network (DMN) and amplitude of low-frequency fluctuation maps were extracted and analyzed. Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests. There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the ε4/ε3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the ε3/ε3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the ε2/ε3 group (P < 0.05, Alphasim corrected). No differences of DMN FCs were found between the ε2/ε3 and ε3/ε3 groups. FCs in the right temporal lobe positively correlated with the performances of vocabulary learning, delayed recall, and graph recall in all participants (P < 0.05). APOE ε4 carriers exhibited significantly increased DMN FCs when compared with ε3 and ε2 carriers. The ε4 affects DMN FCs before brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect. PMID:26717353

  15. Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.

    PubMed

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban

    2012-06-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection.

  16. Abstracting meaning from complex information (gist reasoning) in adult traumatic brain injury.

    PubMed

    Vas, Asha Kuppachi; Spence, Jeffrey; Chapman, Sandra Bond

    2015-01-01

    Gist reasoning (abstracting meaning from complex information) was compared between adults with moderate-to-severe traumatic brain injury (TBI, n = 30) at least one year post injury and healthy adults (n = 40). The study also examined the contribution of executive functions (working memory, inhibition, and switching) and memory (immediate recall and memory for facts) to gist reasoning. The correspondence between gist reasoning and daily function was also examined in the TBI group. Results indicated that the TBI group performed significantly lower than the control group on gist reasoning, even after adjusting for executive functions and memory. Executive function composite was positively associated with gist reasoning (p < .001). Additionally, performance on gist reasoning significantly predicted daily function in the TBI group beyond the predictive ability of executive function alone (p = .011). Synthesizing and abstracting meaning(s) from information (i.e., gist reasoning) could provide an informative index into higher order cognition and daily functionality.

  17. Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain.

    PubMed

    van de Lagemaat, Louie N; Nijhof, Bonnie; Bosch, Daniëlle G M; Kohansal-Nodehi, Mahdokht; Keerthikumar, Shivakumar; Heimel, J Alexander

    2014-01-01

    Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted behavior and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesized to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an aging phenomenon in ASD rather than its underlying cause.

  18. Primary afferent plasticity following deafferentation of the trigeminal brainstem nuclei in the adult rat.

    PubMed

    De Riu, Pier Luigi; Russo, Antonella; Pellitteri, Rosalia; Stanzani, Stefania; Tringali, Giovanni; Roccazzello, Anna Maria; De Riu, Giacomo; Marongiu, Patrizia; Mameli, Ombretta

    2008-09-01

    Alpha-tyrosinated tubulin is a cytoskeletal protein that is involved in axonal growth and is considered a marker of neuronal plasticity in adult mammals. In adult rats, unilateral ablation of the left facial sensorimotor cortical areas induces degeneration of corticotrigeminal projections and marked denervation of the contralateral sensory trigeminal nuclei. Western blotting and real-time-PCR of homogenates of the contralateral trigeminal ganglion (TG) revealed consistent overexpression of growth proteins 15 days after left decortication in comparison with the ipsilateral side. Immunohistochemical analyses indicated marked overexpression of alpha-tyrosinated tubulin in the cells of the ganglion on the right side. Cytoskeletal changes were primarily observed in the small ganglionic neurons. Application of HRP-CT, WGA-HRP, and HRP to infraorbital nerves on both sides 15 days after left decortication showed a significant degree of terminal sprouting and neosynaptogenesis from right primary afferents at the level of the right caudalis and interpolaris trigeminal subnuclei. These observations suggest that the adaptive response of TG neurons to central deafferentation, leading to overcrowding and rearrangement of the trigeminal primary afferent terminals on V spinal subnuclei neurons, could represent the anatomical basis for distortion of facial modalities, perceived as allodynia and hyperalgesia, despite nerve integrity.

  19. Isolation and cultivation of adult primary bovine hepatocytes from abattoir derived liver

    PubMed Central

    Ehrhardt, Sonja; Schmicke, Marion

    2016-01-01

    The aim was to establish a cell culture of adult primary bovine hepatocytes obtained from liver following slaughter and to cultivate the cells in a sandwich culture. Cells and medium samples were taken after separation of cells (day 0), during monolayer (days 1, 2 and 3) and during sandwich culture (days 1, 2, 3, 4, 7, 10 and 14). The mRNA expression of BAX, BCL2L, FAS, IGF-1 and GHR1A was measured as well as urea and LDH. Hepatocytes were obtained by using a two-step collagenase perfusion and were purified thereafter by density gradient centrifugation. The viability was 68.2 ± 9.5 %. In sandwich culture, cells have a typical polygonal hepatocyte-like shape, build cell-cell contacts, and show irregularity of cell borders suggesting bile canaliculi generation. The BAX mRNA expression increased on day 1 as well but decreased steadily until day 3 and remained constant for 14 days. Urea- and LDH-concentrations increased from day 4 to day 7. In conclusion, we found that it is possible to gather viable primary hepatocytes from adult bovine liver after slaughter, and that cells gathered this way show typical morphologies, urea-production and low LDH-leakage especially at day 4 in a sandwich system. PMID:28275320

  20. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    SciTech Connect

    Burton, C.K.; Ho, I.K.; Hoskins, B.

    1986-03-01

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting /sup 3/H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities.

  1. The chemokine receptor cxcr5 regulates the regenerative neurogenesis response in the adult zebrafish brain

    PubMed Central

    2012-01-01

    Background Unlike mammals, zebrafish exhibits extensive neural regeneration after injury in adult stages of its lifetime due to the neurogenic activity of the radial glial cells. However, the genes involved in the regenerative neurogenesis response of the zebrafish brain are largely unknown. Thus, understanding the underlying principles of this regeneration capacity of the zebrafish brain is an interesting research realm that may offer vast clinical ramifications. Results In this paper, we characterized the expression pattern of cxcr5 and analyzed the function of this gene during adult neurogenesis and regeneration of the zebrafish telencephalon. We found that cxcr5 was upregulated transiently in the RGCs and neurons, and the expression in the immune cells such as leukocytes was negligible during both adult neurogenesis and regeneration. We observed that the transgenic misexpression of cxcr5 in the ventricular cells using dominant negative and full-length variants of the gene resulted in altered proliferation and neurogenesis response of the RGCs. When we knocked down cxcr5 using antisense morpholinos and cerebroventricular microinjection, we observed outcomes similar to the overexpression of the dominant negative cxcr5 variant. Conclusions Thus, based on our results, we propose that cxcr5 imposes a proliferative permissiveness to the radial glial cells and is required for differentiation of the RGCs to neurons, highlighting novel roles of cxcr5 in the nervous system of vertebrates. We therefore suggest that cxcr5 is an important cue for ventricular cell proliferation and regenerative neurogenesis in the adult zebrafish telencephalon. Further studies on the role of cxcr5 in mediating neuronal replenishment have the potential to produce clinical ramifications in efforts for regenerative therapeutic applications for human neurological disorders or acute injuries. PMID:22824261

  2. Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain.

    PubMed

    Nokia, Miriam S; Anderson, Megan L; Shors, Tracey J

    2012-12-01

    Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood-brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3-12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesised that chemotherapy disrupts learning via decreases in hippocampal adult neurogenesis and theta activity. Temozolomide was administered to adult male Sprague-Dawley rats in a cyclic manner for several weeks. Treatment was followed by training with different types of eyeblink classical conditioning, a form of associative learning. Chemotherapy reduced both neurogenesis and endogenous theta activity, as well as disrupted learning and related theta-band responses to the conditioned stimulus. The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the 'chemobrain'.

  3. "Unusual brain stone": heavily calcified primary neoplasm with some features suggestive of angiocentric glioma.

    PubMed

    Sajjad, Jahangir; Kaliaperumal, Chandrasekaran; Bermingham, Niamh; Marks, Charles; Keohane, Catherine

    2015-11-01

    This 40-year-old man presented with a 5-month history of progressive right-sided headache associated with visual blurring. He also had a history of epilepsy but had been seizure free with medication for the past 10 years. An initial CT scan of his brain performed 16 years previously had revealed a small area of calcification in the right parietal region. In the current presentation, he had a left-sided homonymous hemianopia but no other neurological deficits. A CT scan of his brain showed a much larger calcified, partly cystic lesion in the right parietal region. Because he was symptomatic, the lesion was excised and the cyst was drained. Histological examination of the excised tissue showed an unusual primary tumor that was difficult to classify but had some features of angiocentric glioma. The heavy calcification, mixed-density cell population, and regions with features of angiocentric glioma were most unusual. The patient remained asymptomatic 5 years after surgery, and follow-up scans did not show recurrence.

  4. Neurons are the Primary Target Cell for the Brain-Tropic Intracellular Parasite Toxoplasma gondii

    PubMed Central

    Dietrich, Hans K.; Nguyen, Elizabeth; MacDonald, Wes R.; Trivedi, Tapasya; Devineni, Asha; Koshy, Anita A.

    2016-01-01

    Toxoplasma gondii, a common brain-tropic parasite, is capable of infecting most nucleated cells, including astrocytes and neurons, in vitro. Yet, in vivo, Toxoplasma is primarily found in neurons. In vitro data showing that interferon-γ-stimulated astrocytes, but not neurons, clear intracellular parasites suggest that neurons alone are persistently infected in vivo because they lack the ability to clear intracellular parasites. Here we test this theory by using a novel Toxoplasma-mouse model capable of marking and tracking host cells that directly interact with parasites, even if the interaction is transient. Remarkably, we find that Toxoplasma shows a strong predilection for interacting with neurons throughout CNS infection. This predilection remains in the setting of IFN-γ depletion; infection with parasites resistant to the major mechanism by which murine astrocytes clear parasites; or when directly injecting parasites into the brain. These findings, in combination with prior work, strongly suggest that neurons are not incidentally infected, but rather they are Toxoplasma’s primary in vivo target. PMID:26895155

  5. Changing molecular profile of brain metastases compared with matched breast primary cancers and impact on clinical outcomes

    PubMed Central

    Thomson, A H; McGrane, J; Mathew, J; Palmer, J; Hilton, D A; Purvis, G; Jenkins, R

    2016-01-01

    Background: Breast cancer commonly metastasises to the brain, but little is known about changes in the molecular profile of the brain secondaries and impact on clinical outcomes. Methods: Patients with samples from brain metastases and matched breast cancers were included. Immunohistochemical analysis for oestrogen receptor, progesterone receptor, p27kip1, cyclin D1, epidermal growth factor receptor, insulin like growth factor 1, insulin like growth factor 1 receptor, vascular endothelial growth factor A, transforming growth factor-β and HER2 receptor was performed. Borderline HER2 results were analysed by fluorescent in situ hybridisation. Levels of expression were compared, with review of effect on clinical outcomes. Results: A total of 41 patients were included. Of the patients, 20% had a change in oestrogen receptor or HER2 in their brain metastasis that could affect therapeutic decisions. There were statistically significant rises in brain metastases for p27kip1 (P=0.023) and cyclin D1 (P=0.030) and a fall in vascular endothelial growth factor A (P=0.012). Overall survival from the time of metastasis increased significantly with oestrogen receptor-positive (P=0.005) and progesterone receptor-positive (P=0.013) brain lesions and with a longer duration from diagnosis of the breast primary (P<0.001). Conclusions: In this cohort there were phenotypic differences in metastatic brain tumours compared with matched primary breast tumours. These could be relevant for aetiology, and have an impact on prognostication, current and future therapies. PMID:26908328

  6. Mutational profiling of brain metastasis from breast cancer: matched pair analysis of targeted sequencing between brain metastasis and primary breast cancer.

    PubMed

    Lee, Ji Yun; Park, Kyunghee; Lim, Sung Hee; Kim, Hae Su; Yoo, Kwai Han; Jung, Ki Sun; Song, Haa-Na; Hong, Mineui; Do, In-Gu; Ahn, TaeJin; Lee, Se Kyung; Bae, Soo Youn; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Kim, Duk-Hwan; Jung, Hae Hyun; Kim, Ji-Yeon; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2015-12-22

    Although breast cancer is the second most common cause of brain metastasis with a notable increase of incidence, genes that mediate breast cancer brain metastasis (BCBM) are not fully understood. To study the molecular nature of brain metastasis, we performed gene expression profiling of brain metastasis and matched primary breast cancer (BC). We used the Ion AmpliSeq Cancer Panel v2 covering 2,855 mutations from 50 cancer genes to analyze 18 primary BC and 42 BCBM including 15 matched pairs. The most common BCBM subtypes were triple-negative (42.9%) and basal-like (36.6%). In a total of 42 BCBM samples, 32 (76.2%) harbored at least one mutation (median 1, range 0-7 mutations). Frequently detected somatic mutations included TP53 (59.5%), MLH1 (14.3%), PIK3CA (14.3%), and KIT (7.1%). We compared BCBM with patient-matched primary BC specimens. There were no significant differences in mutation profiles between the two groups. Notably, gene expression in BCBM such as TP53, PIK3CA, KIT, MLH1, and RB1 also seemed to be present in primary breast cancers. The TP53 mutation frequency was higher in BCBM than in primary BC (59.5% vs 38.9%, respectively). In conclusion, we found actionable gene alterations in BCBM that were maintained in primary BC. Further studies with functional testing and a delineation of the role of these genes in specific steps of the metastatic process should lead to a better understanding of the biology of metastasis and its susceptibility to treatment.

  7. Spred-2 expression is associated with neural repair of injured adult zebrafish brain.

    PubMed

    Lim, Fei Tieng; Ogawa, Satoshi; Parhar, Ishwar S

    2016-11-01

    Sprouty-related protein-2 (Spred-2) is a negative regulator of extracellular signal-regulated kinases (ERK) pathway, which is important for cell proliferation, neuronal differentiation, plasticity and survival. Nevertheless, its general molecular characteristics such as gene expression patterns and potential role in neural repair in the brain remain unknown. Thus, this study aimed to characterise the expression of spred-2 in the zebrafish brain. Digoxigenin-in situ hybridization showed spred-2 mRNA-expressing cells were mainly seen in the proliferative zones such as the olfactory bulb, telencephalon, optic tectum, cerebellum, and the dorsal and ventral hypothalamus, and most of which were neuronal cells. To evaluate the potential role of spred-2 in neuro-regeneration, spred-2 gene expression was examined in the dorsal telencephalon followed by mechanical-lesion. Real-time PCR showed a significant reduction of spred-2 mRNA levels in the telencephalon on 1-day till 2-days post-lesion and gradually increased to normal levels as compared with intact. Furthermore, to confirm involvement of Spred-2 signalling in the cell proliferation after brain injury, double-labelling of spred-2 in-situ hybridization with immunofluorescence of BrdU and phosphorylated-ERK1/2 (p-ERK1/2), a downstream of Spred-2 was performed. Increase of BrdU and p-ERK1/2 immunoreactive cells suggest that a decrease in spred-2 after injury might associated with activation of the ERK pathway to stimulate cell proliferation in the adult zebrafish brain. The present study demonstrates the possible role of Spred-2 signalling in cell proliferative phase during the neural repair in the injured zebrafish brain.

