Diagnosis and Management of Combined Central Diabetes Insipidus and Cerebral Salt Wasting Syndrome After Traumatic Brain Injury.

PubMed

Wu, Xuehai; Zhou, Xiaolan; Gao, Liang; Wu, Xing; Fei, Li; Mao, Ying; Hu, Jin; Zhou, Liangfu

2016-04-01

Combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury (TBI) is rare, is characterized by massive polyuria leading to severe water and electrolyte disturbances, and usually is associated with very high mortality mainly as a result of delayed diagnosis and improper management. We retrospectively reviewed the clinical presentation, management, and outcomes of 11 patients who developed combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury to define distinctive features for timely diagnosis and proper management. The most typical clinical presentation was massive polyuria (10,000 mL/24 hours or >1000 mL/hour) refractory to vasopressin alone but responsive to vasopressin plus cortisone acetate. Other characteristic presentations included low central venous pressure, high brain natriuretic peptide precursor level without cardiac dysfunction, high 24-hour urine sodium excretion and hypovolemia, and much higher urine than serum osmolarity; normal serum sodium level and urine specific gravity can also be present. Timely and adequate infusion of sodium chloride was key in treatment. Of 11 patients, 5 had a good prognosis 3 months later (Extended Glasgow Outcome Scale score ≥6), 1 had an Extended Glasgow Outcome Scale score of 4, 2 died in the hospital of brain hernia, and 3 developed a vegetative state. For combined diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury, massive polyuria is a major typical presentation, and intensive monitoring of fluid and sodium status is key for timely diagnosis. To achieve a favorable outcome, proper sodium chloride supplementation and cortisone acetate and vasopressin coadministration are key. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative Adverse Outcome Pathway for Neurodevelopmental Effects of Thyroid Peroxidase-Induced Thyroid Hormone Synthesis Inhibition

EPA Science Inventory

Adequate levels of thyroid hormones (TH) are needed for proper brain development and deficiencies lead to adverse neurological outcomes in humans and in animal models. Environmental chemicals have been shown to disrupt TH levels, yet the relationship between developmental exposur...

Neurodynamic system theory: scope and limits.

PubMed

Erdi, P

1993-06-01

This paper proposes that neurodynamic system theory may be used to connect structural and functional aspects of neural organization. The paper claims that generalized causal dynamic models are proper tools for describing the self-organizing mechanism of the nervous system. In particular, it is pointed out that ontogeny, development, normal performance, learning, and plasticity, can be treated by coherent concepts and formalism. Taking into account the self-referential character of the brain, autopoiesis, endophysics and hermeneutics are offered as elements of a poststructuralist brain (-mind-computer) theory.

Biocompatible KMnF3 nanoparticular contrast agent with proper plasma retention time for in vivo magnetic resonance imaging.

PubMed

Liu, Zhi-jun; Song, Xiao-xia; Xu, Xian-zhu; Tang, Qun

2014-04-18

Nanoparticular MRI contrast agents are rapidly becoming suitable for use in clinical diagnosis. An ideal nanoparticular contrast agent should be endowed with high relaxivity, biocompatibility, proper plasma retention time, and tissue-specific or tumor-targeting imaging. Herein we introduce PEGylated KMnF3 nanoparticles as a new type of T1 contrast agent. Studies showed that the nanoparticular contrast agent revealed high bio-stability with bovine serum albumin in PBS buffer solution, and presented excellent biocompatibility (low cytotoxicity, undetectable hemolysis and hemagglutination). Meanwhile the new contrast agent possessed proper plasma retention time (circulation half-life t1/2 is approximately 2 h) in the body of the administrated mice. It can be delivered into brain vessels and maintained there for hours, and is mostly cleared from the body within 48 h, as demonstrated by time-resolved MRI and Mn-biodistribution analysis. Those distinguishing features make it suitable to obtain contrast-enhanced brain magnetic resonance angiography. Moreover, through the process of passive targeting delivery, the T1 contrast agent clearly illuminates a brain tumor (glioma) with high contrast image and defined shape. This study demonstrates that PEGylated KMnF3 nanoparticles represent a promising biocompatible vascular contrast agent for magnetic resonance angiography and can potentially be further developed into an active targeted tumor MRI contrast agent.

Stagewise Development, Behavior Genetics, Brain Imaging, and a "Aha Erlebnis"

ERIC Educational Resources Information Center

Molenaar, Peter C. M.

2012-01-01

In this short contribution I introduce myself to the readership of the "International Journal of Developmental Science" by describing some high points in my scientific career, leading up to a major change in my perspective on the proper way to conduct empirical research in developmental science.

Ancient Dietary Wisdom for Tomorrow's Children.

ERIC Educational Resources Information Center

Fallon, Sally

1997-01-01

A review of Dr. Weston Price's work on the nutritional practices of "primitive" peoples and their subsequent levels of physical development shows that animal fats and cholesterol are not villains but vital factors in the diet, necessary for normal growth, proper functioning of the brain and nervous system, protection from disease, and…

Neurodevelopment and Thyroid Hormone Synthesis Inhibition in the Rat: Quantitative Understanding Within the Adverse Outcome Pathway Framework

EPA Science Inventory

Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models. Environmental chemicals have been linked to TH disruption, yet the relationship between developmental exposures an...

Rodent Zic Genes in Neural Network Wiring.

PubMed

Herrera, Eloísa

2018-01-01

The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.

Involvement of Atm and Trp53 in neural cell loss due to Terf2 inactivation during mouse brain development.

PubMed

Kim, Jusik; Choi, Inseo; Lee, Youngsoo

2017-11-01

Maintenance of genomic integrity is one of the critical features for proper neurodevelopment and inhibition of neurological diseases. The signals from both ATM and ATR to TP53 are well-known mechanisms to remove neural cells with DNA damage during neurogenesis. Here we examined the involvement of Atm and Atr in genomic instability due to Terf2 inactivation during mouse brain development. Selective inactivation of Terf2 in neural progenitors induced apoptosis, resulting in a complete loss of the brain structure. This neural loss was rescued partially in both Atm and Trp53 deficiency, but not in an Atr-deficient background in the mouse. Atm inactivation resulted in incomplete brain structures, whereas p53 deficiency led to the formation of multinucleated giant neural cells and the disruption of the brain structure. These giant neural cells disappeared in Lig4 deficiency. These data demonstrate ATM and TP53 are important for the maintenance of telomere homeostasis and the surveillance of telomere dysfunction during neurogenesis.

ERPs and Psychopathology. I. Behavioral process issues.

PubMed

Roth, W T; Tecce, J J; Pfefferbaum, A; Rosenbloom, M; Callaway, E

1984-01-01

The clinical study of ERPs has an inherent defect--a self-selection of clinical populations that hampers equating of clinically defined groups on factors extraneous to the independent variables. Such ex post facto studies increase the likelihood of confounding variables in the interpretation of findings. Hence, the development of lawful relationships between clinical variables and ERPs is impeded and the fulfillment of description, explanation, prediction, and control in brain science is thwarted. Proper methodologies and theory development can increase the likelihood of establishing these lawful relationships. One methodology of potential value in the clinical application of ERPs, particularly in studies of aging, is that of divided attention. Two promising theoretical developments in the understanding of brain functioning and aging are the distraction-arousal hypothesis and the controlled-automatic attention model. The evaluation of ERPs in the study of brain-behavior relations in clinical populations might be facilitated by the differentiation of concurrent, predictive, content, and construct validities.

Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

PubMed

Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

2018-05-16

Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our results suggest that proper control of TGF-β/Smads/CRMP2 signaling pathways is critical for the precise execution of neuronal morphogenesis, whose impairment eventually results in neurodevelopmental disorders. Copyright © 2018 the authors 0270-6474/18/384791-20$15.00/0.

Canavan Disease: A White Matter Disorder

ERIC Educational Resources Information Center

Kumar, Shalini; Mattan, Natalia S.; de Vellis, Jean

2006-01-01

Breakdown of oligodendrocyte-neuron interactions in white matter (WM), such as the loss of myelin, results in axonal dysfunction and hence a disruption of information processing between brain regions. The major feature of leukodystrophies is the lack of proper myelin formation during early development or the onset of myelin loss late in life.…

Genetic Causes of Microcephaly and Lessons for Neuronal Development

PubMed Central

Gilmore, Edward C.; Walsh, Christopher A.

2012-01-01

The study of human developmental microcephaly is providing important insights into brain development. It has become clear that developmental microcephalies are associated with abnormalities in cellular production, and that the pathophysiology of microcephaly provides remarkable insights into how the brain generates the proper number of neurons that determine brain size. Most of the genetic causes of ‘primary’ developmental microcephaly (i.e., not associated with other syndromic features) are associated with centrosomal abnormalities. In addition to other functions, centrosomal proteins control the mitotic spindle, which is essential for normal cell proliferation during mitosis. However, the brain is often uniquely affected when microcephaly genes are mutated implying special centrosomal related functions in neuronal production. Although models explaining how this could occur have some compelling data, they are not without controversy. Interestingly, some of the microcephaly genes show evidence that they were targets of evolutionary selection in primates and human ancestors, suggesting potential evolutionary roles in controlling neuronal number and brain volume across species. Mutations in DNA repair pathway genes also lead to microcephaly. Double stranded DNA breaks appear to be a prominent type of damage that needs to be repaired during brain development, yet why defects in DNA repair affect the brain preferentially and if DNA repair relates to centrosome function, are not clearly understood. PMID:24014418

A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

PubMed

Abdelhamed, Zakia; Vuong, Shawn M; Hill, Lauren; Shula, Crystal; Timms, Andrew; Beier, David; Campbell, Kenneth; Mangano, Francesco T; Stottmann, Rolf W; Goto, June

2018-01-09

Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 ( Ccdc39 ) is responsible for early postnatal hydrocephalus in the progressive hydrocephal us ( prh ) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39 prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development. © 2018. Published by The Company of Biologists Ltd.

Thyroid Hormone Availability and Action during Brain Development in Rodents.

PubMed

Bárez-López, Soledad; Guadaño-Ferraz, Ana

2017-01-01

Thyroid hormones (THs) play an essential role in the development of all vertebrates; in particular adequate TH content is crucial for proper neurodevelopment. TH availability and action in the brain are precisely regulated by several mechanisms, including the secretion of THs by the thyroid gland, the transport of THs to the brain and neural cells, THs activation and inactivation by the metabolic enzymes deiodinases and, in the fetus, transplacental passage of maternal THs. Although these mechanisms have been extensively studied in rats, in the last decade, models of genetically modified mice have been more frequently used to understand the role of the main proteins involved in TH signaling in health and disease. Despite this, there is little knowledge about the mechanisms underlying THs availability in the mouse brain. This mini-review article gathers information from findings in rats, and the latest findings in mice regarding the ontogeny of TH action and the sources of THs to the brain, with special focus on neurodevelopmental stages. Unraveling TH economy and action in the mouse brain may help to better understand the physiology and pathophysiology of TH signaling in brain and may contribute to addressing the neurological alterations due to hypo and hyperthyroidism and TH resistance syndromes.

Social isolation and brain development in the ant Camponotus floridanus.

PubMed

Seid, Marc A; Junge, Erich

2016-06-01

Social interactions play a key role in the healthy development of social animals and are most pronounced in species with complex social networks. When developing offspring do not receive proper social interaction, they show developmental impairments. This effect is well documented in mammalian species but controversial in social insects. It has been hypothesized that the enlargement of the mushroom bodies, responsible for learning and memory, observed in social insects is needed for maintaining the large social networks and/or task allocation. This study examines the impact of social isolation on the development of mushroom bodies of the ant Camponotus floridanus. Ants raised in isolation were shown to exhibit impairment in the growth of the mushroom bodies as well as behavioral differences when compared to ants raised in social groups. These results indicate that social interaction is necessary for the proper development of C. floridanus mushroom bodies.

Social isolation and brain development in the ant Camponotus floridanus

NASA Astrophysics Data System (ADS)

Seid, Marc A.; Junge, Erich

2016-06-01

Social interactions play a key role in the healthy development of social animals and are most pronounced in species with complex social networks. When developing offspring do not receive proper social interaction, they show developmental impairments. This effect is well documented in mammalian species but controversial in social insects. It has been hypothesized that the enlargement of the mushroom bodies, responsible for learning and memory, observed in social insects is needed for maintaining the large social networks and/or task allocation. This study examines the impact of social isolation on the development of mushroom bodies of the ant Camponotus floridanus. Ants raised in isolation were shown to exhibit impairment in the growth of the mushroom bodies as well as behavioral differences when compared to ants raised in social groups. These results indicate that social interaction is necessary for the proper development of C. floridanus mushroom bodies.

Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood-brain barrier: [17O]H2O JJVCPE MRI study.

PubMed

Huber, Vincent J; Igarashi, Hironaka; Ueki, Satoshi; Kwee, Ingrid L; Nakada, Tsutomu

2018-06-13

The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [O]H2O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [O]H2O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB.

Amblyopia

MedlinePlus

Amblyopia, or "lazy eye," is the most common cause of visual impairment in children. It happens when an eye fails to work properly with the brain. The eye may look normal, but the brain favors the ...

The Challenge of Connecting the Dots in the B.R.A.I.N

PubMed Central

Devor, Anna; Bandettini, Peter A.; Boas, David A.; Bower, James M.; Buxton, Richard B.; Cohen, Lawrence B.; Dale, Anders M.; Einevoll, Gaute T.; Fox, Peter T.; Franceschini, Maria Angela; Friston, Karl J.; Fujimoto, James G.; Geyer, Marc A.; Greenberg, Joel H.; Halgren, Eric; Hämäläinen, Matti S.; Helmchen, Fritjof; Hyman, Bradley T.; Jasanoff, Alan; Jernigan, Terry L.; Judd, Lewis L.; Kim, Seong-Gi; Kleinfeld, David; Kopell, Nancy J.; Kutas, Marta; Kwong, Kenneth K.; Larkum, Matthew E.; Lo, Eng H.; Magistretti, Pierre J.; Mandeville, Joseph B.; Masliah, Eliezer; Mitra, Partha P.; Mobley, William C.; Moskowitz, Michael A.; Nimmerjahn, Axel; Reynolds, John H.; Rosen, Bruce R.; Salzberg, Brian M.; Schaffer, Chris B.; Silva, Gabriel A.; So, Peter T. C.; Spitzer, Nicholas C.; Tootell, Roger B.; Van Essen, David C.; Vanduffel, Wim; Vinogradov, Sergei A.; Wald, Larry L.; Wang, Lihong V.; Weber, Bruno; Yodh, Arjun G.

2013-01-01

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has focused scientific attention on the necessary tools to understand the human brain and mind. Here, we outline our collective vision for what we can achieve within a decade with properly targeted efforts, and discuss likely technological deliverables and neuroscience progress. PMID:24139032

Cognitive memory and mapping in a brain-like system for robotic navigation.

PubMed

Tang, Huajin; Huang, Weiwei; Narayanamoorthy, Aditya; Yan, Rui

2017-03-01

Electrophysiological studies in animals may provide a great insight into developing brain-like models of spatial cognition for robots. These studies suggest that the spatial ability of animals requires proper functioning of the hippocampus and the entorhinal cortex (EC). The involvement of the hippocampus in spatial cognition has been extensively studied, both in animal as well as in theoretical studies, such as in the brain-based models by Edelman and colleagues. In this work, we extend these earlier models, with a particular focus on the spatial coding properties of the EC and how it functions as an interface between the hippocampus and the neocortex, as proposed by previous work. By realizing the cognitive memory and mapping functions of the hippocampus and the EC, respectively, we develop a neurobiologically-inspired system to enable a mobile robot to perform task-based navigation in a maze environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Holoprosencephaly: from Homer to Hedgehog.

PubMed

Ming, J E; Muenke, M

1998-03-01

Holoprosencephaly (HPE), a common developmental defect affecting the forebrain and face, is etiologically heterogeneous and exhibits wide phenotypic variation. Graded degrees of severity of the brain malformation are also reflected in the highly variable craniofacial malformations associated with HPE. In addition, individuals with microforms of HPE, who usually have normal cognition and normal brain imaging, are at risk for having children with HPE. Some obligate carriers for HPE may not have any phenotypic abnormalities. Recurrent chromosomal rearrangements in individuals with HPE suggest loci containing genes important for brain development, and abnormalities in these genes may result in HPE. Recently, Sonic Hedgehog (SHH) was the first gene identified as causing HPE in humans. Proper function of SHH depends on cholesterol modification. Other candidate genes that may be involved in HPE include components of the SHH pathway, elements involved in cholesterol metabolism, and genes expressed in the developing forebrain.

[Lean thinking and brain-dead patient assistance in the organ donation process].

PubMed

Pestana, Aline Lima; dos Santos, José Luís Guedes; Erdmann, Rolf Hermann; da Silva, Elza Lima; Erdmann, Alacoque Lorenzini

2013-02-01

Organ donation is a complex process that challenges health system professionals and managers. This study aimed to introduce a theoretical model to organize brain-dead patient assistance and the organ donation process guided by the main lean thinking ideas, which enable production improvement through planning cycles and the development of a proper environment for successful implementation. Lean thinking may make the process of organ donation more effective and efficient and may contribute to improvements in information systematization and professional qualifications for excellence of assistance. The model is configured as a reference that is available for validation and implementation by health and nursing professionals and managers in the management of potential organ donors after brain death assistance and subsequent transplantation demands.

Data-driven identification of intensity normalization region based on longitudinal coherency of 18F-FDG metabolism in the healthy brain.

PubMed

Zhang, Huiwei; Wu, Ping; Ziegler, Sibylle I; Guan, Yihui; Wang, Yuetao; Ge, Jingjie; Schwaiger, Markus; Huang, Sung-Cheng; Zuo, Chuantao; Förster, Stefan; Shi, Kuangyu

2017-02-01

In brain 18 F-FDG PET data intensity normalization is usually applied to control for unwanted factors confounding brain metabolism. However, it can be difficult to determine a proper intensity normalization region as a reference for the identification of abnormal metabolism in diseased brains. In neurodegenerative disorders, differentiating disease-related changes in brain metabolism from age-associated natural changes remains challenging. This study proposes a new data-driven method to identify proper intensity normalization regions in order to improve separation of age-associated natural changes from disease related changes in brain metabolism. 127 female and 128 male healthy subjects (age: 20 to 79) with brain 18 F-FDG PET/CT in the course of a whole body cancer screening were included. Brain PET images were processed using SPM8 and were parcellated into 116 anatomical regions according to the AAL template. It is assumed that normal brain 18 F-FDG metabolism has longitudinal coherency and this coherency leads to better model fitting. The coefficient of determination R 2 was proposed as the coherence coefficient, and the total coherence coefficient (overall fitting quality) was employed as an index to assess proper intensity normalization strategies on single subjects and age-cohort averaged data. Age-associated longitudinal changes of normal subjects were derived using the identified intensity normalization method correspondingly. In addition, 15 subjects with clinically diagnosed Parkinson's disease were assessed to evaluate the clinical potential of the proposed new method. Intensity normalizations by paracentral lobule and cerebellar tonsil, both regions derived from the new data-driven coherency method, showed significantly better coherence coefficients than other intensity normalization regions, and especially better than the most widely used global mean normalization. Intensity normalization by paracentral lobule was the most consistent method within both analysis strategies (subject-based and age-cohort averaging). In addition, the proposed new intensity normalization method using the paracentral lobule generates significantly higher differentiation from the age-associated changes than other intensity normalization methods. Proper intensity normalization can enhance the longitudinal coherency of normal brain glucose metabolism. The paracentral lobule followed by the cerebellar tonsil are shown to be the two most stable intensity normalization regions concerning age-dependent brain metabolism. This may provide the potential to better differentiate disease-related changes from age-related changes in brain metabolism, which is of relevance in the diagnosis of neurodegenerative disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain Activity during Mental Imagery of Gait Versus Gait-Like Plantar Stimulation: A Novel Combined Functional MRI Paradigm to Better Understand Cerebral Gait Control.

PubMed

Labriffe, Matthieu; Annweiler, Cédric; Amirova, Liubov E; Gauquelin-Koch, Guillemette; Ter Minassian, Aram; Leiber, Louis-Marie; Beauchet, Olivier; Custaud, Marc-Antoine; Dinomais, Mickaël

2017-01-01

Human locomotion is a complex sensorimotor behavior whose central control remains difficult to explore using neuroimaging method due to technical constraints, notably the impossibility to walk with a scanner on the head and/or to walk for real inside current scanners. The aim of this functional Magnetic Resonance Imaging (fMRI) study was to analyze interactions between two paradigms to investigate the brain gait control network: (1) mental imagery of gait, and (2) passive mechanical stimulation of the plantar surface of the foot with the Korvit boots. The Korvit stimulator was used through two different modes, namely an organized ("gait like") sequence and a destructured (chaotic) pattern. Eighteen right-handed young healthy volunteers were recruited (mean age, 27 ± 4.7 years). Mental imagery activated a broad neuronal network including the supplementary motor area-proper (SMA-proper), pre-SMA, the dorsal premotor cortex, ventrolateral prefrontal cortex, anterior insula, and precuneus/superior parietal areas. The mechanical plantar stimulation activated the primary sensorimotor cortex and secondary somatosensory cortex bilaterally. The paradigms generated statistically common areas of activity, notably bilateral SMA-proper and right pre-SMA, highlighting the potential key role of SMA in gait control. There was no difference between the organized and chaotic Korvit sequences, highlighting the difficulty of developing a walking-specific plantar stimulation paradigm. In conclusion, this combined-fMRI paradigm combining mental imagery and gait-like plantar stimulation provides complementary information regarding gait-related brain activity and appears useful for the assessment of high-level gait control.

Thyroid Hormone Availability and Action during Brain Development in Rodents

PubMed Central

Bárez-López, Soledad; Guadaño-Ferraz, Ana

2017-01-01

Thyroid hormones (THs) play an essential role in the development of all vertebrates; in particular adequate TH content is crucial for proper neurodevelopment. TH availability and action in the brain are precisely regulated by several mechanisms, including the secretion of THs by the thyroid gland, the transport of THs to the brain and neural cells, THs activation and inactivation by the metabolic enzymes deiodinases and, in the fetus, transplacental passage of maternal THs. Although these mechanisms have been extensively studied in rats, in the last decade, models of genetically modified mice have been more frequently used to understand the role of the main proteins involved in TH signaling in health and disease. Despite this, there is little knowledge about the mechanisms underlying THs availability in the mouse brain. This mini-review article gathers information from findings in rats, and the latest findings in mice regarding the ontogeny of TH action and the sources of THs to the brain, with special focus on neurodevelopmental stages. Unraveling TH economy and action in the mouse brain may help to better understand the physiology and pathophysiology of TH signaling in brain and may contribute to addressing the neurological alterations due to hypo and hyperthyroidism and TH resistance syndromes. PMID:28855863

Feed Your Brain!

ERIC Educational Resources Information Center

Failmezger, Tammie L.

2006-01-01

Language arts teachers and library media specialists bear the responsibility of teaching students how to properly feed their brains. In this article, the author describes how she teaches her students to make wise choices when selecting books. Furthermore, she presents the "Brain Food Pyramid" model that looks similar to the food pyramid but it…

Delayed astrocytic contact with cerebral blood vessels in FGF-2 deficient mice does not compromise permeability properties at the developing blood-brain barrier.

PubMed

Saunders, Norman R; Dziegielewska, Katarzyna M; Unsicker, Klaus; Ek, C Joakim

2016-11-01

The brain functions within a specialized environment tightly controlled by brain barrier mechanisms. Understanding the regulation of barrier formation is important for understanding brain development and may also lead to finding new ways to deliver pharmacotherapies to the brain; access of many potentially promising drugs is severely hindered by these barrier mechanisms. The cellular composition of the neurovascular unit of the blood-brain barrier proper and their effects on regulation of its function are beginning to be understood. One hallmark of the neurovascular unit in the adult is the astroglial foot processes that tightly surround cerebral blood vessels. However their role in barrier formation is still unclear. In this study we examined barrier function in newborn, juvenile and adult mice lacking fibroblast growth factor-2 (FGF-2), which has been shown to result in altered astroglial differentiation during development. We show that during development of FGF-2 deficient mice the astroglial contacts with cerebral blood vessels are delayed compared with wild-type animals. However, this delay did not result in changes to the permeability properties of the blood brain barrier as assessed by exclusion of either small or larger sized molecules at this interface. In addition cerebral vessels were positive for tight-junction proteins and we observed no difference in the ultrastructure of the tight-junctions. The results indicate that the direct contact of astroglia processes to cerebral blood vessels is not necessary for either the formation of the tight-junctions or for basic permeability properties and function of the blood-brain barrier. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1201-1212, 2016. © 2016 Wiley Periodicals, Inc.

The neuropathology of traumatic brain injury.

PubMed

Mckee, Ann C; Daneshvar, Daniel H

2015-01-01

Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at autopsy; however, promising efforts to develop imaging, spinal fluid, and peripheral blood biomarkers are underway to diagnose and monitor the course of disease in living subjects. © 2015 Elsevier B.V. All rights reserved.

Integrating brain, behavior, and phylogeny to understand the evolution of sensory systems in birds

PubMed Central

Wylie, Douglas R.; Gutiérrez-Ibáñez, Cristian; Iwaniuk, Andrew N.

2015-01-01

The comparative anatomy of sensory systems has played a major role in developing theories and principles central to evolutionary neuroscience. This includes the central tenet of many comparative studies, the principle of proper mass, which states that the size of a neural structure reflects its processing capacity. The size of structures within the sensory system is not, however, the only salient variable in sensory evolution. Further, the evolution of the brain and behavior are intimately tied to phylogenetic history, requiring studies to integrate neuroanatomy with behavior and phylogeny to gain a more holistic view of brain evolution. Birds have proven to be a useful group for these studies because of widespread interest in their phylogenetic relationships and a wealth of information on the functional organization of most of their sensory pathways. In this review, we examine the principle of proper mass in relation differences in the sensory capabilities among birds. We discuss how neuroanatomy, behavior, and phylogeny can be integrated to understand the evolution of sensory systems in birds providing evidence from visual, auditory, and somatosensory systems. We also consider the concept of a “trade-off,” whereby one sensory system (or subpathway within a sensory system), may be expanded in size, at the expense of others, which are reduced in size. PMID:26321905

Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry.

PubMed

Pratelli, Marta; Migliarini, Sara; Pelosi, Barbara; Napolitano, Francesco; Usiello, Alessandro; Pasqualetti, Massimo

2017-01-01

Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2 fl ° x conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.

Oligodendrogenesis in the normal and pathological central nervous system

PubMed Central

El Waly, Bilal; Macchi, Magali; Cayre, Myriam; Durbec, Pascale

2014-01-01

Oligodendrocytes (OLGs) are generated late in development and myelination is thus a tardive event in the brain developmental process. It is however maintained whole life long at lower rate, and myelin sheath is crucial for proper signal transmission and neuronal survival. Unfortunately, OLGs present a high susceptibility to oxidative stress, thus demyelination often takes place secondary to diverse brain lesions or pathologies. OLGs can also be the target of immune attacks, leading to primary demyelination lesions. Following oligodendrocytic death, spontaneous remyelination may occur to a certain extent. In this review, we will mainly focus on the adult brain and on the two main sources of progenitor cells that contribute to oligodendrogenesis: parenchymal oligodendrocyte precursor cells (OPCs) and subventricular zone (SVZ)-derived progenitors. We will shortly come back on the main steps of oligodendrogenesis in the postnatal and adult brain, and summarize the key factors involved in the determination of oligodendrocytic fate. We will then shed light on the main causes of demyelination in the adult brain and present the animal models that have been developed to get insight on the demyelination/remyelination process. Finally, we will synthetize the results of studies searching for factors able to modulate spontaneous myelin repair. PMID:24971048

Brain Imaging and Human Nutrition: Which Measures to Use in Intervention Studies?12

PubMed Central

Sizonenko, Stéphane V.; Babiloni, Claudio; Sijben, John W.; Walhovd, Kristine B.

2013-01-01

Throughout the life span, the brain is a metabolically highly active organ that uses a large proportion of total nutrient and energy intake. Furthermore, the development and repair of neural tissue depend on the proper intake of essential structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain from eating, may have an important impact on our cognitive ability and mental performance. Two of the key areas in which diet is thought to play an important role are in optimizing neurodevelopment in children and in preventing neurodegeneration and cognitive decline during aging. From early development to aging, brain imaging can detect structural, functional, and metabolic changes in humans and modifications due to altered nutrition or to additional nutritional supplementation. Inclusion of imaging measures in clinical studies can increase understanding with regard to the modification of brain structure, metabolism, and functional endpoints and may provide early sensitive measures of long-term effects. In this symposium, the utility of existing brain imaging technologies to assess the effects of nutritional intervention in humans is described. Examples of current research showing the utility of these markers are reviewed. PMID:24038255

Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood–brain barrier: [17O]H2O JJVCPE MRI study

PubMed Central

Huber, Vincent J.; Igarashi, Hironaka; Ueki, Satoshi; Kwee, Ingrid L.

2018-01-01

The blood–brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow–Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow–Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [17O]H2O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [17O]H2O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB. PMID:29481527

Neurodevelopmental Abnormalities and Congenital Heart Disease: Insights into Altered Brain Maturation

PubMed Central

Morton, Paul D.; Ishibashi, Nobuyuki; Jonas, Richard A.

2017-01-01

In the past two decades it has become evident that individuals born with congenital heart disease (CHD) are at risk of developing life-long neurological deficits. Multifactorial risk factors contributing to neurodevelopmental abnormalities associated with CHD have been identified; however the underlying etiologies remain largely unknown and efforts to address this issue have only recently begun. There has been a dramatic shift in focus from newly acquired brain injuries associated with corrective and palliative heart surgery to antenatal and preoperative factors governing altered brain maturation in CHD. In this review, we describe key time windows of development during which the immature brain is vulnerable to injury. Special emphasis is placed on the dynamic nature of cellular events and how CHD may adversely impact the cellular units and networks necessary for proper cognitive and motor function. In addition, we describe current gaps in knowledge and offer perspectives about what can be done to improve our understanding of neurological deficits in CHD. Ultimately, a multidisciplinary approach will be essential in order to prevent or improve adverse neurodevelopmental outcomes in individuals surviving CHD. PMID:28302742

Neurodevelopmental Abnormalities and Congenital Heart Disease: Insights Into Altered Brain Maturation.

PubMed

Morton, Paul D; Ishibashi, Nobuyuki; Jonas, Richard A

2017-03-17

In the past 2 decades, it has become evident that individuals born with congenital heart disease (CHD) are at risk of developing life-long neurological deficits. Multifactorial risk factors contributing to neurodevelopmental abnormalities associated with CHD have been identified; however, the underlying causes remain largely unknown, and efforts to address this issue have only recently begun. There has been a dramatic shift in focus from newly acquired brain injuries associated with corrective and palliative heart surgery to antenatal and preoperative factors governing altered brain maturation in CHD. In this review, we describe key time windows of development during which the immature brain is vulnerable to injury. Special emphasis is placed on the dynamic nature of cellular events and how CHD may adversely impact the cellular units and networks necessary for proper cognitive and motor function. In addition, we describe current gaps in knowledge and offer perspectives about what can be done to improve our understanding of neurological deficits in CHD. Ultimately, a multidisciplinary approach will be essential to prevent or improve adverse neurodevelopmental outcomes in individuals surviving CHD. © 2017 American Heart Association, Inc.

What is the Thalamus in Zebrafish?

PubMed Central

Mueller, Thomas

2012-01-01

Current research on the thalamus and related structures in the zebrafish diencephalon identifies an increasing number of both neurological structures and ontogenetic processes as evolutionary conserved between teleosts and mammals. The patterning processes, for example, which during the embryonic development of zebrafish form the thalamus proper appear largely conserved. Yet also striking differences between zebrafish and other vertebrates have been observed, particularly when we look at mature and histologically differentiated brains. A case in point is the migrated preglomerular complex of zebrafish which evolved only within the lineage of ray-finned fish and has no counterpart in mammals or tetrapod vertebrates. Based on its function as a sensory relay station with projections to pallial zones, the preglomerular complex has been compared to specific thalamic nuclei in mammals. However, no thalamic projections to the zebrafish dorsal pallium, which corresponds topologically to the mammalian isocortex, have been identified. Merely one teleostean thalamic nucleus proper, the auditory nucleus, projects to a part of the dorsal telencephalon, the pallial amygdala. Studies on patterning mechanisms identify a rostral and caudal domain in the embryonic thalamus proper. In both, teleosts and mammals, the rostral domain gives rise to GABAergic neurons, whereas glutamatergic neurons originate in the caudal domain of the zebrafish thalamus. The distribution of GABAergic derivatives in the adult zebrafish brain, furthermore, revealed previously overlooked thalamic nuclei and redefined already established ones. These findings require some reconsideration regarding the topological origin of these adult structures. In what follows, I discuss how evolutionary conserved and newly acquired features of the developing and adult zebrafish thalamus can be compared to the mammalian situation. PMID:22586363

p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development

PubMed Central

Contreras, Esteban G.; Sierralta, Jimena

2018-01-01

Background Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called ‘brain sparing’. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Results Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Conclusions Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals. PMID:29621246

p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development.

PubMed

Contreras, Esteban G; Sierralta, Jimena; Glavic, Alvaro

2018-01-01

Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called 'brain sparing'. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals.

The rights and wrongs of blood-brain barrier permeability studies: a walk through 100 years of history

PubMed Central

Saunders, Norman R.; Dreifuss, Jean-Jacques; Dziegielewska, Katarzyna M.; Johansson, Pia A.; Habgood, Mark D.; Møllgård, Kjeld; Bauer, Hans-Christian

2014-01-01

Careful examination of relevant literature shows that many of the most cherished concepts of the blood-brain barrier are incorrect. These include an almost mythological belief in its immaturity that is unfortunately often equated with absence or at least leakiness in the embryo and fetus. The original concept of a blood-brain barrier is often attributed to Ehrlich; however, he did not accept that permeability of cerebral vessels was different from other organs. Goldmann is often credited with the first experiments showing dye (trypan blue) exclusion from the brain when injected systemically, but not when injected directly into it. Rarely cited are earlier experiments of Bouffard and of Franke who showed methylene blue and trypan red stained all tissues except the brain. The term “blood-brain barrier” “Blut-Hirnschranke” is often attributed to Lewandowsky, but it does not appear in his papers. The first person to use this term seems to be Stern in the early 1920s. Studies in embryos by Stern and colleagues, Weed and Wislocki showed results similar to those in adult animals. These were well-conducted experiments made a century ago, thus the persistence of a belief in barrier immaturity is puzzling. As discussed in this review, evidence for this belief, is of poor experimental quality, often misinterpreted and often not properly cited. The functional state of blood-brain barrier mechanisms in the fetus is an important biological phenomenon with implications for normal brain development. It is also important for clinicians to have proper evidence on which to advise pregnant women who may need to take medications for serious medical conditions. Beliefs in immaturity of the blood-brain barrier have held the field back for decades. Their history illustrates the importance of taking account of all the evidence and assessing its quality, rather than selecting papers that supports a preconceived notion or intuitive belief. This review attempts to right the wrongs. Based on careful translation of original papers, some published a century ago, as well as providing discussion of studies claiming to show barrier immaturity, we hope that readers will have evidence on which to base their own conclusions. PMID:25565938

The TINS Lecture. Understanding the roles of Otx1 and Otx2 in the control of brain morphogenesis.

PubMed

Acampora, D; Simeone, A

1999-03-01

The murine homologs of the orthodenticle (otd) gene of Drosophila, Otx1 and Otx2, have an important role in brain morphogenesis. Analysis of Otx1 and Otx2 null mice reveals that Otx1 is required primarily for corticogenesis and sense-organ development,while Otx2 is necessary for specification and maintenance of anterior neural plate as well as for proper gastrulation. Cross-phylum recoveries of Otx1 abnormalities by Drosophila otd, and vice versa, indicate that genetic functions required in mammalian-brain development evolved in a primitive ancestor of flies and mice. Knock-in mouse models in which Otx2 was replaced with Otx1, and vice versa, provide evidence that the existence of Otx1-/- and Otx2-/- divergent phenotypes largely reflects differences in expression patterns rather than in the biochemical activity of OTX1 and OTX2. In evolutionary terms, some of these findings lead us to hypothesize a fascinating and crucial role for Otx genes that contributes to the genetic program required for the specification of the development of the vertebrate head.

Making the Nation Safe in the Twenty-First Century

DTIC Science & Technology

2009-12-01

is an ability to express through storytelling , empathy, creativity, and innovation—all right brain versus left brain attributes (pp. 65–67). One of...skill sets. As will be discussed later, Thomas Pink in his book, A Whole New Mind, would further define these skill sets between the left brain and...right brain characteristics. Finding a proper balance between the two skill sets is arguably one of the greatest contemporary challenges facing the

APLP2 regulates neuronal stem cell differentiation during cortical development.

PubMed

Shariati, S Ali M; Lau, Pierre; Hassan, Bassem A; Müller, Ulrike; Dotti, Carlos G; De Strooper, Bart; Gärtner, Annette

2013-03-01

Expression of amyloid precursor protein (APP) and its two paralogues, APLP1 and APLP2 during brain development coincides with key cellular events such as neuronal differentiation and migration. However, genetic knockout and shRNA studies have led to contradictory conclusions about their role during embryonic brain development. To address this issue, we analysed in depth the role of APLP2 during neurogenesis by silencing APLP2 in vivo in an APP/APLP1 double knockout mouse background. We find that under these conditions cortical progenitors remain in their undifferentiated state much longer, displaying a higher number of mitotic cells. In addition, we show that neuron-specific APLP2 downregulation does not impact the speed or position of migrating excitatory cortical neurons. In summary, our data reveal that APLP2 is specifically required for proper cell cycle exit of neuronal progenitors, and thus has a distinct role in priming cortical progenitors for neuronal differentiation.

Brain perfusion imaging using a Reconstruction-of-Difference (RoD) approach for cone-beam computed tomography

NASA Astrophysics Data System (ADS)

Mow, M.; Zbijewski, W.; Sisniega, A.; Xu, J.; Dang, H.; Stayman, J. W.; Wang, X.; Foos, D. H.; Koliatsos, V.; Aygun, N.; Siewerdsen, J. H.

2017-03-01

Purpose: To improve the timely detection and treatment of intracranial hemorrhage or ischemic stroke, recent efforts include the development of cone-beam CT (CBCT) systems for perfusion imaging and new approaches to estimate perfusion parameters despite slow rotation speeds compared to multi-detector CT (MDCT) systems. This work describes development of a brain perfusion CBCT method using a reconstruction of difference (RoD) approach to enable perfusion imaging on a newly developed CBCT head scanner prototype. Methods: A new reconstruction approach using RoD with a penalized-likelihood framework was developed to image the temporal dynamics of vascular enhancement. A digital perfusion simulation was developed to give a realistic representation of brain anatomy, artifacts, noise, scanner characteristics, and hemo-dynamic properties. This simulation includes a digital brain phantom, time-attenuation curves and noise parameters, a novel forward projection method for improved computational efficiency, and perfusion parameter calculation. Results: Our results show the feasibility of estimating perfusion parameters from a set of images reconstructed from slow scans, sparse data sets, and arc length scans as short as 60 degrees. The RoD framework significantly reduces noise and time-varying artifacts from inconsistent projections. Proper regularization and the use of overlapping reconstructed arcs can potentially further decrease bias and increase temporal resolution, respectively. Conclusions: A digital brain perfusion simulation with RoD imaging approach has been developed and supports the feasibility of using a CBCT head scanner for perfusion imaging. Future work will include testing with data acquired using a 3D-printed perfusion phantom currently and translation to preclinical and clinical studies.

Erythropoietin attenuates loss of potassium chloride co-transporters following prenatal brain injury.

PubMed

Jantzie, L L; Getsy, P M; Firl, D J; Wilson, C G; Miller, R H; Robinson, S

2014-07-01

Therapeutic agents that restore the inhibitory actions of γ-amino butyric acid (GABA) by modulating intracellular chloride concentrations will provide novel avenues to treat stroke, chronic pain, epilepsy, autism, and neurodegenerative and cognitive disorders. During development, upregulation of the potassium-chloride co-transporter KCC2, and the resultant switch from excitatory to inhibitory responses to GABA guide the formation of essential inhibitory circuits. Importantly, maturation of inhibitory mechanisms is also central to the development of excitatory circuits and proper balance between excitatory and inhibitory networks in the developing brain. Loss of KCC2 expression occurs in postmortem samples from human preterm infant brains with white matter lesions. Here we show that late gestation brain injury in a rat model of extreme prematurity impairs the developmental upregulation of potassium chloride co-transporters during a critical postnatal period of circuit maturation in CA3 hippocampus by inducing a sustained loss of oligomeric KCC2 via a calpain-dependent mechanism. Further, administration of erythropoietin (EPO) in a clinically relevant postnatal dosing regimen following the prenatal injury protects the developing brain by reducing calpain activity, restoring oligomeric KCC2 expression and attenuating KCC2 fragmentation, thus providing the first report of a safe therapy to address deficits in KCC2 expression. Together, these data indicate it is possible to reverse abnormalities in KCC2 expression during the postnatal period, and potentially reverse deficits in inhibitory circuit formation central to cognitive impairment and epileptogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Microglia across the lifespan: from origin to function in brain development, plasticity and cognition

PubMed Central

Savage, Julie C.; Hui, Chin Wai; Bisht, Kanchan

2016-01-01

Abstract Microglia are the only immune cells that permanently reside in the central nervous system (CNS) alongside neurons and other types of glial cells. The past decade has witnessed a revolution in our understanding of their roles during normal physiological conditions. Cutting‐edge techniques revealed that these resident immune cells are critical for proper brain development, actively maintain health in the mature brain, and rapidly adapt their function to physiological or pathophysiological needs. In this review, we highlight recent studies on microglial origin (from the embryonic yolk sac) and the factors regulating their differentiation and homeostasis upon brain invasion. Elegant experiments tracking microglia in the CNS allowed studies of their unique roles compared with other types of resident macrophages. Here we review the emerging roles of microglia in brain development, plasticity and cognition, and discuss the implications of the depletion or dysfunction of microglia for our understanding of disease pathogenesis. Immune activation, inflammation and various other conditions resulting in undesirable microglial activity at different stages of life could severely impair learning, memory and other essential cognitive functions. The diversity of microglial phenotypes across the lifespan, between compartments of the CNS, and sexes, as well as their crosstalk with the body and external environment, is also emphasised. Understanding what defines particular microglial phenotypes is of major importance for future development of innovative therapies controlling their effector functions, with consequences for cognition across chronic stress, ageing, neuropsychiatric and neurological diseases. PMID:27104646

Transient Blockade of ERK Phosphorylation in the Critical Period Causes Autistic Phenotypes as an Adult in Mice

PubMed Central

Yufune, Shinya; Satoh, Yasushi; Takamatsu, Isao; Ohta, Hiroyuki; Kobayashi, Yasushi; Takaenoki, Yumiko; Pagès, Gilles; Pouysségur, Jacques; Endo, Shogo; Kazama, Tomiei

2015-01-01

The critical period is a distinct time-window during the neonatal stage when animals display elevated sensitivity to certain environmental stimuli, and particular experiences can have profound and long-lasting effects on behaviors. Increasing evidence suggests that disruption of neuronal activity during the critical period contributes to autistic phenotype, although the pathogenic mechanism is largely unknown. Herein we show that extracellular signal-regulated protein kinases (ERKs) play important roles in proper formation of neural circuits during the critical period. Transient blockade of ERKs phosphorylation at postnatal day 6 (P6) by intraperitoneal injection of blood-brain barrier-penetrating MEK inhibitor, α-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile (SL327) caused significant increase of apoptosis in the forebrain. Furthermore, this induced long-term deleterious effects on brain functioning later in adulthood, resulting in social deficits, impaired memory and reduced long-term potentiation (LTP). Conversely, blockade of ERK phosphorylation at P14 no longer induced apoptosis, nor behavioral deficits, nor the reduced LTP. Thus, surprisingly, these effects of ERKs are strongly age-dependent, indicating that phosphorylation of ERKs during the critical period is absolutely required for proper development of brain functioning. This study provides novel insight into the mechanistic basis for neurodevelopment disorders: various neurodevelopment disorders might be generally linked to defects in ERKs signaling during the critical period. PMID:25993696

Transient Blockade of ERK Phosphorylation in the Critical Period Causes Autistic Phenotypes as an Adult in Mice.

PubMed

Yufune, Shinya; Satoh, Yasushi; Takamatsu, Isao; Ohta, Hiroyuki; Kobayashi, Yasushi; Takaenoki, Yumiko; Pagès, Gilles; Pouysségur, Jacques; Endo, Shogo; Kazama, Tomiei

2015-05-20

The critical period is a distinct time-window during the neonatal stage when animals display elevated sensitivity to certain environmental stimuli, and particular experiences can have profound and long-lasting effects on behaviors. Increasing evidence suggests that disruption of neuronal activity during the critical period contributes to autistic phenotype, although the pathogenic mechanism is largely unknown. Herein we show that extracellular signal-regulated protein kinases (ERKs) play important roles in proper formation of neural circuits during the critical period. Transient blockade of ERKs phosphorylation at postnatal day 6 (P6) by intraperitoneal injection of blood-brain barrier-penetrating MEK inhibitor, α-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile (SL327) caused significant increase of apoptosis in the forebrain. Furthermore, this induced long-term deleterious effects on brain functioning later in adulthood, resulting in social deficits, impaired memory and reduced long-term potentiation (LTP). Conversely, blockade of ERK phosphorylation at P14 no longer induced apoptosis, nor behavioral deficits, nor the reduced LTP. Thus, surprisingly, these effects of ERKs are strongly age-dependent, indicating that phosphorylation of ERKs during the critical period is absolutely required for proper development of brain functioning. This study provides novel insight into the mechanistic basis for neurodevelopment disorders: various neurodevelopment disorders might be generally linked to defects in ERKs signaling during the critical period.

A Brain Unfixed: Unlimited Neurogenesis and Regeneration of the Adult Planarian Nervous System

PubMed Central

Brown, David D. R.; Pearson, Bret J.

2017-01-01

Powerful genetic tools in classical laboratory models have been fundamental to our understanding of how stem cells give rise to complex neural tissues during embryonic development. In contrast, adult neurogenesis in our model systems, if present, is typically constrained to one or a few zones of the adult brain to produce a limited subset of neurons leading to the dogma that the brain is primarily fixed post-development. The freshwater planarian (flatworm) is an invertebrate model system that challenges this dogma. The planarian possesses a brain containing several thousand neurons with very high rates of cell turnover (homeostasis), which can also be fully regenerated de novo from injury in just 7 days. Both homeostasis and regeneration depend on the activity of a large population of adult stem cells, called neoblasts, throughout the planarian body. Thus, much effort has been put forth to understand how the flatworm can continually give rise to the diversity of cell types found in the adult brain. Here we focus on work using single-cell genomics and functional analyses to unravel the cellular hierarchies from stem cell to neuron. In addition, we will review what is known about how planarians utilize developmental signaling to maintain proper tissue patterning, homeostasis, and cell-type diversity in their brains. Together, planarians are a powerful emerging model system to study the dynamics of adult neurogenesis and regeneration. PMID:28588444

Intracranial pressure increases during exposure to a shock wave.

PubMed

Leonardi, Alessandra Dal Cengio; Bir, Cynthia A; Ritzel, Dave V; VandeVord, Pamela J

2011-01-01

Traumatic brain injuries (TBI) caused by improvised explosive devices (IEDs) affect a significant percentage of surviving soldiers wounded in Iraq and Afghanistan. The extent of a blast TBI, especially initially, is difficult to diagnose, as internal injuries are frequently unrecognized and therefore underestimated, yet problems develop over time. Therefore it is paramount to resolve the physical mechanisms by which critical stresses are inflicted on brain tissue from blast wave encounters with the head. This study recorded direct pressure within the brains of male Sprague-Dawley rats during exposure to blast. The goal was to understand pressure wave dynamics through the brain. In addition, we optimized in vivo methods to ensure accurate measurement of intracranial pressure (ICP). Our results demonstrate that proper sealing techniques lead to a significant increase in ICP values, compared to the outside overpressure generated by the blast. Further, the values seem to have a direct relation to a rat's size and age: heavier, older rats had the highest ICP readings. These findings suggest that a global flexure of the skull by the transient shockwave is an important mechanism of pressure transmission inside the brain.

A Report Generator Volume 2

DTIC Science & Technology

1988-01-01

her Nicholle) ( korsakoffs (proper-noun singlp neuter) korsakoffs korekoffs) (huntingtons (proper-noun sing3p neuter) huntingtons huntingtons...hemisphere)) (sub-class (value gerstmann- syndrome 1-constructional-dyspraxia reading-coup aphasia)) (type (value lobe)) (dda (value (location...class)) (dda (value (function damage memory) (location brain))) (importance (value 10)) (damage (value 8))) ( korsakoffs (super-class (value stm)) (sub

In Vitro, Ex Vivo and In Vivo Techniques to Study Neuronal Migration in the Developing Cerebral Cortex

PubMed Central

Azzarelli, Roberta; Oleari, Roberto; Lettieri, Antonella; Andre', Valentina; Cariboni, Anna

2017-01-01

Neuronal migration is a fundamental biological process that underlies proper brain development and neuronal circuit formation. In the developing cerebral cortex, distinct neuronal populations, producing excitatory, inhibitory and modulatory neurotransmitters, are generated in different germinative areas and migrate along various routes to reach their final positions within the cortex. Different technical approaches and experimental models have been adopted to study the mechanisms regulating neuronal migration in the cortex. In this review, we will discuss the most common in vitro, ex vivo and in vivo techniques to visualize and study cortical neuronal migration. PMID:28448448

Distribution of the cystine/glutamate antiporter system xc- in the brain, kidney, and duodenum.

PubMed

Burdo, Joseph; Dargusch, Richard; Schubert, David

2006-05-01

System x(c)(-), one of the main transporters responsible for central nervous system cystine transport, is comprised of two subunits, xCT and 4F2hc. The transport of cystine into cells is rate limiting for glutathione synthesis, the major antioxidant and redox cofactor in the brain. Alterations in glutathione status are prevalent in numerous neurodegenerative diseases, emphasizing the importance of proper cystine homeostasis. However, the distribution of xCT and 4F2hc within the brain and other areas has not been described. Using specific antibodies, both xCT and 4F2hc were localized predominantly to neurons in the mouse and human brain, but some glial cells were labeled as well. Border areas between the brain proper and periphery including the vascular endothelial cells, ependymal cells, choroid plexus, and leptomeninges were also highly positive for the system x(c)(-) components. xCT and 4F2hc are also present at the brush border membranes in the kidney and duodenum. These results indicate that system x(c)(-) is likely to play a role in cellular health throughout many areas of the brain as well as other organs by maintaining intracellular cystine levels, thereby resulting in low levels of oxidative stress.

Different Anaphoric Expressions Are Investigated by Event-Related Brain Potentials

ERIC Educational Resources Information Center

Streb, Judith; Hennighausen, Erwin; Rosler, Frank

2004-01-01

Event-related potentials were recorded to substantiate the claim of a distinct psycholinguistic status of (a) pronouns vs. proper names and (b) ellipses vs. proper names. In two studies 41 students read sentences in which the number of intervening words between the anaphor and its antecedent was either small or large. Comparing the far with the…

Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

PubMed

Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

2017-01-01

Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration

NASA Astrophysics Data System (ADS)

Gibbs, Holly C.; Dodson, Colin R.; Bai, Yuqiang; Lekven, Arne C.; Yeh, Alvin T.

2014-12-01

During embryogenesis, presumptive brain compartments are patterned by dynamic networks of gene expression. The spatiotemporal dynamics of these networks, however, have not been characterized with sufficient resolution for us to understand the regulatory logic resulting in morphogenetic cellular behaviors that give the brain its shape. We have developed a new, integrated approach using ultrashort pulse microscopy [a high-resolution, two-photon fluorescence (2PF)-optical coherence microscopy (OCM) platform using 10-fs pulses] and image registration to study brain patterning and morphogenesis in zebrafish embryos. As a demonstration, we used time-lapse 2PF to capture midbrain-hindbrain boundary morphogenesis and a wnt1 lineage map from embryos during brain segmentation. We then performed in situ hybridization to deposit NBT/BCIP, where wnt1 remained actively expressed, and reimaged the embryos with combined 2PF-OCM. When we merged these datasets using morphological landmark registration, we found that the mechanism of boundary formation differs along the dorsoventral axis. Dorsally, boundary sharpening is dominated by changes in gene expression, while ventrally, sharpening may be accomplished by lineage sorting. We conclude that the integrated visualization of lineage reporter and gene expression domains simultaneously with brain morphology will be useful for understanding how changes in gene expression give rise to proper brain compartmentalization and structure.

Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration.

PubMed

Gibbs, Holly C; Dodson, Colin R; Bai, Yuqiang; Lekven, Arne C; Yeh, Alvin T

2014-12-01

During embryogenesis, presumptive brain compartments are patterned by dynamic networks of gene expression. The spatiotemporal dynamics of these networks, however, have not been characterized with sufficient resolution for us to understand the regulatory logic resulting in morphogenetic cellular behaviors that give the brain its shape. We have developed a new, integrated approach using ultrashort pulse microscopy [a high-resolution, two-photon fluorescence (2PF)-optical coherence microscopy (OCM) platform using 10-fs pulses] and image registration to study brain patterning and morphogenesis in zebrafish embryos. As a demonstration, we used time-lapse 2PF to capture midbrain-hindbrain boundary morphogenesis and a wnt1 lineage map from embryos during brain segmentation. We then performed in situ hybridization to deposit NBT/BCIP, where wnt1 remained actively expressed, and reimaged the embryos with combined 2PF-OCM. When we merged these datasets using morphological landmark registration, we found that the mechanism of boundary formation differs along the dorsoventral axis. Dorsally, boundary sharpening is dominated by changes in gene expression, while ventrally, sharpening may be accomplished by lineage sorting. We conclude that the integrated visualization of lineage reporter and gene expression domains simultaneously with brain morphology will be useful for understanding how changes in gene expression give rise to proper brain compartmentalization and structure.

Convolutional neural network for high-accuracy functional near-infrared spectroscopy in a brain-computer interface: three-class classification of rest, right-, and left-hand motor execution.

PubMed

Trakoolwilaiwan, Thanawin; Behboodi, Bahareh; Lee, Jaeseok; Kim, Kyungsoo; Choi, Ji-Woong

2018-01-01

The aim of this work is to develop an effective brain-computer interface (BCI) method based on functional near-infrared spectroscopy (fNIRS). In order to improve the performance of the BCI system in terms of accuracy, the ability to discriminate features from input signals and proper classification are desired. Previous studies have mainly extracted features from the signal manually, but proper features need to be selected carefully. To avoid performance degradation caused by manual feature selection, we applied convolutional neural networks (CNNs) as the automatic feature extractor and classifier for fNIRS-based BCI. In this study, the hemodynamic responses evoked by performing rest, right-, and left-hand motor execution tasks were measured on eight healthy subjects to compare performances. Our CNN-based method provided improvements in classification accuracy over conventional methods employing the most commonly used features of mean, peak, slope, variance, kurtosis, and skewness, classified by support vector machine (SVM) and artificial neural network (ANN). Specifically, up to 6.49% and 3.33% improvement in classification accuracy was achieved by CNN compared with SVM and ANN, respectively.

Drosophila Activin- and the Activin-like product Dawdle function redundantly to regulate proliferation in the larval brain.

PubMed

Zhu, Changqi C; Boone, Jason Q; Jensen, Philip A; Hanna, Scott; Podemski, Lynn; Locke, John; Doe, Chris Q; O'Connor, Michael B

2008-02-01

The Drosophila Activin-like ligands Activin-beta and Dawdle control several aspects of neuronal morphogenesis, including mushroom body remodeling, dorsal neuron morphogenesis and motoneuron axon guidance. Here we show that the same two ligands act redundantly through the Activin receptor Babo and its transcriptional mediator Smad2 (Smox), to regulate neuroblast numbers and proliferation rates in the developing larval brain. Blocking this pathway results in the development of larvae with small brains and aberrant photoreceptor axon targeting, and restoring babo function in neuroblasts rescued these mutant phenotypes. These results suggest that the Activin signaling pathway is required for producing the proper number of neurons to enable normal connection of incoming photoreceptor axons to their targets. Furthermore, as the Activin pathway plays a key role in regulating propagation of mouse and human embryonic stem cells, our observation that it also regulates neuroblast numbers and proliferation in Drosophila suggests that involvement of Activins in controlling stem cell propagation may be a common regulatory feature of this family of TGF-beta-type ligands.

Stranger in a Strange Land: Using Heterotopic Transplantations to Study Nature vs Nurture in Brain Development.

PubMed

Petros, Timothy J

2018-01-01

The mammalian brain develops from a simple sheet of neuroepithelial cells into an incredibly complex structure containing billions of neurons with trillions of synapses. Understanding how intrinsic genetic programs interact with environmental cues to generate neuronal diversity and proper connectivity is one of the most daunting challenges in developmental biology. We recently explored this issue in forebrain GABAergic inhibitory interneurons, an extremely diverse population of neurons that are classified into distinct subtypes based on morphology, neurochemical markers, and electrophysiological properties. Immature interneurons were harvested from one brain region and transplanted into a different region, allowing us to assess how challenging cells in a new environment affected their fate. Do these grafted cells adopt characteristics of the host environment or retain features from the donor environment? We found that the proportion of interneuron subgroups is determined by the host region, but some interneuron subtypes maintain features attributable to the donor environment. In this commentary, I expound on potential mechanisms that could underlie these observations and explore the implications of these findings in a greater context of developmental neuroscience.

Tonic and Rhythmic Spinal Activity Underlying Locomotion.

PubMed

Ivanenko, Yury P; Gurfinkel, Victor S; Selionov, Victor A; Solopova, Irina A; Sylos-Labini, Francesca; Guertin, Pierre A; Lacquaniti, Francesco

2017-05-12

In recent years, many researches put significant efforts into understanding and assessing the functional state of the spinal locomotor circuits in humans. Various techniques have been developed to stimulate the spinal cord circuitries, which may include both diffuse and quite specific tuning effects. Overall, the findings indicate that tonic and rhythmic spinal activity control are not separate phenomena but are closely integrated to properly initiate and sustain stepping. The spinal cord does not simply transmit information to and from the brain. Its physiologic state determines reflex, postural and locomotor control and, therefore, may affect the recovery of the locomotor function in individuals with spinal cord and brain injuries. This review summarizes studies that examine the rhythmogenesis capacity of cervical and lumbosacral neuronal circuitries in humans and its importance in developing central pattern generator-modulating therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Clk post-transcriptional control denoises circadian transcription both temporally and spatially.

PubMed

Lerner, Immanuel; Bartok, Osnat; Wolfson, Victoria; Menet, Jerome S; Weissbein, Uri; Afik, Shaked; Haimovich, Daniel; Gafni, Chen; Friedman, Nir; Rosbash, Michael; Kadener, Sebastian

2015-05-08

The transcription factor CLOCK (CLK) is essential for the development and maintenance of circadian rhythms in Drosophila. However, little is known about how CLK levels are controlled. Here we show that Clk mRNA is strongly regulated post-transcriptionally through its 3' UTR. Flies expressing Clk transgenes without normal 3' UTR exhibit variable CLK-driven transcription and circadian behaviour as well as ectopic expression of CLK-target genes in the brain. In these flies, the number of the key circadian neurons differs stochastically between individuals and within the two hemispheres of the same brain. Moreover, flies carrying Clk transgenes with deletions in the binding sites for the miRNA bantam have stochastic number of pacemaker neurons, suggesting that this miRNA mediates the deterministic expression of CLK. Overall our results demonstrate a key role of Clk post-transcriptional control in stabilizing circadian transcription, which is essential for proper development and maintenance of circadian rhythms in Drosophila.

GEMC1 is a critical regulator of multiciliated cell differentiation.

PubMed

Terré, Berta; Piergiovanni, Gabriele; Segura-Bayona, Sandra; Gil-Gómez, Gabriel; Youssef, Sameh A; Attolini, Camille Stephan-Otto; Wilsch-Bräuninger, Michaela; Jung, Carole; Rojas, Ana M; Marjanović, Marko; Knobel, Philip A; Palenzuela, Lluís; López-Rovira, Teresa; Forrow, Stephen; Huttner, Wieland B; Valverde, Miguel A; de Bruin, Alain; Costanzo, Vincenzo; Stracker, Travis H

2016-05-02

The generation of multiciliated cells (MCCs) is required for the proper function of many tissues, including the respiratory tract, brain, and germline. Defects in MCC development have been demonstrated to cause a subclass of mucociliary clearance disorders termed reduced generation of multiple motile cilia (RGMC). To date, only two genes, Multicilin (MCIDAS) and cyclin O (CCNO) have been identified in this disorder in humans. Here, we describe mice lacking GEMC1 (GMNC), a protein with a similar domain organization as Multicilin that has been implicated in DNA replication control. We have found that GEMC1-deficient mice are growth impaired, develop hydrocephaly with a high penetrance, and are infertile, due to defects in the formation of MCCs in the brain, respiratory tract, and germline. Our data demonstrate that GEMC1 is a critical regulator of MCC differentiation and a candidate gene for human RGMC or related disorders. © 2016 The Authors.

Delineation of separate brain regions used for scientific versus engineering modes of thinking

NASA Astrophysics Data System (ADS)

Patterson, Clair C.