  8. New aspects in fenestrated capillary and tissue dynamics in the sensory circumventricular organs of adult brains.

    PubMed

    Miyata, Seiji

    2015-01-01

    The blood-brain barrier (BBB) generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs), which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP), have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs) sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF) signaling may be involved in angiogenesis and neurogliogenesis, both of

  9. Global integration of the hot-state brain network of appetite predicts short term weight loss in older adult

    PubMed Central

    Paolini, Brielle M.; Laurienti, Paul J.; Simpson, Sean L.; Burdette, Jonathan H.; Lyday, Robert G.; Rejeski, W. Jack

    2015-01-01

    Obesity is a public health crisis in North America. While lifestyle interventions for weight loss (WL) remain popular, the rate of success is highly variable. Clearly, self-regulation of eating behavior is a challenge and patterns of activity across the brain may be an important determinant of success. The current study prospectively examined whether integration across the Hot-State Brain Network of Appetite (HBN-A) predicts WL after 6-months of treatment in older adults. Our metric for network integration was global efficiency (GE). The present work is a sub-study (n = 56) of an ongoing randomized clinical trial involving WL. Imaging involved a baseline food-cue visualization functional MRI (fMRI) scan following an overnight fast. Using graph theory to build functional brain networks, we demonstrated that regions of the HBN-A (insula, anterior cingulate cortex (ACC), superior temporal pole (STP), amygdala and the parahippocampal gyrus) were highly integrated as evidenced by the results of a principal component analysis (PCA). After accounting for known correlates of WL (baseline weight, age, sex, and self-regulatory efficacy) and treatment condition, which together contributed 36.9% of the variance in WL, greater GE in the HBN-A was associated with an additional 19% of the variance. The ACC of the HBN-A was the primary driver of this effect, accounting for 14.5% of the variance in WL when entered in a stepwise regression following the covariates, p = 0.0001. The HBN-A is comprised of limbic regions important in the processing of emotions and visceral sensations and the ACC is key for translating such processing into behavioral consequences. The improved integration of these regions may enhance awareness of body and emotional states leading to more successful self-regulation and to greater WL. This is the first study among older adults to prospectively demonstrate that, following an overnight fast, GE of the HBN-A during a food visualization task is predictive of

  10. Global integration of the hot-state brain network of appetite predicts short term weight loss in older adult.

    PubMed

    Paolini, Brielle M; Laurienti, Paul J; Simpson, Sean L; Burdette, Jonathan H; Lyday, Robert G; Rejeski, W Jack

    2015-01-01

    Obesity is a public health crisis in North America. While lifestyle interventions for weight loss (WL) remain popular, the rate of success is highly variable. Clearly, self-regulation of eating behavior is a challenge and patterns of activity across the brain may be an important determinant of success. The current study prospectively examined whether integration across the Hot-State Brain Network of Appetite (HBN-A) predicts WL after 6-months of treatment in older adults. Our metric for network integration was global efficiency (GE). The present work is a sub-study (n = 56) of an ongoing randomized clinical trial involving WL. Imaging involved a baseline food-cue visualization functional MRI (fMRI) scan following an overnight fast. Using graph theory to build functional brain networks, we demonstrated that regions of the HBN-A (insula, anterior cingulate cortex (ACC), superior temporal pole (STP), amygdala and the parahippocampal gyrus) were highly integrated as evidenced by the results of a principal component analysis (PCA). After accounting for known correlates of WL (baseline weight, age, sex, and self-regulatory efficacy) and treatment condition, which together contributed 36.9% of the variance in WL, greater GE in the HBN-A was associated with an additional 19% of the variance. The ACC of the HBN-A was the primary driver of this effect, accounting for 14.5% of the variance in WL when entered in a stepwise regression following the covariates, p = 0.0001. The HBN-A is comprised of limbic regions important in the processing of emotions and visceral sensations and the ACC is key for translating such processing into behavioral consequences. The improved integration of these regions may enhance awareness of body and emotional states leading to more successful self-regulation and to greater WL. This is the first study among older adults to prospectively demonstrate that, following an overnight fast, GE of the HBN-A during a food visualization task is predictive of

  11. Coping, quality of life, and hope in adults with primary antibody deficiencies

    PubMed Central

    Sigstad, Hanne Marie Høybråten; Stray-Pedersen, Asbjørg; Frøland, Stig S

    2005-01-01

    Background Living with a chronic disease, such as primary antibody deficiency, will often have consequences for quality of life. Previous quality-of-life studies in primary antibody deficiency patients have been limited to different treatment methods. We wanted to study how adults with primary antibody deficiencies manage their conditions and to identify factors that are conducive to coping, good quality of life and hope. Methods Questionnaires were sent to all patients ≥20 years of age with primary antibody deficiencies who were served by Rikshospitalet University Hospital. The questionnaires consisted of several standardized scales: Ferrans and Powers Quality of Life Index (QLI), Short Form-36 (SF-36), Jalowiec Coping Scale (JCS), Nowotny Hope Scale (NHS), and one scale we devised with questions about resources and pressures in the past. Of a total of 91, 55 patients (aged 23–76 years) answered the questionnaires. The questionnaire study were supplemented with selected interviews of ten extreme cases, five with low and five with high quality of life scores. Results Among the 55 patients, low quality of life scores were related to unemployment, infections in more than four organs, more than two additional diseases, or more than two specific occurrences of stress in the last 2–3 months. Persons with selective IgA deficiency had significantly higher QLI scores than those with other antibody deficiencies. An optimistic coping style was most frequent used, and hope values were moderately high. Based on the interviews, the patients could be divided into three groups: 1) low QLI scores, low hope values, and reduced coping, 2) low QLI scores, moderate hope values, and good coping, and 3) high QLI scores, moderate to strong hope values, and good coping. Coping was related to the patients' sense of closeness and competence. Conclusion Low quality of life scores in adults with primary antibody deficiencies were linked to unemployment and disease-related strains

  12. Neuroprotective effect of chondroitinase ABC on primary and secondary brain injury after stroke in hypertensive rats.

    PubMed

    Chen, Xin-ran; Liao, Song-jie; Ye, Lan-xiang; Gong, Qiong; Ding, Qiao; Zeng, Jin-sheng; Yu, Jian

    2014-01-16

    Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12 U/d for 7 days) 24 h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction.

  13. Rapid Genotyping of Animals Followed by Establishing Primary Cultures of Brain Neurons

    PubMed Central

    Huang, Zhengmin; Harata, N. Charles

    2015-01-01

    High-resolution analysis of the morphology and function of mammalian neurons often requires the genotyping of individual animals followed by the analysis of primary cultures of neurons. We describe a set of procedures for: labeling newborn mice to be genotyped, rapid genotyping, and establishing low-density cultures of brain neurons from these mice. Individual mice are labeled by tattooing, which allows for long-term identification lasting into adulthood. Genotyping by the described protocol is fast and efficient, and allows for automated extraction of nucleic acid with good reliability. This is useful under circumstances where sufficient time for conventional genotyping is not available, e.g., in mice that suffer from neonatal lethality. Primary neuronal cultures are generated at low density, which enables imaging experiments at high spatial resolution. This culture method requires the preparation of glial feeder layers prior to neuronal plating. The protocol is applied in its entirety to a mouse model of the movement disorder DYT1 dystonia (ΔE-torsinA knock-in mice), and neuronal cultures are prepared from the hippocampus, cerebral cortex and striatum of these mice. This protocol can be applied to mice with other genetic mutations, as well as to animals of other species. Furthermore, individual components of the protocol can be used for isolated sub-projects. Thus this protocol will have wide applications, not only in neuroscience but also in other fields of biological and medical sciences. PMID:25742545

  14. Incidence of diabetes mellitus type 2 complications among Saudi adult patients at primary health care center

    PubMed Central

    Alsenany, Samira; Al Saif, Amer

    2015-01-01

    [Purpose] This study analyzed type 2 diabetes and its role in complications among adult Saudi patients. [Subjects] Patients attending four primary health care centers in Jeddah were enrolled. [Methods] A cross-sectional design study among Saudi patients attending Ministry of Health primary health care centers in Jeddah was selected for use by the Primary Health Care administration. Patients were interviewed with structured questionnaires to determine the presence of diabetes and risk factors using questions about the history of any disease. [Results] Diabetes mellitus was present in 234 subjects during the data collection period (March–June 2014). Mean patient age was 58 years; diabetes prevalence was 42% in males and 58% in females. The mean age for diabetes onset in males and females was 34 and 39 years, respectively. There was a higher incidence of obesity (75%) associated with a sedentary lifestyle (body mass index ≥25) in females (N= 96; 40%) compared with males (N= 87; 36%). In this study, >44% of individuals aged 55 or older had severe to uncontrolled diabetes with long-term complications. The age-adjusted incidence of hypertension and coronary heart disease was 38% and 24%, respectively, showing a clear incidence of diabetes associated with cardiovascular disease in Saudi Arabia. [Conclusion] This study found that a multifactorial approach to managing diabetes complication risks is needed. PMID:26180307

  15. Protein-engineered scaffolds for in vitro 3D culture of primary adult intestinal organoids.

    PubMed

    DiMarco, Rebecca L; Dewi, Ruby E; Bernal, Gabriela; Kuo, Calvin; Heilshorn, Sarah C

    2015-10-15

    Though in vitro culture of primary intestinal organoids has gained significant momentum in recent years, little has been done to investigate the impact of microenvironmental cues provided by the encapsulating matrix on the growth and development of these fragile cultures. In this work, the impact of various in vitro culture parameters on primary adult murine organoid formation and growth are analyzed with a focus on matrix properties and geometric culture configuration. The air-liquid interface culture configuration was found to result in enhanced organoid formation relative to a traditional submerged configuration. Additionally, through use of a recombinantly engineered extracellular matrix (eECM), the effects of biochemical and biomechanical cues were independently studied. Decreasing mechanical stiffness and increasing cell adhesivity were found to increase organoid yield. Tuning of eECM properties was used to obtain organoid formation efficiency values identical to those observed in naturally harvested collagen I matrices but within a stiffer construct with improved ease of physical manipulation. Increased ability to remodel the surrounding matrix through mechanical or enzymatic means was also shown to enhance organoid formation. As the engineering and tunability of recombinant matrices is essentially limitless, continued property optimization may result in further improved matrix performance and may help to identify additional microenvironmental cues that directly impact organoid formation, development, differentiation, and functional behavior. Continued culture of primary organoids in recombinant matrices could therefore prove to be largely advantageous in the field of intestinal tissue engineering for applications in regenerative medicine and in vitro tissue mimics.

  16. Reading in the brain of children and adults: A meta‐analysis of 40 functional magnetic resonance imaging studies

    PubMed Central

    Martin, Anna; Schurz, Matthias; Kronbichler, Martin

    2015-01-01

    Abstract We used quantitative, coordinate‐based meta‐analysis to objectively synthesize age‐related commonalities and differences in brain activation patterns reported in 40 functional magnetic resonance imaging (fMRI) studies of reading in children and adults. Twenty fMRI studies with adults (age means: 23–34 years) were matched to 20 studies with children (age means: 7–12 years). The separate meta‐analyses of these two sets showed a pattern of reading‐related brain activation common to children and adults in left ventral occipito‐temporal (OT), inferior frontal, and posterior parietal regions. The direct statistical comparison between the two meta‐analytic maps of children and adults revealed higher convergence in studies with children in left superior temporal and bilateral supplementary motor regions. In contrast, higher convergence in studies with adults was identified in bilateral posterior OT/cerebellar and left dorsal precentral regions. The results are discussed in relation to current neuroanatomical models of reading and tentative functional interpretations of reading‐related activation clusters in children and adults are provided. Hum Brain Mapp 36:1963–1981, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25628041

  17. Ribosomal protein L11 is related to brain maturation during the adult phase in Apis cerana cerana (Hymenoptera, Apidae).

    PubMed

    Meng, Fei; Lu, Wenjing; Yu, Feifei; Kang, Mingjiang; Guo, Xingqi; Xu, Baohua

    2012-05-01

    Ribosomal proteins (RPs) play pivotal roles in developmental regulation. The loss or mutation of ribosomal protein L11 (RPL11) induces various developmental defects. However, few RPs have been functionally characterized in Apis cerana cerana. In this study, we isolated a single copy gene, AccRPL11, and characterized its connection to brain maturation. AccRPL11 expression was highly concentrated in the adult brain and was significantly induced by abiotic stresses such as pesticides and heavy metals. Immunofluorescence assays demonstrated that AccRPL11 was localized to the medulla, lobula and surrounding tissues of esophagus in the brain. The post-transcriptional knockdown of AccRPL11 gene expression resulted in a severe decrease in adult brain than in other tissues. The expression levels of other brain development-related genes, p38, ERK2, CacyBP and CREB, were also reduced. Immunofluorescence signal attenuation was also observed in AccRPL11-rich regions of the brain in dsAccRPL11-injected honeybees. Taken together, these results suggest that AccRPL11 may be functional in brain maturation in honeybee adults.

  18. Ribosomal protein L11 is related to brain maturation during the adult phase in Apis cerana cerana (Hymenoptera, Apidae)

    NASA Astrophysics Data System (ADS)

    Meng, Fei; Lu, Wenjing; Yu, Feifei; Kang, Mingjiang; Guo, Xingqi; Xu, Baohua

    2012-05-01

    Ribosomal proteins (RPs) play pivotal roles in developmental regulation. The loss or mutation of ribosomal protein L11 ( RPL11) induces various developmental defects. However, few RPs have been functionally characterized in Apis cerana cerana. In this study, we isolated a single copy gene, AccRPL11, and characterized its connection to brain maturation. AccRPL11 expression was highly concentrated in the adult brain and was significantly induced by abiotic stresses such as pesticides and heavy metals. Immunofluorescence assays demonstrated that AccRPL11 was localized to the medulla, lobula and surrounding tissues of esophagus in the brain. The post-transcriptional knockdown of AccRPL11 gene expression resulted in a severe decrease in adult brain than in other tissues. The expression levels of other brain development-related genes, p38, ERK2, CacyBP and CREB, were also reduced. Immunofluorescence signal attenuation was also observed in AccRPL11-rich regions of the brain in ds AccRPL11-injected honeybees. Taken together, these results suggest that AccRPL11 may be functional in brain maturation in honeybee adults.