1994-08-01

Powerful, latent abilities for extreme sophistication in abstract rationalization as potential biological adaptive behavioral responses were installed entirely through accident and inadvertence by biological evolution in the Homo sapiens sapiens species of brain. These potentials were never used, either in precursor species as factors in evolutionary increase in hominid brain mass, nor in less sophisticated forms within social environments characterized by Hss tribal brain population densities. Those latent abilities for unnatural biological adaptive behavior were forced to become manifest in various ways by growths in sophistication of communication interactions engendered by large growths in brain population densities brought on by developments in agriculture at the onset of the Holocene. It is proposed that differences probably exist between regions of the Hss brain involved in utilitarian, engineering types of problem conceptualization-solving versus regions of the brain involved in nonutilitarian, artistic-scientific types of problem conceptualization-solving. Populations isolated on separate continents from diffusive contact and influence on cultural developments, and selected for comparison of developments during equivalent stages of technological and social sophistication in matching 4000 year periods, show, at the ends of those periods, marked differences in aesthetic attributes expressed in cosmogonies, music, and writing (nonutilitarian thinking related to science and art). On the other hand the two cultures show virtually identical developments in three major stages of metallurgical technologies (utilitarian thinking related to engineering). Such archaeological data suggest that utilitarian modes of thought may utilize combinations of neuronal circuits in brain regions that are conserved among tribal populations territorially separated from each other for tens of thousands of years. Such conservation may not be true for neuronal circuits involved in nonutilitarian modes of thought. It is postulated that neuronal circuits involved in nonutilitarian modes of thought are located in specific regions of the brain that are divergent features between populations that have been territorially separated for tens of thousands of years. Anatomical PET and NMRI studies of brains of modern descendants of these cultures are proposed that would seek to define these inferred differences through proper protocols of stimulation devised by those investigators.

Cryptococcoma mimicking a brain tumor in an immunocompetent patient: case report of an extremely rare presentation.

PubMed

Paiva, Aline Lariessy Campos; Aguiar, Guilherme Brasileiro de; Lovato, Renan Maximilian; Zanetti, Arthus Vilar Deolindo; Panagopoulos, Alexandros Theodoros; Veiga, José Carlos Esteves

2017-11-06

Central nervous system (CNS) infectious diseases have high prevalence in developing countries and their proper diagnosis and treatment are very important for public health planning. Cryptococcus neoformans is a fungus that may cause several CNS manifestations, especially in immunocompromised patients. Cryptococcal meningitis is the most common type of involvement. Mass-effect lesions are uncommon: they are described as cryptococcomas and their prevalence is even lower among immunocompetent patients. The aim here was to report an extremely rare case of cryptococcoma causing a mass effect and mimicking a brain tumor in an immunocompetent patient. The literature on CNS cryptococcal infections was reviewed with emphasis on cryptococcomas. Clinical, surgical and radiological data on a female patient with this rare presentation of cryptococcoma mimicking a brain tumor are described. A 54-year-old female patient presented to the emergency department with a rapid-onset progressive history of confusion and completely dependency for basic activities. Neuroimaging showed a left occipital lesion and neurosurgical treatment was proposed. From histopathological evaluation, a diagnosis of cryptococcoma was established. She received clinical support with antifungals, but despite optimal clinical treatment, her condition evolved to death. Cryptococcal infections have several forms of presentation and, in immunocompetent patients, their manifestation may be even more different. Cryptococcoma is an extremely rare presentation in which proper surgical and clinical treatment should be instituted as quickly as possible, but even so, there is a high mortality rate.

Using event-related potentials to study perinatal nutrition and brain development in infants of diabetic mothers.

PubMed

deRegnier, Raye-Ann; Long, Jeffrey D; Georgieff, Michael K; Nelson, Charles A

2007-01-01

Proper prenatal and postnatal nutrition is essential for optimal brain development and function. The early use of event-related potentials enables neuroscientists to study the development of cognitive function from birth and to evaluate the role of specific nutrients in development. Perinatal iron deficiency occurs in severely affected infants of diabetic mothers. In animal models, severe perinatal iron deficiency targets the explicit memory system of the brain. Cross-sectional ERP studies have shown that infants of diabetic mothers have impairments in recognition memory from birth through 8 months of age. The purpose of this study was to evaluate longitudinal development of recognition memory using ERPs in infants of diabetic mothers compared with control infants. Infants of diabetic mothers were divided into high and low risk status based upon their birth weights and iron status and compared with healthy control infants. Infants were tested in the newborn period for auditory recognition memory, at 6 months for visual recognition memory and at 8 months for cross modal memory. ERPs were evaluated for developmental changes in the slow waves that are thought to reflect memory and the Nc component that is thought to reflect attention. The results of the study showed differences in development between the IDMs and control infants in the development of the slow waves over the left anterior temporal leads and age-related patterns of development in the NC component. These results are consistent with animal models showing that perinatal iron deficiency affects the development of the memory networks of the brain. This study highlights the value of using ERPs to translate basic science information obtained from animal models to the development of the human infant.

Using Event-Related Potentials to Study Perinatal Nutrition and Brain Development in Infants of Diabetic Mothers

PubMed Central

deRegnier, Raye-Ann; Long, Jeffrey D.; Georgieff, Michael K.; Nelson, Charles A.

2009-01-01

Proper prenatal and postnatal nutrition is essential for optimal brain development and function. The early use of event-related potentials enables neuroscientists to study the development of cognitive function from birth and to evaluate the role of specific nutrients in development. Perinatal iron deficiency occurs in severely affected infants of diabetic mothers. In animal models, severe perinatal iron deficiency targets the explicit memory system of the brain. Cross-sectional ERP studies have shown that infants of diabetic mothers have impairments in recognition memory from birth through 8 months of age. The purpose of this study was to evaluate longitudinal development of recognition memory using ERPs in infants of diabetic mothers compared with control infants. Infants of diabetic mothers were divided into high and low risk status based upon their birthweights and iron status and compared with healthy control infants. Infants were tested in the newborn period for auditory recognition memory, at 6 months for visual recognition memory and at 8 months for cross modal memory. ERPs were evaluated for developmental changes in the slow waves that are thought to reflect memory and the Nc component that is thought to reflect attention. The results of the study showed differences in development between the IDMs and control infants in the development of the slow waves over the left anterior temporal leads and age-related patterns of development in the NC component. These results are consistent with animal models showing that perinatal iron deficiency affects the development of the memory networks of the brain. This study highlights the value of using ERPs to translate basic science information obtained from animal models to the development of the human infant. PMID:17559331

Canonical WNT signaling components in vascular development and barrier formation.

PubMed

Zhou, Yulian; Wang, Yanshu; Tischfield, Max; Williams, John; Smallwood, Philip M; Rattner, Amir; Taketo, Makoto M; Nathans, Jeremy

2014-09-01

Canonical WNT signaling is required for proper vascularization of the CNS during embryonic development. Here, we used mice with targeted mutations in genes encoding canonical WNT pathway members to evaluate the exact contribution of these components in CNS vascular development and in specification of the blood-brain barrier (BBB) and blood-retina barrier (BRB). We determined that vasculature in various CNS regions is differentially sensitive to perturbations in canonical WNT signaling. The closely related WNT signaling coreceptors LDL receptor-related protein 5 (LRP5) and LRP6 had redundant functions in brain vascular development and barrier maintenance; however, loss of LRP5 alone dramatically altered development of the retinal vasculature. The BBB in the cerebellum and pons/interpeduncular nuclei was highly sensitive to decrements in canonical WNT signaling, and WNT signaling was required to maintain plasticity of barrier properties in mature CNS vasculature. Brain and retinal vascular defects resulting from ablation of Norrin/Frizzled4 signaling were ameliorated by stabilizing β-catenin, while inhibition of β-catenin-dependent transcription recapitulated the vascular development and barrier defects associated with loss of receptor, coreceptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly through β-catenin-dependent transcriptional regulation. Together, these data strongly support a model in which identical or nearly identical canonical WNT signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB.

Dietary Omega-3 Fatty Acid Deficiency and High Fructose intake in the Development of Metabolic Syndrome Brain, Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease

PubMed Central

Simopoulos, Artemis P.

2013-01-01

Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS). Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD), promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health. PMID:23896654

Robust Brain Hyperglycemia during General Anesthesia: Relationships with Metabolic Brain Inhibition and Vasodilation

PubMed Central

Bola, R. Aaron; Kiyatkin, Eugene A.

2016-01-01

Glucose is the main energetic substrate for the metabolic activity of brain cells and its proper delivery into the extracellular space is essential for maintaining normal neural functions. Under physiological conditions, glucose continuously enters the extracellular space from arterial blood via gradient-dependent facilitated diffusion governed by the GLUT-1 transporters. Due to this gradient-dependent mechanism, glucose levels rise in the brain after consumption of glucose-containing foods and drinks. Glucose entry is also accelerated due to local neuronal activation and neuro-vascular coupling, resulting in transient hyperglycemia to prevent any metabolic deficit. Here, we explored another mechanism that is activated during general anesthesia and results in significant brain hyperglycemia. By using enzyme-based glucose biosensors we demonstrate that glucose levels in the nucleus accumbens (NAc) strongly increase after iv injection of Equthesin, a mixture of chloral hydrate and sodium pentobarbital, which is often used for general anesthesia in rats. By combining electrochemical recordings with brain, muscle, and skin temperature monitoring, we show that the gradual increase in brain glucose occurring during the development of general anesthesia tightly correlate with decreases in brain-muscle temperature differentials, suggesting that this rise in glucose is related to metabolic inhibition. While the decreased consumption of glucose by brain cells could contribute to the development of hyperglycemia, an exceptionally strong positive correlation (r = 0.99) between glucose rise and increases in skin-muscle temperature differentials was also found, suggesting the strong vasodilation of cerebral vessels as the primary mechanism for accelerated entry of glucose into brain tissue. Our present data could explain drastic differences in basal glucose levels found in awake and anesthetized animal preparations. They also suggest that glucose entry into brain tissue could be strongly modulated by pharmacological drugs via drug-induced changes in metabolic activity and the tone of cerebral vessels. PMID:26913008

Fetal Alcohol Spectrum Disorders: An Overview from the Glia Perspective.

PubMed

Wilhelm, Clare J; Guizzetti, Marina

2015-01-01

Alcohol consumption during pregnancy can produce a variety of central nervous system (CNS) abnormalities in the offspring resulting in a broad spectrum of cognitive and behavioral impairments that constitute the most severe and long-lasting effects observed in fetal alcohol spectrum disorders (FASD). Alcohol-induced abnormalities in glial cells have been suspected of contributing to the adverse effects of alcohol on the developing brain for several years, although much research still needs to be done to causally link the effects of alcohol on specific brain structures and behavior to alterations in glial cell development and function. Damage to radial glia due to prenatal alcohol exposure may underlie observations of abnormal neuronal and glial migration in humans with Fetal Alcohol Syndrome (FAS), as well as primate and rodent models of FAS. A reduction in cell number and altered development has been reported for several glial cell types in animal models of FAS. In utero alcohol exposure can cause microencephaly when alcohol exposure occurs during the brain growth spurt a period characterized by rapid astrocyte proliferation and maturation; since astrocytes are the most abundant cells in the brain, microenchephaly may be caused by reduced astrocyte proliferation or survival, as observed in in vitro and in vivo studies. Delayed oligodendrocyte development and increased oligodendrocyte precursor apoptosis has also been reported in experimental models of FASD, which may be linked to altered myelination/white matter integrity found in FASD children. Children with FAS exhibit hypoplasia of the corpus callosum and anterior commissure, two areas requiring guidance from glial cells and proper maturation of oligodendrocytes. Finally, developmental alcohol exposure disrupts microglial function and induces microglial apoptosis; given the role of microglia in synaptic pruning during brain development, the effects of alcohol on microglia may be involved in the abnormal brain plasticity reported in FASD. The consequences of prenatal alcohol exposure on glial cells, including radial glia and other transient glial structures present in the developing brain, astrocytes, oligodendrocytes and their precursors, and microglia contributes to abnormal neuronal development, reduced neuron survival and disrupted brain architecture and connectivity. This review highlights the CNS structural abnormalities caused by in utero alcohol exposure and outlines which abnormalities are likely mediated by alcohol effects on glial cell development and function.

Atypical Brain Responses to Reward Cues in Autism as Revealed by Event-Related Potentials

ERIC Educational Resources Information Center

Kohls, Gregor; Peltzer, Judith; Schulte-Ruther, Martin; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2011-01-01

Social motivation deficit theories suggest that children with autism do not properly anticipate and appreciate the pleasure of social stimuli. In this study, we investigated event-related brain potentials evoked by cues that triggered social versus monetary reward anticipation in children with autism. Children with autism showed attenuated P3…

How Should Educational Neuroscience Conceptualise the Relation between Cognition and Brain Function? Mathematical Reasoning as a Network Process

ERIC Educational Resources Information Center

Varma, Sashank; Schwartz, Daniel L.

2008-01-01

Background: There is increasing interest in applying neuroscience findings to topics in education. Purpose: This application requires a proper conceptualization of the relation between cognition and brain function. This paper considers two such conceptualizations. The area focus understands each cognitive competency as the product of one (and only…

Neurotrophic Factors and Maternal Nutrition During Pregnancy.

PubMed

Dhobale, M

2017-01-01

Maternal nutrition is one of the major determinants of pregnancy outcome. It has been suggested that reduced intakes or lack of specific nutrients during pregnancy influences the length of gestation, proper placental and fetal growth during pregnancy. Maternal nutrition, particularly micronutrients such as folate and vitamin B 12 , and long-chain polyunsaturated fatty acids (LCPUFA) are the major determinants of the one carbon cycle and are suggested to be at the heart of intrauterine programming of diseases in adult life. LCPUFA play a key role in the normal feto-placental development, as well as in the development and functional maturation of the brain and central nervous system and also regulate the levels of neurotrophic factors. These neurotrophic factors are known to regulate the development of the placenta at the materno-fetal interface and act in a paracrine and endocrine manner. Neurotrophic factors like brain-derived neurotrophic factor and nerve growth factor are proteins involved in angiogenesis and potentiate the placental development. This chapter mainly focuses on micronutrients since they play a main physiological role during pregnancy. © 2017 Elsevier Inc. All rights reserved.

Insights into the regulation of neuronal viability by nucleophosmin/B23.

PubMed

Pfister, Jason A; D'Mello, Santosh R

2015-06-01

The vastness of the neuronal network that constitutes the human brain proves challenging when trying to understand its complexity. Furthermore, due to the senescent state they enter into upon maturation, neurons lack the ability to regenerate in the face of insult, injury or death. Consequently, their excessive death can be detrimental to the proper functioning of the brain. Therefore, elucidating the mechanisms regulating neuronal survival is, while challenging, of great importance as the incidence of neurological disease is becoming more prevalent in today's society. Nucleophosmin/B23 (NPM) is an abundant and ubiquitously expressed protein that regulates vital cellular processes such as ribosome biogenesis, cell proliferation and genomic stability. As a result, it is necessary for proper embryonic development, but has also been implicated in many cancers. While highly studied in the context of proliferative cells, there is a lack of understanding NPM's role in post-mitotic neurons. By exploring its role in healthy neurons as well as its function in the regulation of cell death and neurodegeneration, there can be a better understanding of how these diseases initiate and progress. Owing to what is thus far known about its function in the cell, NPM could be an attractive therapeutic target in the treatment of neurodegenerative diseases. © 2015 by the Society for Experimental Biology and Medicine.

Balancing Act: Maintaining Amino Acid Levels in the Autistic Brain.

PubMed

Maynard, Thomas M; Manzini, M Chiara

2017-02-08

The ever-expanding number of genes that are mutated in autism is showing us how imbalances in fundamental cellular processes can lead to disease. A recent study by Tărlungeanu et al. (2016) identifies a form of ASD resulting from a failure of the brain to properly import amino acids. Copyright © 2017 Elsevier Inc. All rights reserved.

Biochemical Fractionation and Stable Isotope Dilution Liquid Chromatography-mass Spectrometry for Targeted and Microdomain-specific Protein Quantification in Human Postmortem Brain Tissue*

PubMed Central

MacDonald, Matthew L.; Ciccimaro, Eugene; Prakash, Amol; Banerjee, Anamika; Seeholzer, Steven H.; Blair, Ian A.; Hahn, Chang-Gyu

2012-01-01

Synaptic architecture and its adaptive changes require numerous molecular events that are both highly ordered and complex. A majority of neuropsychiatric illnesses are complex trait disorders, in which multiple etiologic factors converge at the synapse via many signaling pathways. Investigating the protein composition of synaptic microdomains from human patient brain tissues will yield valuable insights into the interactions of risk genes in many disorders. These types of studies in postmortem tissues have been limited by the lack of proper study paradigms. Thus, it is necessary not only to develop strategies to quantify protein and post-translational modifications at the synapse, but also to rigorously validate them for use in postmortem human brain tissues. In this study we describe the development of a liquid chromatography-selected reaction monitoring method, using a stable isotope-labeled neuronal proteome standard prepared from the brain tissue of a stable isotope-labeled mouse, for the multiplexed quantification of target synaptic proteins in mammalian samples. Additionally, we report the use of this method to validate a biochemical approach for the preparation of synaptic microdomain enrichments from human postmortem prefrontal cortex. Our data demonstrate that a targeted mass spectrometry approach with a true neuronal proteome standard facilitates accurate and precise quantification of over 100 synaptic proteins in mammalian samples, with the potential to quantify over 1000 proteins. Using this method, we found that protein enrichments in subcellular fractions prepared from human postmortem brain tissue were strikingly similar to those prepared from fresh mouse brain tissue. These findings demonstrate that biochemical fractionation methods paired with targeted proteomic strategies can be used in human brain tissues, with important implications for the study of neuropsychiatric disease. PMID:22942359

Targeting the Brain with a Neuroprotective Omega-3 Fatty Acid to Enhance Neurogenesis in Hypoxic Condition in Culture.

PubMed

Lo Van, Amanda; Sakayori, Nobuyuki; Hachem, Mayssa; Belkouch, Mounir; Picq, Madeleine; Fourmaux, Baptiste; Lagarde, Michel; Osumi, Noriko; Bernoud-Hubac, Nathalie

2018-06-01

Docosahexaenoic acid (DHA, 22:6n-3) is an essential omega-3 polyunsaturated fatty acid (PUFA) that is required for proper brain development and cerebral functions. While DHA deficiency in the brain was shown to be linked to the emergence of cerebral diseases, a dietary intake of omega-3 PUFA could prevent or attenuate neurologic disturbances linked with aging or neurodegenerative diseases. In this context, targeting the brain with DHA might offer great promise in developing new therapeutics for neurodegenerative diseases. We previously synthesized a stabilized form of DHA-containing lysophosphatidylcholine a major vector of DHA transportation to the brain, which is 1-acetyl,2-docoshexaenoyl-glycerophosphocholine, named AceDoPC®. Injection of AceDoPC® or DHA after experimental ischemic stroke showed that both molecules had neuroprotective effects but AceDoPC® was the most potent. This study aims to investigate the beneficial effects of DHA either unesterified or esterified within AceDoPC® on a model of neurogenesis in vitro, under physiological or pathological conditions. The effect of protectin DX (PDX, a double lipoxygenase product of DHA) was also tested. We cultured neural stem progenitor cells (NSPCs) derived from the adult mouse brain under normal or hypoxigenic (ischemic) conditions in vitro. Neurogenesis study of cell cultures with AceDoPC® showed enhanced neurogenesis compared to addition of unesterified DHA, PDX, or vehicle control, especially under pathological conditions. Our studies of the potential mechanisms involved in neuroprotection hinted that AceDoPC® neuroprotective and regenerative effects might be due in part to its anti-oxidative effects. These results indicate the potential for novel therapeutics against stroke that target the brain.

Temporary Depletion of Microglia during the Early Postnatal Period Induces Lasting Sex-Dependent and Sex-Independent Effects on Behavior in Rats

PubMed Central

2016-01-01

Abstract Microglia are the primary immune cells of the brain and function in multiple ways to facilitate proper brain development. However, our current understanding of how these cells influence the later expression of normal behaviors is lacking. Using the laboratory rat, we administered liposomal clodronate centrally to selectively deplete microglia in the developing postnatal brain. We then assessed a range of developmental, juvenile, and adult behaviors. Liposomal clodronate treatment on postnatal days 0, 2, and 4 depleted microglia with recovery by about 10 days of age and induced a hyperlocomotive phenotype, observable in the second postnatal week. Temporary microglia depletion also increased juvenile locomotion in the open field test and decreased anxiety-like behaviors in the open field and elevated plus maze. These same rats displayed reductions in predator odor–induced avoidance behavior, but increased their risk assessment behaviors compared with vehicle-treated controls. In adulthood, postnatal microglia depletion resulted in significant deficits in male-specific sex behaviors. Using factor analysis, we identified two underlying traits—behavioral disinhibition and locomotion—as being significantly altered by postnatal microglia depletion. These findings further implicate microglia as being critically important to the development of juvenile and adult behavior. PMID:27957532

Perspectives and new aspects of metalloproteinases' inhibitors in therapy of CNS disorders: from chemistry to medicine.

PubMed

Boguszewska-Czubara, Anna; Budzynska, Barbara; Skalicka-Wozniak, Krystyna; Kurzepa, Jacek

2018-05-13

Matrix metalloproteinases (MMPs) play a key role in remodelling of the extracellular matrix (ECM) and, at the same time, influence cell differentiation, migration, proliferation and survival. Their importance in variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders has been known for many years but special attention should be paid on the role of MMPs in the central nervous system (CNS) disorders. Till now, there are not many well documented physiological MMP target proteins in the brain and only some pathological ones. Numerous neurodegenerative diseases is a consequence or result in disturbed remodeling of brain ECM, therefore proper action of MMPs as well as control of their activity may play crucial roles in the development and the progress of these diseases. In present review we discuss the role of metalloproteinase inhibitors, from the well-known natural endogenous tissue inhibitors of metalloproteinases (TIMPs) through exogenous synthetic ones like (4-phenoxyphenylsulfonyl)methylthiirane (SB-3CT), tetracyclines, batimastat (BB-94) and FN-439. As the MMP-TIMP system has been well described in physiological development as well as in pathological conditions mainly in neoplasctic diseases, the knowledge about the enzymatic system in mammalian brain tissue remain still poorly understood in this context. Therefore, we focus on MMPs inhibition in the context of physiological function of adult brain as well as pathological conditions including neurodegenerative diseases, brain injuries and others. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

PubMed Central

Ross, Emily J; Graham, Devon L; Money, Kelli M; Stanwood, Gregg D

2015-01-01

Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose–response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures. PMID:24938210

Dissociable Effects on Birdsong of Androgen Signaling in Cortex-Like Brain Regions of Canaries

PubMed Central

2017-01-01

The neural basis of how learned vocalizations change during development and in adulthood represents a major challenge facing cognitive neuroscience. This plasticity in the degree to which learned vocalizations can change in both humans and songbirds is linked to the actions of sex steroid hormones during ontogeny but also in adulthood in the context of seasonal changes in birdsong. We investigated the role of steroid hormone signaling in the brain on distinct features of birdsong using adult male canaries (Serinus canaria), which show extensive seasonal vocal plasticity as adults. Specifically, we bilaterally implanted the potent androgen receptor antagonist flutamide in two key brain regions that control birdsong. We show that androgen signaling in the motor cortical-like brain region, the robust nucleus of the arcopallium (RA), controls syllable and trill bandwidth stereotypy, while not significantly affecting higher order features of song such syllable-type usage (i.e., how many times each syllable type is used) or syllable sequences. In contrast, androgen signaling in the premotor cortical-like brain region, HVC (proper name), controls song variability by increasing the variability of syllable-type usage and syllable sequences, while having no effect on syllable or trill bandwidth stereotypy. Other aspects of song, such as the duration of trills and the number of syllables per song, were also differentially affected by androgen signaling in HVC versus RA. These results implicate androgens in regulating distinct features of complex motor output in a precise and nonredundant manner. SIGNIFICANCE STATEMENT Vocal plasticity is linked to the actions of sex steroid hormones, but the precise mechanisms are unclear. We investigated this question in adult male canaries (Serinus canaria), which show extensive vocal plasticity throughout their life. We show that androgens in two cortex-like vocal control brain regions regulate distinct aspects of vocal plasticity. For example, in HVC (proper name), androgens regulate variability in syntax but not phonology, whereas androgens in the robust nucleus of the arcopallium (RA) regulate variability in phonology but not syntax. Temporal aspects of song were also differentially affected by androgen signaling in HVC versus RA. Thus, androgen signaling may reduce vocal plasticity by acting in a nonredundant and precise manner in the brain. PMID:28821656

Dendritic Learning as a Paradigm Shift in Brain Learning.

PubMed

Sardi, Shira; Vardi, Roni; Goldental, Amir; Tugendhaft, Yael; Uzan, Herut; Kanter, Ido

2018-06-20

Experimental and theoretical results reveal a new underlying mechanism for fast brain learning process, dendritic learning, as opposed to the misdirected research in neuroscience over decades, which is based solely on slow synaptic plasticity. The presented paradigm indicates that learning occurs in closer proximity to the neuron, the computational unit, dendritic strengths are self-oscillating, and weak synapses, which comprise the majority of our brain and previously were assumed to be insignificant, play a key role in plasticity. The new learning sites of the brain call for a reevaluation of current treatments for disordered brain functionality and for a better understanding of proper chemical drugs and biological mechanisms to maintain, control and enhance learning.

Neural Development Under Conditions of Spaceflight

NASA Technical Reports Server (NTRS)

Kosik, Kenneth S.; Steward, Oswald; Temple, Meredith D.; Denslow, Maria J.

2003-01-01

One of the key tasks the developing brain must learn is how to navigate within the environment. This skill depends on the brain's ability to establish memories of places and things in the environment so that it can form cognitive maps. Earth's gravity defines the plane of orientation of the spatial environment in which animals navigate, and cognitive maps are based on this plane of orientation. Given that experience during early development plays a key role in the development of other aspects of brain function, experience in a gravitational environment is likely to be essential for the proper organization of brain regions mediating learning and memory of spatial information. Since the hippocampus is the brain region responsible for cognitive mapping abilities, this study evaluated the development of hippocampal structure and function in rats that spent part of their early development in microgravity. Litters of male and female Sprague-Dawley rats were launched into space aboard the Space Shuttle Columbia on either postnatal day eight (P8) or 14 (P14) and remained in space for 16 days. Upon return to Earth, the rats were tested for their ability to remember spatial information and navigate using a variety of tests (the Morris water maze, a modified radial arm maze, and an open field apparatus). These rats were then tested physiologically to determine whether they exhibited normal synaptic plasticity in the hippocampus. In a separate group of rats (flight and controls), the hippocampus was analyzed using anatomical, molecular biological, and biochemical techniques immediately postlanding. There were remarkably few differences between the flight groups and their Earth-bound controls in either the navigation and spatial memory tasks or activity-induced synaptic plasticity. Microscopic and immunocytochemical analyses of the brain also did not reveal differences between flight animals and ground-based controls. These data suggest that, within the developmental window studied, microgravity has minimal long-term impact on cognitive mapping function and cellular substrates important for this function. Any differences due to development in microgravity were transient and returned to normal soon after return to Earth.

How are 'Barack Obama' and 'President Elect' differentially stored in the brain? An ERP investigation on the processing of proper and common noun pairs.

PubMed

Proverbio, Alice Mado; Mariani, Serena; Zani, Alberto; Adorni, Roberta

2009-09-23

One of the most debated issues in the cognitive neuroscience of language is whether distinct semantic domains are differentially represented in the brain. Clinical studies described several anomic dissociations with no clear neuroanatomical correlate. Neuroimaging studies have shown that memory retrieval is more demanding for proper than common nouns in that the former are purely arbitrary referential expressions. In this study a semantic relatedness paradigm was devised to investigate neural processing of proper and common nouns. 780 words (arranged in pairs of Italian nouns/adjectives and the first/last names of well known persons) were presented. Half pairs were semantically related ("Woody Allen" or "social security"), while the others were not ("Sigmund Parodi" or "judicial cream"). All items were balanced for length, frequency, familiarity and semantic relatedness. Participants were to decide about the semantic relatedness of the two items in a pair. RTs and N400 data suggest that the task was more demanding for common nouns. The LORETA neural generators for the related-unrelated contrast (for proper names) included the left fusiform gyrus, right medial temporal gyrus, limbic and parahippocampal regions, inferior parietal and inferior frontal areas, which are thought to be involved in the conjoined processing a familiar face with the relevant episodic information. Person name was more emotional and sensory vivid than common noun semantic access. When memory retrieval is not required, proper name access (conspecifics knowledge) is not more demanding. The neural generators of N400 to unrelated items (unknown persons and things) did not differ as a function of lexical class, thus suggesting that proper and common nouns are not treated differently as belonging to different grammatical classes.

How Are ‘Barack Obama’ and ‘President Elect’ Differentially Stored in the Brain? An ERP Investigation on the Processing of Proper and Common Noun Pairs

PubMed Central

Proverbio, Alice Mado; Mariani, Serena; Zani, Alberto; Adorni, Roberta

2009-01-01

Background One of the most debated issues in the cognitive neuroscience of language is whether distinct semantic domains are differentially represented in the brain. Clinical studies described several anomic dissociations with no clear neuroanatomical correlate. Neuroimaging studies have shown that memory retrieval is more demanding for proper than common nouns in that the former are purely arbitrary referential expressions. In this study a semantic relatedness paradigm was devised to investigate neural processing of proper and common nouns. Methodology/Principal Findings 780 words (arranged in pairs of Italian nouns/adjectives and the first/last names of well known persons) were presented. Half pairs were semantically related (“Woody Allen” or “social security”), while the others were not (“Sigmund Parodi” or “judicial cream”). All items were balanced for length, frequency, familiarity and semantic relatedness. Participants were to decide about the semantic relatedness of the two items in a pair. RTs and N400 data suggest that the task was more demanding for common nouns. The LORETA neural generators for the related-unrelated contrast (for proper names) included the left fusiform gyrus, right medial temporal gyrus, limbic and parahippocampal regions, inferior parietal and inferior frontal areas, which are thought to be involved in the conjoined processing a familiar face with the relevant episodic information. Person name was more emotional and sensory vivid than common noun semantic access. Conclusions/Significance When memory retrieval is not required, proper name access (conspecifics knowledge) is not more demanding. The neural generators of N400 to unrelated items (unknown persons and things) did not differ as a function of lexical class, thus suggesting that proper and common nouns are not treated differently as belonging to different grammatical classes. PMID:19774070

Aquaporin-4 deletion in mice reduces encephalopathy and brain edema in experimental acute liver failure.

PubMed

Rama Rao, Kakulavarapu V; Verkman, A S; Curtis, Kevin M; Norenberg, Michael D

2014-03-01

Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6% ± 0.3 and 2.3 ± 0.4%, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. Published by Elsevier Inc.

Aquaporin-4 Deletion in Mice Reduces Encephalopathy and Brain Edema in Experimental Acute Liver Failure

PubMed Central

Rama Rao, Kakulavarapu V.; Verkman, A. S.; Curtis, Kevin M.; Norenberg, Michael D.

2014-01-01

Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6 ± 0.3 and 2.3 ± 0.4 %, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. PMID:24321433

Restless Legs Syndrome

MedlinePlus

... caused by an imbalance of the brain chemical dopamine, which sends messages to control muscle movement. Heredity ... deficiency, often with anemia. When kidneys don't function properly, iron stores in your blood can decrease. ...

Minerals

MedlinePlus

Minerals are important for your body to stay healthy. Your body uses minerals for many different jobs, including keeping your bones, muscles, heart, and brain working properly. Minerals are also important for making enzymes and hormones. ...

Arginine-guanidinoacetate-creatine pathway in preterm newborns: creatine biosynthesis in newborns.

PubMed

Lage, Sergio; Andrade, Fernando; Prieto, José Angel; Asla, Izaskun; Rodríguez, Amaya; Ruiz, Nerea; Echeverría, Juncal; Luz Couce, María; Sanjurjo, Pablo; Aldámiz-Echevarría, Luis

2013-01-01

The phosphocreatine/creatine system is fundamental for the proper development of the embryonic brain. Being born prematurely might alter the creatine biosynthesis pathway, in turn affecting creatine supply to the developing brain. We enrolled 53 preterm and very preterm infants and 55 full-term newborns. The levels of urinary guanidinoacetate, creatine, creatinine and amino acids were measured in the preterm and very preterm groups, 48 h and 9 days after birth and at discharge, and 48 h after birth in the full-term group. Guanidinoacetate concentrations of both preterm and very preterm newborns were significantly higher at discharge than the values for the full-term group at 48 h, while very preterm infants showed urinary creatine values significantly lower than those measured in the full-term group. Our results suggest an impairment of the creatine biosynthesis pathway in preterm and very preterm newborns, which could lead to creatine depletion affecting the neurological outcome in prematurely born infants.

Synaptogenesis in the CNS: An Odyssey from Wiring Together to Firing Together

PubMed Central

Munno, David W; Syed, Naweed I

2003-01-01

To acquire a better comprehension of nervous system function, it is imperative to understand how synapses are assembled during development and subsequently altered throughout life. Despite recent advances in the fields of neurodevelopment and synaptic plasticity, relatively little is known about the mechanisms that guide synapse formation in the central nervous system (CNS). Although many structural components of the synaptic machinery are pre-assembled prior to the arrival of growth cones at the site of their potential targets, innumerable changes, central to the proper wiring of the brain, must subsequently take place through contact-mediated cell-cell communications. Identification of such signalling molecules and a characterization of various events underlying synaptogenesis are pivotal to our understanding of how a brain cell completes its odyssey from ‘wiring together to firing together’. Here we attempt to provide a comprehensive overview that pertains directly to the cellular and molecular mechanisms of selection, formation and refinement of synapses during the development of the CNS in both vertebrates and invertebrates. PMID:12897180

Detecting stripe artifacts in ultrasound images.

PubMed

Maciak, Adam; Kier, Christian; Seidel, Günter; Meyer-Wiethe, Karsten; Hofmann, Ulrich G

2009-10-01

Brain perfusion diseases such as acute ischemic stroke are detectable through computed tomography (CT)-/magnetic resonance imaging (MRI)-based methods. An alternative approach makes use of ultrasound imaging. In this low-cost bedside method, noise and artifacts degrade the imaging process. Especially stripe artifacts show a similar signal behavior compared to acute stroke or brain perfusion diseases. This document describes how stripe artifacts can be detected and eliminated in ultrasound images obtained through harmonic imaging (HI). On the basis of this new method, both proper identification of areas with critically reduced brain tissue perfusion and classification between brain perfusion defects and ultrasound stripe artifacts are made possible.

Learning-related brain hemispheric dominance in sleeping songbirds.

PubMed

Moorman, Sanne; Gobes, Sharon M H; van de Kamp, Ferdinand C; Zandbergen, Matthijs A; Bolhuis, Johan J

2015-03-12

There are striking behavioural and neural parallels between the acquisition of speech in humans and song learning in songbirds. In humans, language-related brain activation is mostly lateralised to the left hemisphere. During language acquisition in humans, brain hemispheric lateralisation develops as language proficiency increases. Sleep is important for the formation of long-term memory, in humans as well as in other animals, including songbirds. Here, we measured neuronal activation (as the expression pattern of the immediate early gene ZENK) during sleep in juvenile zebra finch males that were still learning their songs from a tutor. We found that during sleep, there was learning-dependent lateralisation of spontaneous neuronal activation in the caudomedial nidopallium (NCM), a secondary auditory brain region that is involved in tutor song memory, while there was right hemisphere dominance of neuronal activation in HVC (used as a proper name), a premotor nucleus that is involved in song production and sensorimotor learning. Specifically, in the NCM, birds that imitated their tutors well were left dominant, while poor imitators were right dominant, similar to language-proficiency related lateralisation in humans. Given the avian-human parallels, lateralised neural activation during sleep may also be important for speech and language acquisition in human infants.

Learning-related brain hemispheric dominance in sleeping songbirds

PubMed Central

Moorman, Sanne; Gobes, Sharon M. H.; van de Kamp, Ferdinand C.; Zandbergen, Matthijs A.; Bolhuis, Johan J.

2015-01-01

There are striking behavioural and neural parallels between the acquisition of speech in humans and song learning in songbirds. In humans, language-related brain activation is mostly lateralised to the left hemisphere. During language acquisition in humans, brain hemispheric lateralisation develops as language proficiency increases. Sleep is important for the formation of long-term memory, in humans as well as in other animals, including songbirds. Here, we measured neuronal activation (as the expression pattern of the immediate early gene ZENK) during sleep in juvenile zebra finch males that were still learning their songs from a tutor. We found that during sleep, there was learning-dependent lateralisation of spontaneous neuronal activation in the caudomedial nidopallium (NCM), a secondary auditory brain region that is involved in tutor song memory, while there was right hemisphere dominance of neuronal activation in HVC (used as a proper name), a premotor nucleus that is involved in song production and sensorimotor learning. Specifically, in the NCM, birds that imitated their tutors well were left dominant, while poor imitators were right dominant, similar to language-proficiency related lateralisation in humans. Given the avian-human parallels, lateralised neural activation during sleep may also be important for speech and language acquisition in human infants. PMID:25761654

NG2 glia are required for vessel network formation during embryonic development

PubMed Central

Minocha, Shilpi; Valloton, Delphine; Brunet, Isabelle; Eichmann, Anne

2015-01-01

The NG2+ glia, also known as polydendrocytes or oligodendrocyte precursor cells, represent a new entity among glial cell populations in the central nervous system. However, the complete repertoire of their roles is not yet identified. The embryonic NG2+ glia originate from the Nkx2.1+ progenitors of the ventral telencephalon. Our analysis unravels that, beginning from E12.5 until E16.5, the NG2+ glia populate the entire dorsal telencephalon. Interestingly, their appearance temporally coincides with the establishment of blood vessel network in the embryonic brain. NG2+ glia are closely apposed to developing cerebral vessels by being either positioned at the sprouting tip cells or tethered along the vessel walls. Absence of NG2+ glia drastically affects the vascular development leading to severe reduction of ramifications and connections by E18.5. By revealing a novel and fundamental role for NG2+ glia, our study brings new perspectives to mechanisms underlying proper vessels network formation in embryonic brains. DOI: http://dx.doi.org/10.7554/eLife.09102.001 PMID:26651999

CRISPR-engineered genome editing for the next generation neurological disease modeling.

PubMed

Feng, Weijun; Liu, Hai-Kun; Kawauchi, Daisuke

2018-02-02

Neurological disorders often occur because of failure of proper brain development and/or appropriate maintenance of neuronal circuits. In order to understand roles of causative factors (e.g. genes, cell types) in disease development, generation of solid animal models has been one of straight-forward approaches. Recent next generation sequencing studies on human patient-derived clinical samples have identified various types of recurrent mutations in individual neurological diseases. While these discoveries have prompted us to evaluate impact of mutated genes on these neurological diseases, a feasible but flexible genome editing tool had remained to be developed. An advance of genome editing technology using the clustered regularly interspaced short palindromic repeats (CRISPR) with the CRISPR-associated protein (Cas) offers us a tremendous potential to create a variety of mutations in the cell, leading to "next generation" disease models carrying disease-associated mutations. We will here review recent progress of CRISPR-based brain disease modeling studies and discuss future requirement to tackle current difficulties in usage of these technologies. Copyright © 2017 Elsevier Inc. All rights reserved.

Axon growth regulation by a bistable molecular switch.

PubMed

Padmanabhan, Pranesh; Goodhill, Geoffrey J

2018-04-25

For the brain to function properly, its neurons must make the right connections during neural development. A key aspect of this process is the tight regulation of axon growth as axons navigate towards their targets. Neuronal growth cones at the tips of developing axons switch between growth and paused states during axonal pathfinding, and this switching behaviour determines the heterogeneous axon growth rates observed during brain development. The mechanisms controlling this switching behaviour, however, remain largely unknown. Here, using mathematical modelling, we predict that the molecular interaction network involved in axon growth can exhibit bistability, with one state representing a fast-growing growth cone state and the other a paused growth cone state. Owing to stochastic effects, even in an unchanging environment, model growth cones reversibly switch between growth and paused states. Our model further predicts that environmental signals could regulate axon growth rate by controlling the rates of switching between the two states. Our study presents a new conceptual understanding of growth cone switching behaviour, and suggests that axon guidance may be controlled by both cell-extrinsic factors and cell-intrinsic growth regulatory mechanisms. © 2018 The Author(s).

The impact of microglial activation on blood-brain barrier in brain diseases

PubMed Central

da Fonseca, Anna Carolina Carvalho; Matias, Diana; Garcia, Celina; Amaral, Rackele; Geraldo, Luiz Henrique; Freitas, Catarina; Lima, Flavia Regina Souza

2014-01-01

The blood-brain barrier (BBB), constituted by an extensive network of endothelial cells (ECs) together with neurons and glial cells, including microglia, forms the neurovascular unit (NVU). The crosstalk between these cells guarantees a proper environment for brain function. In this context, changes in the endothelium-microglia interactions are associated with a variety of inflammation-related diseases in brain, where BBB permeability is compromised. Increasing evidences indicate that activated microglia modulate expression of tight junctions, which are essential for BBB integrity and function. On the other hand, the endothelium can regulate the state of microglial activation. Here, we review recent advances that provide insights into interactions between the microglia and the vascular system in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative disorders. PMID:25404894

Quantification of traumatic meningeal injury using dynamic contrast enhanced (DCE) fluid-attenuated inversion recovery (FLAIR) imaging

NASA Astrophysics Data System (ADS)

Castro, Marcelo A.; Williford, Joshua P.; Cota, Martin R.; MacLaren, Judy M.; Dardzinski, Bernard J.; Latour, Lawrence L.; Pham, Dzung L.; Butman, John A.

2016-03-01

Traumatic meningeal injury is a novel imaging marker of traumatic brain injury, which appears as enhancement of the dura on post-contrast T2-weighted FLAIR images, and is likely associated with inflammation of the meninges. Dynamic Contrast Enhanced MRI provides a better discrimination of abnormally perfused regions. A method to properly identify those regions is presented. Images of seventeen patients scanned within 96 hours of head injury with positive traumatic meningeal injury were normalized and aligned. The difference between the pre- and last post-contrast acquisitions was segmented and voxels in the higher class were spatially clustered. Spatial and morphological descriptors were used to identify the regions of enhancement: a) centroid; b) distance to the brain mask from external voxels; c) distance from internal voxels; d) size; e) shape. The method properly identified thirteen regions among all patients. The method failed in one case due to the presence of a large brain lesion that altered the mask boundaries. Most false detections were correctly rejected resulting in a sensitivity and specificity of 92.9% and 93.6%, respectively.

Jet Engine Control Using Ethernet with a BRAIN (Postprint)

DTIC Science & Technology

2008-07-01

current communications may be mitigated. 15. SUBJECT TERMS BRAIN, Braided Ring Availability Integrity Network, Gas turbine, FADEC , disturbed...urrent state of the art engine controls have converged on the notion of the Full Authority Digital Engine Control ( FADEC ), which consists of a centralized...is completely dependent on the proper operation of the controller. In current systems, the FADEC is often located on the relatively cool engine fan

Sialic Acids in the Brain: Gangliosides and Polysialic Acid in Nervous System Development, Stability, Disease, and Regeneration

PubMed Central

Gerardy-Schahn, Rita; Hildebrandt, Herbert

2014-01-01

Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper development, maintenance, and health of the nervous system. PMID:24692354

Nutrient-driven O-GlcNAc in proteostasis and neurodegeneration.

PubMed

Akan, Ilhan; Olivier-Van Stichelen, Stephanie; Bond, Michelle R; Hanover, John A

2018-01-01

Proteostasis is essential in the mammalian brain where post-mitotic cells must function for decades to maintain synaptic contacts and memory. The brain is dependent on glucose and other metabolites for proper function and is spared from metabolic deficits even during starvation. In this review, we outline how the nutrient-sensitive nucleocytoplasmic post-translational modification O-linked N-acetylglucosamine (O-GlcNAc) regulates protein homeostasis. The O-GlcNAc modification is highly abundant in the mammalian brain and has been linked to proteopathies, including neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's. C. elegans, Drosophila, and mouse models harboring O-GlcNAc transferase- and O-GlcNAcase-knockout alleles have helped define the role O-GlcNAc plays in development as well as age-associated neurodegenerative disease. These enzymes add and remove the single monosaccharide from protein serine and threonine residues, respectively. Blocking O-GlcNAc cycling is detrimental to mammalian brain development and interferes with neurogenesis, neural migration, and proteostasis. Findings in C. elegans and Drosophila model systems indicate that the dynamic turnover of O-GlcNAc is critical for maintaining levels of key transcriptional regulators responsible for neurodevelopment cell fate decisions. In addition, pathways of autophagy and proteasomal degradation depend on a transcriptional network that is also reliant on O-GlcNAc cycling. Like the quality control system in the endoplasmic reticulum which uses a 'mannose timer' to monitor protein folding, we propose that cytoplasmic proteostasis relies on an 'O-GlcNAc timer' to help regulate the lifetime and fate of nuclear and cytoplasmic proteins. O-GlcNAc-dependent developmental alterations impact metabolism and growth of the developing mouse embryo and persist into adulthood. Brain-selective knockout mouse models will be an important tool for understanding the role of O-GlcNAc in the physiology of the brain and its susceptibility to neurodegenerative injury. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

The Schizophrenia Risk Gene MIR137 Acts as a Hippocampal Gene Network Node Orchestrating the Expression of Genes Relevant to Nervous System Development and Function

PubMed Central

Loohuis, Nikkie FM Olde; Kasri, Nael Nadif; Glennon, Jeffrey C; van Bokhoven, Hans; Hébert, Sébastien S; Kaplan, Barry B.; Martens, Gerard JM; Aschrafi, Armaz

2016-01-01

MicroRNAs (miRs) are small regulatory molecules, which orchestrate neuronal development and plasticity through modulation of complex gene networks. microRNA-137 (miR-137) is a brain-enriched RNA with a critical role in regulating brain development and in mediating synaptic plasticity. Importantly, mutations in this miR are associated with the pathoetiology of schizophrenia (SZ), and there is a widespread assumption that disruptions in miR-137 expression lead to aberrant expression of gene regulatory networks associated with SZ. To systematically identify the mRNA targets for this miR, we performed miR-137 gain- and loss-of-function experiments in primary rat hippocampal neurons and profiled differentially expressed mRNAs through next-generation sequencing. We identified 500 genes that were bidirectionally activated or repressed in their expression by the modulation of miR-137 levels. Gene ontology analysis using two independent software resources suggested functions for these miR-137-regulated genes in neurodevelopmental processes, neuronal maturation processes and cell maintenance, all of which known to be critical for proper brain circuitry formation. Since many of the putative miR-137 targets identified here also have been previously shown to be associated with SZ, we propose that this miR acts as a critical gene network hub contributing to the pathophysiology of this neurodevelopmental disorder. PMID:26925706

Nano carriers for drug transport across the blood-brain barrier.

PubMed

Li, Xinming; Tsibouklis, John; Weng, Tingting; Zhang, Buning; Yin, Guoqiang; Feng, Guangzhu; Cui, Yingde; Savina, Irina N; Mikhalovska, Lyuba I; Sandeman, Susan R; Howel, Carol A; Mikhalovsky, Sergey V

2017-01-01

Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug-carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully discussed.

Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review).

PubMed

Agnati, Luigi F; Marcoli, Manuela; Leo, Giuseppina; Maura, Guido; Guidolin, Diego

2017-03-01

In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. However, the new concept of a hierarchic role of ISF of the various organs is introduced. Additionally, it is suggested that particularly for some chemico‑physical parameters, oscillatory rhythms within their proper set‑ranges should be considered a fundamental component of homeostasis. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio‑pathological states. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Furthermore, the evolutionary links between brain and kidney and their synergistic role in H2O/Na balance and brain temperature control are discussed. Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis.

Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review)

PubMed Central

Agnati, Luigi F.; Marcoli, Manuela; Leo, Giuseppina; Maura, Guido; Guidolin, Diego

2017-01-01

In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. However, the new concept of a hierarchic role of ISF of the various organs is introduced. Additionally, it is suggested that particularly for some chemico-physical parameters, oscillatory rhythms within their proper set-ranges should be considered a fundamental component of homeostasis. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio-pathological states. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Furthermore, the evolutionary links between brain and kidney and their synergistic role in H2O/Na balance and brain temperature control are discussed. Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis. PMID:28204813

Quantitative brain tissue oximetry, phase spectroscopy and imaging the range of homeostasis in piglet brain.

PubMed

Chance, Britton; Ma, Hong Yan; Nioka, Shoko

2003-01-01

The quantification of tissue oxygen by frequency or time domain methods has been discussed in a number of prior publications where the meaning of the tissue hemoglobin oxygen saturation was unclear and where the CW instruments were unsuitable for proper quantitative measurements [1, 2]. The development of the IQ Phase Meter has greatly simplified and made reliable the difficult determination of precise phase and amplitude signals from brain. This contribution reports on the calibration of the instrument in model systems and the use of the instrument to measure tissue saturation (StO2) in a small animal model. In addition, a global interpretation of the meaning of tissue oxygen has been formulated based on the idea that autoregulation will maintain tissue oxygen at a fixed value over a range of arterial and venous oxygen values over the range of autoregulation. Beyond that range, the tissue oxygen is still correctly measured but, as expected, approaches the arterial saturation at low metabolic rates and the venous saturation at high metabolic rates of mitochondria.

Genetics Home Reference: RNAse T2-deficient leukoencephalopathy

MedlinePlus

... abundant in the brain. Ribonucleases help break down RNA, a chemical cousin of DNA. Studies suggest that ... in angiogenesis or an immune system response to RNA that has not been properly broken down. Learn ...

Applying Superresolution Localization-Based Microscopy to Neurons

PubMed Central

ZHONG, HAINING

2016-01-01

Proper brain function requires the precise localization of proteins and signaling molecules on a nanometer scale. The examination of molecular organization at this scale has been difficult in part because it is beyond the reach of conventional, diffraction-limited light microscopy. The recently developed method of superresolution, localization-based fluorescent microscopy (LBM), such as photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM), has demonstrated a resolving power at a 10 nm scale and is poised to become a vital tool in modern neuroscience research. Indeed, LBM has revealed previously unknown cellular architectures and organizational principles in neurons. Here, we discuss the principles of LBM, its current applications in neuroscience, and the challenges that must be met before its full potential is achieved. We also present the unpublished results of our own experiments to establish a sample preparation procedure for applying LBM to study brain tissue. PMID:25648102

Memory and Self–Neuroscientific Landscapes

PubMed Central

Markowitsch, Hans J.

2013-01-01

Relations between memory and the self are framed from a number of perspectives—developmental aspects, forms of memory, interrelations between memory and the brain, and interactions between the environment and memory. The self is seen as dividable into more rudimentary and more advanced aspects. Special emphasis is laid on memory systems and within them on episodic autobiographical memory which is seen as a pure human form of memory that is dependent on a proper ontogenetic development and shaped by the social environment, including culture. Self and episodic autobiographical memory are seen as interlocked in their development and later manifestation. Aside from content-based aspects of memory, time-based aspects are seen along two lines—the division between short-term and long-term memory and anterograde—future-oriented—and retrograde—past-oriented memory. The state dependency of episodic autobiographical is stressed and implications of it—for example, with respect to the occurrence of false memories and forensic aspects—are outlined. For the brain level, structural networks for encoding, consolidation, storage, and retrieval are discussed both by referring to patient data and to data obtained in normal participants with functional brain imaging methods. It is elaborated why descriptions from patients with functional or dissociative amnesia are particularly apt to demonstrate the facets in which memory, self, and personal temporality are interwoven. PMID:24967303

Two distinct modes of forebrain circuit dynamics underlie temporal patterning in the vocalizations of young songbirds

PubMed Central

Aronov, Dmitriy; Veit, Lena; Goldberg, Jesse H.; Fee, Michale S.

2011-01-01

Accurate timing is a critical aspect of motor control, yet the temporal structure of many mature behaviors emerges during learning from highly variable exploratory actions. How does a developing brain acquire the precise control of timing in behavioral sequences? To investigate the development of timing, we analyzed the songs of young juvenile zebra finches. These highly variable vocalizations, akin to human babbling, gradually develop into temporally-stereotyped adult songs. We find that the durations of syllables and silences in juvenile singing are formed by a mixture of two distinct modes of timing – a random mode producing broadly-distributed durations early in development, and a stereotyped mode underlying the gradual emergence of stereotyped durations. Using lesions, inactivations, and localized brain cooling we investigated the roles of neural dynamics within two premotor cortical areas in the production of these temporal modes. We find that LMAN (lateral magnocellular nucleus of the nidopallium) is required specifically for the generation of the random mode of timing, and that mild cooling of LMAN causes an increase in the durations produced by this mode. On the contrary, HVC (used as a proper name) is required specifically for producing the stereotyped mode of timing, and its cooling causes a slowing of all stereotyped components. These results show that two neural pathways contribute to the timing of juvenile songs, and suggest an interesting organization in the forebrain, whereby different brain areas are specialized for the production of distinct forms of neural dynamics. PMID:22072687

A half-truth is a whole lie: on the necessity of investigating sex influences on the brain.

PubMed

Cahill, Larry

2012-06-01

Sex influences are proving to be extremely widespread on brain function, including the human brain. Ample evidence now proves that the sex of subjects can influence, ever reverse, findings, hence conclusions, at all levels of brain science, down to the molecular level, often in completely unanticipated ways. Thus the still-prominent assumption that sex influences may be safely ignored by neurobiologists is invalid and must be abandoned. The failure to properly consider the issue fills the literature with conclusions tenuous at best, false at worst. The continuing, widespread resistance to investigating sex influences among brain scientists, a resistance largely rooted in deeply entrenched biases against the topic, is becoming increasingly scientifically indefensible and strongly retards progress in our field.

Attitudes to brain death and organ procurement among university students and critical care physicians in poland.

PubMed

Kubler, A; Lipinska-Gediga, M; Kedziora, J; Kubler, M

2009-06-01

The practice of retrieving vital organs from brain-dead heart-beating donors is legally and medically accepted in Poland, but public beliefs and opinions regarding these matters have not been sufficiently explored. The purpose of this study was to evaluate the attitude of university students to the concepts of brain death and organ retrieval, compared with the attitude of critical care physicians. The cohorts of 989 students and 139 physicians completed a questionnaire based on a survey instrument developed in an earlier reported study on Ohio residents. Participants assessed 3 scenarios: (1) brain death, (2) coma, and (3) vegetative state. More than 48% of students classified the patient from the brain death scenario as alive, and 51% of them were willing to donate organs of this patient. Ninety percent of students classified the patients in coma and in a vegetative state as alive, but still 34% of them would donate organs of those patients. The group of physicians properly determined the patients' diagnoses, but 10% of them accepted organ procurement from patients in coma and in a vegetative state. Our results supported the earlier observations of low public knowledge and inadequate understanding of brain death criteria and organ procurement processes. The majority of students were willing to accept organ procurement from severely ill but alive patients, in contrast with physicians. A considerable increase in public educational activity in this field is urgently recommended.

Evaluating structural connectomics in relation to different Q-space sampling techniques.

PubMed

Rodrigues, Paulo; Prats-Galino, Alberto; Gallardo-Pujol, David; Villoslada, Pablo; Falcon, Carles; Prckovska, Vesna

2013-01-01

Brain networks are becoming forefront research in neuroscience. Network-based analysis on the functional and structural connectomes can lead to powerful imaging markers for brain diseases. However, constructing the structural connectome can be based upon different acquisition and reconstruction techniques whose information content and mutual differences has not yet been properly studied in a unified framework. The variations of the structural connectome if not properly understood can lead to dangerous conclusions when performing these type of studies. In this work we present evaluation of the structural connectome by analysing and comparing graph-based measures on real data acquired by the three most important Diffusion Weighted Imaging techniques: DTI, HARDI and DSI. We thus come to several important conclusions demonstrating that even though the different techniques demonstrate differences in the anatomy of the reconstructed fibers the respective connectomes show variations of 20%.

The RNA-binding protein, ZC3H14, is required for proper poly(A) tail length control, expression of synaptic proteins, and brain function in mice.

PubMed

Rha, Jennifer; Jones, Stephanie K; Fidler, Jonathan; Banerjee, Ayan; Leung, Sara W; Morris, Kevin J; Wong, Jennifer C; Inglis, George Andrew S; Shapiro, Lindsey; Deng, Qiudong; Cutler, Alicia A; Hanif, Adam M; Pardue, Machelle T; Schaffer, Ashleigh; Seyfried, Nicholas T; Moberg, Kenneth H; Bassell, Gary J; Escayg, Andrew; García, Paul S; Corbett, Anita H

2017-10-01

A number of mutations in genes that encode ubiquitously expressed RNA-binding proteins cause tissue specific disease. Many of these diseases are neurological in nature revealing critical roles for this class of proteins in the brain. We recently identified mutations in a gene that encodes a ubiquitously expressed polyadenosine RNA-binding protein, ZC3H14 (Zinc finger CysCysCysHis domain-containing protein 14), that cause a nonsyndromic, autosomal recessive form of intellectual disability. This finding reveals the molecular basis for disease and provides evidence that ZC3H14 is essential for proper brain function. To investigate the role of ZC3H14 in the mammalian brain, we generated a mouse in which the first common exon of the ZC3H14 gene, exon 13 is removed (Zc3h14Δex13/Δex13) leading to a truncated ZC3H14 protein. We report here that, as in the patients, Zc3h14 is not essential in mice. Utilizing these Zc3h14Δex13/Δex13mice, we provide the first in vivo functional characterization of ZC3H14 as a regulator of RNA poly(A) tail length. The Zc3h14Δex13/Δex13 mice show enlarged lateral ventricles in the brain as well as impaired working memory. Proteomic analysis comparing the hippocampi of Zc3h14+/+ and Zc3h14Δex13/Δex13 mice reveals dysregulation of several pathways that are important for proper brain function and thus sheds light onto which pathways are most affected by the loss of ZC3H14. Among the proteins increased in the hippocampi of Zc3h14Δex13/Δex13 mice compared to control are key synaptic proteins including CaMK2a. This newly generated mouse serves as a tool to study the function of ZC3H14 in vivo. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Metabolic drift in the aging brain.

PubMed

Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael; Benton, H Paul; Epstein, Adrian A; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E; Boska, Michael D; Gendelman, Howard E; Fox, Howard S; Siuzdak, Gary

2016-05-01

Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication.

A novel perivascular cell population in the zebrafish brain.

PubMed

Venero Galanternik, Marina; Castranova, Daniel; Gore, Aniket V; Blewett, Nathan H; Jung, Hyun Min; Stratman, Amber N; Kirby, Martha R; Iben, James; Miller, Mayumi F; Kawakami, Koichi; Maraia, Richard J; Weinstein, Brant M

2017-04-11

The blood-brain barrier is essential for the proper homeostasis and function of the CNS, but its mechanism of function is poorly understood. Perivascular cells surrounding brain blood vessels are thought to be important for blood-brain barrier establishment, but their roles are not well defined. Here, we describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as Fluorescent Granular Perithelial cells (FGPs), perivascular macrophages, or 'Mato Cells' in mammals. Despite their macrophage-like morphology and perivascular location, zebrafish FGPs appear molecularly most similar to lymphatic endothelium, and our imaging studies suggest that these cells emerge by differentiation from endothelium of the optic choroidal vascular plexus. Our findings provide the first report of a perivascular cell population in the brain derived from vascular endothelium.

Analysis of dual tree M-band wavelet transform based features for brain image classification.

PubMed

Ayalapogu, Ratna Raju; Pabboju, Suresh; Ramisetty, Rajeswara Rao

2018-04-29

The most complex organ in the human body is the brain. The unrestrained growth of cells in the brain is called a brain tumor. The cause of a brain tumor is still unknown and the survival rate is lower than other types of cancers. Hence, early detection is very important for proper treatment. In this study, an efficient computer-aided diagnosis (CAD) system is presented for brain image classification by analyzing MRI of the brain. At first, the MRI brain images of normal and abnormal categories are modeled by using the statistical features of dual tree m-band wavelet transform (DTMBWT). A maximum margin classifier, support vector machine (SVM) is then used for the classification and validated with k-fold approach. Results show that the system provides promising results on a repository of molecular brain neoplasia data (REMBRANDT) with 97.5% accuracy using 4 th level statistical features of DTMBWT. Viewing the experimental results, we conclude that the system gives a satisfactory performance for the brain image classification. © 2018 International Society for Magnetic Resonance in Medicine.

The standard-based open workflow system in GeoBrain (Invited)

NASA Astrophysics Data System (ADS)

Di, L.; Yu, G.; Zhao, P.; Deng, M.

2013-12-01

GeoBrain is an Earth science Web-service system developed and operated by the Center for Spatial Information Science and Systems, George Mason University. In GeoBrain, a standard-based open workflow system has been implemented to accommodate the automated processing of geospatial data through a set of complex geo-processing functions for advanced production generation. The GeoBrain models the complex geoprocessing at two levels, the conceptual and concrete. At the conceptual level, the workflows exist in the form of data and service types defined by ontologies. The workflows at conceptual level are called geo-processing models and cataloged in GeoBrain as virtual product types. A conceptual workflow is instantiated into a concrete, executable workflow when a user requests a product that matches a virtual product type. Both conceptual and concrete workflows are encoded in Business Process Execution Language (BPEL). A BPEL workflow engine, called BPELPower, has been implemented to execute the workflow for the product generation. A provenance capturing service has been implemented to generate the ISO 19115-compliant complete product provenance metadata before and after the workflow execution. The generation of provenance metadata before the workflow execution allows users to examine the usability of the final product before the lengthy and expensive execution takes place. The three modes of workflow executions defined in the ISO 19119, transparent, translucent, and opaque, are available in GeoBrain. A geoprocessing modeling portal has been developed to allow domain experts to develop geoprocessing models at the type level with the support of both data and service/processing ontologies. The geoprocessing models capture the knowledge of the domain experts and are become the operational offering of the products after a proper peer review of models is conducted. An automated workflow composition has been experimented successfully based on ontologies and artificial intelligence technology. The GeoBrain workflow system has been used in multiple Earth science applications, including the monitoring of global agricultural drought, the assessment of flood damage, the derivation of national crop condition and progress information, and the detection of nuclear proliferation facilities and events.