  19. Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature.

    PubMed

    Li, Qing-Quan; Qiao, Guan-Qun; Ma, Jun; Fan, Hong-Wei; Li, Ying-Bin

    2015-02-01

    The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  20. Cacna1c: Protecting young hippocampal neurons in the adult brain.

    PubMed

    De Jesús-Cortés, Héctor; Rajadhyaksha, Anjali M; Pieper, Andrew A

    2016-01-01

    Neuropsychiatric disease is the leading cause of disability in the United States, and fourth worldwide.(1,2) Not surprisingly, human genetic studies have revealed a common genetic predisposition for many forms of neuropsychiatric disease, potentially explaining why overlapping symptoms are commonly observed across multiple diagnostic categories. For example, the CACNA1C gene was recently identified in the largest human genome-wide association study to date as a risk loci held in common across 5 major forms of neuropsychiatric disease: bipolar disorder, schizophrenia, major depressive disorder (MDD), autism spectrum disorder and attention deficit-hyperactivity disorder.(3) This gene encodes for the Cav1.2 subunit of the L-type voltage-gated calcium channel (LTCC), accounting for 85% of LTCCs in the brain, while the Cav1.3 subunit comprises the remainder.(4) In neurons, LTCCs mediate calcium influx in response to membrane depolarization,(5) thereby regulating neurotransmission and gene expression. Here, we describe our recent finding that Cav1.2 also controls survival of young hippocampal neurons in the adult brain, which has been linked to the etiology and treatment of neuropsychiatric disease. We also describe the effective restoration of young hippocampal neuron survival in adult Cav1.2 forebrain-specific conditional knockout mice using the neuroprotective compound P7C3-A20.

  1. Neuronal sources of hedgehog modulate neurogenesis in the adult planarian brain

    PubMed Central

    Currie, Ko W; Molinaro, Alyssa M; Pearson, Bret J

    2016-01-01

    The asexual freshwater planarian is a constitutive adult, whose central nervous system (CNS) is in a state of constant homeostatic neurogenesis. However, very little is known about the extrinsic signals that act on planarian stem cells to modulate rates of neurogenesis. We have identified two planarian homeobox transcription factors, Smed-nkx2.1 and Smed-arx, which are required for the maintenance of cholinergic, GABAergic, and octopaminergic neurons in the planarian CNS. These very same neurons also produce the planarian hedgehog ligand (Smed-hh), which appears to communicate with brain-adjacent stem cells to promote normal levels of neurogenesis. Planarian stem cells nearby the brain express core hh signal transduction genes, and consistent hh signaling levels are required to maintain normal production of neural progenitor cells and new mature cholinergic neurons, revealing an important mitogenic role for the planarian hh signaling molecule in the adult CNS. DOI: http://dx.doi.org/10.7554/eLife.19735.001 PMID:27864883

  2. Nerve growth factor in the adult brain of a teleostean model for aging research: Nothobranchius furzeri.

    PubMed

    D'Angelo, L; Castaldo, L; Cellerino, A; de Girolamo, P; Lucini, C

    2014-07-01

    Nerve growth factor (NGF) acts on central nervous system neurons, regulating naturally occurring cell death, synaptic connectivity, fiber guidance and dendritic morphology. The dynamically regulated production of NGF beginning in development, extends throughout adult life and aging, exerting numerous roles through a surprising variety of neurons and glial cells. This study analyzes the localization of NGF in the brain of the teleost fish Nothobranchius furzeri, an emerging model for aging research due to its short lifespan. Immunochemical and immunohistochemical experiments were performed by employing an antibody mapping at the N-terminus of the mature chain human origin NGF. Western blot analysis revealed an intense and well defined band of 20 kDa, which corresponds to proNGF of N. furzeri. Immunohistochemistry revealed NGF immunoreactivity (IR) diffused throughout all regions of telencephalon, diencephalon, mesencephalon and rhomboencephalon. It was detected in neurons and in glial cells, the latter mostly lining the mesencephalic and rhomboencephalic ventricles. Particularly in neurons, NGF IR was localized in perikarya and, to a less extent, in fibers. The widespread distribution of proNGF suggests that it might modulate numerous physiological functions in the adult brain of N. furzeri. The present survey constitutes a baseline study to enhance the understanding of the mechanisms underlying the role of NGF during aging processes.

  3. Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria

    PubMed Central

    Chao, L.L.; Mueller, S.G.; Buckley, S.T.; Peek, K.; Raptentsetseng, S.; Elman, J.; Yaffe, K.; Miller, B.L.; Kramer, J.H.; Madison, C.; Mungas, D.; Schuff, N.; Weiner, M.W.

    2008-01-01

    We sought to determine whether there are structural and metabolic changes in the brains of older adults with cognitive complaints yet who do not meet MCI criteria (i.e., preMCI). We compared the volumes of regional lobar gray matter (GM) and medial temporal lobe structures, including the hippocampus, entorhinal cortex (ERC), fusiform and parahippocampal gyri, and metabolite ratios from the posterior cingulate in individuals who had a Clinical Demetia Rating (CDR) of 0.5, but who did not meet MCI criteria (preMCI, N = 17), patients with mild cognitive impairment (MCI, N = 13), and cognitively normal controls (N = 18). Controls had more ERC, fusiform, and frontal gray matter volume than preMCI and MCI subjects and greater parahippocampal volume and more posterior cingulate N-acetylaspartate (NAA)/myoinosotil (mI) than MCI. There were no significant differences between MCI and preMCI subjects on any of these measures. These findings suggest there are neurodegenerative changes in the brains of older adults who have cognitive complaints severe enough to qualify for CDR = 0.5 yet show no deficits on formal neuropsychological testing. The results further support the hypothesis that detection of individuals with very mild forms of Alzheimer's disease (AD) may be facilitated by use of the CDR, which emphasizes changes in cognition over time within individuals rather than comparison with group norms. PMID:18550226

  4. Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria.

    PubMed

    Chao, L L; Mueller, S G; Buckley, S T; Peek, K; Raptentsetseng, S; Elman, J; Yaffe, K; Miller, B L; Kramer, J H; Madison, C; Mungas, D; Schuff, N; Weiner, M W

    2010-03-01

    We sought to determine whether there are structural and metabolic changes in the brains of older adults with cognitive complaints yet who do not meet MCI criteria (i.e., preMCI). We compared the volumes of regional lobar gray matter (GM) and medial temporal lobe structures, including the hippocampus, entorhinal cortex (ERC), fusiform and parahippocampal gyri, and metabolite ratios from the posterior cingulate in individuals who had a Clinical Demetia Rating (CDR) of 0.5, but who did not meet MCI criteria (preMCI, N=17), patients with mild cognitive impairment (MCI, N=13), and cognitively normal controls (N=18). Controls had more ERC, fusiform, and frontal gray matter volume than preMCI and MCI subjects and greater parahippocampal volume and more posterior cingulate N-acetylaspartate (NAA)/myoinosotil (mI) than MCI. There were no significant differences between MCI and preMCI subjects on any of these measures. These findings suggest there are neurodegenerative changes in the brains of older adults who have cognitive complaints severe enough to qualify for CDR=0.5 yet show no deficits on formal neuropsychological testing. The results further support the hypothesis that detection of individuals with very mild forms of Alzheimer's disease (AD) may be facilitated by use of the CDR, which emphasizes changes in cognition over time within individuals rather than comparison with group norms.

  5. MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain.

    PubMed

    Nguyen, Minh Vu Chuong; Du, Fang; Felice, Christy A; Shan, Xiwei; Nigam, Aparna; Mandel, Gail; Robinson, John K; Ballas, Nurit

    2012-07-18

    Mutations in the X-linked gene, methyl-CpG binding protein 2 (Mecp2), underlie a wide range of neuropsychiatric disorders, most commonly, Rett Syndrome (RTT), a severe autism spectrum disorder that affects approximately one in 10,000 female live births. Because mutations in the Mecp2 gene occur in the germ cells with onset of neurological symptoms occurring in early childhood, the role of MeCP2 has been ascribed to brain maturation at a specific developmental window. Here, we show similar kinetics of onset and progression of RTT-like symptoms in mice, including lethality, if MeCP2 is removed postnatally during the developmental stage that coincides with RTT onset, or adult stage. For the first time, we show that brains that lose MeCP2 at these two different stages are actively shrinking, resulting in higher than normal neuronal cell density. Furthermore, we show that mature dendritic arbors of pyramidal neurons are severely retracted and dendritic spine density is dramatically reduced. In addition, hippocampal astrocytes have significantly less complex ramified processes. These changes accompany a striking reduction in the levels of several synaptic proteins, including CaMKII α/β, AMPA, and NMDA receptors, and the synaptic vesicle proteins Vglut and Synapsin, which represent critical modifiers of synaptic function and dendritic arbor structure. Importantly, the mRNA levels of these synaptic proteins remains unchanged, suggesting that MeCP2 likely regulates these synaptic proteins post-transcriptionally, directly or indirectly. Our data suggest a crucial role for MeCP2 in post-transcriptional regulation of critical synaptic proteins involved in maintaining mature neuronal networks during late stages of postnatal brain development.

  6. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods

    PubMed Central

    Barth, Claudia; Villringer, Arno; Sacher, Julia

    2015-01-01

    Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo. PMID:25750611

  7. Physical Activity and Brain Function in Older Adults at Increased Risk for Alzheimer’s Disease

    PubMed Central

    Smith, J. Carson; Nielson, Kristy A.; Woodard, John L.; Seidenberg, Michael; Rao, Stephen M.

    2013-01-01

    Leisure-time physical activity (PA) and exercise training are known to help maintain cognitive function in healthy older adults. However, relatively little is known about the effects of PA on cognitive function or brain function in those at increased risk for Alzheimer’s disease through the presence of the apolipoproteinE epsilon4 (APOE-ε4) allele, diagnosis of mild cognitive impairment (MCI), or the presence of metabolic disease. Here, we examine the question of whether PA and exercise interventions may differentially impact cognitive trajectory, clinical outcomes, and brain structure and function among individuals at the greatest risk for AD. The literature suggests that the protective effects of PA on risk for future dementia appear to be larger in those at increased genetic risk for AD. Exercise training is also effective at helping to promote stable cognitive function in MCI patients, and greater cardiorespiratory fitness is associated with greater brain volume in early-stage AD patients. In APOE-ε4 allele carriers compared to non-carriers, greater levels of PA may be more effective in reducing amyloid burden and are associated with greater activation of semantic memory-related neural circuits. A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for AD. PMID:24961307

  8. Pre-Adult MRI of Brain Cancer and Neurological Injury: Multivariate Analyses.

    PubMed

    Levman, Jacob; Takahashi, Emi

    2016-01-01

    Brain cancer and neurological injuries, such as stroke, are life-threatening conditions for which further research is needed to overcome the many challenges associated with providing optimal patient care. Multivariate analysis (MVA) is a class of pattern recognition technique involving the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of neuroimaging challenges, including identifying variables associated with patient outcomes; understanding an injury's etiology, development, and progression; creating diagnostic tests; assisting in treatment monitoring; and more. Compared to adults, imaging of the developing brain has attracted less attention from MVA researchers, however, remarkable MVA growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to brain injury and cancer in neurological fetal, neonatal, and pediatric magnetic resonance imaging (MRI). With a wide variety of MRI modalities providing physiologically meaningful biomarkers and new biomarker measurements constantly under development, MVA techniques hold enormous potential toward combining available measurements toward improving basic research and the creation of technologies that contribute to improving patient care.

  9. Pre-Adult MRI of Brain Cancer and Neurological Injury: Multivariate Analyses

    PubMed Central

    Levman, Jacob; Takahashi, Emi

    2016-01-01

    Brain cancer and neurological injuries, such as stroke, are life-threatening conditions for which further research is needed to overcome the many challenges associated with providing optimal patient care. Multivariate analysis (MVA) is a class of pattern recognition technique involving the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of neuroimaging challenges, including identifying variables associated with patient outcomes; understanding an injury’s etiology, development, and progression; creating diagnostic tests; assisting in treatment monitoring; and more. Compared to adults, imaging of the developing brain has attracted less attention from MVA researchers, however, remarkable MVA growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to brain injury and cancer in neurological fetal, neonatal, and pediatric magnetic resonance imaging (MRI). With a wide variety of MRI modalities providing physiologically meaningful biomarkers and new biomarker measurements constantly under development, MVA techniques hold enormous potential toward combining available measurements toward improving basic research and the creation of technologies that contribute to improving patient care. PMID:27446888

  10. Efficient Uptake and Dissemination of Scrapie Prion Protein by Astrocytes and Fibroblasts from Adult Hamster Brain

    PubMed Central

    Hollister, Jason R.; Lee, Kil Sun; Dorward, David W.; Baron, Gerald S.

    2015-01-01

    Prion infections target neurons and lead to neuronal loss. However, the role of non-neuronal cells in the initiation and spread of infection throughout the brain remains unclear despite the fact these cells can also propagate prion infectivity. To evaluate how different brain cells process scrapie prion protein (PrPres) during acute infection, we exposed neuron-enriched and non-neuronal cell cultures from adult hamster brain to fluorescently-labeled purified PrPres and followed the cultures by live cell confocal imaging over time. Non-neuronal cells present in both types of cultures, specifically astrocytes and fibroblasts, internalized PrPres more efficiently than neurons. PrPres was trafficked to late endosomal/lysosomal compartments and rapidly transported throughout the cell bodies and processes of all cell types, including contacts between astrocytes and neurons. These observations suggest that astrocytes and meningeal fibroblasts play an as yet unappreciated role in prion infections via efficient uptake and dissemination of PrPres. PMID:25635871

  11. Efficient uptake and dissemination of scrapie prion protein by astrocytes and fibroblasts from adult hamster brain.

    PubMed

    Hollister, Jason R; Lee, Kil Sun; Dorward, David W; Baron, Gerald S

    2015-01-01

    Prion infections target neurons and lead to neuronal loss. However, the role of non-neuronal cells in the initiation and spread of infection throughout the brain remains unclear despite the fact these cells can also propagate prion infectivity. To evaluate how different brain cells process scrapie prion protein (PrPres) during acute infection, we exposed neuron-enriched and non-neuronal cell cultures from adult hamster brain to fluorescently-labeled purified PrPres and followed the cultures by live cell confocal imaging over time. Non-neuronal cells present in both types of cultures, specifically astrocytes and fibroblasts, internalized PrPres more efficiently than neurons. PrPres was trafficked to late endosomal/lysosomal compartments and rapidly transported throughout the cell bodies and processes of all cell types, including contacts between astrocytes and neurons. These observations suggest that astrocytes and meningeal fibroblasts play an as yet unappreciated role in prion infections via efficient uptake and dissemination of PrPres.