Multi-scale radiomic analysis of sub-cortical regions in MRI related to autism, gender and age

NASA Astrophysics Data System (ADS)

Chaddad, Ahmad; Desrosiers, Christian; Toews, Matthew

2017-03-01

We propose using multi-scale image textures to investigate links between neuroanatomical regions and clinical variables in MRI. Texture features are derived at multiple scales of resolution based on the Laplacian-of-Gaussian (LoG) filter. Three quantifier functions (Average, Standard Deviation and Entropy) are used to summarize texture statistics within standard, automatically segmented neuroanatomical regions. Significance tests are performed to identify regional texture differences between ASD vs. TDC and male vs. female groups, as well as correlations with age (corrected p < 0.05). The open-access brain imaging data exchange (ABIDE) brain MRI dataset is used to evaluate texture features derived from 31 brain regions from 1112 subjects including 573 typically developing control (TDC, 99 females, 474 males) and 539 Autism spectrum disorder (ASD, 65 female and 474 male) subjects. Statistically significant texture differences between ASD vs. TDC groups are identified asymmetrically in the right hippocampus, left choroid-plexus and corpus callosum (CC), and symmetrically in the cerebellar white matter. Sex-related texture differences in TDC subjects are found in primarily in the left amygdala, left cerebellar white matter, and brain stem. Correlations between age and texture in TDC subjects are found in the thalamus-proper, caudate and pallidum, most exhibiting bilateral symmetry.

Annotation and Structural Analysis of Sialylated Human Milk Oligosaccharides

PubMed Central

Wu, Shuai; Grimm, Rudolf; German, J. Bruce; Lebrilla, Carlito B.

2011-01-01

Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates’ brain development. Due to their negative charge and hydrophilic nature, they also help modulate cell-cell interactions. It has also been shown that sialic acids are involved in regulating the immune response and aid in brain development. In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. The precursor ions were further examined with collision-induced dissociation (CID). By applying the proper collision energy, isomers can be readily differentiated by diagnostic peaks and characteristic fragmentation patterns. A set of 30 SHMO structures with retention times, accurate masses and MS/MS spectra was deduced and incorporated into an HMO library. When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification. PMID:21133381

A dedicated neonatal brain imaging system

PubMed Central

Winchman, Tobias; Padormo, Francesco; Teixeira, Rui; Wurie, Julia; Sharma, Maryanne; Fox, Matthew; Hutter, Jana; Cordero‐Grande, Lucilio; Price, Anthony N.; Allsop, Joanna; Bueno‐Conde, Jose; Tusor, Nora; Arichi, Tomoki; Edwards, A. D.; Rutherford, Mary A.; Counsell, Serena J.; Hajnal, Joseph V.

2016-01-01

Purpose The goal of the Developing Human Connectome Project is to acquire MRI in 1000 neonates to create a dynamic map of human brain connectivity during early development. High‐quality imaging in this cohort without sedation presents a number of technical and practical challenges. Methods We designed a neonatal brain imaging system (NBIS) consisting of a dedicated 32‐channel receive array coil and a positioning device that allows placement of the infant's head deep into the coil for maximum signal‐to‐noise ratio (SNR). Disturbance to the infant was minimized by using an MRI‐compatible trolley to prepare and transport the infant and by employing a slow ramp‐up and continuation of gradient noise during scanning. Scan repeats were minimized by using a restart capability for diffusion MRI and retrospective motion correction. We measured the 1) SNR gain, 2) number of infants with a completed scan protocol, and 3) number of anatomical images with no motion artifact using NBIS compared with using an adult 32‐channel head coil. Results The NBIS has 2.4 times the SNR of the adult coil and 90% protocol completion rate. Conclusion The NBIS allows advanced neonatal brain imaging techniques to be employed in neonatal brain imaging with high protocol completion rates. Magn Reson Med 78:794–804, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. PMID:27643791

The Down syndrome-related protein kinase DYRK1A phosphorylates p27Kip1 and Cyclin D1 and induces cell cycle exit and neuronal differentiation

PubMed Central

Soppa, Ulf; Schumacher, Julian; Florencio Ortiz, Victoria; Pasqualon, Tobias; Tejedor, Francisco J; Becker, Walter

2014-01-01

A fundamental question in neurobiology is how the balance between proliferation and differentiation of neuronal precursors is maintained to ensure that the proper number of brain neurons is generated. Substantial evidence implicates DYRK1A (dual specificity tyrosine-phosphorylation-regulated kinase 1A) as a candidate gene responsible for altered neuronal development and brain abnormalities in Down syndrome. Recent findings support the hypothesis that DYRK1A is involved in cell cycle control. Nonetheless, how DYRK1A contributes to neuronal cell cycle regulation and thereby affects neurogenesis remains poorly understood. In the present study we have investigated the mechanisms by which DYRK1A affects cell cycle regulation and neuronal differentiation in a human cell model, mouse neurons, and mouse brain. Dependent on its kinase activity and correlated with the dosage of overexpression, DYRK1A blocked proliferation of SH-SY5Y neuroblastoma cells within 24 h and arrested the cells in G1 phase. Sustained overexpression of DYRK1A induced G0 cell cycle exit and neuronal differentiation. Furthermore, we provide evidence that DYRK1A modulated protein stability of cell cycle-regulatory proteins. DYRK1A reduced cellular Cyclin D1 levels by phosphorylation on Thr286, which is known to induce proteasomal degradation. In addition, DYRK1A phosphorylated p27Kip1 on Ser10, resulting in protein stabilization. Inhibition of DYRK1A kinase activity reduced p27Kip1 Ser10 phosphorylation in cultured hippocampal neurons and in embryonic mouse brain. In aggregate, these results suggest a novel mechanism by which overexpression of DYRK1A may promote premature neuronal differentiation and contribute to altered brain development in Down syndrome. PMID:24806449

Neuroglia in ageing and disease.

PubMed

Verkhratsky, Alexei; Rodríguez, José J; Parpura, Vladimir

2014-08-01

The proper operation of the mammalian brain requires dynamic interactions between neurones and glial cells. Various types of glial cells are susceptible to morpho-functional changes in a variety of brain pathological states, including toxicity, neurodevelopmental, neurodegenerative and psychiatric disorders. Morphological modifications include a change in the glial cell size and shape; the latter is evident by changes of the appearance and number of peripheral processes. The most blatant morphological change is associated with the alteration of the sheer number of neuroglia cells in the brain. Functionally, glial cells can undergo various metabolic and biochemical changes, the majority of which reflect upon homeostasis of neurotransmitters, in particular that of glutamate, as well as on defence mechanisms provided by neuroglia. Not only glial cells exhibit changes associated with the pathology of the brain but they also change with brain aging.

Microglia: An Active Player in the Regulation of Synaptic Activity

PubMed Central

Ji, Kyungmin; Miyauchi, Jeremy; Tsirka, Stella E.

2013-01-01

Synaptic plasticity is critical for elaboration and adaptation in the developing and developed brain. It is well established that astrocytes play an important role in the maintenance of what has been dubbed “the tripartite synapse”. Increasing evidence shows that a fourth cell type, microglia, is critical to this maintenance as well. Microglia are the resident macrophages of the central nervous system (CNS). Because of their well-characterized inflammatory functions, research has primarily focused on their innate immune properties. The role of microglia in the maintenance of synapses in development and in homeostasis is not as well defined. A number of significant findings have shed light on the critical role of microglia at the synapse. It is becoming increasingly clear that microglia play a seminal role in proper synaptic development and elimination. PMID:24303218

Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain

PubMed Central

Duran, Jordi; Saez, Isabel; Gruart, Agnès; Guinovart, Joan J; Delgado-García, José M

2013-01-01

Glycogen is the only carbohydrate reserve of the brain, but its overall contribution to brain functions remains unclear. Although it has traditionally been considered as an emergency energetic reservoir, increasing evidence points to a role of glycogen in the normal activity of the brain. To address this long-standing question, we generated a brain-specific Glycogen Synthase knockout (GYS1Nestin-KO) mouse and studied the functional consequences of the lack of glycogen in the brain under alert behaving conditions. These animals showed a significant deficiency in the acquisition of an associative learning task and in the concomitant activity-dependent changes in hippocampal synaptic strength. Long-term potentiation (LTP) evoked in the hippocampal CA3-CA1 synapse was also decreased in behaving GYS1Nestin-KO mice. These results unequivocally show a key role of brain glycogen in the proper acquisition of new motor and cognitive abilities and in the underlying changes in synaptic strength. PMID:23281428

The biological significance of brain barrier mechanisms: help or hindrance in drug delivery to the central nervous system?

PubMed Central

Saunders, Norman R.; Habgood, Mark D.; Møllgård, Kjeld; Dziegielewska, Katarzyna M.

2016-01-01

Barrier mechanisms in the brain are important for its normal functioning and development. Stability of the brain’s internal environment, particularly with respect to its ionic composition, is a prerequisite for the fundamental basis of its function, namely transmission of nerve impulses. In addition, the appropriate and controlled supply of a wide range of nutrients such as glucose, amino acids, monocarboxylates, and vitamins is also essential for normal development and function. These are all cellular functions across the interfaces that separate the brain from the rest of the internal environment of the body. An essential morphological component of all but one of the barriers is the presence of specialized intercellular tight junctions between the cells comprising the interface: endothelial cells in the blood-brain barrier itself, cells of the arachnoid membrane, choroid plexus epithelial cells, and tanycytes (specialized glial cells) in the circumventricular organs. In the ependyma lining the cerebral ventricles in the adult brain, the cells are joined by gap junctions, which are not restrictive for intercellular movement of molecules. But in the developing brain, the forerunners of these cells form the neuroepithelium, which restricts exchange of all but the smallest molecules between cerebrospinal fluid and brain interstitial fluid because of the presence of strap junctions between the cells. The intercellular junctions in all these interfaces are the physical basis for their barrier properties. In the blood-brain barrier proper, this is combined with a paucity of vesicular transport that is a characteristic of other vascular beds. Without such a diffusional restrain, the cellular transport mechanisms in the barrier interfaces would be ineffective. Superimposed on these physical structures are physiological mechanisms as the cells of the interfaces contain various metabolic transporters and efflux pumps, often ATP-binding cassette (ABC) transporters, that provide an important component of the barrier functions by either preventing entry of or expelling numerous molecules including toxins, drugs, and other xenobiotics. In this review, we summarize these influx and efflux mechanisms in normal developing and adult brain, as well as indicating their likely involvement in a wide range of neuropathologies. There have been extensive attempts to overcome the barrier mechanisms that prevent the entry of many drugs of therapeutic potential into the brain. We outline those that have been tried and discuss why they may so far have been largely unsuccessful. Currently, a promising approach appears to be focal, reversible disruption of the blood-brain barrier using focused ultrasound, but more work is required to evaluate the method before it can be tried in patients. Overall, our view is that much more fundamental knowledge of barrier mechanisms and development of new experimental methods will be required before drug targeting to the brain is likely to be a successful endeavor. In addition, such studies, if applied to brain pathologies such as stroke, trauma, or multiple sclerosis, will aid in defining the contribution of brain barrier pathology to these conditions, either causative or secondary. PMID:26998242

Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

NASA Astrophysics Data System (ADS)

Subramaniam, Prasad

Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on the synthesis and use of a biodegradable dendritic polypeptide-based nanocarrier for the delivery of multiple anticancer drugs and siRNA to brain tumor cells. The co-delivery of important anticancer agents using a single platform was shown to increase the efficacy of the drugs manyfold, ensuring the cancer cell-specific delivery and minimizing dose limiting toxicities of the individual drugs. This would be of immense importance when used in vivo.

[Fibromyalgia syndrome after comprehensive treatment of breast cancer: a case report].

PubMed

Ding, Xia; Li, Yan; Cui, Yiyi; Shen, Yingying; Gu, Jianzhong; Guo, Yong

2016-05-25

Fibromyalgia syndrome after comprehensive treatment of breast cancer is rare and seldom reported. Here we present a case of a 50-year-old female patient,who was admitted to the hospital because of generalized fibromyalgia for 3 months and brain metastasis after the right breast carcinoma surgery for 1 month, and the clinical diagnosis was brain metastasis from breast carcinoma combined with fibromyalgia syndrome. The fibromyalgia were relieved with proper symptomatic treatment but the patient eventually died of tumor progression.

What's Unique about Unique Entities? An fMRI Investigation of the Semantics of Famous Faces and Landmarks

PubMed Central

Olson, Ingrid R.

2012-01-01

Famous people and artifacts are referred to as “unique entities” (UEs) due to the unique nature of the knowledge we have about them. Past imaging and lesion experiments have indicated that the anterior temporal lobes (ATLs) as having a special role in the processing of UEs. It has remained unclear which attributes of UEs were responsible for the observed effects in imaging experiments. In this study, we investigated what factors of UEs influence brain activity. In a training paradigm, we systematically varied the uniqueness of semantic associations, the presence/absence of a proper name, and the number of semantic associations to determine factors modulating activity in regions subserving the processing of UEs. We found that a conjunction of unique semantic information and proper names modulated activity within a section of the left ATL. Overall, the processing of UEs involved a wider left-hemispheric cortical network. Within these regions, brain activity was significantly affected by the unique semantic attributes especially in the presence of a proper name, but we could not find evidence for an effect of the number of semantic associations. Findings are discussed in regard to current models of ATL function, the neurophysiology of semantics, and social cognitive processing. PMID:22021913

Imaging of Neuronal Activity in Awake Mice by Measurements of Flavoprotein Autofluorescence Corrected for Cerebral Blood Flow.

PubMed

Takahashi, Manami; Urushihata, Takuya; Takuwa, Hiroyuki; Sakata, Kazumi; Takado, Yuhei; Shimizu, Eiji; Suhara, Tetsuya; Higuchi, Makoto; Ito, Hiroshi

2017-01-01

Green fluorescence imaging (e.g., flavoprotein autofluorescence imaging, FAI) can be used to measure neuronal activity and oxygen metabolism in living brains without expressing fluorescence proteins. It is useful for understanding the mechanism of various brain functions and their abnormalities in age-related brain diseases. However, hemoglobin in cerebral blood vessels absorbs green fluorescence, hampering accurate assessments of brain function in animal models with cerebral blood vessel dysfunctions and subsequent cerebral blood flow (CBF) alterations. In the present study, we developed a new method to correct FAI signals for hemoglobin-dependent green fluorescence reductions by simultaneous measurements of green fluorescence and intrinsic optical signals. Intrinsic optical imaging enabled evaluations of light absorption and scatters by hemoglobin, which could then be applied to corrections of green fluorescence intensities. Using this method, enhanced flavoprotein autofluorescence by sensory stimuli was successfully detected in the brains of awake mice, despite increases of CBF, and hemoglobin interference. Moreover, flavoprotein autofluorescence could be properly quantified in a resting state and during sensory stimulation by a CO 2 inhalation challenge, which modified vascular responses without overtly affecting neuronal activities. The flavoprotein autofluorescence signal data obtained here were in good agreement with the previous findings from a condition with drug-induced blockade of cerebral vasodilation, justifying the current assaying methodology. Application of this technology to studies on animal models of brain diseases with possible changes of CBF, including age-related neurological disorders, would provide better understanding of the mechanisms of neurovascular coupling in pathological circumstances.

Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier

PubMed Central

Strazielle, Nathalie; Ghersi-Egea, Jean-François

2016-01-01

The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the blood-brain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer added-value for the treatment of central nervous system diseases. For instance, targeting the CSF spaces, adjacent tissue, or the choroid plexuses themselves is of interest for the treatment of neuroinflammatory and infectious diseases, cerebral amyloid angiopathy, selected brain tumors, hydrocephalus or neurohumoral dysregulation. Selected CSF-borne materials seem to reach deep cerebral structures by mechanisms that need to be understood in the context of chronic CSF delivery. Drug delivery through both barriers can reduce CSF sink action towards parenchymal drugs. Finally, targeting the choroid plexus-CSF system can be especially relevant in the context of neonatal and pediatric diseases of the central nervous system. Transcytosis appears the most promising mechanism to target in order to improve drug delivery through brain barriers. The choroid plexus epithelium displays strong vesicular trafficking and secretory activities that deserve to be explored in the context of cerebral drug delivery. Folate transport and exosome release into the CSF, plasma protein transport, and various receptor-mediated endocytosis pathways may prove useful mechanisms to exploit for efficient drug delivery into the CSF. This calls for a clear evaluation of transcytosis mechanisms at the blood-CSF barrier, and a thorough evaluation of CSF drug delivery rates. PMID:27464721

A survey of the quality of nursing services for brain trauma patients in the emergency wards of hospitals in Guilan Province, Iran (2012).

PubMed

Majidi, Seyed Ali; Ayoubian, Ali; Mardani, Sheida; Hashemidehaghi, Zahra

2014-01-01

Head trauma is the main cause of disabilities and death among young people, and the side effects of head trauma pose some of the greatest medical challenges. Rapid diagnosis and the use of proper treatments can prevent more severe brain damage. The purpose of this research was to determine the quality of nursing services provided to brain trauma patients in hospitals in Guilan Province, Iran. The study was conducted as a descriptive, cross-sectional study in the emergency wards of selected hospitals in Guilan in 2012. The research population was comprised of all the brain trauma patients in these hospitals. We developed a two-section questionnaire, ascertained its validity, and determined that it had a reliability of 88% (Cronbach's alpha). Subsequently, we used the questionnaire for gathering data. The data were analyzed using SPSS statistical software, and descriptive analysis tests (frequency rate and average) and deductive analyses tests (chi-squared) also were used. The results showed that the quality of health services provided to brain-trauma patients in the emergency ward was at the moderate level of 58.8% of the cases and at a low level in 41.2% of the cases. Based on the results that showed that the services were of moderate quality, the staff members in the emergency ward were required to update their knowledge and use the required measures to minimize or prevent side effects in brain-trauma patients; clearly, mastery of such measures was a real need among the emergency ward's staff.

Differential expression of endothelial nutrient transporters (MCT1 and GLUT1) in the developing eyes of mice.

PubMed

Kishimoto, Ayuko; Takahashi-Iwanaga, Hiromi; Watanabe M, Masahiko; Iwanaga, Toshihiko

2016-12-01

The blood-brain barrier in the neonatal brain expresses the monocarboxylate transporter (MCT)-1 rather than the glucose transporter (GLUT)-1, due to the special energy supply during the suckling period. The hyaloid vascular system, consisting of the vasa hyaloidea propria and tunica vasculosa lentis, is a temporary vasculature present only during the early development of mammalian eyes and later regresses. Although the ocular vasculature manifests such a unique developmental process, no information is available concerning the expression of endothelial nutrient transporters in the developing eye. The present immunohistochemical study using whole mount preparations of murine eyes found that the hyaloid vascular system predominantly expressed GLUT1 in the endothelium, in contrast to the brain endothelium. Characteristically, the endothelium in peripheral regions of the neonatal hyaloid vessels displayed a mosaic pattern of MCT1-immunoreactive cells scattered within the GLUT1-expressing endothelium. The proper retinal vessels first developed by sprouting angiogenesis endowed with filopodia, which were absolutely free from the immunoreactivities of GLUT1 and MCT1. The remodeling retinal capillary networks and veins in the surface layer of the retina mainly expressed MCT1 until the weaning period. Immunostaining of MCT1 in the retina revealed fine radicular processes projecting from the endothelium, differing from the MCT1-immunonegative filopodia. These findings suggest that the expression of nutrient transporters in the ocular blood vessels is differentially regulated at a cellular level and that the neonatal eyes provide an interesting model for research on nutrient transporters in the endothelium. Copyright © 2016 Elsevier Ltd. All rights reserved.

Convergent synaptic and circuit substrates underlying autism genetic risks.

PubMed

McGee, Aaron; Li, Guohui; Lu, Zhongming; Qiu, Shenfeng

2014-02-01

There has been a surge of diagnosis of autism spectrum disorders (ASD) over the past decade. While large, high powered genome screening studies of children with ASD have identified numerous genetic risk factors, research efforts to understanding how each of these risk factors contributes to the development autism has met with limited success. Revealing the mechanisms by which these genetic risk factors affect brain development and predispose a child to autism requires mechanistic understanding of the neurobiological changes underlying this devastating group of developmental disorders at multifaceted molecular, cellular and system levels. It has been increasingly clear that the normal trajectory of neurodevelopment is compromised in autism, in multiple domains as much as aberrant neuronal production, growth, functional maturation, patterned connectivity, and balanced excitation and inhibition of brain networks. Many autism risk factors identified in humans have been now reconstituted in experimental mouse models to allow mechanistic interrogation of the biological role of the risk gene. Studies utilizing these mouse models have revealed that underlying the enormous heterogeneity of perturbed cellular events, mechanisms directing synaptic and circuit assembly may provide a unifying explanation for the pathophysiological changes and behavioral endophenotypes seen in autism, although synaptic perturbations are far from being the only alterations relevant for ASD. In this review, we discuss synaptic and circuit abnormalities obtained from several prevalent mouse models, particularly those reflecting syndromic forms of ASD that are caused by single gene perturbations. These compiled results reveal that ASD risk genes contribute to proper signaling of the developing gene networks that maintain synaptic and circuit homeostasis, which is fundamental to normal brain development.

Connecting Artificial Brains to Robots in a Comprehensive Simulation Framework: The Neurorobotics Platform.

PubMed

Falotico, Egidio; Vannucci, Lorenzo; Ambrosano, Alessandro; Albanese, Ugo; Ulbrich, Stefan; Vasquez Tieck, Juan Camilo; Hinkel, Georg; Kaiser, Jacques; Peric, Igor; Denninger, Oliver; Cauli, Nino; Kirtay, Murat; Roennau, Arne; Klinker, Gudrun; Von Arnim, Axel; Guyot, Luc; Peppicelli, Daniel; Martínez-Cañada, Pablo; Ros, Eduardo; Maier, Patrick; Weber, Sandro; Huber, Manuel; Plecher, David; Röhrbein, Florian; Deser, Stefan; Roitberg, Alina; van der Smagt, Patrick; Dillman, Rüdiger; Levi, Paul; Laschi, Cecilia; Knoll, Alois C; Gewaltig, Marc-Oliver

2017-01-01

Combined efforts in the fields of neuroscience, computer science, and biology allowed to design biologically realistic models of the brain based on spiking neural networks. For a proper validation of these models, an embodiment in a dynamic and rich sensory environment, where the model is exposed to a realistic sensory-motor task, is needed. Due to the complexity of these brain models that, at the current stage, cannot deal with real-time constraints, it is not possible to embed them into a real-world task. Rather, the embodiment has to be simulated as well. While adequate tools exist to simulate either complex neural networks or robots and their environments, there is so far no tool that allows to easily establish a communication between brain and body models. The Neurorobotics Platform is a new web-based environment that aims to fill this gap by offering scientists and technology developers a software infrastructure allowing them to connect brain models to detailed simulations of robot bodies and environments and to use the resulting neurorobotic systems for in silico experimentation. In order to simplify the workflow and reduce the level of the required programming skills, the platform provides editors for the specification of experimental sequences and conditions, environments, robots, and brain-body connectors. In addition to that, a variety of existing robots and environments are provided. This work presents the architecture of the first release of the Neurorobotics Platform developed in subproject 10 "Neurorobotics" of the Human Brain Project (HBP). At the current state, the Neurorobotics Platform allows researchers to design and run basic experiments in neurorobotics using simulated robots and simulated environments linked to simplified versions of brain models. We illustrate the capabilities of the platform with three example experiments: a Braitenberg task implemented on a mobile robot, a sensory-motor learning task based on a robotic controller, and a visual tracking embedding a retina model on the iCub humanoid robot. These use-cases allow to assess the applicability of the Neurorobotics Platform for robotic tasks as well as in neuroscientific experiments.

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

PubMed Central

Khalin, Igor; Alyautdin, Renad; Kocherga, Ganna; Bakar, Muhamad Abu

2015-01-01

Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood–retinal barrier and blood–cochlear barrier, which have a comparable structure to the blood–brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration. PMID:25995632

Guidance of retinal axons in mammals.

PubMed

Herrera, Eloísa; Erskine, Lynda; Morenilla-Palao, Cruz

2017-11-26

In order to navigate through the surrounding environment many mammals, including humans, primarily rely on vision. The eye, composed of the choroid, sclera, retinal pigmented epithelium, cornea, lens, iris and retina, is the structure that receives the light and converts it into electrical impulses. The retina contains six major types of neurons involving in receiving and modifying visual information and passing it onto higher visual processing centres in the brain. Visual information is relayed to the brain via the axons of retinal ganglion cells (RGCs), a projection known as the optic pathway. The proper formation of this pathway during development is essential for normal vision in the adult individual. Along this pathway there are several points where visual axons face 'choices' in their direction of growth. Understanding how these choices are made has advanced significantly our knowledge of axon guidance mechanisms. Thus, the development of the visual pathway has served as an extremely useful model to reveal general principles of axon pathfinding throughout the nervous system. However, due to its particularities, some cellular and molecular mechanisms are specific for the visual circuit. Here we review both general and specific mechanisms involved in the guidance of mammalian RGC axons when they are traveling from the retina to the brain to establish precise and stereotyped connections that will sustain vision. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disruption of behavior and brain metabolism in artificially reared rats.

PubMed

Aguirre-Benítez, Elsa L; Porras, Mercedes G; Parra, Leticia; González-Ríos, Jacquelina; Garduño-Torres, Dafne F; Albores-García, Damaris; Avendaño, Arturo; Ávila-Rodríguez, Miguel A; Melo, Angel I; Jiménez-Estrada, Ismael; Mendoza-Garrido, Ma Eugenia; Toriz, César; Diaz, Daniel; Ibarra-Coronado, Elizabeth; Mendoza-Ángeles, Karina; Hernández-Falcón, Jesús

2017-12-01

Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[ 18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017. © 2017 Wiley Periodicals, Inc.

Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes.

PubMed

Mazaika, Paul K; Weinzimer, Stuart A; Mauras, Nelly; Buckingham, Bruce; White, Neil H; Tsalikian, Eva; Hershey, Tamara; Cato, Allison; Aye, Tandy; Fox, Larry; Wilson, Darrell M; Tansey, Michael J; Tamborlane, William; Peng, Daniel; Raman, Mira; Marzelli, Matthew; Reiss, Allan L

2016-02-01

Early-onset type 1 diabetes may affect the developing brain during a critical window of rapid brain maturation. Structural MRI was performed on 141 children with diabetes (4-10 years of age at study entry) and 69 age-matched control subjects at two time points spaced 18 months apart. For the children with diabetes, the mean (±SD) HbA1c level was 7.9 ± 0.9% (63 ± 9.8 mmol/mol) at both time points. Relative to control subjects, children with diabetes had significantly less growth of cortical gray matter volume and cortical surface area and significantly less growth of white matter volume throughout the cortex and cerebellum. For the population with diabetes, the change in the blood glucose level at the time of scan across longitudinal time points was negatively correlated with the change in gray and white matter volumes, suggesting that fluctuating glucose levels in children with diabetes may be associated with corresponding fluctuations in brain volume. In addition, measures of hyperglycemia and glycemic variation were significantly negatively correlated with the development of surface curvature. These results demonstrate that early-onset type 1 diabetes has widespread effects on the growth of gray and white matter in children whose blood glucose levels are well within the current treatment guidelines for the management of diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Integrated But Not Whole? Applying an Ontological Account of Human Organismal Unity to the Brain Death Debate.

PubMed

Moschella, Melissa

2016-10-01

As is clear in the 2008 report of the President's Council on Bioethics, the brain death debate is plagued by ambiguity in the use of such key terms as 'integration' and 'wholeness'. Addressing this problem, I offer a plausible ontological account of organismal unity drawing on the work of Hoffman and Rosenkrantz, and then apply that account to the case of brain death, concluding that a brain dead body lacks the unity proper to a human organism, and has therefore undergone a substantial change. I also show how my view can explain hard cases better than one in which biological integration (as understood by Alan Shewmon and the President's Council) is taken to imply ontological wholeness or unity. © 2016 John Wiley & Sons Ltd.

Successful outcome of transplant of kidneys recovered from a brain-dead liver transplant recipient: case report.

PubMed

Domagała, Piotr; Kwiatkowski, Artur; Drozdowski, Jakub; Ostrowski, Krzysztof; Wszola, Michal; Diuwe, Piotr; Durlik, Magdalena; Paczek, Leszek; Chmura, Andrzej

2012-12-01

Few reports describing the use of organs donated by transplant recipients have been published. In this case report, kidneys procured from a brain-dead liver recipient were transplanted successfully. A 21-year-old man was referred for liver transplant after an overdose of acetaminophen. The patient's kidney function was initially normal, with proper urine production and normal kidney laboratory parameters. On the third day after admission, the patient's kidney laboratory parameters became elevated and hepatic encephalopathy requiring mechanical ventilation developed. An orthotopic liver transplant was performed the next day. The patient did not recover consciousness, and brain death was diagnosed on the third day after the liver transplant surgery. The maximum serum concentration of creatinine was 5.8 mg/dL (513 μmol/L) before kidney recovery, and urine production was normal. The kidneys were recovered with organ-perfusion support and were preserved by using machine perfusion. The kidneys were transplanted into 2 male recipients. Twelve months after transplant, the recipients remained in good health with satisfactory kidney function. This case demonstrates that transplanting kidneys recovered from liver transplant recipients is possible and beneficial, thus expanding the pool of potential donors.

Morphological patterns of the collateral sulcus in the human brain.

PubMed

Huntgeburth, Sonja C; Petrides, Michael

2012-04-01

The collateral sulcal complex is an important landmark on the medial surface of the temporal lobe. Anteriorly, it delineates the limbic regions of the parahippocampal gyrus from the visual-processing areas of the fusiform gyrus. Posteriorly, it continues into the occipital lobe, bearing no relationship to the memory-related limbic regions. Given the considerable extent of the sulcus and functional heterogeneity of the surrounding cortex, an investigation of the morphology of this sulcus was carried out to examine whether it is continuous or a series of sulcal parts, i.e. independent sulci classified together under the name collateral sulcus. We investigated the collateral sulcal complex using magnetic resonance images taking into account the three-dimensional nature of the brain. Our examination demonstrated three separate sulcal segments: (i) an anterior segment, the rhinal sulcus, delineating the uncus from the adjacent temporal neocortex, (ii) a middle segment, the collateral sulcus proper, forming the lateral border of the posterior parahippocampal cortex, and (iii) a caudal segment, the occipital extent of the collateral sulcus, within the occipital lobe. Three relationships exist between the rhinal sulcus and collateral sulcus proper, only one being clearly identifiable from the surface. Posteriorly, the collateral sulcus proper and the occipital collateral sulcus, although appearing continuous on the brain surface, can be separated in the depth of the sulcus in all cases. These results provide quantification of the location and variability within standard stereotaxic space for the three collateral sulcus segments that could be used to aid accurate identification of functional activation peaks derived from neuroimaging studies. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Evaluation of drug effects on cerebral blood flow and glucose uptake in un-anesthetized and un-stimulated rats: application of free-moving apparatus enabling to keep rats free during PET/SPECT tracer injection and uptake.

PubMed

Sugita, Taku; Kondo, Yusuke; Ishino, Seigo; Mori, Ikuo; Horiguchi, Takashi; Ogawa, Mikako; Magata, Yasuhiro

2018-05-15

The purpose of this study is the development of novel fluorine-18-fluorodeoxyglucose (F-FDG)-PET and Tc-hexamethylpropylene amine oxime (HMPAO) SPECT methods with free-moving apparatus on conscious rats to investigate brain activity without the effects of anesthesia and tactual stimulation. We also assessed the sensitivity of the experimental system by an intervention study using fluoxetine as a reference drug. A catheter was inserted into the femoral vein and connected to a free-moving cannula system. After fluoxetine administration, the rats were given an injection of F-FDG or Tc-HMPAO via the intravenous cannula and released into a free-moving cage. After the tracer was trapped in the brain, the rats were anesthetized and scanned with PET or SPECT scanners. Then a volume of interest analysis and statistical parametric mapping were performed. We could inject the tracer without touching the rats, while keeping them conscious until the tracers were distributed and trapped in the brain using the developed system. The effects of fluoxetine on glucose uptake and cerebral blood flow were perceptively detected by volume of interest and statistical parametric mapping analysis. We successfully developed free-moving F-FDG-PET and Tc-HMPAO-SPECT imaging systems and detected detailed glucose uptake and cerebral blood flow changes in the conscious rat brain with fluoxetine administration. This system is expected to be useful to assess brain activity without the effects of anesthesia and tactual stimulation to evaluate drug effect or animal brain function.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Metabolic drift in the aging brain

PubMed Central

Ivanisevic, Julijana; Stauch, Kelly L.; Petrascheck, Michael; Benton, H. Paul; Epstein, Adrian A.; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E.; Boska, Michael D.; Gendelman, Howard E.; Fox, Howard S.; Siuzdak, Gary

2016-01-01

Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energy metabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication. PMID:27182841

A novel perivascular cell population in the zebrafish brain

PubMed Central

Galanternik, Marina Venero; Castranova, Daniel; Gore, Aniket V; Blewett, Nathan H; Jung, Hyun Min; Stratman, Amber N; Kirby, Martha R; Iben, James; Miller, Mayumi F; Kawakami, Koichi; Maraia, Richard J; Weinstein, Brant M

2017-01-01

The blood-brain barrier is essential for the proper homeostasis and function of the CNS, but its mechanism of function is poorly understood. Perivascular cells surrounding brain blood vessels are thought to be important for blood-brain barrier establishment, but their roles are not well defined. Here, we describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as Fluorescent Granular Perithelial cells (FGPs), perivascular macrophages, or ‘Mato Cells’ in mammals. Despite their macrophage-like morphology and perivascular location, zebrafish FGPs appear molecularly most similar to lymphatic endothelium, and our imaging studies suggest that these cells emerge by differentiation from endothelium of the optic choroidal vascular plexus. Our findings provide the first report of a perivascular cell population in the brain derived from vascular endothelium. DOI: http://dx.doi.org/10.7554/eLife.24369.001 PMID:28395729

Visual task performance in the blind with the BrainPort V100 Vision Aid.

PubMed

Stronks, H Christiaan; Mitchell, Ellen B; Nau, Amy C; Barnes, Nick

2016-10-01

The BrainPort® V100 Vision Aid is a non-invasive assistive device for the blind based on sensory substitution. The device translates camera images into electrotactile stimuli delivered to the tongue. The BrainPort has recently received the CE mark and FDA approval and it is currently marketed to augment, rather than replace, the traditional assistive technologies such as the white cane or guide dog. Areas covered: In this work, we will review the functional studies performed to date with the BrainPort and we will highlight the critical factors that determine device performance, including the technology behind the BrainPort, the impediments to assessing device performance, and the impact of device training and rehabilitation. Expert commentary: The BrainPort enables blind people to perceive light, identify simple objects, recognize short words, localize simple objects, and detect motion and orientation of objects. To achieve this, proper rehabilitation and training regimes are crucial.

Discordant timing between antennae disrupts sun compass orientation in migratory monarch butterflies

PubMed Central

Guerra, Patrick A; Merlin, Christine; Gegear, Robert J; Reppert, Steven M

2014-01-01

To navigate during their long-distance migration, monarch butterflies (Danaus plexippus) use a time-compensated sun compass. The sun compass timing elements reside in light-entrained circadian clocks in the antennae. Here we show that either antenna is sufficient for proper time compensation. However, migrants with either antenna painted black (to block light entrainment) and the other painted clear (to permit light entrainment) display disoriented group flight. Remarkably, when the black-painted antenna is removed, re-flown migrants with a single, clear-painted antenna exhibit proper orientation behaviour. Molecular correlates of clock function reveal that period and timeless expression is highly rhythmic in brains and clear-painted antennae, while rhythmic clock gene expression is disrupted in black-painted antennae. Our work shows that clock outputs from each antenna are processed and integrated together in the monarch time-compensated sun compass circuit. This dual timing system is a novel example of the regulation of a brain-driven behaviour by paired organs. PMID:22805565

Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor.

PubMed

Zanin, Juan Pablo; Abercrombie, Elizabeth; Friedman, Wilma J

2016-07-19

Cerebellar granule cell progenitors (GCP) proliferate extensively in the external granule layer (EGL) of the developing cerebellum prior to differentiating and migrating. Mechanisms that regulate the appropriate timing of cell cycle withdrawal of these neuronal progenitors during brain development are not well defined. The p75 neurotrophin receptor (p75(NTR)) is highly expressed in the proliferating GCPs, but is downregulated once the cells leave the cell cycle. This receptor has primarily been characterized as a death receptor for its ability to induce neuronal apoptosis following injury. Here we demonstrate a novel function for p75(NTR) in regulating proper cell cycle exit of neuronal progenitors in the developing rat and mouse EGL, which is stimulated by proNT3. In the absence of p75(NTR), GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits.

Differential Modulation of Excitatory and Inhibitory Neurons during Periodic Stimulation

PubMed Central

Mahmud, Mufti; Vassanelli, Stefano

2016-01-01

Non-invasive transcranial neuronal stimulation, in addition to deep brain stimulation, is seen as a promising therapeutic and diagnostic approach for an increasing number of neurological diseases such as epilepsy, cluster headaches, depression, specific type of blindness, and other central nervous system disfunctions. Improving its effectiveness and widening its range of use may strongly rely on development of proper stimulation protocols that are tailored to specific brain circuits and that are based on a deep knowledge of different neuron types response to stimulation. To this aim, we have performed a simulation study on the behavior of excitatory and inhibitory neurons subject to sinusoidal stimulation. Due to the intrinsic difference in membrane conductance properties of excitatory and inhibitory neurons, we show that their firing is differentially modulated by the wave parameters. We analyzed the behavior of the two neuronal types for a broad range of stimulus frequency and amplitude and demonstrated that, within a small-world network prototype, parameters tuning allow for a selective enhancement or suppression of the excitation/inhibition ratio. PMID:26941602

Hypogonadism after traumatic brain injury.

PubMed

Hohl, Alexandre; Mazzuco, Tânia Longo; Coral, Marisa Helena César; Schwarzbold, Marcelo; Walz, Roger

2009-11-01

Traumatic brain injury (TBI) is the most common cause of death and disability in young adults. Post-TBI neuroendocrine disorders have been increasingly acknowledged in recent years due to their potential contribution to morbidity and, probably, to mortality after trauma. Marked alterations of the hypothalamic-pituitary axis during the post-TBI acute and chronic phases have been reported. Prospective and longitudinal studies have shown that some abnormalities are transitory. On the other hand, there is a high frequency (15% to 68%) of pituitary hormone deficiency among TBI survivors in a long term setting. Post-TBI hypogonadism is a common finding after cranial trauma, and it is predicted to develop in 16% of the survivors in the long term. Post-TBI hypogonadism has been associated with adverse results in the acute and chronic phases after injury. These data reinforce the need for identification of hormonal deficiencies and their proper treatment, in order to optimize patient recovery, improve their life quality, and avoid the negative consequences of non-treated hypogonadism in the long term.

LOCALIZATION OF GOLD IN MOUSE BRAIN IN RELATION TO GOLD THIOGLUCOSE OBESITY

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

Debons, A.F.; Silver, L.; Cronkite, E.P.

1962-04-01

Administration of gold thioglucose led to the development of hyperphagia and obesity in mice; this confirmed findings by previous investigators. By employing neutron activation analysis and radioautography, it was observed that this syndrome was associated with focal accumulation of gold in the hypothalamus. Animals treated with gold thiomalate failed to show any hypothalamic Iocalization of gold radioautographically or any evidence of the syndrome of hyperphagla and obesity. In additlon, other foci of gold locallzation were found in gold thioglucose-treated but not in the gold thiomalate-treated animals. Gamma spectroscopy studies made possible quantitative measurements of the gold content ln the brainsmore » of both treated groups. Gold thioglucose-treated as well as gold thiomalate-treated animals had appreciable quantities of gold in the brain proper. Phosphorus-32 generated by neutron activation of the sulfur moiety of gold thioglucose proved to be insigniflcant in its contribution to the radioautographic flndings. Implication of the above findings for the glucostatic theory of appetite regulation is discussed. (auth)« less

Intensive care medicine and organ donation: exploring the last frontiers?

PubMed

Escudero, D; Otero, J

2015-01-01

The main, universal problem for transplantation is organ scarcity. The gap between offer and demand grows wider every year and causes many patients in waiting list to die. In Spain, 90% of transplants are done with organs taken from patients deceased in brain death but this has a limited potential. In order to diminish organ shortage, alternative strategies such as donations from living donors, expanded criteria donors or donation after circulatory death, have been developed. Nevertheless, these types of donors also have their limitations and so are not able to satisfy current organ demand. It is necessary to reduce family denial and to raise donation in brain death thus generalizing, among other strategies, non-therapeutic elective ventilation. As intensive care doctors, cornerstone to the national donation programme, we must consolidate our commitment with society and organ transplantation. We must contribute with the values proper to our specialization and try to reach self-sufficiency by rising organ obtainment. Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Development, Characterization, and Implementation of a System for Focused Ultrasound-Mediated Blood-Brain Barrier Opening in Mice

NASA Astrophysics Data System (ADS)

Valdez, Michael Aaron

The blood-brain barrier BBB refers to the set of specialized endothelial cells that line the vasculature in the brain and effectively control movement of molecules into and out of the brain. While necessary for proper brain function, the BBB blocks 98% of drugs from entering the brain and is the most significant barrier to developing therapies for neurodegenerative diseases. Active transport allows some specific molecules to cross the BBB, but therapeutic development using this route has had limited success. A number of techniques have been used to bypass the BBB, but are often highly invasive and ineffective. Over the last two decades, a minimally invasive technique to transiently open the BBB has been under development that utilizes transcranial focused ultrasound (FUS) in combination with intravascular microbubble contrast agents. This method is often carried out in conjunction with magnetic resonance imaging (MRI) to guide and assess BBB opening and has been referred to as MRI guided FUS (MRgFUS). Because of the utility of mouse models of neurological disease and the exploratory nature of MRgFUS, systems that allow BBB opening in mice are a useful and necessary tool to develop and evaluate this method for clinical application. In this dissertation project, a custom built, cost-effective FUS system for opening the BBB in mice was developed, with the objective of using this device to deliver therapeutics to the brain. Being a custom device, it was necessary to evaluate the ultrasound output, verify in vivo safety, and anticipate the therapeutic effect. The scope of the work herein consists of the design, construction, and evaluation of system that fulfills these requirements. The final constructed system cost was an order of magnitude less than any commercially available MRgFUS system. At this low price point, the hardware could allow the implementation of the methodology in many more research areas than previously possible. Additionally, to anticipate the therapeutic effect, molecules of pharmacologically-relevant sizes were delivered to brain with a novel, multispectral approach. Results demonstrated that the device was able to safely open the BBB, and macromolecule delivery showed that both molecule size and FUS pressure both influence the amount and distribution of molecules in the brain. Using different ultrasound pressures, the threshold for BBB opening was found to be ≥ 180 kPa (0.13 MI). The threshold for damage was found to be ≥ 420 kPa (0.30 MI), and was minor at this pressure, but extensive for higher pressure (870 kPa, 0.62 MI), in which minor damage was caused by this pressure. Performing a novel implementation of a diffusion model on the fluorescence images of 500, 70, and 3 kDa dextran resulted in calculated diffusion coefficients of 0.032 +/- 0.015, 12 +/- 6.0, and 0.13 +/- 0.094 square microns per second, respectively.

[Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].

PubMed

Indo, Yasuhiro

2015-05-01

Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper.

RMND5 from Xenopus laevis is an E3 ubiquitin-ligase and functions in early embryonic forebrain development.

PubMed

Pfirrmann, Thorsten; Villavicencio-Lorini, Pablo; Subudhi, Abinash K; Menssen, Ruth; Wolf, Dieter H; Hollemann, Thomas

2015-01-01

In Saccharomyces cerevisiae the Gid-complex functions as an ubiquitin-ligase complex that regulates the metabolic switch between glycolysis and gluconeogenesis. In higher organisms six conserved Gid proteins form the CTLH protein-complex with unknown function. Here we show that Rmnd5, the Gid2 orthologue from Xenopus laevis, is an ubiquitin-ligase embedded in a high molecular weight complex. Expression of rmnd5 is strongest in neuronal ectoderm, prospective brain, eyes and ciliated cells of the skin and its suppression results in malformations of the fore- and midbrain. We therefore suggest that Xenopus laevis Rmnd5, as a subunit of the CTLH complex, is a ubiquitin-ligase targeting an unknown factor for polyubiquitination and subsequent proteasomal degradation for proper fore- and midbrain development.

Evaluation of Cross-Protocol Stability of a Fully Automated Brain Multi-Atlas Parcellation Tool.

PubMed

Liang, Zifei; He, Xiaohai; Ceritoglu, Can; Tang, Xiaoying; Li, Yue; Kutten, Kwame S; Oishi, Kenichi; Miller, Michael I; Mori, Susumu; Faria, Andreia V

2015-01-01

Brain parcellation tools based on multiple-atlas algorithms have recently emerged as a promising method with which to accurately define brain structures. When dealing with data from various sources, it is crucial that these tools are robust for many different imaging protocols. In this study, we tested the robustness of a multiple-atlas, likelihood fusion algorithm using Alzheimer's Disease Neuroimaging Initiative (ADNI) data with six different protocols, comprising three manufacturers and two magnetic field strengths. The entire brain was parceled into five different levels of granularity. In each level, which defines a set of brain structures, ranging from eight to 286 regions, we evaluated the variability of brain volumes related to the protocol, age, and diagnosis (healthy or Alzheimer's disease). Our results indicated that, with proper pre-processing steps, the impact of different protocols is minor compared to biological effects, such as age and pathology. A precise knowledge of the sources of data variation enables sufficient statistical power and ensures the reliability of an anatomical analysis when using this automated brain parcellation tool on datasets from various imaging protocols, such as clinical databases.

Connecting Artificial Brains to Robots in a Comprehensive Simulation Framework: The Neurorobotics Platform

PubMed Central

Falotico, Egidio; Vannucci, Lorenzo; Ambrosano, Alessandro; Albanese, Ugo; Ulbrich, Stefan; Vasquez Tieck, Juan Camilo; Hinkel, Georg; Kaiser, Jacques; Peric, Igor; Denninger, Oliver; Cauli, Nino; Kirtay, Murat; Roennau, Arne; Klinker, Gudrun; Von Arnim, Axel; Guyot, Luc; Peppicelli, Daniel; Martínez-Cañada, Pablo; Ros, Eduardo; Maier, Patrick; Weber, Sandro; Huber, Manuel; Plecher, David; Röhrbein, Florian; Deser, Stefan; Roitberg, Alina; van der Smagt, Patrick; Dillman, Rüdiger; Levi, Paul; Laschi, Cecilia; Knoll, Alois C.; Gewaltig, Marc-Oliver

2017-01-01

Combined efforts in the fields of neuroscience, computer science, and biology allowed to design biologically realistic models of the brain based on spiking neural networks. For a proper validation of these models, an embodiment in a dynamic and rich sensory environment, where the model is exposed to a realistic sensory-motor task, is needed. Due to the complexity of these brain models that, at the current stage, cannot deal with real-time constraints, it is not possible to embed them into a real-world task. Rather, the embodiment has to be simulated as well. While adequate tools exist to simulate either complex neural networks or robots and their environments, there is so far no tool that allows to easily establish a communication between brain and body models. The Neurorobotics Platform is a new web-based environment that aims to fill this gap by offering scientists and technology developers a software infrastructure allowing them to connect brain models to detailed simulations of robot bodies and environments and to use the resulting neurorobotic systems for in silico experimentation. In order to simplify the workflow and reduce the level of the required programming skills, the platform provides editors for the specification of experimental sequences and conditions, environments, robots, and brain–body connectors. In addition to that, a variety of existing robots and environments are provided. This work presents the architecture of the first release of the Neurorobotics Platform developed in subproject 10 “Neurorobotics” of the Human Brain Project (HBP).1 At the current state, the Neurorobotics Platform allows researchers to design and run basic experiments in neurorobotics using simulated robots and simulated environments linked to simplified versions of brain models. We illustrate the capabilities of the platform with three example experiments: a Braitenberg task implemented on a mobile robot, a sensory-motor learning task based on a robotic controller, and a visual tracking embedding a retina model on the iCub humanoid robot. These use-cases allow to assess the applicability of the Neurorobotics Platform for robotic tasks as well as in neuroscientific experiments. PMID:28179882

On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors.

PubMed

Fedder, Karlie N; Sabo, Shasta L

2015-12-14

Proper formation and maturation of synapses during development is a crucial step in building the functional neural circuits that underlie perception and behavior. It is well established that experience modifies circuit development. Therefore, understanding how synapse formation is controlled by synaptic activity is a key question in neuroscience. In this review, we focus on the regulation of excitatory presynaptic terminal development by glutamate, the predominant excitatory neurotransmitter in the brain. We discuss the evidence that NMDA receptor activation mediates these effects of glutamate and present the hypothesis that local activation of presynaptic NMDA receptors (preNMDARs) contributes to glutamate-dependent control of presynaptic development. Abnormal glutamate signaling and aberrant synapse development are both thought to contribute to the pathogenesis of a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, epilepsy, anxiety, depression, and schizophrenia. Therefore, understanding how glutamate signaling and synapse development are linked is important for understanding the etiology of these diseases.

Integrating research and clinical neuroimaging for the evaluation of traumatic brain injury recovery

NASA Astrophysics Data System (ADS)

Senseney, Justin; Ollinger, John; Graner, John; Lui, Wei; Oakes, Terry; Riedy, Gerard

2015-03-01

Advanced MRI research and other imaging modalities may serve as biomarkers for the evaluation of traumatic brain injury (TBI) recovery. However, these advanced modalities typically require off-line processing which creates images that are incompatible with radiologist viewing software sold commercially. AGFA Impax is an example of such a picture archiving and communication system(PACS) that is used by many radiology departments in the United States Military Health System. By taking advantage of Impax's use of the Digital Imaging and Communications in Medicine (DICOM) standard, we developed a system that allows for advanced medical imaging to be incorporated into clinical PACS. Radiology research can now be conducted using existing clinical imaging display platforms resources in combination with image processingtechniques that are only available outside of the clinical scanning environment. We extracted the spatial and identification elements of theDICOM standard that are necessary to allow research images to be incorporatedinto a clinical radiology system, and developed a tool that annotates research images with the proper tags. This allows for the evaluation of imaging representations of biological markers that may be useful in theevaluation of TBI and TBI recovery.

Malformation syndromes caused by disorders of cholesterol synthesis

PubMed Central

Porter, Forbes D.; Herman, Gail E.

2011-01-01

Cholesterol homeostasis is critical for normal growth and development. In addition to being a major membrane lipid, cholesterol has multiple biological functions. These roles include being a precursor molecule for the synthesis of steroid hormones, neuroactive steroids, oxysterols, and bile acids. Cholesterol is also essential for the proper maturation and signaling of hedgehog proteins, and thus cholesterol is critical for embryonic development. After birth, most tissues can obtain cholesterol from either endogenous synthesis or exogenous dietary sources, but prior to birth, the human fetal tissues are dependent on endogenous synthesis. Due to the blood-brain barrier, brain tissue cannot utilize dietary or peripherally produced cholesterol. Generally, inborn errors of cholesterol synthesis lead to both a deficiency of cholesterol and increased levels of potentially bioactive or toxic precursor sterols. Over the past couple of decades, a number of human malformation syndromes have been shown to be due to inborn errors of cholesterol synthesis. Herein, we will review clinical and basic science aspects of Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis, HEM dysplasia, X-linked dominant chondrodysplasia punctata, Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects Syndrome, sterol-C-4 methyloxidase-like deficiency, and Antley-Bixler syndrome. PMID:20929975

Preterm EEG: a multimodal neurophysiological protocol.

PubMed

Stjerna, Susanna; Voipio, Juha; Metsäranta, Marjo; Kaila, Kai; Vanhatalo, Sampsa

2012-02-18

Since its introduction in early 1950s, electroencephalography (EEG) has been widely used in the neonatal intensive care units (NICU) for assessment and monitoring of brain function in preterm and term babies. Most common indications are the diagnosis of epileptic seizures, assessment of brain maturity, and recovery from hypoxic-ischemic events. EEG recording techniques and the understanding of neonatal EEG signals have dramatically improved, but these advances have been slow to penetrate through the clinical traditions. The aim of this presentation is to bring theory and practice of advanced EEG recording available for neonatal units. In the theoretical part, we will present animations to illustrate how a preterm brain gives rise to spontaneous and evoked EEG activities, both of which are unique to this developmental phase, as well as crucial for a proper brain maturation. Recent animal work has shown that the structural brain development is clearly reflected in early EEG activity. Most important structures in this regard are the growing long range connections and the transient cortical structure, subplate. Sensory stimuli in a preterm baby will generate responses that are seen at a single trial level, and they have underpinnings in the subplate-cortex interaction. This brings neonatal EEG readily into a multimodal study, where EEG is not only recording cortical function, but it also tests subplate function via different sensory modalities. Finally, introduction of clinically suitable dense array EEG caps, as well as amplifiers capable of recording low frequencies, have disclosed multitude of brain activities that have as yet been overlooked. In the practical part of this video, we show how a multimodal, dense array EEG study is performed in neonatal intensive care unit from a preterm baby in the incubator. The video demonstrates preparation of the baby and incubator, application of the EEG cap, and performance of the sensory stimulations.

GABA and Glutamate Pathways Are Spatially and Developmentally Affected in the Brain of Mecp2-Deficient Mice

PubMed Central

Matagne, Valérie; Ghata, Adeline; Villard, Laurent; Roux, Jean-Christophe

2014-01-01

Proper brain functioning requires a fine-tuning between excitatory and inhibitory neurotransmission, a balance maintained through the regulation and release of glutamate and GABA. Rett syndrome (RTT) is a rare genetic disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene affecting the postnatal brain development. Dysfunctions in the GABAergic and glutamatergic systems have been implicated in the neuropathology of RTT and a disruption of the balance between excitation and inhibition, together with a perturbation of the electrophysiological properties of GABA and glutamate neurons, were reported in the brain of the Mecp2-deficient mouse. However, to date, the extent and the nature of the GABA/glutamate deficit affecting the Mecp2-deficient mouse brain are unclear. In order to better characterize these deficits, we simultaneously analyzed the GABA and glutamate levels in Mecp2-deficient mice at 2 different ages (P35 and P55) and in several brain areas. We used a multilevel approach including the quantification of GABA and glutamate levels, as well as the quantification of the mRNA and protein expression levels of key genes involved in the GABAergic and glutamatergic pathways. Our results show that Mecp2-deficient mice displayed regional- and age-dependent variations in the GABA pathway and, to a lesser extent, in the glutamate pathway. The implication of the GABA pathway in the RTT neuropathology was further confirmed using an in vivo treatment with a GABA reuptake inhibitor that significantly improved the lifespan of Mecp2-deficient mice. Our results confirm that RTT mouse present a deficit in the GABAergic pathway and suggest that GABAergic modulators could be interesting therapeutic agents for this severe neurological disorder. PMID:24667344

Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way.

PubMed

Fontebasso, Adam M; Jabado, Nada

2015-01-01

Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the cancer genome of brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of brain tumors, including the most malignant and common variants in children: gliomas and medulloblastoma. Notably, studies of pediatric brain tumors have identified unexpected oncogenic pathways implicated in tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the mitogen-activated protein kinase pathway, considered to be a hallmark of pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target and critical markers for therapy that will help refine pathological grading. We summarize these novel findings in pediatric brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and therapy assignment in the clinical setting.

Risk factors for proper oral language development in children: a systematic literature review.

PubMed

Gurgel, Léia Gonçalves; Vidor, Deisi Cristina Gollo Marques; Joly, Maria Cristina Rodrigues Azevedo; Reppold, Caroline Tozzi

2014-01-01

To conduct a systematic review of literature production related to risk factors for proper oral language development in children. We used the terms "child language," "risk factors," and "randomized controlled trial" in MEDLINE (accessed via PubMed), Lilacs, SciELO, and The Cochrane Library from January 1980 to February 2014. Randomized controlled trials involving the study of some risk factors related to child language were included. Works with individuals who were not from the age group 0-12 years and presented no reliable definition of risk factors were excluded. The research findings were classified according to their theme and categorized methodological aspects. We observed the lack of a standardized list of risk factors for language available for health professionals. The main risk factor mentioned was family dynamics, followed by interaction with parents, immediate social environment, and encouragement given to the child in the first years of life. It was also observed that organic hazards such as brain injury, persistent otitis media, and cardiac surgery, besides the type of food and parental counseling, may be related to language disorders. More randomized controlled trials involving the evaluation of risk factors for child language and the creation of further studies involving children above 6 years of age and males are needed.

The gastrointestinal-brain axis in humans as an evolutionary advance of the root-leaf axis in plants: A hypothesis linking quantum effects of light on serotonin and auxin.

PubMed

Tonello, Lucio; Gashi, Bekim; Scuotto, Alessandro; Cappello, Glenda; Cocchi, Massimo; Gabrielli, Fabio; Tuszynski, Jack A

2018-01-01

Living organisms tend to find viable strategies under ambient conditions that optimize their search for, and utilization of, life-sustaining resources. For plants, a leading role in this process is performed by auxin, a plant hormone that drives morphological development, dynamics, and movement to optimize the absorption of light (through branches and leaves) and chemical "food" (through roots). Similarly to auxin in plants, serotonin seems to play an important role in higher animals, especially humans. Here, it is proposed that morphological and functional similarities between (i) plant leaves and the animal/human brain and (ii) plant roots and the animal/human gastro-intestinal tract have general features in common. Plants interact with light and use it for biological energy, whereas, neurons in the central nervous system seem to interact with bio-photons and use them for proper brain function. Further, as auxin drives roots "arborescence" within the soil, similarly serotonin seems to facilitate enteric nervous system connectivity within the human gastro-intestinal tract. This auxin/serotonin parallel suggests the root-branches axis in plants may be an evolutionary precursor to the gastro-intestinal-brain axis in humans. Finally, we hypothesize that light might be an important factor, both in gastro-intestinal dynamics and brain function. Such a comparison may indicate a key role for the interaction of light and serotonin in neuronal physiology (possibly in both the central nervous system and the enteric nervous system), and according to recent work, mind and consciousness.

De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features.

PubMed

Tanaka, Akemi J; Cho, Megan T; Retterer, Kyle; Jones, Julie R; Nowak, Catherine; Douglas, Jessica; Jiang, Yong-Hui; McConkie-Rosell, Allyn; Schaefer, G Bradley; Kaylor, Julie; Rahman, Omar A; Telegrafi, Aida; Friedman, Bethany; Douglas, Ganka; Monaghan, Kristin G; Chung, Wendy K

2016-01-01

We identified five unrelated individuals with significant global developmental delay and intellectual disability (ID), dysmorphic facial features and frequent microcephaly, and de novo predicted loss-of-function variants in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). Our findings are consistent with recently reported de novo mutations in CHAMP1 in five other individuals with similar features. CHAMP1 is a zinc finger protein involved in kinetochore-microtubule attachment and is required for regulating the proper alignment of chromosomes during metaphase in mitosis. Mutations in CHAMP1 may affect cell division and hence brain development and function, resulting in developmental delay and ID.

Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus

PubMed Central

Park, Raehee; Moon, Uk Yeol; Park, Jun Young; Hughes, Lucinda J.; Johnson, Randy L.; Cho, Seo-Hee; Kim, Seonhee

2016-01-01

Timely generation and normal maturation of ependymal cells along the aqueduct are critical for preventing physical blockage between the third and fourth ventricles and the development of fetal non-communicating hydrocephalus. Our study identifies Yap, the downstream effector of the evolutionarily conserved Hippo pathway, as a central regulator for generating developmentally controlled ependymal cells along the ventricular lining of the aqueduct. Yap function is necessary for proper proliferation of progenitors and apical attachment of ependymal precursor cells. Importantly, an injury signal initiated by lysophosphatidic acid (LPA), an upstream regulator of Yap that can cause fetal haemorrhagic hydrocephalus, deregulates Yap in the developing aqueduct. LPA exposure leads to the loss of N-cadherin concentrations at the apical endfeet, which can be partially restored by forced Yap expression and more efficiently by phosphomimetic Yap. These results reveal a novel function of Yap in retaining tissue junctions during normal development and after fetal brain injury. PMID:26754915

Drosophila Pax6 promotes development of the entire eye-antennal disc, thereby ensuring proper adult head formation

PubMed Central

Zhu, Jinjin; Palliyil, Sneha; Ran, Chen; Kumar, Justin P.

2017-01-01

Paired box 6 (Pax6) is considered to be the master control gene for eye development in all seeing animals studied so far. In vertebrates, it is required not only for lens/retina formation but also for the development of the CNS, olfactory system, and pancreas. Although Pax6 plays important roles in cell differentiation, proliferation, and patterning during the development of these systems, the underlying mechanism remains poorly understood. In the fruit fly, Drosophila melanogaster, Pax6 also functions in a range of tissues, including the eye and brain. In this report, we describe the function of Pax6 in Drosophila eye-antennal disc development. Previous studies have suggested that the two fly Pax6 genes, eyeless (ey) and twin of eyeless (toy), initiate eye specification, whereas eyegone (eyg) and the Notch (N) pathway independently regulate cell proliferation. Here, we show that Pax6 controls eye progenitor cell survival and proliferation through the activation of teashirt (tsh) and eyg, thereby indicating that Pax6 initiates both eye specification and proliferation. Although simultaneous loss of ey and toy during early eye-antennal disc development disrupts the development of all head structures derived from the eye-antennal disc, overexpression of N or tsh in the absence of Pax6 rescues only antennal and head epidermis development. Furthermore, overexpression of tsh induces a homeotic transformation of the fly head into thoracic structures. Taking these data together, we demonstrate that Pax6 promotes development of the entire eye-antennal disc and that the retinal determination network works to repress alternative tissue fates, which ensures proper development of adult head structures. PMID:28584125

Gaming control using a wearable and wireless EEG-based brain-computer interface device with novel dry foam-based sensors

PubMed Central

2012-01-01

A brain-computer interface (BCI) is a communication system that can help users interact with the outside environment by translating brain signals into machine commands. The use of electroencephalographic (EEG) signals has become the most common approach for a BCI because of their usability and strong reliability. Many EEG-based BCI devices have been developed with traditional wet- or micro-electro-mechanical-system (MEMS)-type EEG sensors. However, those traditional sensors have uncomfortable disadvantage and require conductive gel and skin preparation on the part of the user. Therefore, acquiring the EEG signals in a comfortable and convenient manner is an important factor that should be incorporated into a novel BCI device. In the present study, a wearable, wireless and portable EEG-based BCI device with dry foam-based EEG sensors was developed and was demonstrated using a gaming control application. The dry EEG sensors operated without conductive gel; however, they were able to provide good conductivity and were able to acquire EEG signals effectively by adapting to irregular skin surfaces and by maintaining proper skin-sensor impedance on the forehead site. We have also demonstrated a real-time cognitive stage detection application of gaming control using the proposed portable device. The results of the present study indicate that using this portable EEG-based BCI device to conveniently and effectively control the outside world provides an approach for researching rehabilitation engineering. PMID:22284235

Keyword extraction, ranking, and organization for the neuroinformatics platform.