  12. Self-reported electrical appliance use and risk of adult brain tumors.

    PubMed

    Kleinerman, Ruth A; Linet, Martha S; Hatch, Elizabeth E; Tarone, Robert E; Black, Peter M; Selker, Robert G; Shapiro, William R; Fine, Howard A; Inskip, Peter D

    2005-01-15

    Electrical appliances produce the highest intensity exposures to residential extremely low frequency electromagnetic fields. The authors investigated whether appliances may be associated with adult brain tumors in a hospital-based case-control study at three centers in the United States from 1994 to 1998. A total of 410 glioma, 178 meningioma, and 90 acoustic neuroma cases and 686 controls responded to a self-administered questionnaire about 14 electrical appliances. There was little evidence of association between brain tumors and curling iron, heating pad, vibrating massager, electric blanket, heated water bed, sound system, computer, television, humidifier, microwave oven, and electric stove. Ever use of hair dryers was associated with glioma (odds ratio = 1.7, 95% confidence interval: 1.1, 2.5), but there was no evidence of increasing risk with increasing amount of use. In men, meningioma was associated with electric shaver use (odds ratio = 10.9, 95% confidence interval: 2.3, 50), and odds ratios increased with cumulative minutes of use, although they were based on only two nonexposed cases. Recall bias for appliances used regularly near the head or chance may provide an alternative explanation for the observed associations. Overall, results indicate that extremely low frequency electromagnetic fields from commonly used household appliances are unlikely to increase the risk of brain tumors.

  13. Expression of FoxP2 during zebrafish development and in the adult brain.

    PubMed

    Shah, Rina; Medina-Martinez, Olga; Chu, Li-Fang; Samaco, Rodney C; Jamrich, Milan

    2006-01-01

    Fox (forkhead) genes encode transcription factors that play important roles in the regulation of embryonic patterning as well as in tissue specific gene expression. Mutations in the human FOXP2 gene cause abnormal speech development. Here we report the structure and expression pattern of zebrafish FoxP2. In zebrafish, this gene is first expressed at the 20-somite stage in the presumptive telencephalon. At this stage there is a significant overlap of FoxP2 expression with the expression of the emx homeobox genes. However, in contrast to emx1, FoxP2 is not expressed in the pineal gland or in the pronephric duct. After 72 hours of development, the expression of zebrafish FoxP2 becomes more complex in the brain. The developing optic tectum becomes the major area of FoxP2 expression. In the adult brain, the highest concentrations of the FoxP2 transcript can be observed in the optic tectum. In the cerebellum, only the caudal lobes show high levels of Foxp2 expression. These regions correspond to the vestibulocerebellum of mammals. Several other regions of the brain also show high levels of Foxp2 expression.

  14. Long-chain omega-3 fatty acids improve brain function and structure in older adults.

    PubMed

    Witte, A Veronica; Kerti, Lucia; Hermannstädter, Henrike M; Fiebach, Jochen B; Schreiber, Stephan J; Schuchardt, Jan Philipp; Hahn, Andreas; Flöel, Agnes

    2014-11-01

    Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) may be beneficial for the aging brain. We tested in a prospective interventional design whether high levels of supplementary LC-n3-FA would improve cognition, and addressed potential mechanisms underlying the effects. Sixty-five healthy subjects (50-75 years, 30 females) successfully completed 26 weeks of either fish oil (2.2 g/day LC-n3-FA) or placebo intake. Before and after the intervention period, cognitive performance, structural neuroimaging, vascular markers, and blood parameters were assayed. We found a significant increase in executive functions after LC-n3-FA compared with placebo (P = 0.023). In parallel, LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal, temporal, parietal, and limbic areas primarily of the left hemisphere, and on carotid intima media thickness and diastolic blood pressure. Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor, and negatively with changes in peripheral fasting insulin. This double-blind randomized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults, and elucidates underlying mechanisms. Our findings suggest novel strategies to maintain cognitive functions into old age.

  15. Neurobiological markers of exercise-related brain plasticity in older adults.

    PubMed

    Voss, Michelle W; Erickson, Kirk I; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S; Alves, Heloisa; Szabo, Amanda; Phillips, Siobhan M; Wójcicki, Thomas R; Mailey, Emily L; Olson, Erin A; Gothe, Neha; Vieira-Potter, Victoria J; Martin, Stephen A; Pence, Brandt D; Cook, Marc D; Woods, Jeffrey A; McAuley, Edward; Kramer, Arthur F

    2013-02-01

    The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age=66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF.

  16. Organization and cellular arrangement of two neurogenic regions in the adult ferret (Mustela putorius furo) brain.

    PubMed

    Takamori, Yasuharu; Wakabayashi, Taketoshi; Mori, Tetsuji; Kosaka, Jun; Yamada, Hisao

    2014-06-01

    In the adult mammalian brain, two neurogenic regions have been characterized, the subventricular zone (SVZ) of the lateral ventricle (LV) and the subgranular zone (SGZ) of the dentate gyrus (DG). Despite remarkable knowledge of rodents, the detailed arrangement of neurogenic regions in most mammals is poorly understood. In this study, we used immunohistochemistry and cell type-specific antibodies to investigate the organization of two germinal regions in the adult ferret, which belongs to the order Carnivora and is widely used as a model animal with a gyrencephalic brain. From the SVZ to the olfactory bulb, doublecortin-positive cells tended to organize in chain-like clusters, which are surrounded by a meshwork of astrocytes. This structure is homologous to the rostral migratory stream (RMS) described in other species. Different from rodents, the horizontal limb of the RMS emerges directly from the LV, and the anterior region of the LV extends rostrally and reached the olfactory bulb. In the DG, glial fibrillary acidic protein-positive cells with long radial processes as well as doublecortin-positive cells are oriented in the SGZ. In both regions, doublecortin-positive cells showed characteristic morphology and were positive for polysialylated-neural cell adhesion molecule, beta-III tubulin, and lamin B1 (intense staining). Proliferating cells were detected in both regions using antibodies against proliferating cell nuclear antigen and phospho-histone H3. These observations demonstrate that the two neurogenic regions in ferrets have a similar cellular composition as those of other mammalian species despite anatomical differences in the brain.

  17. Sensitivity to theta-burst timing permits LTP in dorsal striatal adult brain slice

    PubMed Central

    Hawes, Sarah L.; Gillani, Fawad; Evans, Rebekah C.; Benkert, Elizabeth A.

    2013-01-01

    Long-term potentiation (LTP) of excitatory afferents to the dorsal striatum likely occurs with learning to encode new skills and habits, yet corticostriatal LTP is challenging to evoke reliably in brain slice under physiological conditions. Here we test the hypothesis that stimulating striatal afferents with theta-burst timing, similar to recently reported in vivo temporal patterns corresponding to learning, evokes LTP. Recording from adult mouse brain slice extracellularly in 1 mM Mg2+, we find LTP in dorsomedial and dorsolateral striatum is preferentially evoked by certain theta-burst patterns. In particular, we demonstrate that greater LTP is produced using moderate intraburst and high theta-range frequencies, and that pauses separating bursts of stimuli are critical for LTP induction. By altering temporal pattern alone, we illustrate the importance of burst-patterning for LTP induction and demonstrate that corticostriatal long-term depression is evoked in the same preparation. In accord with prior studies, LTP is greatest in dorsomedial striatum and relies on N-methyl-d-aspartate receptors. We also demonstrate a requirement for both Gq- and Gs/olf-coupled pathways, as well as several kinases associated with memory storage: PKC, PKA, and ERK. Our data build on previous reports of activity-directed plasticity by identifying effective values for distinct temporal parameters in variants of theta-burst LTP induction paradigms. We conclude that those variants which best match reports of striatal activity during learning behavior are most successful in evoking dorsal striatal LTP in adult brain slice without altering artificial cerebrospinal fluid. Future application of this approach will enable diverse investigations of plasticity serving striatal-based learning. PMID:23926032

  18. Brain system size and adult-adult play in primates: a comparative analysis of the roles of the non-visual neocortex and the amygdala.

    PubMed

    Pellis, Sergio M; Iwaniuk, Andrew N

    2002-08-21

    Recent studies have shown that contrary to expectation, larger-brained species within mammalian orders are not more likely to engage in play. This is true for juvenile rodents, juvenile marsupials and adult primates. Neither does the relative size of the neocortex predict the prevalence of play in species of marsupials and primates. Two methodological limitations may account for the lack of such relationships. Firstly, play may only vary systematically with specific brain areas, not overall size increases in brain tissue. Secondly, the play indices used to measure the variation in play across species may be insufficiently sensitive to the effects of changes in brain size. In this study, we attempt to deal with the first methodological problem. The adult-adult play fighting among species of primates was correlated with the relative size of the non-visual cortex and the amygdala. The statistical analyses used took into account the problems of scaling and corrected for degree of phylogenetic relatedness among the species. The size of the non-visual cortex failed to predict the prevalence of play fighting occurring in either sexual or non-sexual contexts. In contrast, the size of the amygdala significantly predicted the prevalence of sexual play, but not non-sexual play. That is, species with larger sized amygdala are more likely to engage in sexual play. These findings provide new insights into the role of different brain systems in the regulation of play behavior.

  19. Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults

    PubMed Central

    List, Jonathan; Ott, Stefanie; Bukowski, Martin; Lindenberg, Robert; Flöel, Agnes

    2015-01-01

    Recurrent mild traumatic brain injuries (mTBIs) are regarded as an independent risk factor for developing dementia in later life. We here aimed to evaluate associations between recurrent mTBIs, cognition, and gray matter volume and microstructure as revealed by structural magnetic resonance imaging (MRI) in the chronic phase after mTBIs in young adulthood. We enrolled 20 young-to-middle-aged subjects, who reported two or more sports-related mTBIs, with the last mTBI > 6 months prior to study enrolment (mTBI group), and 21 age-, sex- and education matched controls with no history of mTBI (control group). All participants received comprehensive neuropsychological testing, and high resolution T1-weighted and diffusion tensor MRI in order to assess cortical thickness (CT) and microstructure, hippocampal volume, and ventricle size. Compared to the control group, subjects of the mTBI group presented with lower CT within the right temporal lobe and left insula using an a priori region of interest approach. Higher number of mTBIs was associated with lower CT in bilateral insula, right middle temporal gyrus and right entorhinal area. Our results suggest persistent detrimental effects of recurrent mTBIs on CT already in young-to-middle-aged adults. If additional structural deterioration occurs during aging, subtle neuropsychological decline may progress to clinically overt dementia earlier than in age-matched controls, a hypothesis to be assessed in future prospective trials. PMID:26052275

  20. Impact of Patient Portal Secure Messages and Electronic Visits on Adult Primary Care Office Visits

    PubMed Central

    Crane, Sarah J.; Chaudhry, Rajeev; Ebbert, Jon O.; Ytterberg, Karen; Tulledge-Scheitel, Sidna M.; Stroebel, Robert J.

    2014-01-01

    Abstract Introduction: Secure messages and electronic visits (“e-visits”) through patient portals provide patients with alternatives to face-to-face appointments, telephone contact, letters, and e-mails. Limited information exists on how portal messaging impacts face-to-face visits in primary care. Materials and Methods: We conducted a retrospective cohort study of 2,357 primary care patients who used electronic messaging (both secure messages and e-visits) on a patient portal. Face-to-face appointment frequencies (visits/year) of each patient were calculated before and after the first message in a matched-pairs analysis. We analyzed visit frequencies with and without adjustments for a first message surge in visits, and we examined subgroups of high message utilizers and long-term users. Results: Primary care patients who sent at least one message (secure message or e-visit) had a mean of 2.43 (standard deviation [SD] 2.3) annual face-to-face visits before the first message and 2.47 (SD 2.8) after, a nonsignificant difference (p=0.45). After adjustment for a first message surge in visits, no significant visit frequency differences were observed (mean, 2.35 annual visits per patient both before and after first message; p=0.93). Subgroup analysis also showed no significant change in visit frequency for patients with higher message utilization or for those who had used the messaging feature longer. Conclusions: No significant change in face-to-face visit frequency was observed following implementation of portal messaging. Secure messaging and e-visits through a patient portal may not result in a change of adult primary care face-to-face visits. PMID:24350803

  1. Purines regulate adult brain subventricular zone cell functions: contribution of reactive astrocytes.

    PubMed

    Boccazzi, Marta; Rolando, Chiara; Abbracchio, Maria P; Buffo, Annalisa; Ceruti, Stefania

    2014-03-01

    Brain injuries modulate activation of neural stem cells (NSCs) in the adult brain. In pathological conditions, the concentrations of extracellular nucleotides (eNTs) raise several folds, contribute to reactive gliosis, and possibly directly affect subventricular zone (SVZ) cell functioning. Among eNTs and derived metabolites, the P2Y1 receptor agonist ADP strongly promotes astrogliosis and might also influence SVZ progenitor activity. Here, we tested the ability of the stable P2Y1 agonist adenosine 5'-O-(2-thiodiphosphate) (ADPβS) to control adult NSC functions both in vitro and in vivo, with a focus on the possible effects exerted by reactive astrocytes. In the absence of growth factors, ADPβS promoted proliferation and differentiation of SVZ progenitors. Moreover, ADPβS-activated astrocytes markedly changed the pattern of released cytokines and chemokines, and strongly modulated neurosphere-forming capacity of SVZ progenitors. Notably, a significant enhancement in proliferation was observed when SVZ cells, initially grown in the supernatant of astrocytes exposed to ADPβS, were shifted to normal medium. In vivo, ADPβS administration in the lateral ventricle of adult mice by osmotic minipumps caused diffused reactive astrogliosis, and a strong response of SVZ progenitors. Indeed, proliferation of glial fibrillary acidic protein-positive NSCs increased and led to a significant expansion of SVZ transit-amplifying progenitors and neuroblasts. Lineage tracing experiments performed in the GLAST::CreERT2;Rosa-YFP transgenic mice further demonstrated that ADPβS promoted proliferation of glutamate/aspartate transporter-positive progenitors and sustained their progression toward the generation of rapidly dividing progenitors. Altogether, our results show that the purinergic system crucially affects SVZ progenitor activities both directly and through the involvement of reactive astrocytes.