PubMed

Usui, S; Palmes, P; Nagata, K; Taniguchi, T; Ueda, N

2007-04-01

Brain-related researches encompass many fields of studies and usually involve worldwide collaborations. Recognizing the value of these international collaborations for efficient use of resources and improving the quality of brain research, the International Neuroinformatics Coordinating Facility (INCF) started to coordinate the effort of establishing neuroinformatics (NI) centers and portal sites among the different participating countries. These NI centers and portal sites will serve as the conduit for the interchange of information and brain-related resources among different countries. In Japan, several NI platforms under the support of NIJC (NI Japan Center) are being developed with one platform called, Visiome, already operating and publicly accessible at "http://www.platform.visiome.org". Each of these platforms requires their own set of keywords that represent important terms covering their respective fields of study. One important function of this predefined keyword list is to help contributors classify the contents of their contributions and group related resources. It is vital, therefore, that this predefined list should be properly chosen to cover the necessary areas. Currently, the process of identifying these appropriate keywords relies on the availability of human experts which does not scale well considering that different areas are rapidly evolving. This problem prompted us to develop a tool to automatically filter the most likely terms preferred by human experts. We tested the effectiveness of the proposed approach using the abstracts of the Vision Research Journal (VR) and Investigative Ophthalmology and Visual Science Journal (IOVS) as source files.

Cerebral salt-wasting syndrome due to hemorrhagic brain infarction: a case report.

PubMed

Tanaka, Tomotaka; Uno, Hisakazu; Miyashita, Kotaro; Nagatsuka, Kazuyuki

2014-07-23

Cerebral salt-wasting syndrome is a condition featuring hyponatremia and dehydration caused by head injury, operation on the brain, subarachnoid hemorrhage, brain tumor and so on. However, there are a few reports of cerebral salt-wasting syndrome caused by cerebral infarction. We describe a patient with cerebral infarction who developed cerebral salt-wasting syndrome in the course of hemorrhagic transformation. A 79-year-old Japanese woman with hypertension and arrhythmia was admitted to our hospital for mild consciousness disturbance, conjugate deviation to right, left unilateral spatial neglect and left hemiparesis. Magnetic resonance imaging revealed a broad ischemic change in right middle cerebral arterial territory. She was diagnosed as cardiogenic cerebral embolism because atrial fibrillation was detected on electrocardiogram on admission. She showed hyponatremia accompanied by polyuria complicated at the same time with the development of hemorrhagic transformation on day 14 after admission. Based on her hypovolemic hyponatremia, she was evaluated as not having syndrome of inappropriate secretion of antidiuretic hormone but cerebral salt-wasting syndrome. She fortunately recovered with proper fluid replacement and electrolyte management. This is a rare case of cerebral infarction and cerebral salt-wasting syndrome in the course of hemorrhagic transformation. It may be difficult to distinguish cerebral salt-wasting syndrome from syndrome of inappropriate antidiuretic hormone, however, an accurate assessment is needed to reveal the diagnosis of cerebral salt-wasting syndrome because the recommended fluid management is opposite in the two conditions.

Exercising our brains: how physical activity impacts synaptic plasticity in the dentate gyrus.

PubMed

Christie, Brian R; Eadie, Brennan D; Kannangara, Timal S; Robillard, Julie M; Shin, James; Titterness, Andrea K

2008-01-01

Exercise that engages the cardiovascular system has a myriad of effects on the body; however, we usually do not give much consideration to the benefits it may have for our minds. An increasing body of evidence suggests that exercise can have some remarkable effects on the brain. In this article, we will introduce how exercise can impact the capacity for neurons in the brain to communicate with one another. To properly convey this information, we will first briefly introduce the field of synaptic plasticity and then examine how the introduction of exercise to the experimental setting can actually alter the basic properties of synaptic plasticity in the brain. Next, we will examine some of the candidate physiological processes that might underlay these alterations. Finally, we will close by noting that, taken together, this data points toward our brains being dynamic systems that are in a continual state of flux and that physical exercise may help us to maximize the performance of both our body and our minds.

Time, Memory, and Consciousness a View from the Brain

NASA Astrophysics Data System (ADS)

Markowitsch, Hans J.

2005-10-01

Memory can be defined as mental time traveling. Seen in this way, memory provides the glue which combines different time episodes and leads to a coherent view of one's own person. The importance of time becomes apparent in a neuroscientific comparison of animals and human beings. All kinds of animals have biorhythms -- times when they sleep, prefer or avoid sex, or move to warmer places. Mammalian brains have a number of time sensitive structures damage to which alters a subject's behavior to his or her environment. For human beings, damage to certain brain regions may alter the sense of time and consciousness of time in quite different ways. Furthermore, brain damage, drugs, or psychiatric disturbances may lead to an impaired perception of time, sometimes leading to major positive or negative accelerations in time perception. An impaired time perception alters consciousness and awareness of oneself. A proper synchronized action of time perception, brain activation, memory processing, and autonoetic (self-aware) consciousness provides the bases of an integrated personality.

Case Report: A Case of Severe Cerebral Malaria Managed with Therapeutic Hypothermia and Other Modalities for Brain Edema.

PubMed

Gad, AbdAllah; Ali, Sajjad; Zahoor, Talal; Azarov, Nick

2018-04-01

Malarial infections are uncommon in the United States and almost all reported cases stem from recent travelers coming from endemic countries. Cerebral malaria (CM) is a severe form of the disease usually affecting children and individuals with limited immunity. Despite proper management, mortality from CM can reach up to 25%, especially when it is associated with brain edema. Inefficient management of the edema may result in brain herniation and death. Uniform guidelines for management of CM-associated brain edema are lacking. In this report, we present a case of CM with associated severe brain edema that was successfully managed using a unique combination of therapeutic hypothermia, hypertonic saline, mannitol, and hyperventilation along with the antimalarial drugs quinidine and doxycycline. Our use of hypothermia was based on its proven benefit for improving neurological outcomes in post-cardiac arrest patients and previous in vitro research, suggesting its potential inhibitory role on malaria growth.

Brain tumor modeling: glioma growth and interaction with chemotherapy

NASA Astrophysics Data System (ADS)

Banaem, Hossein Y.; Ahmadian, Alireza; Saberi, Hooshangh; Daneshmehr, Alireza; Khodadad, Davood

2011-10-01

In last decade increasingly mathematical models of tumor growths have been studied, particularly on solid tumors which growth mainly caused by cellular proliferation. In this paper we propose a modified model to simulate the growth of gliomas in different stages. Glioma growth is modeled by a reaction-advection-diffusion. We begin with a model of untreated gliomas and continue with models of polyclonal glioma following chemotherapy. From relatively simple assumptions involving homogeneous brain tissue bounded by a few gross anatomical landmarks (ventricles and skull) the models have been expanded to include heterogeneous brain tissue with different motilities of glioma cells in grey and white matter. Tumor growth is characterized by a dangerous change in the control mechanisms, which normally maintain a balance between the rate of proliferation and the rate of apoptosis (controlled cell death). Result shows that this model closes to clinical finding and can simulate brain tumor behavior properly.

Spatiotemporal characterization of mTOR kinase activity following kainic acid induced status epilepticus and analysis of rat brain response to chronic rapamycin treatment.

PubMed

Macias, Matylda; Blazejczyk, Magdalena; Kazmierska, Paulina; Caban, Bartosz; Skalecka, Agnieszka; Tarkowski, Bartosz; Rodo, Anna; Konopacki, Jan; Jaworski, Jacek

2013-01-01

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain.

Spatiotemporal Characterization of mTOR Kinase Activity Following Kainic Acid Induced Status Epilepticus and Analysis of Rat Brain Response to Chronic Rapamycin Treatment

PubMed Central

Macias, Matylda; Blazejczyk, Magdalena; Kazmierska, Paulina; Caban, Bartosz; Skalecka, Agnieszka; Tarkowski, Bartosz; Rodo, Anna; Konopacki, Jan; Jaworski, Jacek

2013-01-01

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain. PMID:23724051

Computational modeling of blast wave interaction with a human body and assessment of traumatic brain injury

NASA Astrophysics Data System (ADS)

Tan, X. G.; Przekwas, A. J.; Gupta, R. K.

2017-11-01

The modeling of human body biomechanics resulting from blast exposure poses great challenges because of the complex geometry and the substantial material heterogeneity. We developed a detailed human body finite element model representing both the geometry and the materials realistically. The model includes the detailed head (face, skull, brain and spinal cord), the neck, the skeleton, air cavities (lungs) and the tissues. Hence, it can be used to properly model the stress wave propagation in the human body subjected to blast loading. The blast loading on the human was generated from a simulated C4 explosion. We used the highly scalable solvers in the multi-physics code CoBi for both the blast simulation and the human body biomechanics. The meshes generated for these simulations are of good quality so that relatively large time-step sizes can be used without resorting to artificial time scaling treatments. The coupled gas dynamics and biomechanics solutions were validated against the shock tube test data. The human body models were used to conduct parametric simulations to find the biomechanical response and the brain injury mechanism due to blasts impacting the human body. Under the same blast loading condition, we showed the importance of inclusion of the whole body.

Tracking brain motion during the cardiac cycle using spiral cine-DENSE MRI

PubMed Central

Zhong, Xiaodong; Meyer, Craig H.; Schlesinger, David J.; Sheehan, Jason P.; Epstein, Frederick H.; Larner, James M.; Benedict, Stanley H.; Read, Paul W.; Sheng, Ke; Cai, Jing

2009-01-01

Cardiac-synchronized brain motion is well documented, but the accurate measurement of such motion on the pixel-by-pixel basis has been hampered by the lack of proper imaging technique. In this article, the authors present the implementation of an autotracking spiral cine displacement-encoded stimulation echo (DENSE) magnetic resonance imaging (MRI) technique for the measurement of pulsatile brain motion during the cardiac cycle. Displacement-encoded dynamic MR images of three healthy volunteers were acquired throughout the cardiac cycle using the spiral cine-DENSE pulse sequence gated to the R wave of an electrocardiogram. Pixelwise Lagrangian displacement maps were computed, and 2D displacement as a function of time was determined for selected regions of interests. Different intracranial structures exhibited characteristic motion amplitude, direction, and pattern throughout the cardiac cycle. Time-resolved displacement curves revealed the pathway of pulsatile motion from brain stem to peripheral brain lobes. These preliminary results demonstrated that the spiral cine-DENSE MRI technique can be used to measure cardiac-synchronized pulsatile brain motion on the pixel-by-pixel basis with high temporal∕spatial resolution and sensitivity. PMID:19746774

MR Anatomy of Deep Brain Nuclei with Special Reference to Specific Diseases and Deep Brain Stimulation Localization

PubMed Central

Telford, Ryan; Vattoth, Surjith

2014-01-01

Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832

Calmodulin Methyltransferase Is Required for Growth, Muscle Strength, Somatosensory Development and Brain Function

PubMed Central

Haziza, Sitvanit; Magnani, Roberta; Lan, Dima; Keinan, Omer; Saada, Ann; Hershkovitz, Eli; Yanay, Nurit; Cohen, Yoram; Nevo, Yoram; Houtz, Robert L.; Sheffield, Val C.; Golan, Hava; Parvari, Ruti

2015-01-01

Calmodulin lysine methyl transferase (CaM KMT) is ubiquitously expressed and highly conserved from plants to vertebrates. CaM is frequently trimethylated at Lys-115, however, the role of CaM methylation in vertebrates has not been studied. CaM KMT was found to be homozygously deleted in the 2P21 deletion syndrome that includes 4 genes. These patients present with cystinuria, severe intellectual disabilities, hypotonia, mitochondrial disease and facial dysmorphism. Two siblings with deletion of three of the genes included in the 2P21 deletion syndrome presented with cystinuria, hypotonia, a mild/moderate mental retardation and a respiratory chain complex IV deficiency. To be able to attribute the functional significance of the methylation of CaM in the mouse and the contribution of CaM KMT to the clinical presentation of the 2p21deletion patients, we produced a mouse model lacking only CaM KMT with deletion borders as in the human 2p21deletion syndrome. No compensatory activity for CaM methylation was found. Impairment of complexes I and IV, and less significantly III, of the mitochondrial respiratory chain was more pronounced in the brain than in muscle. CaM KMT is essential for normal body growth and somatosensory development, as well as for the proper functioning of the adult mouse brain. Developmental delay was demonstrated for somatosensory function and for complex behavior, which involved both basal motor function and motivation. The mutant mice also had deficits in motor learning, complex coordination and learning of aversive stimuli. The mouse model contributes to the evaluation of the role of methylated CaM. CaM methylation appears to have a role in growth, muscle strength, somatosensory development and brain function. The current study has clinical implications for human patients. Patients presenting slow growth and muscle weakness that could result from a mitochondrial impairment and mental retardation should be considered for sequence analysis of the CaM KMT gene. PMID:26247364

Calmodulin Methyltransferase Is Required for Growth, Muscle Strength, Somatosensory Development and Brain Function.

PubMed

Haziza, Sitvanit; Magnani, Roberta; Lan, Dima; Keinan, Omer; Saada, Ann; Hershkovitz, Eli; Yanay, Nurit; Cohen, Yoram; Nevo, Yoram; Houtz, Robert L; Sheffield, Val C; Golan, Hava; Parvari, Ruti

2015-08-01

Calmodulin lysine methyl transferase (CaM KMT) is ubiquitously expressed and highly conserved from plants to vertebrates. CaM is frequently trimethylated at Lys-115, however, the role of CaM methylation in vertebrates has not been studied. CaM KMT was found to be homozygously deleted in the 2P21 deletion syndrome that includes 4 genes. These patients present with cystinuria, severe intellectual disabilities, hypotonia, mitochondrial disease and facial dysmorphism. Two siblings with deletion of three of the genes included in the 2P21 deletion syndrome presented with cystinuria, hypotonia, a mild/moderate mental retardation and a respiratory chain complex IV deficiency. To be able to attribute the functional significance of the methylation of CaM in the mouse and the contribution of CaM KMT to the clinical presentation of the 2p21deletion patients, we produced a mouse model lacking only CaM KMT with deletion borders as in the human 2p21deletion syndrome. No compensatory activity for CaM methylation was found. Impairment of complexes I and IV, and less significantly III, of the mitochondrial respiratory chain was more pronounced in the brain than in muscle. CaM KMT is essential for normal body growth and somatosensory development, as well as for the proper functioning of the adult mouse brain. Developmental delay was demonstrated for somatosensory function and for complex behavior, which involved both basal motor function and motivation. The mutant mice also had deficits in motor learning, complex coordination and learning of aversive stimuli. The mouse model contributes to the evaluation of the role of methylated CaM. CaM methylation appears to have a role in growth, muscle strength, somatosensory development and brain function. The current study has clinical implications for human patients. Patients presenting slow growth and muscle weakness that could result from a mitochondrial impairment and mental retardation should be considered for sequence analysis of the CaM KMT gene.

Using Kitchen Appliance Analogies to Improve Students' Reasoning about Neurological Results

ERIC Educational Resources Information Center

Vishton, Peter M.

2005-01-01

This article describes and evaluates a new technique for teaching students to interpret studies of patients with brain injuries. This technique asks students to consider how knives and blenders lose specific functionality when they are damaged. This approach better prepares students to make proper inferences from behavioral deficits observed after…

Detecting phase transitions in a neural network and its application to classification of syndromes in traditional Chinese medicine

NASA Astrophysics Data System (ADS)

Chen, J.; Xi, G.; Wang, W.

2008-02-01

Detecting phase transitions in neural networks (determined or random) presents a challenging subject for phase transitions play a key role in human brain activity. In this paper, we detect numerically phase transitions in two types of random neural network(RNN) under proper parameters.

Scrapie resistant goats: Keep your herd healthy and help your business with a new gene test

USDA-ARS?s Scientific Manuscript database

Classical scrapie is an infectious disease of goats and sheep that causes slowly progressive but ultimately fatal degeneration of the brain, with advanced cases often hindering their ability to move properly. Currently, a single diagnosis of classical scrapie results in permanent quarantine or eutha...

Integrating some mind and brain views of transference: the phenomena.

PubMed

Levin, F M

1997-01-01

Because understanding the underpinnings of transferential learning allows the analyst to more effectively exploit transference in the clinical situation, as well as to advance psychoanalytic theory, the functions and mechanisms of transference phenomena in learning are subjected to an interdisciplinary analysis. Through transference the brain creates hierarchical databases that make emotional sense of the world, especially the world of human relationships. Transference plays a role in defense and resistance clinically; less explored but equally important is the adaptive potential of transference and its effect on an individual's readiness for structural change through the activation of working memory. Most investigators within psychoanalysis have not considered the importance of similarity judgments and memory priming, especially as these help to explain why transference and its proper handling are effective in treatment. Yet there are complex relationships among transference, similarity judgment, and memory priming that tie together psychoanalysis, cognitive psychology, and neurophysiology. Evidence increasingly suggests a relationship between transference and the transfer of knowledge between various content domains (databases) of mind and brain, which is essential to cognitive and emotional learning. There are indications as well that transference decisively facilitates learning readiness ("windows") in general by means of two of its components: free association and spontaneous (self-initiated) activity. The important question of which mind/brain mechanisms motivate transference is not yet understood comprehensively. However, Vygotsky's work on the zone of proximal development (ZPD), M.Stern's teleonomic theory, schema theory, and neural network theory offer further insights into what motivates transference.

Anesthesia Management of Organ Donors.

PubMed

Xia, Victor W; Braunfeld, Michelle

2017-09-01

The shortage of suitable organs is the biggest obstacle for transplants. At present, most organs for transplant in the United States are from donation after neurologic determination of death (brain death). Potential organs for transplant need to maintain their viability during a series of insults, including the original disease, physiologic derangements during the dying process, ischemia, and reperfusion. Proper donor management before, during, and after procurement has potential to increase the number and quality of organs from donors. Anesthesiologists need to understand the physiologic derangements associated with brain death and the updated donor management during the periprocurement period. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurovascular abnormalities in brain disorders: highlights with angiogenesis and magnetic resonance imaging studies.

PubMed

Chen, Chiao-Chi V; Chen, Yu-Chen; Hsiao, Han-Yun; Chang, Chen; Chern, Yijuang

2013-07-05

The coupling between neuronal activity and vascular responses is controlled by the neurovascular unit (NVU), which comprises multiple cell types. Many different types of dysfunction in these cells may impair the proper control of vascular responses by the NVU. Magnetic resonance imaging, which is the most powerful tool available to investigate neurovascular structures or functions, will be discussed in the present article in relation to its applications and discoveries. Because aberrant angiogenesis and vascular remodeling have been increasingly reported as being implicated in brain pathogenesis, this review article will refer to this hallmark event when suitable.

A massively asynchronous, parallel brain.

PubMed

Zeki, Semir

2015-05-19

Whether the visual brain uses a parallel or a serial, hierarchical, strategy to process visual signals, the end result appears to be that different attributes of the visual scene are perceived asynchronously--with colour leading form (orientation) by 40 ms and direction of motion by about 80 ms. Whatever the neural root of this asynchrony, it creates a problem that has not been properly addressed, namely how visual attributes that are perceived asynchronously over brief time windows after stimulus onset are bound together in the longer term to give us a unified experience of the visual world, in which all attributes are apparently seen in perfect registration. In this review, I suggest that there is no central neural clock in the (visual) brain that synchronizes the activity of different processing systems. More likely, activity in each of the parallel processing-perceptual systems of the visual brain is reset independently, making of the brain a massively asynchronous organ, just like the new generation of more efficient computers promise to be. Given the asynchronous operations of the brain, it is likely that the results of activities in the different processing-perceptual systems are not bound by physiological interactions between cells in the specialized visual areas, but post-perceptually, outside the visual brain.

Ultrastructural findings in transplanted experimental brain tumors and their significance for the cytogenesis of such tumors.

PubMed

Mennel, H D

1988-01-01

Tumors induced by transplacental action in the spinal cord of rats were transplanted into the brains of the same rat strain. They were followed up by electron microscopy during the first ten passages. Three architectural features were detected: First pure tumor parts, second myelin breakdown and phagocytosis, and third the resulting accumulation of resting macrophages. Architecture two and three were interpreted as result of considerable phagocytotic activity of tumor cells localized within the white substance of the brain and spinal cord. Only architecture one was considered to represent proper tumor. Since this was low differentiated and partial astrocytic differentiation only occurred around vessels to remarkable extent, the thesis is put forward that these transplacentally induced tumors correspond to human primitive neuroectodermal tumors.

The Psychophysics of Brain Rhythms

PubMed Central

VanRullen, Rufin; Dubois, Julien

2011-01-01

It is becoming increasingly apparent that brain oscillations in various frequency bands play important roles in perceptual and attentional processes. Understandably, most of the associated experimental evidence comes from human or animal electrophysiological studies, allowing direct access to the oscillatory activities. However, such periodicities in perception and attention should, in theory, also be observable using the proper psychophysical tools. Here, we review a number of psychophysical techniques that have been used by us and other authors, in successful and sometimes unsuccessful attempts, to reveal the rhythmic nature of perceptual and attentional processes. We argue that the two existing and largely distinct debates about discrete vs. continuous perception and parallel vs. sequential attention should in fact be regarded as two facets of the same question: how do brain rhythms shape the psychological operations of perception and attention? PMID:21904532

Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome

PubMed Central

Denise, Cook; Erin, Nuro; Keith, K. Murai

2014-01-01

Fragile X Syndrome (FXS) is considered the most common form of inherited intellectual disability. It is caused by reductions in the expression level or function of a single protein, the Fragile X Mental Retardation Protein (FMRP), a translational regulator which binds to approximately 4% of brain messenger RNAs. Accumulating evidence suggests that FXS is a complex disorder of cognition, involving interactions between genetic and environmental influences, leading to difficulties in acquiring key life skills including motor skills, language, and proper social behaviors. Since many FXS patients also present with one or more features of autism spectrum disorders (ASDs), insights gained from studying the monogenic basis of FXS could pave the way to a greater understanding of underlying features of multigenic ASDs. Here we present an overview of the FXS and FMRP field with the goal of demonstrating how loss of a single protein involved in translational control affects multiple stages of brain development and leads to debilitating consequences on human cognition. We also focus on studies which have rescued or improved FXS symptoms in mice using genetic or therapeutic approaches to reduce protein expression. We end with a brief description of how deficits in translational control are implicated in FXS and certain cases of ASDs, with many recent studies demonstrating that ASDs are likely caused by increases or decreases in the levels of certain key synaptic proteins. The study of FXS and its underlying single genetic cause offers an invaluable opportunity to study how a single gene influences brain development and behavior. © 2013 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 74: 147–177, 2014 PMID:23723176

[Is personalism or utilitarianism an adequate foundation of medical ethics?].

PubMed

Biesaga, T

1998-01-01

The article rejects utilitarianism as a proper theory for medical ethics. Utilitarians lavishly use various slogans of effective action, development and better civilization. However, the principle of prosperity of humanity in the utilitarian interpretation makes the value of the human person subject to society. Social interest threatens the individual here because it defines his/her value of life. The drift towards maximalization of benefits and prosperity of humanity strikes the seriously ill, e.g. babies with brain damages, Down's syndrome, etc., people after accidents and with serious brain defects, the terminally ill. The principle of quality of life (lebensunwertes Leben) used by utylitarians allows them to argue, that euthanasia, abortion is in the interest of the patient. Some utilitarians openly admit that such ideas as "universal happiness", "prosperity", "benefit" are empty ideas, fictions to which one cannot attribute any contents. So utilitarianism, not defining its fundamental ideas, can easily change medical ethics in a theory of elimination of the uncomfortable people. Therefore, as a theory utilitarianism cannot serve as the basis for medical ethics.

Mechanisms of Divalent Metal Toxicity in Affective Disorders

PubMed Central

Menon, Archita Venugopal; Chang, JuOae; Kim, Jonghan

2016-01-01

Metals are required for proper brain development and play an important role in a number of neurobiological functions. The Divalent Metal Transporter 1 (DMT1) is a major metal transporter involved in the absorption and metabolism of several essential metals like iron and manganese. However, non-essential divalent metals are also transported through this transporter. Therefore, altered expression of DMT1 can modify the absorption of toxic metals and metal-induced toxicity. An accumulating body of evidence has suggested that increased metal stores in the brain are associated with elevated oxidative stress mediated by the ability of metals to catalyze redox reactions, resulting in abnormal neurobehavioral function and the progression of neurodegenerative diseases. Metal overload has also been implicated in impaired emotional behavior, although the underlying mechanisms are not well understood with limited information. The current review focuses on psychiatric dysfunction associated with imbalanced metabolism of metals that are transported by DMT1. The investigations with respect to the toxic effects of metal overload on behavior and their underlying mechanisms of toxicity could provide several new therapeutic targets to treat metal-associated affective disorders. PMID:26551072

Modeling of cortical signals using echo state networks

NASA Astrophysics Data System (ADS)

Zhou, Hanying; Wang, Yongji; Huang, Jiangshuai

2009-10-01

Diverse modeling frameworks have been utilized with the ultimate goal of translating brain cortical signals into prediction of visible behavior. The inputs to these models are usually multidimensional neural recordings collected from relevant regions of a monkey's brain while the outputs are the associated behavior which is typically the 2-D or 3-D hand position of a primate. Here our task is to set up a proper model in order to figure out the move trajectories by input the neural signals which are simultaneously collected in the experiment. In this paper, we propose to use Echo State Networks (ESN) to map the neural firing activities into hand positions. ESN is a newly developed recurrent neural network(RNN) model. Besides its dynamic property and short term memory just as other recurrent neural networks have, it has a special echo state property which endows it with the ability to model nonlinear dynamic systems powerfully. What distinguished it from transitional recurrent neural networks most significantly is its special learning method. In this paper we train this net with a refined version of its typical training method and get a better model.

Design and Implementation of a Brain Computer Interface System for Controlling a Robotic Claw

NASA Astrophysics Data System (ADS)

Angelakis, D.; Zoumis, S.; Asvestas, P.

2017-11-01

The aim of this paper is to present the design and implementation of a brain-computer interface (BCI) system that can control a robotic claw. The system is based on the Emotiv Epoc headset, which provides the capability of simultaneous recording of 14 EEG channels, as well as wireless connectivity by means of the Bluetooth protocol. The system is initially trained to decode what user thinks to properly formatted data. The headset communicates with a personal computer, which runs a dedicated software application, implemented under the Processing integrated development environment. The application acquires the data from the headset and invokes suitable commands to an Arduino Uno board. The board decodes the received commands and produces corresponding signals to a servo motor that controls the position of the robotic claw. The system was tested successfully on a healthy, male subject, aged 28 years. The results are promising, taking into account that no specialized hardware was used. However, tests on a larger number of users is necessary in order to draw solid conclusions regarding the performance of the proposed system.

Leptin is associated with exaggerated brain reward and emotion responses to food images in adolescent obesity.

PubMed

Jastreboff, Ania M; Lacadie, Cheryl; Seo, Dongju; Kubat, Jessica; Van Name, Michelle A; Giannini, Cosimo; Savoye, Mary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia; Sinha, Rajita

2014-11-01

In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors. Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE). This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Tissue Modeling and Analyzing with Finite Element Method: A Review for Cranium Brain Imaging

PubMed Central

Yue, Xianfang; Wang, Li; Wang, Ruonan

2013-01-01

For the structure mechanics of human body, it is almost impossible to conduct mechanical experiments. Then the finite element model to simulate mechanical experiments has become an effective tool. By introducing several common methods for constructing a 3D model of cranial cavity, this paper carries out systematically the research on the influence law of cranial cavity deformation. By introducing the new concepts and theory to develop the 3D cranial cavity model with the finite-element method, the cranial cavity deformation process with the changing ICP can be made the proper description and reasonable explanation. It can provide reference for getting cranium biomechanical model quickly and efficiently and lay the foundation for further biomechanical experiments and clinical applications. PMID:23476630

Crucial roles of Pox neuro in the developing ellipsoid body and antennal lobes of the Drosophila brain

PubMed Central

Minocha, Shilpi; Boll, Werner

2017-01-01

The paired box gene Pox neuro (Poxn) is expressed in two bilaterally symmetric neuronal clusters of the developing adult Drosophila brain, a protocerebral dorsal cluster (DC) and a deutocerebral ventral cluster (VC). We show that all cells that express Poxn in the developing brain are postmitotic neurons. During embryogenesis, the DC and VC consist of only 20 and 12 neurons that express Poxn, designated embryonic Poxn-neurons. The number of Poxn-neurons increases only during the third larval instar, when the DC and VC increase dramatically to about 242 and 109 Poxn-neurons, respectively, virtually all of which survive to the adult stage, while no new Poxn-neurons are added during metamorphosis. Although the vast majority of Poxn-neurons express Poxn only during third instar, about half of them are born by the end of embryogenesis, as demonstrated by the absence of BrdU incorporation during larval stages. At late third instar, embryonic Poxn-neurons, which begin to express Poxn during embryogenesis, can be easily distinguished from embryonic-born and larval-born Poxn-neurons, which begin to express Poxn only during third instar, (i) by the absence of Pros, (ii) their overt differentiation of axons and neurites, and (iii) the strikingly larger diameter of their cell bodies still apparent in the adult brain. The embryonic Poxn-neurons are primary neurons that lay out the pioneering tracts for the secondary Poxn-neurons, which differentiate projections and axons that follow those of the primary neurons during metamorphosis. The DC and the VC participate only in two neuropils of the adult brain. The DC forms most, if not all, of the neurons that connect the bulb (lateral triangle) with the ellipsoid body, a prominent neuropil of the central complex, while the VC forms most of the ventral projection neurons of the antennal lobe, which connect it ipsilaterally to the lateral horn, bypassing the mushroom bodies. In addition, Poxn-neurons of the VC are ventral local interneurons of the antennal lobe. In the absence of Poxn protein in the developing brain, embryonic Poxn-neurons stall their projections and cannot find their proper target neuropils, the bulb and ellipsoid body in the case of the DC, or the antennal lobe and lateral horn in the case of the VC, whereby the absence of the ellipsoid body neuropil is particularly striking. Poxn is thus crucial for pathfinding both in the DC and VC. Additional implications of our results are discussed. PMID:28441464

3 CFR 8446 - Proclamation 8446 of October 30, 2009. National Alzheimer's Disease Awareness Month, 2009

Code of Federal Regulations, 2010 CFR

2010-01-01

..., we must leave no avenue unexplored. Embryonic stem cells may hold the key for us to better understand... Executive Order lifting the ban on Federal funding for embryonic stem cell research, with proper guidelines... are now able to start treatments earlier, slowing the loss of brain cells and the progression of...