  2. Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome.

    PubMed

    Gu, Li-Na; Zhang, Min; Zhu, Hui; Liu, Jing-Yao

    2016-10-01

    Neuromyelitis optica spectrum disorder often co-exists with primary Sjögren's syndrome. We compared the clinical features of 16 neuromyelitis optica spectrum disorder patients with (n = 6) or without primary Sjögren's syndrome (n = 10). All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinuclear autoantibody, anti-Sjögren's-syndrome-related antigen A antibodies, anti-Sjögren's-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjögren's syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% (4/6) of patients with primary Sjögren's syndrome and in 60% (6/10) of patients without primary Sjögren's syndrome. More brain abnormalities were observed in patients without primary Sjögren's syndrome than in those with primary Sjögren's syndrome. Segments lesions (> 3 centrum) were noted in 50% (5/10) of patients without primary Sjögren's syndrome and in 67% (4/6) of patients with primary Sjögren's syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome are similar. However, neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome have a high frequency of brain abnormalities.

  3. Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome

    PubMed Central

    Gu, Li-na; Zhang, Min; Zhu, Hui; Liu, Jing-yao

    2016-01-01

    Neuromyelitis optica spectrum disorder often co-exists with primary Sjögren's syndrome. We compared the clinical features of 16 neuromyelitis optica spectrum disorder patients with (n = 6) or without primary Sjögren's syndrome (n = 10). All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinuclear autoantibody, anti-Sjögren's-syndrome-related antigen A antibodies, anti-Sjögren's-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjögren's syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% (4/6) of patients with primary Sjögren's syndrome and in 60% (6/10) of patients without primary Sjögren's syndrome. More brain abnormalities were observed in patients without primary Sjögren's syndrome than in those with primary Sjögren's syndrome. Segments lesions (> 3 centrum) were noted in 50% (5/10) of patients without primary Sjögren's syndrome and in 67% (4/6) of patients with primary Sjögren's syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome are similar. However, neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome have a high frequency of brain abnormalities. PMID:27904495

  4. In-hospital Mobility Variations across Primary Diagnoses among Older Adults

    PubMed Central

    Valiani, Vincenzo; Gao, Shiyao; Chen, Zhiguo; Swami, Sunil; Harle, Christopher A.; Lipori, Gigi; Sourdet, Sandrine; Wu, Samuel; Nayfield, Susan G.; Sabbá, Carlo; Pahor, Marco; Manini, Todd M.

    2016-01-01

    Objectives To examine the relationship between primary diagnoses and mobility impairment and recovery among hospitalized older adults. Design Prospective cohort study. Setting UF Health Shands Hospital, an 852-bed level I trauma center located in Gainesville, Florida. Participants 18,551 older adults (≥65 years) with 29,148 hospitalizations between 1/2009 and 4/2014. Measurements Incident and discharge mobility impairment and recovery were assessed using the Braden activity subscale score that was recorded by the nursing staff at every shift change–approximately three times per day. Primary diagnosis ICD-9 codes were used as predictors and re-categorized by using the Agency for Health Care Research and Quality Clinical Classification Software. Results Out of the 15,498 hospital records where the patient was initially observed to “walk frequently”, 3,186 (20.6%) developed incident mobility impairment (chair-fast or bedfast). Primary diagnoses with a surgical or invasive procedure were the most prevalent (77.2 %) among the hospital observations with incident mobility impairment; otherwise primary diagnoses without surgery were much more associated with discharge mobility impairment (59%). The highest incidence of mobility impairment occurred in patients with heart valve disorders and aortic and peripheral/visceral artery aneurysms (6.24 and 6.05 events per 30 person-days, respectively); septicemia showed the highest incidence rate for mobility limitation at discharge (0.94 events per 30 person-days). Mobility impairment was observed in 13,650 (46.8% of total) records at admission and 5,930 (43.44%) were observed to recover to a state of walking occasionally or frequently. Osteoarthritis and cancer of gastrointestinal organs/peritoneum had the highest incidence rate for mobility recovery (7.68 and 5.63 events per 30 person-days respectively). Conclusions Approximately 1 out of 5 patients who were mobile at admission became significantly impaired during

  5. Adult sports-related traumatic brain injury in United States trauma centers.

    PubMed

    Winkler, Ethan A; Yue, John K; Burke, John F; Chan, Andrew K; Dhall, Sanjay S; Berger, Mitchel S; Manley, Geoffrey T; Tarapore, Phiroz E

    2016-04-01

    OBJECTIVE Sports-related traumatic brain injury (TBI) is an important public health concern estimated to affect 300,000 to 3.8 million people annually in the United States. Although injuries to professional athletes dominate the media, this group represents only a small proportion of the overall population. Here, the authors characterize the demographics of sports-related TBI in adults from a community-based trauma population and identify predictors of prolonged hospitalization and increased morbidity and mortality rates. METHODS Utilizing the National Sample Program of the National Trauma Data Bank (NTDB), the authors retrospectively analyzed sports-related TBI data from adults (age ≥ 18 years) across 5 sporting categories-fall or interpersonal contact (FIC), roller sports, skiing/snowboarding, equestrian sports, and aquatic sports. Multivariable regression analysis was used to identify predictors of prolonged hospital length of stay (LOS), medical complications, inpatient mortality rates, and hospital discharge disposition. Statistical significance was assessed at α < 0.05, and the Bonferroni correction for multiple comparisons was applied for each outcome analysis. RESULTS From 2003 to 2012, in total, 4788 adult sports-related TBIs were documented in the NTDB, which represented 18,310 incidents nationally. Equestrian sports were the greatest contributors to sports-related TBI (45.2%). Mild TBI represented nearly 86% of injuries overall. Mean (± SEM) LOSs in the hospital or intensive care unit (ICU) were 4.25 ± 0.09 days and 1.60 ± 0.06 days, respectively. The mortality rate was 3.0% across all patients, but was statistically higher in TBI from roller sports (4.1%) and aquatic sports (7.7%). Age, hypotension on admission to the emergency department (ED), and the severity of head and extracranial injuries were statistically significant predictors of prolonged hospital and ICU LOSs, medical complications, failure to discharge to home, and death. Traumatic

  6. Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer

    ClinicalTrials.gov

    2014-04-21

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Malignant Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineocytoma; Malignant Neoplasm; Meningeal Melanocytoma; Radiation Toxicity; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma

  7. Measuring inhibitory control in children and adults: brain imaging and mental chronometry.

    PubMed

    Houdé, Olivier; Borst, Grégoire

    2014-01-01

    Jean Piaget underestimated the cognitive capabilities of infants, preschoolers, and elementary schoolchildren, and overestimated the capabilities of adolescents and even adults which are often biased by illogical intuitions and overlearned strategies (i.e., "fast thinking" in Daniel Kahneman's words). The crucial question is now to understand why, despite rich precocious knowledge about physical and mathematical principles observed over the last three decades in infants and young children, older children, adolescents and even adults are nevertheless so often bad reasoners. We propose that inhibition of less sophisticated solutions (or heuristics) by the prefrontal cortex is a domain-general executive ability that supports children's conceptual insights associated with more advanced Piagetian stages, such as number-conservation and class inclusion. Moreover, this executive ability remains critical throughout the whole life and even adults may sometimes need "prefrontal pedagogy" in order to learn inhibiting intuitive heuristics (or biases) in deductive reasoning tasks. Here we highlight some of the discoveries from our lab in the field of cognitive development relying on two methodologies used for measuring inhibitory control: brain imaging and mental chronometry (i.e., the negative priming paradigm). We also show that this new approach opens an avenue for re-examining persistent errors in standard classroom-learning tasks.

  8. Measuring inhibitory control in children and adults: brain imaging and mental chronometry

    PubMed Central

    Houdé, Olivier; Borst, Grégoire

    2014-01-01

    Jean Piaget underestimated the cognitive capabilities of infants, preschoolers, and elementary schoolchildren, and overestimated the capabilities of adolescents and even adults which are often biased by illogical intuitions and overlearned strategies (i.e., “fast thinking” in Daniel Kahneman’s words). The crucial question is now to understand why, despite rich precocious knowledge about physical and mathematical principles observed over the last three decades in infants and young children, older children, adolescents and even adults are nevertheless so often bad reasoners. We propose that inhibition of less sophisticated solutions (or heuristics) by the prefrontal cortex is a domain-general executive ability that supports children’s conceptual insights associated with more advanced Piagetian stages, such as number-conservation and class inclusion. Moreover, this executive ability remains critical throughout the whole life and even adults may sometimes need “prefrontal pedagogy” in order to learn inhibiting intuitive heuristics (or biases) in deductive reasoning tasks. Here we highlight some of the discoveries from our lab in the field of cognitive development relying on two methodologies used for measuring inhibitory control: brain imaging and mental chronometry (i.e., the negative priming paradigm). We also show that this new approach opens an avenue for re-examining persistent errors in standard classroom-learning tasks. PMID:24994993

  9. Functional Connectivity Abnormalities of Brain Regions with Structural Deficits in Young Adult Male Smokers

    PubMed Central

    Bu, Limei; Yu, Dahua; Su, Shaoping; Ma, Yao; von Deneen, Karen M.; Luo, Lin; Zhai, Jinquan; Liu, Bo; Cheng, Jiadong; Guan, Yanyan; Li, Yangding; Bi, Yanzhi; Xue, Ting; Lu, Xiaoqi; Yuan, Kai

    2016-01-01

    Smoking is one of the most prevalent dependence disorders. Previous studies have detected structural and functional deficits in smokers. However, few studies focused on the changes of resting state functional connectivity (RSFC) of the brain regions with structural deficits in young adult smokers. Twenty-six young adult smokers and 26 well-matched healthy non-smokers participated in our study. Voxel-based morphometry (VBM) and RSFC were employed to investigate the structural and functional changes in young adult smokers. Compared with healthy non-smokers, young smokers showed increased gray matter (GM) volume in the left putamen and decreased GM volume in the left anterior cingulate cortex (ACC). Moreover, GM volume in the left ACC has a negative correlation trend with pack-years and GM volume in the left putamen was positively correlated with pack-years. The left ACC and putamen with abnormal volumes were chosen as the regions of interest (ROIs) for the RSFC analysis. We found that smokers showed increased RSFC between the left ACC and right amygdala and between the left putamen and right anterior insula. We revealed structural and functional deficits within the frontostriatal circuits in young smokers, which may shed new insights into the neural mechanisms of smoking. PMID:27757078

  10. Mapping of brain lipid binding protein (Blbp) in the brain of adult zebrafish, co-expression with aromatase B and links with proliferation.

    PubMed

    Diotel, Nicolas; Vaillant, Colette; Kah, Olivier; Pellegrini, Elisabeth

    2016-01-01

    Adult fish exhibit a strong neurogenic capacity due to the persistence of radial glial cells. In zebrafish, radial glial cells display well-established markers such as the estrogen-synthesizing enzyme (AroB) and the brain lipid binding protein (Blbp), which is known to strongly bind omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). While Blpb is mainly described in the telencephalon of adult zebrafish, its expression in the remaining regions of the brain is poorly documented. The present study was designed to further investigate Blbp expression in the brain, its co-expression with AroB, and its link with radial glial cells proliferation in zebrafish. We generated a complete and detailed mapping of Blbp expression in the whole brain and show its complete co-expression with AroB, except in some tectal and hypothalamic regions. By performing PCNA and Blbp immunohistochemistry on cyp19a1b-GFP (AroB-GFP) fish, we also demonstrated preferential Blbp expression in proliferative radial glial cells in almost all regions studied. To our knowledge, this is the first complete and detailed mapping of Blbp-expressing cells showing strong association between Blbp and radial glial cell proliferation in the adult brain of fish. Given that zebrafish is now recognized models for studying neurogenesis and brain repair, our data provide detailed characterization of Blbp in the entire brain and open up a broad field of research investigating the role of omega-3 polyunsaturated fatty acids in neural stem cell activity in fish.

  11. Assessing the Quality of a Nonrandomized Pragmatic Trial for Primary Prevention of Falls among Older Adults

    PubMed Central

    Albert, Steven M.; Edelstein, Offer; King, Jennifer; Flatt, Jason; Lin, Chyongchiou J.; Boudreau, Robert; Newman, Anne B.

    2014-01-01

    Background Current approaches to falls prevention mostly rely on secondary and tertiary prevention and target individuals at high risk of falls. An alternative is primary prevention, in which all seniors are screened, referred as appropriate, and educated regarding falls risk. Little information is available on research designs that allow investigation of this approach in the setting of aging services delivery, where randomization may not be possible. Methods Healthy Steps for Older Adults, a statewide program of the Pennsylvania (PA) Department of Aging, involves a combination of education about falls and screening for balance problems, with referral to personal physicians and home safety assessments. We developed a nonrandomized statewide trial, Falls Free PA, to assess its effectiveness in reducing falls incidence over 12 months. We recruited 814 seniors who completed the program (503 first time participants, 311 people repeating the program) and 1020 who did not participate in the program, from the same sites. We assessed the quality of this nonrandomized design by examining recruitment, follow-up across study groups, and comparability at baseline. Results Of older adults approached in senior centers, 90.5% (n=2219) signed informed consent, and 1834 (82.4%) completed baseline assessments and were eligible for follow-up. Attrition in the three groups over 12 months was low and non-differential (<10% for withdrawal and <2% for other loss to follow-up). Median follow-up, which involved standardized monthly assessment of falls, was 10 months in all study groups. At baseline the groups did not differ in measures of health or falls risk factors. Conclusions Comparable status at baseline, recruitment from common sites, and similar experience with retention suggest that the nonrandomized design will be effective for assessment of this approach to primary prevention of falls. PMID:24488533

  12. Activity, Inhibition, and Induction of Cytochrome P450 2J2 in Adult Human Primary Cardiomyocytes

    PubMed Central

    Evangelista, Eric A.; Kaspera, Rüdiger; Mokadam, Nahush A.; Jones, J. P.

    2013-01-01

    Cytochrome P450 2J2 plays a significant role in the epoxidation of arachidonic acid to signaling molecules important in cardiovascular events. CYP2J2 also contributes to drug metabolism and is responsible for the intestinal clearance of ebastine. However, the interaction between arachidonic acid metabolism and drug metabolism in cardiac tissue, the main expression site of CYP2J2, has not been examined. Here we investigate an adult-derived human primary cardiac cell line as a suitable model to study metabolic drug interactions (inhibition and induction) of CYP2J2 in cardiac tissue. The primary human cardiomyocyte cell line demonstrated similar mRNA-expression profiles of P450 enzymes to adult human ventricular tissue. CYP2J2 was the dominant isozyme with minor contributions from CYP2D6 and CYP2E1. Both terfenadine and astemizole oxidation were observed in this cell line, whereas midazolam was not metabolized suggesting lack of CYP3A activity. Compared with recombinant CYP2J2, terfenadine was hydroxylated in cardiomyocytes at a similar Km value of 1.5 μM. The Vmax of terfenadine hydroxylation in recombinant enzyme was found to be 29.4 pmol/pmol P450 per minute and in the cells 6.0 pmol/pmol P450 per minute. CYP2J2 activity in the cell line was inhibited by danazol, astemizole, and ketoconazole in submicromolar range, but also by xenobiotics known to cause cardiac adverse effects. Of the 14 compounds tested for CYP2J2 induction, only rosiglitazone increased mRNA expression, by 1.8-fold. This cell model can be a useful in vitro model to investigate the role of CYP2J2-mediated drug metabolism, arachidonic acid metabolism, and their association to drug induced cardiotoxicity. PMID:24021950

  13. Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis

    PubMed Central

    Carlson, Kaitlin S.

    2016-01-01

    Abstract The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether the olfactory system requires 5-HT for even its most basic behavioral functions. To address this question, we established a conditional genetic approach to specifically target adult brain tryptophan hydroxylase 2 (Tph2), encoding the rate-limiting enzyme in brain 5-HT synthesis, and nearly eliminate 5-HT from the mouse forebrain. Using this novel model, we investigated the behavior of 5-HT–depleted mice during performance in an olfactory go/no-go task. Surprisingly, the near elimination of 5-HT from the forebrain, including the olfactory bulbs, had no detectable effect on the ability of mice to perform the odor-based task. Tph2-targeted mice not only were able to learn the task, but also had levels of odor acuity similar to those of control mice when performing coarse odor discrimination. Both groups of mice spent similar amounts of time sampling odors during decision-making. Furthermore, odor reversal learning was identical between 5-HT–depleted and control mice. These results suggest that 5-HT neurotransmission is not necessary for the most essential aspects of olfaction, including odor learning, discrimination, and certain forms of cognitive flexibility. PMID:27896310

  14. Higher brain BDNF gene expression is associated with slower cognitive decline in older adults

    PubMed Central

    Yu, Lei; Boyle, Patricia A.; Schneider, Julie A.; De Jager, Philip L.; Bennett, David A.

    2016-01-01

    Objectives: We tested whether brain-derived neurotrophic factor (BDNF) gene expression levels are associated with cognitive decline in older adults. Methods: Five hundred thirty-five older participants underwent annual cognitive assessments and brain autopsy at death. BDNF gene expression was measured in the dorsolateral prefrontal cortex. Linear mixed models were used to examine whether BDNF expression was associated with cognitive decline adjusting for age, sex, and education. An interaction term was added to determine whether this association varied with clinical diagnosis proximate to death (no cognitive impairment, mild cognitive impairment, or dementia). Finally, we examined the extent to which the association of Alzheimer disease (AD) pathology with cognitive decline varied by BDNF expression. Results: Higher brain BDNF expression was associated with slower cognitive decline (p < 0.001); cognitive decline was about 50% slower with the 90th percentile BDNF expression vs 10th. This association was strongest in individuals with dementia. The level of BDNF expression was lower in individuals with pathologic AD (p = 0.006), but was not associated with macroscopic infarcts, Lewy body disease, or hippocampal sclerosis. BDNF expression remained associated with cognitive decline in a model adjusting for age, sex, education, and neuropathologies (p < 0.001). Furthermore, the effect of AD pathology on cognitive decline varied by BDNF expression such that the effect was strongest for high levels of AD pathology (p = 0.015); thus, in individuals with high AD pathology (90th percentile), cognitive decline was about 40% slower with the 90th percentile BDNF expression vs 10th. Conclusions: Higher brain BDNF expression is associated with slower cognitive decline and may also reduce the deleterious effects of AD pathology on cognitive decline. PMID:26819457

  15. Prolongation of Relaxation Time in Extraocular Muscles With Brain Derived Neurotrophic Factor in Adult Rabbit

    PubMed Central

    Nelson, Krysta R.; Stevens, Shanlee M.; McLoon, Linda K.

    2016-01-01

    Purpose We tested the hypothesis that short-term treatment with brain derived neurotrophic factor (BDNF) would alter the contractile characteristics of rabbit extraocular muscle (EOM). Methods One week after injections of BDNF in adult rabbit superior rectus muscles, twitch properties were determined in treated and control muscles in vitro. Muscles were also examined for changes in mean cross-sectional areas, neuromuscular junction size, and percent of myofibers expressing specific myosin heavy chain isoforms, and sarcoendoplasmic reticulum calcium ATPases (SERCA) 1 and 2. Results Brain derived neurotrophic factor–treated muscles had prolonged relaxation times compared with control muscles. Time to 50% relaxation, time to 100% relaxation, and maximum rate of relaxation were increased by 24%, 27%, and 25%, respectively. No significant differences were seen in time to peak force, twitch force, or maximum rate of contraction. Brain derived neurotrophic factor treatment significantly increased mean cross-sectional areas of slow twitch and tonic myofibers, with increased areas ranging from 54% to 146%. Brain derived neurotrophic factor also resulted in an increased percentage of slow twitch myofibers in the orbital layers, ranging from 54% to 77%, and slow-tonic myofibers, ranging from 44% to 62%. No significant changes were seen SERCA1 or 2 expression or in neuromuscular junction size. Conclusions Short-term treatment with BDNF significantly prolonged the duration and rate of relaxation time and increased expression of both slow-twitch and slow-tonic myosin-expressing myofibers without changes in neuromuscular junctions or SERCA expression. The changes induced by BDNF treatment might have potential therapeutic value in dampening/reducing uncontrolled eye oscillations in nystagmus. PMID:27802489

  16. Immunolocalization of androgen receptors and aromatase enzyme in the adult musk shrew brain.

    PubMed

    Veney, S L; Rissman, E F

    2000-07-01

    In the brain and other tissues, estrogens are produced by aromatization of androgens. Biochemical data suggest that aromatase enzyme is regulated by the androgen receptor (AR). Neurons that contain either AR or aromatase (AROM) enzyme reside in many of the same brain regions. In this report, we examined the codistribution of AR- and AROM-enzyme-immunoreactive (-ir) neurons in several regions of the adult male and female musk shrew brain. Data were collected from the intermediate nucleus of the lateral septum (LS), medial anterior (BNSTMA) and medial posterointerior (BNSTMP) divisions of the bed nucleus of the stria terminalis, medial preoptic area (mPOA), ventromedial nucleus of the hypothalamus (VMN), medial (MeA), cortical and central nuclei of the amygdala. Males had significantly more AR-ir neurons in the BNSTMP, mPOA, VMN and LS as compared to females. With the exception of the BNSTMA and LS, males had more AROM-ir neurons in each region than females. Furthermore, males had significantly more double-labeled neurons than females in the BNSTMP, mPOA, VMN, LS and MeA. The percentage of AROM-ir neurons that also contained AR immunoreactivity ranged from 13 to 82% depending on sex and region. The highest percentage of dual-labeled neurons (79% in females and 82% in males) was found in the VMN. Taken together, these data show that there is extensive cellular colocalization of AR and AROM enzyme in specific regions of the musk shrew brain. We propose that in both sexes, androgen receptors may act as transcription factors to regulate AROM enzyme.

  17. Beyond high-dose methotrexate and brain radiotherapy: novel targets and agents for primary CNS lymphoma

    PubMed Central

    Ponzoni, M.; Issa, S.; Batchelor, T. T.; Rubenstein, J. L.

    2014-01-01

    Background While there has been significant progress in outcomes for patients diagnosed with primary central nervous system (CNS) lymphoma (PCNSL), survival rates will likely plateau with the current armamentarium of agents used to treat these patients. Moreover, given that PCNSL increasingly impacts an older population, a significant proportion of patients are not eligible for intensive therapies such as high-dose chemotherapy or whole-brain radiation. There is a need for the development of novel agents, which target key survival pathways in order to continue to make progress in this disease. Patients and methods We reviewed the key molecular pathways and genomic aberrations in PCNSL in order to identify candidate targets. We focused on molecules and pathways that have been identified and confirmed by more than one investigator or methodology. Results While PCNSL tumors usually express a BCL6+, MUM1+ ‘activated, germinal center’ immunophenotype, they exhibit multiple shared genetic properties with ABC-type diffuse large B-cell lymphomas. Candidate targets and pathways include NFkB, the B-cell receptor, the JAK/STAT pathway, IRF4, BCL-6 as well as PIM kinases. Elements of the tumor microenvironment that may be exploited therapeutically include chemokine pathways, as well as macrophage and T-cell responses. Conclusions There is a significant need for developing novel therapies in PCNSL, given that an increasing proportion of patients are not eligible for high-dose chemotherapy and brain radiation is associated with detrimental cognitive side-effects. We provide an overview of potential drug targets and novel agents that may be integrated with existing strategies in order to make further progress in this disease. PMID:24265352

  18. Long-term memory shapes the primary olfactory center of an insect brain.

    PubMed

    Hourcade, Benoît; Perisse, Emmanuel; Devaud, Jean-Marc; Sandoz, Jean-Christophe

    2009-10-01

    The storage of stable memories is generally considered to rely on changes in the functional properties and/or the synaptic connectivity of neural networks. However, these changes are not easily tractable given the complexity of the learning procedures and brain circuits studied. Such a search can be narrowed down by studying memories of specific stimuli in a given sensory modality and by working on networks with a modular and relatively simple organization. We have therefore focused on associative memories of individual odors and the possible related changes in the honeybee primary olfactory center, the antennal lobe (AL). As this brain structure is organized in well-identified morpho-functional units, the glomeruli, we looked for evidence of structural and functional plasticity in these units in relation with the bees' ability to store long-term memories (LTMs) of specific odors. Restrained bees were trained to form an odor-specific LTM in an appetitive Pavlovian conditioning protocol. The stability and specificity of this memory was tested behaviorally 3 d after conditioning. At that time, we performed both a structural and a functional analysis on a subset of 17 identified glomeruli by measuring glomerular volume under confocal microscopy, and odor-evoked activity, using in vivo calcium imaging. We show that long-term olfactory memory for a given odor is associated with volume increases in a subset of glomeruli. Independent of these structural changes, odor-evoked activity was not modified. Lastly, we show that structural glomerular plasticity can be predicted based on a putative model of interglomerular connections.

  19. Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and CNS Homeostasis

    PubMed Central

    Tran, Khiem A.; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F.; Göthert, Joachim R.; Malik, Asrar B.; Valyi-Nagy, Tibor; Zhao, You-Yang

    2015-01-01

    Background The blood-brain barrier (BBB) formed by brain endothelial cells (ECs) interconnected by tight junctions (TJs) is essential for the homeostasis of the central nervous system (CNS). Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Methods and Results Using a mouse model with tamoxifen-inducible EC-restricted disruption of ctnnb1 (iCKO), here we show that endothelial β-catenin signaling is essential for maintaining BBB integrity and CNS homeostasis in adult. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and CNS inflammation, and all died postictal. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of specific TJ proteins Claudin-1 and -3 in adult brain ECs. The clinical relevance of the data is indicated by the observation of decreased expression of Claudin-1 and nuclear β-catenin in brain ECs of hemorrhagic lesions of hemorrhagic stroke patients. Conclusion These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity and CNS inflammation. PMID:26538583

  20. Compound heterozygote mutations in SPG7 in a family with adult-onset primary lateral sclerosis

    PubMed Central

    Yang, Yi; Lynch, David R.; Lukas, Thomas; Ahmeti, Kreshnik; Sleiman, Patrick M.A.; Ryan, Eanna; Schadt, Kimberly A.; Newman, Jordan H.; Deng, Han-Xiang; Siddique, Nailah

    2016-01-01

    Objective: To identify the genetic defect for adult-onset primary lateral sclerosis (PLS) in a family with 5 patients. Methods: Whole-exome sequencing was performed to identify the shared genetic variants in 3 affected members in a PLS family with 5 affected individuals. Sanger sequencing was used for validation of the variants and for cosegregation analysis. Mitochondrial activity for both patients and unaffected siblings was measured using a SeaHorse metabolic analyzer. Results: Whole-exome sequencing and subsequent cosegregation analysis demonstrated that compound heterozygous missense variants L695P and I743T in SPG7 were the only mutations cosegregating with the disease in an autosomal recessive fashion in this family. The parents and siblings are genetically heterozygous and clinically unaffected. Functional studies suggested that the PLS-associated SPG7 mutants affect mitochondrial function when glucose is reduced. Conclusions: Compound heterozygote mutations in SPG7 are associated with adult-onset PLS, extending the spectrum of SPG7-linked neurologic diseases. Patients with the PLS phenotype should have genetic testing for paraplegin, especially when the condition is familial. PMID:27123479

  1. A quality-of-life measure for adults with primary ciliary dyskinesia: QOL–PCD

    PubMed Central

    Behan, Laura; Dunn Galvin, Audrey; Alpern, Adrianne; Morris, Anjana M.; Carroll, Mary P.; Knowles, Michael R.; Leigh, Margaret W.; Quittner, Alexandra L.

    2015-01-01

    Primary ciliary dyskinesia (PCD) is characterised by chronic suppurative lung disease, rhino-sinusitis, hearing impairment and sub-fertility. We have developed the first multidimensional measure to assess health-related quality of life (HRQoL) in adults with PCD (QOL–PCD). Following a literature review and expert panel meeting, open-ended interviews with patients investigated the impact of PCD on HRQoL in the UK and North America (n=21). Transcripts were content analysed to derive saturation matrices. Items were rated for relevance by patients (n=49). Saturation matrices, relevance scores, literature review, evaluation of existing measures, and expert opinion contributed to development of a preliminary questionnaire. The questionnaire was refined following cognitive interviews (n=18). Open-ended interviews identified a spectrum of issues unique to adults with PCD. Saturation matrices confirmed comprehensive coverage of content. QOL–PCD includes 48 items covering the following seven domains: Physical Functioning, Emotional Functioning, Treatment Burden, Respiratory and Sinus Symptoms, Ears and Hearing, Social Functioning, and Vitality and Health Perceptions. Cognitive testing confirmed that content was comprehensive and the items were well-understood by respondents. Content validity and cognitive testing supported the items and structure. QOL–PCD has been translated into other languages and is awaiting psychometric testing. PMID:25976687

  2. Voluntary physical exercise promotes ocular dominance plasticity in adult mouse primary visual cortex.

    PubMed

    Kalogeraki, Evgenia; Greifzu, Franziska; Haack, Franziska; Löwel, Siegrid

    2014-11-12

    Ocular dominance (OD) plasticity in the mouse primary visual cortex (V1) declines during aging and is absent beyond postnatal day (P) 110 when mice are raised in standard cages (SCs; Lehmann and Löwel, 2008). In contrast, raising mice in an enriched environment (EE) preserved a juvenile-like OD plasticity into late adulthood (Greifzu et al., 2014). EE raising provides the mice with more social interactions, voluntary physical exercise, and cognitive stimulation compared with SC, raising the question whether all components are needed or whether one of them is already sufficient to prolong plasticity. To test whether voluntary physical exercise alone already prolongs the sensitive phase for OD plasticity, we raised mice from 7 d before birth to adulthood in slightly larger than normal SCs with or without a running wheel (RW). When the mice were older than P135, we visualized V1 activity before and after monocular deprivation (MD) using intrinsic signal optical imaging. Adult RW-raised mice continued to show an OD shift toward the open eye after 7 d of MD, while age-matched SC mice without a RW did not show OD plasticity. Notably, running just during the 7 d MD period restored OD plasticity in adult SC-raised mice. In addition, the OD shift of the RW mice was mediated by a decrease of deprived-eye responses in V1, a signature of "juvenile-like" plasticity. We conclude that voluntary physical exercise alone is sufficient to promote plasticity in adult mouse V1.

  3. Donepezil in Treating Young Patients With Primary Brain Tumors Previously Treated With Radiation Therapy to the Brain

    ClinicalTrials.gov

    2016-07-26

    Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Long-term Effects Secondary to Cancer Therapy in Children; Neurotoxicity; Psychosocial Effects of Cancer and Its Treatment; Radiation Toxicity

  4. Developmental time course and effects of immunostressors that alter hormone-responsive behavior on microglia in the peripubertal and adult female mouse brain

    PubMed Central

    Blaustein, Jeffrey D.

    2017-01-01

    In female mice, the experience of being shipped from the breeder facility or a single injection of the bacterial endotoxin, lipopolysaccharide (LPS), during pubertal development alters the behavioral response to estradiol in adulthood as demonstrated by perturbations of estradiol’s effects on sexual behavior, cognitive function, as well as its anxiolytic and anti-depressive properties. Microglia, the primary type of immunocompetent cell within the brain, contribute to brain development and respond to stressors with marked and long-lasting morphological and functional changes. Here, we describe the morphology of microglia and their response to shipping and LPS in peripubertal and adult female mice. Peripubertal mice have more microglia with long, thick processes in the hippocampus, amygdala and hypothalamus as compared with adult mice in the absence of an immune challenge. An immune challenge also increases immunoreactivity (IR) of ionized calcium binding adaptor molecule 1 (Iba1), which is constitutively expressed in microglia. In the hippocampus, the age of animal was without effect on the increase in Iba1- IR following shipping from the breeder facility or LPS exposure. In the amygdala, we observed more Iba1-IR following shipping or LPS treatment in peripubertal mice, compared to adult mice. In the hypothalamus, there was a disassociation of the effects of shipping and LPS treatment as LPS treatment, but not shipping, induced an increase in Iba1-IR. Taken together these data indicate that microglial morphologies differ between pubertal and adult mice; moreover, the microglial response to complex stressors is greater in pubertal mice as compared to adult mice. PMID:28158270

  5. Primary brain tumors treated with steroids and radiotherapy: Low CD4 counts and risk of infection

    SciTech Connect

    Hughes, Michael A.; Parisi, Michele; Grossman, Stuart; Kleinberg, Lawrence . E-mail: kleinla@jhmi.edu

    2005-08-01

    Purpose: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. Methods and Materials: CD4 counts were measured during RT in 70 of 76 consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. Results: CD4 counts decreased to <200/mm{sup 3} in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm{sup 3} before RT, but 6 (24%) of 25 fell to <200/mm{sup 3} during RT. Patients with counts <200/mm{sup 3} were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of

  6. Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

    PubMed

    Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

    2006-05-01

    Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.

  7. Most Uninsured Adults Could Schedule Primary Care Appointments Before The ACA, But Average Price Was $160.

    PubMed

    Saloner, Brendan; Polsky, Daniel; Kenney, Genevieve M; Hempstead, Katherine; Rhodes, Karin V

    2015-05-01

    Provisions of the Affordable Care Act (ACA) allow millions more Americans to obtain health insurance. However, a sizable number of people remain uninsured because they live in states that have not expanded Medicaid coverage or because they feel that Marketplace coverage is not affordable. Using data from a ten-state telephone survey in which callers posed as patients, we examined prices for primary care visits offered by physician offices to new uninsured patients in 2012-13, prior to ACA insurance expansions. Patients were quoted a mean price of $160. Significantly lower prices for the uninsured were offered by family practice offices compared to general internists, in offices participating in Medicaid managed care plans, and in federally qualified health centers. Prices were also lower for offices in ZIP codes with higher poverty rates. Only 18 percent of uninsured callers were told that they could bring less than the full amount to the visit and arrange to pay the rest later. ACA insurance expansions could greatly decrease out-of-pocket spending for low-income adults seeking primary care. However, benefits of health reform are likely to be greater in states expanding Medicaid eligibility.

  8. Cardiorespiratory fitness and brain diffusion tensor imaging in adults over 80 years of age.

    PubMed

    Tian, Qu; Simonsick, Eleanor M; Erickson, Kirk I; Aizenstein, Howard J; Glynn, Nancy W; Boudreau, Robert M; Newman, Anne B; Kritchevsky, Stephen B; Yaffe, Kristine; Harris, Tamara; Rosano, Caterina

    2014-11-07

    A positive association between cardiorespiratory fitness (CRF) and white matter integrity has been consistently reported in older adults. However, it is unknown whether this association exists in adults over 80 with a range of chronic disease conditions and low physical activity participation, which can influence both CRF and brain health. This study examined whether higher CRF was associated with greater microstructural integrity of gray and white matter in areas related to memory and information processing in adults over 80 and examined moderating effects of chronic diseases and physical activity. CRF was measured as time to walk 400 m as quickly as possible with concurrent 3T diffusion tensor imaging in 164 participants (57.1% female, 40.3% black). Fractional anisotropy (FA) was computed for cingulum, uncinate and superior longitudinal fasciculi. Mean diffusivity (MD) was computed for dorsolateral prefrontal cortex, hippocampus, parahippocampus, and entorhinal cortex. Moderating effects were tested using hierarchical regression models. Higher CRF was associated with higher FA in cingulum and lower MD in hippocampus and entorhinal cortex (β, sex-adjusted p: -0.182, 0.019; 0.165, 0.035; and 0.220, 0.006, respectively). Hypertension attenuated the association with MD in entorhinal cortex. Moderating effects of chronic diseases and physical activity in walking and climbing stairs on these associations were not significant. The association of higher CRF with greater microstructural integrity in selected subcortical areas appears robust, even among very old adults with a range of chronic diseases. Intervention studies should investigate whether increasing CRF can preserve memory and information processing by improving microstructure and potential effects of hypertension management.

  9. Current Self-Reported Symptoms of Attention Deficit/Hyperactivity Disorder Are Associated with Total Brain Volume in Healthy Adults

    PubMed Central

    Hoogman, Martine; Rijpkema, Mark; Janss, Luc; Brunner, Han; Fernandez, Guillen; Buitelaar, Jan; Franke, Barbara; Arias-Vásquez, Alejandro

    2012-01-01

    Background Reduced total brain volume is a consistent finding in children with Attention Deficit/Hyperactivity Disorder (ADHD). In order to get a better understanding of the neurobiology of ADHD, we take the first step in studying the dimensionality of current self-reported adult ADHD symptoms, by looking at its relation with total brain volume. Methodology/Principal Findings In a sample of 652 highly educated adults, the association between total brain volume, assessed with magnetic resonance imaging, and current number of self-reported ADHD symptoms was studied. The results showed an association between these self-reported ADHD symptoms and total brain volume. Post-hoc analysis revealed that the symptom domain of inattention had the strongest association with total brain volume. In addition, the threshold for impairment coincides with the threshold for brain volume reduction. Conclusions/Significance This finding improves our understanding of the biological substrates of self-reported ADHD symptoms, and suggests total brain volume as a target intermediate phenotype for future gene-finding in ADHD. PMID:22348063

  10. New Perspectives on Genomic Imprinting, an Essential and Multifaceted Mode of Epigenetic Control in the Developing and Adult Brain

    PubMed Central

    Perez, Julio D.; Rubinstein, Nimrod D.; Dulac, Catherine

    2016-01-01

    Mammalian evolution entailed multiple innovations in gene regulation, including the emergence of genomic imprinting, an epigenetic regulation leading to the preferential expression of a gene from its maternal or paternal allele. Genomic imprinting is highly prevalent in the brain, yet, until recently, its central roles in neural processes have not been fully appreciated. Here, we provide a comprehensive survey of adult and developmental brain functions influenced by imprinted genes, from neural development and wiring to synaptic function and plasticity, energy balance, social behaviors, emotions, and cognition. We further review the widespread identification of parental biases alongside monoallelic expression in brain tissues, discuss their potential roles in dosage regulation of key neural pathways, and suggest possible mechanisms underlying the dynamic regulation of imprinting in the brain. This review should help provide a better understanding of the significance of genomic imprinting in the normal and pathological brain of mammals including humans. PMID:27145912

  11. Exploring Spirituality in Family Caregivers of Patients With Primary Malignant Brain Tumors Across the Disease Trajectory

    PubMed Central

    Newberry, Alyssa G.; Jean Choi, Chien-Wen; Donovan, Heidi S.; Schulz, Richard; Bender, Catherine; Given, Barbara; Sherwood, Paula

    2013-01-01

    Purpose/Objectives To determine whether the perceived level of spirituality in family caregivers of patients with primary malignant brain tumors (PMBTs) changes across the disease trajectory. Design Ongoing descriptive, longitudinal study. Setting Southwestern Pennsylvania. Sample 50 family caregivers of patients with PMBT. Methods Caregivers and care recipients were recruited at time of diagnosis. Participants were interviewed at two subse-quent time points, four and eight months following diagnosis. Main Research Variables Care recipients’ symptoms, neuro-psychologic status, and physical function, as well as caregiver social support. Findings Results showed no significant difference in spirituality scores reported at baseline and eight months (p = 0.8), suggesting that spirituality may be a stable trait across the disease trajectory. Conclusions Spirituality remains relatively stable along the course of the disease trajectory. Reports of caregiver depressive symptoms and anxiety were lower when paired with higher reports of spirituality. Implications for Nursing Clinicians can better identify caregivers at risk for negative outcomes by identifying those who report lower levels of spirituality. Future interventions should focus on the development and implementation of interventions that provide protective buffers such as increased social support. Knowledge Translation Spirituality is a relatively stable trait. High levels of spirituality can serve as a protective buffer from negative mental health outcomes. Caregivers with low levels of spirituality may be at risk for greater levels of burden, anxiety, and stress. PMID:23615145

  12. Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala’s nucleus

    PubMed Central

    Teipel, Stefan J.; Flatz, Wilhelm; Ackl, Nibal; Grothe, Michel; Kilimann, Ingo; Bokde, Arun L.W.; Grinberg, Lea; Amaro, Edson; Kljajevic, Vanja; Alho, Eduardo; Knels, Christina; Ebert, Anne; Heinsen, Helmut; Danek, Adrian

    2014-01-01

    Primary progressive aphasia (PPA) is characterized by left hemispheric frontotemporal cortical atrophy. Evidence from anatomical studies suggests that the nucleus subputaminalis (NSP), a subnucleus of the cholinergic basal forebrain, may be involved in the pathological process of PPA. Therefore, we studied the pattern of cortical and basal forebrain atrophy in 10 patients with a clinical diagnosis of PPA and 18 healthy age-matched controls using high-resolution magnetic resonance imaging (MRI). We determined the cholinergic basal forebrain nuclei according to Mesulam’s nomenclature and the NSP in MRI reference space based on histological sections and the MRI scan of a post-mortem brain in cranio. Using voxel-based analysis, we found left hemispheric cortical atrophy in PPA patients compared with controls, including prefrontal, lateral temporal and medial temporal lobe areas. We detected cholinergic basal forebrain atrophy in left predominant localizations of Ch4p, Ch4am, Ch4al, Ch3 and NSP. For the first time, we have described the pattern of basal forebrain atrophy in PPA and confirmed the involvement of NSP that had been predicted based on theoretical considerations. Our findings may enhance understanding of the role of cholinergic degeneration for the regional specificity of the cortical destruction leading to the syndrome of PPA. PMID:24434193

  13. Changes of Brain Connectivity in the Primary Motor Cortex After Subcortical Stroke

    PubMed Central

    Li, Yongxin; Wang, Defeng; Zhang, Heye; Wang, Ya; Wu, Ping; Zhang, Hongwu; Yang, Yang; Huang, Wenhua

    2016-01-01

    Abstract The authors investigated the changes in connectivity networks of the bilateral primary motor cortex (M1) of subcortical stroke patients using a multimodal neuroimaging approach with antiplatelet therapy. Nineteen patients were scanned at 2 time points: before and 1 month after the treatment. The authors assessed the resting-state functional connectivity (FC) and probabilistic fiber tracking of left and right M1 of every patient, and then compared these results to the 15 healthy controls. The authors also evaluated the correlations between the neuroimaging results and clinical scores. Compared with the controls, the patients showed a significant decrease of FC in the contralateral motor cortex before treatment, and the disrupted FC was restored after treatment. The fiber tracking results in the controls indicated that the body of the corpus callosum should be the main pathway connecting the M1 and contralateral hemispheres. All patients exhibited reduced probability of structural connectivity within this pathway before treatment and which was restored after treatment. Significant correlations were also found in these patients between the connectivity results and clinical scores, which might imply that the connectivity of M1 can be used to evaluate the motor skills in stroke patients. These findings can help elucidate the neural mechanisms responsible for the brain connectivity recovery after stroke. PMID:26871777

  14. PACAP27 regulates ciliary function in primary cultures of rat brain ependymal cells.

    PubMed

    Mönkkönen, K S; Mnkkönen, K S; Hirst, R A; Laitinen, J T; O'Callaghan, C

    2008-01-01

    Ependymal cells line the brain ventricles and separate the CSF from the underlying neuronal tissue. The function of ependymal cilia is largely unclear however they are reported to be involved in the regulation of CSF homeostasis and host defence against pathogens. Here we present data that implicates a role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the inhibition of ependymal ciliary function, and also that the PACAP effects are not entirely dependent on adenylyl cyclase activation. Primary ependymal cultures were treated with increasing doses of PACAP27 or adenylyl cyclase toxin (ACT), and ciliary beating was recorded using high-speed digital video imaging. Ciliary beat frequency (CBF) and amplitude were determined from the videos. Ependymal CBF and ciliary amplitude were attenuated by PACAP27 in a concentration- and time-dependent manner. The peptide antagonist PACAP6-27 blocked PACAP27-induced decreases in amplitude and CBF. Treatment with ACT caused a decrease in amplitude but had no effect on CBF, this suggests that the inhibition of CBF and amplitude seen with PACAP27 may not be completely explained by G(s)-AC-cAMP pathway. We present here the first observational study to show that activation of PAC1 receptors with PACAP27 has an important role to play in the regulation of ependymal ciliary function.

  15. Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults

    PubMed Central

    Burzynska, Agnieszka Z.; Wong, Chelsea N.; Voss, Michelle W.; Cooke, Gillian E.; Gothe, Neha P.; Fanning, Jason; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60–80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SDBOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SDBOLD. We conclude that SDBOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SDBOLD is modifiable with interventions aimed to increase PA and CRF in older adults. PMID:26244873

  16. Perivascular instruction of cell genesis and fate in the adult brain.

    PubMed

    Goldman, Steven A; Chen, Zhuoxun

    2011-10-26

    The perivascular niche for neurogenesis was first reported as the co-association of newly generated neurons and their progenitors with both dividing and mitotically quiescent endothelial cells in restricted regions of the brain in adult birds and mammals alike. This review attempts to summarize our present understanding of the interaction of blood vessels with neural stem and progenitor cells, addressing both glial and neuronal progenitor cell interactions in the perivascular niche. We review the molecular interactions that are most critical to the endothelial control of stem and progenitor cell mobilization and differentiation. The focus throughout will be on defining those perivascular ligand-receptor interactions shared among these systems, as well as those that clearly differ as a function of cell type and setting, by which specificity may be achieved in the development of targeted therapeutics.

  17. Self-administered written prompts to teach home accident prevention skills to adults with brain injuries.

    PubMed Central

    O'Reilly, M F; Green, G; Braunling-McMorrow, D

    1990-01-01

    This study evaluated the use of written checklists and task analyses as self-administered prompts to teach home accident prevention skills to 4 adults with brain injuries. Subsequent to baseline, participants used written checklists that identified potential in-home hazards but did not prompt behaviors necessary for hazard remediation. Written individualized task analyses, incorporating specific behavioral steps for correcting hazards that participants had failed to remediate during the checklist phase, were used to prompt appropriate responding when necessary. These were subsequently faded to transfer stimulus control to the natural conditions. A multiple probe technique across participants and settings was used. Results indicated that the checklist alone was sufficient to increase appropriate responses to many of the potential hazards. Individualized task analyses, when needed, resulted in appropriate remediation of all potential hazards. Generalization to untrained potential hazards occurred to some degree for all participants. Follow-up results showed that most skills trained were maintained over a 1-month period. PMID:2074235

  18. Clinical utility of the Wechsler Adult Intelligence Scale-Fourth Edition after traumatic brain injury.

    PubMed

    Donders, Jacobus; Strong, Carrie-Ann H

    2015-02-01

    The performance of 100 patients with traumatic brain injury (TBI) on the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) was compared with that of 100 demographically matched neurologically healthy controls. Processing Speed was the only WAIS-IV factor index that was able to discriminate between persons with moderate-severe TBI on the one hand and persons with either less severe TBI or neurologically healthy controls on the other hand. The Processing Speed index also had acceptable sensitivity and specificity when differentiating between patients with TBI who either did or did not have scores in the clinically significant range on the Trail Making Test. It is concluded that WAIS-IV Processing Speed has acceptable clinical utility in the evaluation of patients with moderate-severe TBI but that it should be supplemented with other measures to assure sufficient accuracy in the diagnostic process.

  19. Atypical brain laterality in adults with ADHD during dichotic listening for emotional intonation and words.

    PubMed

    Hale, T Sigi; Zaidel, Eran; McGough, James J; Phillips, Joseph M; McCracken, James T

    2006-01-01

    Few studies directly examined the nature of hemispheric specialization and interaction in ADHD. The present experiment investigated left/right brain dynamics in unmedicated right handed adults with ADHD (n = 19) and in controls (n = 19), using a dichotic listening task to assess hemispheric differences in word and emotion recognition. We also assessed how focusing attention on a single ear modulated lateralized performance and affected cross-callosal interference effects. Analysis of variance indicated that ADHD subjects showed reduced left hemisphere specialization, were better at processing emotions, and worse at processing words compared to controls. These differences were eliminated during focused attention. Finally, during presumed right hemisphere processing of linguistic stimuli, subjects with ADHD showed reduced left hemisphere interference. We concluded that ADHD subjects demonstrated greater right hemisphere and reduced left hemisphere contribution during this task relative to controls. We posit that these hemispheric differences were due to management or use of available cognitive resources rather than inherent capacity.

  20. Functional optoacoustic neuro-tomography of calcium fluxes in adult zebrafish brain in vivo.

    PubMed

    Deán-Ben, X Luís; Gottschalk, Sven; Sela, Gali; Shoham, Shy; Razansky, Daniel

    2017-03-01

    Genetically-encoded calcium indicators (GECIs) have revolutionized neuroimaging by enabling mapping of the activity of entire neuronal populations in vivo. Visualization of these powerful activity sensors has to date been limited to depth-restricted microscopic studies due to intense light scattering in the brain. We demonstrate, for the first time, in vivo real-time volumetric optoacoustic monitoring of calcium transients in adult transgenic zebrafish expressing the GCaMP5G calcium indicator. Fast changes in optoacoustic traces associated with GCaMP5G activity were detectable in the presence of other strongly absorbing endogenous chromophores, such as hemoglobin. The new functional optoacoustic neuroimaging method can visualize neural activity at penetration depths and spatio-temporal resolution scales not covered with the existing neuroimaging techniques.

  1. The evidence for increased L1 activity in the site of human adult brain neurogenesis.

    PubMed

    Kurnosov, Alexey A; Ustyugova, Svetlana V; Nazarov, Vadim I; Minervina, Anastasia A; Komkov, Alexander Yu; Shugay, Mikhail; Pogorelyy, Mikhail V; Khodosevich, Konstantin V; Mamedov, Ilgar Z; Lebedev, Yuri B

    2015-01-01

    Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

  2. New Hippocampal Neurons Are Not Obligatory for Memory Formation; Cyclin D2 Knockout Mice with No Adult Brain Neurogenesis Show Learning

    ERIC Educational Resources Information Center

    Jaholkowski, Piotr; Kiryk, Anna; Jedynak, Paulina; Abdallah, Nada M. Ben; Knapska, Ewelina; Kowalczyk, Anna; Piechal, Agnieszka; Blecharz-Klin, Kamilla; Figiel, Izabela; Lioudyno, Victoria; Widy-Tyszkiewicz, Ewa; Wilczynski, Grzegorz M.; Lipp, Hans-Peter; Kaczmarek, Leszek; Filipkowski, Robert K.

    2009-01-01

    The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to be quite firmly established in spite of some criticism and lack of understanding of what the new neurons serve the brain for. Also, the few experiments showing that blocking adult neurogenesis causes learning deficits used irradiation and various drugs…

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

    PubMed Central

    Courtney, Amy; Courtney, Michael

    2015-01-01

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

  4. Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging

    PubMed Central

    Sun, Felicia W.; Stepanovic, Michael R.; Andreano, Joseph

    2016-01-01

    Decline in cognitive skills, especially in memory, is often viewed as part of “normal” aging. Yet some individuals “age better” than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20–30 years younger (i.e., “superagers”), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60–80 years old) based on their performance compared to young adults (18–32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function. SIGNIFICANCE STATEMENT Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with

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

    PubMed

    Napoli, Alessandro; Obeid, Iyad

    2016-03-01

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

  6. Existential Well-Being and Meaning Making in the Context of Primary Brain Tumor: Conceptualization and Implications for Intervention

    PubMed Central

    Ownsworth, Tamara; Nash, Kimberley

    2015-01-01

    When faced with a significant threat to life, people tend to reflect more intensely upon existential issues, such as the meaning and purpose of one’s life. Brain tumor poses a serious threat to a person’s life, functioning, and personhood. Although recognized as an important dimension of quality of life, existential well-being is not well understood and reflects an overlooked area of support for people with brain tumor. This perspective article reviews the historical underpinnings of the concept of existential well-being and integrates this discussion with theoretical perspectives and research on meaning making and psychological adjustment to primary brain tumor. We then provide an overview of psychosocial support interventions for people with brain tumor and describe the findings of a recently published psychotherapy trial targeting existential well-being. Overall, this article highlights the importance of assessing the existential support needs of people with primary brain tumor and their family members, and providing different avenues of support to facilitate the meaning-making process across the illness trajectory. PMID:25964883

  7. Activity-dependent Notch signalling in the hypothalamic-neurohypophysial system of adult mouse brains.

    PubMed

    Mannari, T; Miyata, S

    2014-08-01

    Notch signalling has a key role in cell fate specification in developing brains; however, recent studies have shown that Notch signalling also participates in the regulation of synaptic plasticity in adult brains. In the present study, we examined the expression of Notch3 and Delta-like ligand 4 (DLL4) in the hypothalamic-neurohypophysial system (HNS) of the adult mouse. The expression of DLL4 was higher in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) compared to adjacent hypothalamic regions. Double-labelling immunohistochemistry using vesicular GABA transporter and glutamate transporter revealed that DLL4 was localised at a subpopulation of excitatory and inhibitory axonal boutons against somatodendrites of arginine vasopressin (AVP)- and oxytocin (OXT)-containing magnocellular neurones. In the neurohypophysis (NH), the expression of DLL4 was seen at OXT- but not AVP-containing axonal terminals. The expression of Notch3 was seen at somatodendrites of AVP- and OXT-containing magnocellular neurones in the SON and PVN and at pituicytes in the NH. Chronic physiological stimulation by salt loading, which remarkably enhances the release of AVP and OXT, decreased the number of DLL4-immunoreactive axonal boutons in the SON and PVN. Moreover, chronic and acute osmotic stimulation promoted proteolytic cleavage of Notch3 to yield the intracellular fragments of Notch3 in the HNS. Thus, the present study demonstrates activity-dependent reduction of DLL4 expression and proteolytic cleavage of Notch3 in the HNS, suggesting that Notch signalling possibly participates in synaptic interaction in the hypothalamic nuclei and neuroglial interaction in the NH.

  8. Abnormal Brain Connectivity Patterns in Adults with ADHD: A Coherence Study

    PubMed Central

    Sato, João Ricardo; Hoexter, Marcelo Queiroz; Castellanos, Xavier Francisco; Rohde, Luis A.

    2012-01-01

    Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach – unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. The median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. In addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits. PMID:23049834

  9. A Comprehensive Study of the Anatomical Variations of the Circle of Willis in Adult Human Brains

    PubMed Central

    Iqbal, S.

    2013-01-01

    Background: Cerebrovascular diseases such as stroke, aneurysms and arterio-venous malformations are very much prevalent in our country. Circle of Willis, as an anastomotic polygon at the base of the brain forms an important collateral network to maintain adequate cerebral perfusion. Changes in the normal morphology of the circle may condition the appearance and severity of symptoms of cerebrovascular disorders, such as aneurysms, infarctions and other vascular anomalies. A possible link between abnormalities of the circle of Willis and the mentally ill patients has been observed. Aim and Objectives: The aim of the present study is to have an intimate knowledge of the variations in the cerebral arterial circle and to clarify the clinical importance of these variations in certain forms of cerebrovascular diseases. So an attempt was made to analyse the anatomical variations of the circle in a random population. Material and Methods: The work was based on fifty adult brains from persons died of diverse causes. The materials were obtained during routine autopsy studies. The base of the brain including the brain stem with intact arterial circle was preserved in 10% formalin for 10 days. The circle of Willis and its major branches were carefully dissected under water using a magnifying lens. The variations were recorded and photographed. Results: Majority of the circles (52%) showed anomalies. Hypoplasia was the most frequent anomaly and was found in 24% of the brains. Accessory vessels in the form of duplications/triplications of anterior communicating artery were seen in 12% of the circles. The embryonic origin of the posterior cerebral artery from the internal carotid persisted in 10% of the circles. An incomplete circle due to the absence of one or other posterior communicating artery was found in 6% of the specimens.Variations are more frequent in posterior half of the circle. Conclusion: The anatomical variations of the circle of Willis were probably genetically

  10. BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics.

    PubMed

    Roberds, S L; Anderson, J; Basi, G; Bienkowski, M J; Branstetter, D G; Chen, K S; Freedman, S B; Frigon, N L; Games, D; Hu, K; Johnson-Wood, K; Kappenman, K E; Kawabe, T T; Kola, I; Kuehn, R; Lee, M; Liu, W; Motter, R; Nichols, N F; Power, M; Robertson, D W; Schenk, D; Schoor, M; Shopp, G M; Shuck, M E; Sinha, S; Svensson, K A; Tatsuno, G; Tintrup, H; Wijsman, J; Wright, S; McConlogue, L

    2001-06-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major components of plaque, beta-amyloid peptides (Abetas), are produced from amyloid precursor protein (APP) by the activity of beta- and gamma-secretases. beta-secretase activity cleaves APP to define the N-terminus of the Abeta1-x peptides and, therefore, has been a long- sought therapeutic target for treatment of AD. The gene encoding a beta-secretase for beta-site APP cleaving enzyme (BACE) was identified recently. However, it was not known whether BACE was the primary beta-secretase in mammalian brain nor whether inhibition of beta-secretase might have effects in mammals that would preclude its utility as a therapeutic target. In the work described herein, we generated two lines of BACE knockout mice and characterized them for pathology, beta-secretase activity and Abeta production. These mice appeared to develop normally and showed no consistent phenotypic differences from their wild-type littermates, including overall normal tissue morphology and brain histochemistry, normal blood and urine chemistries, normal blood-cell composition, and no overt behavioral and neuromuscular effects. Brain and primary c