Origin, Utilization, and Recycling of Nucleosides in the Central Nervous System

ERIC Educational Resources Information Center

Ipata, Piero Luigi

2011-01-01

The brain relies on the salvage of preformed purine and pyrimidine rings, mainly in the form of nucleosides, to maintain its nucleotide pool in the proper qualitative and quantitative balance. The transport of nucleosides from blood into neurons and glia is considered to be an essential prerequisite to enter their metabolic utilization in the…

Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.

PubMed

Chittajallu, R; Wester, J C; Craig, M T; Barksdale, E; Yuan, X Q; Akgül, G; Fang, C; Collins, D; Hunt, S; Pelkey, K A; McBain, C J

2017-07-28

Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.

A single day of 5-azacytidine exposure during development induces neurodegeneration in neonatal mice and neurobehavioral deficits in adult mice.

PubMed

Subbanna, Shivakumar; Nagre, Nagaraja N; Shivakumar, Madhu; Basavarajappa, Balapal S

2016-12-01

The present study was undertaken to evaluate the immediate and long-term effects of a single-day exposure to 5-Azacytidine (5-AzaC), a DNA methyltransferase inhibitor, on neurobehavioral abnormalities in mice. Our findings suggest that the 5-AzaC treatment significantly inhibited DNA methylation, impaired extracellular signal-regulated kinase (ERK1/2) activation and reduced expression of the activity-regulated cytoskeleton-associated protein (Arc). These events lead to the activation of caspase-3 (a marker for neurodegeneration) in several brain regions, including the hippocampus and cortex, two brain areas that are essential for memory formation and memory storage, respectively. 5-AzaC treatment of P7 mice induced significant deficits in spatial memory, social recognition, and object memory in adult mice and deficits in long-term potentiation (LTP) in adult hippocampal slices. Together, these data demonstrate that the inhibition of DNA methylation by 5-AzaC treatment in P7 mice causes neurodegeneration and impairs ERK1/2 activation and Arc protein expression in neonatal mice and induces behavioral abnormalities in adult mice. DNA methylation-mediated mechanisms appear to be necessary for the proper maturation of synaptic circuits during development, and disruption of this process by 5-AzaC could lead to abnormal cognitive function. Published by Elsevier Inc.

Role of JAK/STAT signaling in neuroepithelial stem cell maintenance and proliferation in the Drosophila optic lobe

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

Wang, Wei; Li, Yonggang; Zhou, Liya

2011-07-15

Highlights: {yields} JAK/STAT activity is graded in the Drosophila optic lobe neuroepithelium. {yields} Inactivation of JAK signaling causes disintegration of the optic lobe neuroepithelium and depletion of the neuroepithelial stem cells. {yields} JAK pathway overactivation promotes neuroepithelial overgrowth. {yields} Notch signaling acts downstream of JAK/STAT to promote neuroepithelial growth and expansion. -- Abstract: During Drosophila optic lobe development, proliferation and differentiation must be tightly modulated to reach its normal size for proper functioning. The JAK/STAT pathway plays pleiotropic roles in Drosophila development and in the larval brain, has been shown to inhibit medulla neuroblast formation. In this study, we findmore » that JAK/STAT activity is required for the maintenance and proliferation of the neuroepithelial stem cells in the optic lobe. In loss-of-function JAK/STAT mutant brains, the neuroepithelial cells lose epithelial cell characters and differentiate prematurely while ectopic activation of this pathway is sufficient to induce neuroepithelial overgrowth in the optic lobe. We further show that Notch signaling acts downstream of JAK/STAT to control the maintenance and growth of the optic lobe neuroepithelium. Thus, in addition to its role in suppression of neuroblast formation, the JAK/STAT pathway is necessary and sufficient for optic lobe neuroepithelial growth.« less

The sodium-activated potassium channel Slack is required for optimal cognitive flexibility in mice.

PubMed

Bausch, Anne E; Dieter, Rebekka; Nann, Yvette; Hausmann, Mario; Meyerdierks, Nora; Kaczmarek, Leonard K; Ruth, Peter; Lukowski, Robert

2015-07-01

Kcnt1 encoded sodium-activated potassium channels (Slack channels) are highly expressed throughout the brain where they modulate the firing patterns and general excitability of many types of neurons. Increasing evidence suggests that Slack channels may be important for higher brain functions such as cognition and normal intellectual development. In particular, recent findings have shown that human Slack mutations produce very severe intellectual disability and that Slack channels interact directly with the Fragile X mental retardation protein (FMRP), a protein that when missing or mutated results in Fragile X syndrome (FXS), the most common form of inherited intellectual disability and autism in humans. We have now analyzed a recently developed Kcnt1 null mouse model in several behavioral tasks to assess which aspects of memory and learning are dependent on Slack. We demonstrate that Slack deficiency results in mildly altered general locomotor activity, but normal working memory, reference memory, as well as cerebellar control of motor functions. In contrast, we find that Slack channels are required for cognitive flexibility, including reversal learning processes and the ability to adapt quickly to unfamiliar situations and environments. Our data reveal that hippocampal-dependent spatial learning capabilities require the proper function of Slack channels. © 2015 Bausch et al.; Published by Cold Spring Harbor Laboratory Press.

The sodium-activated potassium channel Slack is required for optimal cognitive flexibility in mice

PubMed Central

Bausch, Anne E.; Dieter, Rebekka; Nann, Yvette; Hausmann, Mario; Meyerdierks, Nora; Kaczmarek, Leonard K.

2015-01-01

Kcnt1 encoded sodium-activated potassium channels (Slack channels) are highly expressed throughout the brain where they modulate the firing patterns and general excitability of many types of neurons. Increasing evidence suggests that Slack channels may be important for higher brain functions such as cognition and normal intellectual development. In particular, recent findings have shown that human Slack mutations produce very severe intellectual disability and that Slack channels interact directly with the Fragile X mental retardation protein (FMRP), a protein that when missing or mutated results in Fragile X syndrome (FXS), the most common form of inherited intellectual disability and autism in humans. We have now analyzed a recently developed Kcnt1 null mouse model in several behavioral tasks to assess which aspects of memory and learning are dependent on Slack. We demonstrate that Slack deficiency results in mildly altered general locomotor activity, but normal working memory, reference memory, as well as cerebellar control of motor functions. In contrast, we find that Slack channels are required for cognitive flexibility, including reversal learning processes and the ability to adapt quickly to unfamiliar situations and environments. Our data reveal that hippocampal-dependent spatial learning capabilities require the proper function of Slack channels. PMID:26077685

Mitochondrial Chaperones in the Brain: Safeguarding Brain Health and Metabolism?

PubMed

Castro, José Pedro; Wardelmann, Kristina; Grune, Tilman; Kleinridders, André

2018-01-01

The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis), cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function) has been observed during aging, metabolic diseases such as type 2 diabetes and in neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD) or even Huntington's (HD) diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.

Integrated trimodal SSEP experimental setup for visual, auditory and tactile stimulation

NASA Astrophysics Data System (ADS)

Kuś, Rafał; Spustek, Tomasz; Zieleniewska, Magdalena; Duszyk, Anna; Rogowski, Piotr; Suffczyński, Piotr

2017-12-01

Objective. Steady-state evoked potentials (SSEPs), the brain responses to repetitive stimulation, are commonly used in both clinical practice and scientific research. Particular brain mechanisms underlying SSEPs in different modalities (i.e. visual, auditory and tactile) are very complex and still not completely understood. Each response has distinct resonant frequencies and exhibits a particular brain topography. Moreover, the topography can be frequency-dependent, as in case of auditory potentials. However, to study each modality separately and also to investigate multisensory interactions through multimodal experiments, a proper experimental setup appears to be of critical importance. The aim of this study was to design and evaluate a novel SSEP experimental setup providing a repetitive stimulation in three different modalities (visual, tactile and auditory) with a precise control of stimuli parameters. Results from a pilot study with a stimulation in a particular modality and in two modalities simultaneously prove the feasibility of the device to study SSEP phenomenon. Approach. We developed a setup of three separate stimulators that allows for a precise generation of repetitive stimuli. Besides sequential stimulation in a particular modality, parallel stimulation in up to three different modalities can be delivered. Stimulus in each modality is characterized by a stimulation frequency and a waveform (sine or square wave). We also present a novel methodology for the analysis of SSEPs. Main results. Apart from constructing the experimental setup, we conducted a pilot study with both sequential and simultaneous stimulation paradigms. EEG signals recorded during this study were analyzed with advanced methodology based on spatial filtering and adaptive approximation, followed by statistical evaluation. Significance. We developed a novel experimental setup for performing SSEP experiments. In this sense our study continues the ongoing research in this field. On the other hand, the described setup along with the presented methodology is a considerable improvement and an extension of methods constituting the state-of-the-art in the related field. Device flexibility both with developed analysis methodology can lead to further development of diagnostic methods and provide deeper insight into information processing in the human brain.

Surgical management of symptomatic brain stem cavernoma in a developing country: technical difficulties and outcome.

PubMed

Farhoud, Ahmed; Aboul-Enein, Hisham

2016-07-01

Brain stem cavernomas (BSCs) are angiographically occult vascular malformations in an intricate location. Surgical excision of symptomatic BSCs represents a neurosurgical challenge especially in developing countries. We reviewed the clinical data and surgical outcome of 24 consecutive cases surgically treated for brain stem cavernoma at the Neurosurgery Department, Alexandria University, between 2006 and 2014. All patients were followed up for at least 12 months after surgery and the mean follow-up period was 45 months. All patients suffered from at least two clinically significant hemorrhagic episodes before surgery. There were 10 males and 14 females. The mean age was 34 years (range 12 to 58 years). Fourteen cases had pontine cavernomas, 7 cases had midbrain cavernomas, and in 3 cases, the lesion was found in the medulla oblongata. The most commonly used approach in this series was the midline suboccipital approach with or without telovelar exposure (9 cases). There was a single postoperative mortality in this series due to pneumonia. Fourteen cases (58.3 %) showed initial worsening of their preoperative neurological status, most of which was transient and only three patients had permanent new deficits and one case had a permanent worsening of her preoperatively existing hemiparesis. There was neither immediate nor long-term rebleeding in any of our cases. In spite of the significant associated risks, surgery for BSCs in properly selected patients can have favorable outcomes in most cases. Surgery markedly improves the risk of rebleeding and should be considered in patients with accessible lesions.

Increasing our understanding of human cognition through the study of Fragile X Syndrome.

PubMed

Cook, Denise; Nuro, Erin; Murai, Keith K

2014-02-01

Fragile X Syndrome (FXS) is considered the most common form of inherited intellectual disability. It is caused by reductions in the expression level or function of a single protein, the Fragile X Mental Retardation Protein (FMRP), a translational regulator which binds to approximately 4% of brain messenger RNAs. Accumulating evidence suggests that FXS is a complex disorder of cognition, involving interactions between genetic and environmental influences, leading to difficulties in acquiring key life skills including motor skills, language, and proper social behaviors. Since many FXS patients also present with one or more features of autism spectrum disorders (ASDs), insights gained from studying the monogenic basis of FXS could pave the way to a greater understanding of underlying features of multigenic ASDs. Here we present an overview of the FXS and FMRP field with the goal of demonstrating how loss of a single protein involved in translational control affects multiple stages of brain development and leads to debilitating consequences on human cognition. We also focus on studies which have rescued or improved FXS symptoms in mice using genetic or therapeutic approaches to reduce protein expression. We end with a brief description of how deficits in translational control are implicated in FXS and certain cases of ASDs, with many recent studies demonstrating that ASDs are likely caused by increases or decreases in the levels of certain key synaptic proteins. The study of FXS and its underlying single genetic cause offers an invaluable opportunity to study how a single gene influences brain development and behavior. Copyright © 2013 Wiley Periodicals, Inc.

Perioperative considerations for neurosurgical procedures in the gravid patient: Continuing Professional Development.

PubMed

Chowdhury, Tumul; Chowdhury, Meenakshi; Schaller, Bernhard; Cappellani, Ronald B; Daya, Jayesh

2013-11-01

The complexity of neurosurgical procedures and their interactions with maternal and fetal physiologies are key factors in determining the overall maternal and fetal outcome. The literature and guidelines provide only partial information regarding the standard of care in these cases. The purpose of this Continuing Professional Development module is to review the issues related to common neurosurgical conditions and their optimal anesthetic management. The most common neurosurgical conditions found in pregnancy include brain tumours, cerebrovascular diseases, spinal pathologies, and neurotrauma. Though rare, these conditions and related procedures may affect maternal and fetal outcome. Maternal considerations should be given priority in cases of emergent surgeries irrespective of trimester. In the early first trimester, risk of fetal loss and congenital malformation are substantial; hence, proper counselling should be given to the mother with special emphasis on therapeutic abortion. When indicated, anticonvulsants should be started as early as possible and continued throughout pregnancy. Surgical procedures can be performed with relative safety during the second trimester and early third trimester. After 34 weeks, delivery seems to be the first choice, and the role of regional anesthesia in this situation should be carefully planned after proper review of neurosurgical pathology and maternal condition. During acute neurological deterioration, however, Cesarean delivery under general anesthesia should be anticipated. A multidisciplinary approach with good communication amongst all team members certainly plays a crucial role for successful management of such cases.

Optimal design of a bank of spatio-temporal filters for EEG signal classification.

PubMed

Higashi, Hiroshi; Tanaka, Toshihisa

2011-01-01

The spatial weights for electrodes called common spatial pattern (CSP) are known to be effective in EEG signal classification for motor imagery based brain computer interfaces (MI-BCI). To achieve accurate classification in CSP, the frequency filter should be properly designed. To this end, several methods for designing the filter have been proposed. However, the existing methods cannot consider plural brain activities described with different frequency bands and different spatial patterns such as activities of mu and beta rhythms. In order to efficiently extract these brain activities, we propose a method to design plural filters and spatial weights which extract desired brain activity. The proposed method designs finite impulse response (FIR) filters and the associated spatial weights by optimization of an objective function which is a natural extension of CSP. Moreover, we show by a classification experiment that the bank of FIR filters which are designed by introducing an orthogonality into the objective function can extract good discriminative features. Moreover, the experiment result suggests that the proposed method can automatically detect and extract brain activities related to motor imagery.

Penetrating brain injury with a metal bar and a knife: Report of two interesting cases.

PubMed

Tabibkhooei, Alireza; Taheri, Morteza; Rohani, Sadra; Chanideh, Iran; Rahatlou, Hessam

2018-04-01

Introduction Penetrating brain injury (PBI) is uncommon among the civilian population. Here, we report two interesting cases of PBI. Case presentation The first patient was a 20-year-old male who sustained a penetrating head injury with a metal bar during an accident at work. The patient underwent early surgical intervention, and related meningitis was treated with antibiotics. The patient was discharged 45 days later with no deficit. The second patient was a 34-year-old male who was the victim of a violence attack and was admitted to hospital. He was struck by a knife to his right temporal bone. A brain computed tomography scan and magnetic resonance imaging (MRI) demonstrated the tract of the knife within the brain parenchyma. The patient underwent conservative treatment. After several weeks, the patient was discharged in good health. Conclusion Although severe PBI has a poorer prognosis than a blunt brain injury, in treating of these patients, aggressive and timely surgical intervention, proper wide-spectrum antibiotic administration, stringent and diligent care in the intensive-care unit and careful management of the associated complications are mandated.

Determination of cyanidin 3-glucoside in rat brain, liver and kidneys by UPLC/MS-MS and its application to a short-term pharmacokinetic study.

PubMed

Fornasaro, Stefano; Ziberna, Lovro; Gasperotti, Mattia; Tramer, Federica; Vrhovšek, Urška; Mattivi, Fulvio; Passamonti, Sabina

2016-03-11

Anthocyanins exert neuroprotection in various in vitro and in vivo experimental models. However, no details regarding their brain-related pharmacokinetics are so far available to support claims about their direct neuronal bioactivity as well as to design proper formulations of anthocyanin-based products. To gather this missing piece of knowledge, we intravenously administered a bolus of 668 nmol cyanidin 3-glucoside (C3G) in anaesthetized Wistar rats and shortly after (15 s to 20 min) we collected blood, brain, liver, kidneys and urine samples. Extracts thereof were analysed for C3G and its expected metabolites using UPLC/MS-MS. The data enabled to calculate a set of pharmacokinetics parameters. The main finding was the distinctive, rapid distribution of C3G in the brain, with an apparently constant plasma/brain ratio in the physiologically relevant plasma concentration range (19-355 nM). This is the first report that accurately determines the distribution pattern of C3G in the brain, paving the way to the rational design of future tests of neuroprotection by C3G in animal models and humans.

Determination of cyanidin 3-glucoside in rat brain, liver and kidneys by UPLC/MS-MS and its application to a short-term pharmacokinetic study

PubMed Central

Fornasaro, Stefano; Ziberna, Lovro; Gasperotti, Mattia; Tramer, Federica; Vrhovšek, Urška; Mattivi, Fulvio; Passamonti, Sabina

2016-01-01

Anthocyanins exert neuroprotection in various in vitro and in vivo experimental models. However, no details regarding their brain-related pharmacokinetics are so far available to support claims about their direct neuronal bioactivity as well as to design proper formulations of anthocyanin-based products. To gather this missing piece of knowledge, we intravenously administered a bolus of 668 nmol cyanidin 3-glucoside (C3G) in anaesthetized Wistar rats and shortly after (15 s to 20 min) we collected blood, brain, liver, kidneys and urine samples. Extracts thereof were analysed for C3G and its expected metabolites using UPLC/MS-MS. The data enabled to calculate a set of pharmacokinetics parameters. The main finding was the distinctive, rapid distribution of C3G in the brain, with an apparently constant plasma/brain ratio in the physiologically relevant plasma concentration range (19–355 nM). This is the first report that accurately determines the distribution pattern of C3G in the brain, paving the way to the rational design of future tests of neuroprotection by C3G in animal models and humans. PMID:26965389

From Embryonic Development to Human Diseases: The Functional Role of Caveolae/Caveolin

PubMed Central

Sohn, Jihee; Brick, Rachel M.; Tuan, Rocky S.

2017-01-01

Caveolae, an almost ubiquitous, structural component of the plasma membrane, play a critical role in many functions essential for proper cell function, including membrane trafficking, signal transduction, extracellular matrix remodeling, and tissue regeneration. Three main types of caveolin proteins have been identified from caveolae since the discovery of caveolin-1 in the early 1990s. All three (Cav-1, Cav-2, and Cav-3) play crucial roles in mammalian physiology, and can effect pathogenesis in a wide range of human diseases. While many biological activities of caveolins have been uncovered since its discovery, their role and regulation in embryonic develop remain largely poorly understood, although there is increasing evidence that caveolins may be linked to lung and brain birth defects. Further investigations are clearly needed to decipher how caveolae/caveolins mediate cellular functions and activities of normal embryogenesis and how their perturbations contribute to developmental disorders. PMID:26991990

Congenital disorder of true cyclopia with polydactylia: case report and review of the literature.

PubMed

Deftereou, T E; Tsoulopoulos, V; Alexiadis, G; Papadopoulos, E; Chouridou, E; Katotomichelakis, M; Lambropoulou, M

2013-01-01

Cyclopia is a rare type of holoprosencephaly and a congenital disorder characterized by the failure of the embryonic forebrain to properly divide the orbits of the eye into two cavities (the embryonic forebrain is normally responsible for inducing the development of the orbits). As a result a birth defect in which there is only one eye is developed. This eye is centrally placed in the area normally occupied by the root of the nose. As a rule, there is a missing nose or a non-functioning nose in the form of a proboscis (a tubular appendage) located above the central eye. In this report the macroscopic, radiographic, and immunohistochemical findings of a case of true cyclopia in a female fetus are described. Cyclopia is a lethal condition that is associated with dramatic symmetric deformities of the nose, skull, orbits, and brain.

Could Perinatal Asphyxia Induce a Synaptopathy? New Highlights from an Experimental Model

PubMed Central

Herrera, María Inés; Udovin, Lucas Daniel; Kusnier, Carlos; Kölliker-Frers, Rodolfo; de Souza, Wanderley

2017-01-01

Birth asphyxia also termed perinatal asphyxia is an obstetric complication that strongly affects brain structure and function. Central nervous system is highly susceptible to oxidative damage caused by perinatal asphyxia while activation and maturity of the proper pathways are relevant to avoiding abnormal neural development. Perinatal asphyxia is associated with high morbimortality in term and preterm neonates. Although several studies have demonstrated a variety of biochemical and molecular pathways involved in perinatal asphyxia physiopathology, little is known about the synaptic alterations induced by perinatal asphyxia. Nearly 25% of the newborns who survive perinatal asphyxia develop neurological disorders such as cerebral palsy and certain neurodevelopmental and learning disabilities where synaptic connectivity disturbances may be involved. Accordingly, here we review and discuss the association of possible synaptic dysfunction with perinatal asphyxia on the basis of updated evidence from an experimental model. PMID:28326198

Effects of Aging in Multisensory Integration: A Systematic Review

PubMed Central

de Dieuleveult, Alix L.; Siemonsma, Petra C.; van Erp, Jan B. F.; Brouwer, Anne-Marie

2017-01-01

Multisensory integration (MSI) is the integration by the brain of environmental information acquired through more than one sense. Accurate MSI has been shown to be a key component of successful aging and to be crucial for processes underlying activities of daily living (ADLs). Problems in MSI could prevent older adults (OA) to age in place and live independently. However, there is a need to know how to assess changes in MSI in individuals. This systematic review provides an overview of tests assessing the effect of age on MSI in the healthy elderly population (aged 60 years and older). A literature search was done in Scopus. Articles from the earliest records available to January 20, 2016, were eligible for inclusion if assessing effects of aging on MSI in the healthy elderly population compared to younger adults (YA). These articles were rated for risk of bias with the Newcastle-Ottawa quality assessment. Out of 307 identified research articles, 49 articles were included for final review, describing 69 tests. The review indicated that OA maximize the use of multiple sources of information in comparison to YA (20 studies). In tasks that require more cognitive function, or when participants need to adapt rapidly to a situation, or when a dual task is added to the experiment, OA have problems selecting and integrating information properly as compared to YA (19 studies). Additionally, irrelevant or wrong information (i.e., distractors) has a greater impact on OA than on YA (21 studies). OA failing to weigh sensory information properly, has not been described in previous reviews. Anatomical changes (i.e., reduction of brain volume and differences of brain areas’ recruitment) and information processing changes (i.e., general cognitive slowing, inverse effectiveness, larger time window of integration, deficits in attentional control and increased noise at baseline) can only partly explain the differences between OA and YA regarding MSI. Since we have an interest in successful aging and early detection of MSI issues in the elderly population, the identified tests form a good starting point to develop a clinically useful toolkit to assess MSI in healthy OA. PMID:28400727

Stratified active screening: where neurotechnology meets public health.

PubMed

Valdés, Pedro; Obrador-Fragoso, Adianez

2007-10-01

Nearly one quarter of the global burden of disease stems from neurological, psychiatric and neurodevelopmental disorders due to malformations or dysfunctions of the central nervous system.[1] Such neuropsychiatric conditions influence quality of life worldwide, causing one third of years lost due to disability (YDL).[2] Ranging from congenital conditions to dementias of the elderly, these disorders appear throughout the life cycle and also account for a substantial proportion of mortality. Recent advances in neuroimaging and neuroinformatics have opened the way for early identification of dysfunctional brain networks, providing essential information for the early detection, proper diagnosis, treatment selection, and follow-up of people with disabilities due to brain disorders.

Stratified active screening: where neurotechnology meets public health.

PubMed

Valdés, Pedro; Obrador-Fragoso, Adianez

2008-10-01

Nearly one quarter of the global burden of disease stems from neurological, psychiatric and neurodevelopmental disorders due to malformations or dysfunctions of the central nervous system.[1] Such neuropsychiatric conditions influence quality of life worldwide, causing one third of years lost due to disability (YDL).[2] Ranging from congenital conditions to dementias of the elderly, these disorders appear throughout the life cycle and also account for a substantial proportion of mortality. Recent advances in neuroimaging and neuroinformatics have opened the way for early identification of dysfunctional brain networks, providing essential information for the early detection, proper diagnosis, treatment selection, and follow-up of people with disabilities due to brain disorders.

Stratified active screening: where neurotechnology meets public health.

PubMed

Valdés, Pedro; Obrador-Fragoso, Adianez

2009-01-01

Nearly one quarter of the global burden of disease stems from neurological, psychiatric and neurodevelopmental disorders due to malformations or dysfunctions of the central nervous system.[1] Such neuropsychiatric conditions influence quality of life worldwide, causing one third of years lost due to disability (YDL).[2] Ranging from congenital conditions to dementias of the elderly, these disorders appear throughout the life cycle and also account for a substantial proportion of mortality. Recent advances in neuroimaging and neuroinformatics have opened the way for early identification of dysfunctional brain networks, providing essential information for the early detection, proper diagnosis, treatment selection, and follow-up of people with disabilities due to brain disorders.

A Parallel Independent Component Analysis Approach to Investigate Genomic Influence on Brain Function

PubMed Central

Liu, Jingyu; Demirci, Oguz; Calhoun, Vince D.

2009-01-01

Relationships between genomic data and functional brain images are of great interest but require new analysis approaches to integrate the high-dimensional data types. This letter presents an extension of a technique called parallel independent component analysis (paraICA), which enables the joint analysis of multiple modalities including interconnections between them. We extend our earlier work by allowing for multiple interconnections and by providing important overfitting controls. Performance was assessed by simulations under different conditions, and indicated reliable results can be extracted by properly balancing overfitting and underfitting. An application to functional magnetic resonance images and single nucleotide polymorphism array produced interesting findings. PMID:19834575

A Parallel Independent Component Analysis Approach to Investigate Genomic Influence on Brain Function.

PubMed

Liu, Jingyu; Demirci, Oguz; Calhoun, Vince D

2008-01-01

Relationships between genomic data and functional brain images are of great interest but require new analysis approaches to integrate the high-dimensional data types. This letter presents an extension of a technique called parallel independent component analysis (paraICA), which enables the joint analysis of multiple modalities including interconnections between them. We extend our earlier work by allowing for multiple interconnections and by providing important overfitting controls. Performance was assessed by simulations under different conditions, and indicated reliable results can be extracted by properly balancing overfitting and underfitting. An application to functional magnetic resonance images and single nucleotide polymorphism array produced interesting findings.

The biochemical, nanomechanical and chemometric signatures of brain cancer

NASA Astrophysics Data System (ADS)

Abramczyk, Halina; Imiela, Anna

2018-01-01

Raman spectroscopy and imaging combined with AFM topography and mechanical indentation by AFM have been shown to be an effective tool for analysis and discrimination of human brain tumors from normal structures. Raman methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n = 5) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma (IV grade), and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational spectra and Raman images we provide a real-time feedback that is label-free method to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, and proteins. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm- 1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the lipid and protein contents of tumorous brain tissue compared to the non-tumor tissue. Almost all brain tumors have the Raman intensity ratios significantly higher (1.99 ± 0.026) than that found in non-tumor brain tissue, which is 1.456 ± 0.02, and indicates that the relative amount of lipids compared to proteins is significantly higher in the normal brain tissue. Mechanical indentation using AFM on sliced human brain tissues (medulloblastoma, grade IV) revealed that the mechanical properties of this tissue are strongly heterogeneous, between 1.8 and 75.7 kPa, and the mean of 27.16 kPa. The sensitivity and specificity obtained directly from PLSDA and cross validation gives a sensitivity and specificity of 98.5% and 96% and 96.3% and 92% for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development.

Self-regulation of brain oscillations as a treatment for aberrant brain connections in children with autism.

PubMed

Pineda, J A; Juavinett, A; Datko, M

2012-12-01

Autism is a highly varied developmental disorder typically characterized by deficits in reciprocal social interaction, difficulties with verbal and nonverbal communication, and restricted interests and repetitive behaviors. Although a wide range of behavioral, pharmacological, and alternative medicine strategies have been reported to ameliorate specific symptoms for some individuals, there is at present no cure for the condition. Nonetheless, among the many incompatible observations about aspects of the development, anatomy, and functionality of the autistic brain, it is widely agreed that it is characterized by widespread aberrant connectivity. Such disordered connectivity, be it increased, decreased, or otherwise compromised, may complicate healthy synchronization and communication among and within different neural circuits, thereby producing abnormal processing of sensory inputs necessary for normal social life. It is widely accepted that the innate properties of brain electrical activity produce pacemaker elements and linked networks that oscillate synchronously or asynchronously, likely reflecting a type of functional connectivity. Using phase coherence in multiple frequency EEG bands as a measure of functional connectivity, studies have shown evidence for both global hypoconnectivity and local hyperconnectivity in individuals with ASD. However, the nature of the brain's experience-dependent structural plasticity suggests that these abnormal patterns may be reversed with the proper type of treatment. Indeed, neurofeedback (NF) training, an intervention based on operant conditioning that results in self-regulation of brain electrical oscillations, has shown promise in addressing marked abnormalities in functional and structural connectivity. It is hypothesized that neurofeedback produces positive behavioral changes in ASD children by normalizing the aberrant connections within and between neural circuits. NF exploits the brain's plasticity to normalize aberrant connectivity patterns apparent in the autistic brain. By grounding this training in known anatomical (e.g., mirror neuron system) and functional markers (e.g., mu rhythms) of autism, NF training holds promise to support current treatments for this complex disorder. The proposed hypothesis specifically states that neurofeedback-induced alpha mu (8-12Hz) rhythm suppression or desynchronization, a marker of cortical activation, should induce neuroplastic changes and lead to normalization in relevant mirroring networks that have been associated with higher-order social cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.

A massively asynchronous, parallel brain

PubMed Central

Zeki, Semir

2015-01-01

Whether the visual brain uses a parallel or a serial, hierarchical, strategy to process visual signals, the end result appears to be that different attributes of the visual scene are perceived asynchronously—with colour leading form (orientation) by 40 ms and direction of motion by about 80 ms. Whatever the neural root of this asynchrony, it creates a problem that has not been properly addressed, namely how visual attributes that are perceived asynchronously over brief time windows after stimulus onset are bound together in the longer term to give us a unified experience of the visual world, in which all attributes are apparently seen in perfect registration. In this review, I suggest that there is no central neural clock in the (visual) brain that synchronizes the activity of different processing systems. More likely, activity in each of the parallel processing-perceptual systems of the visual brain is reset independently, making of the brain a massively asynchronous organ, just like the new generation of more efficient computers promise to be. Given the asynchronous operations of the brain, it is likely that the results of activities in the different processing-perceptual systems are not bound by physiological interactions between cells in the specialized visual areas, but post-perceptually, outside the visual brain. PMID:25823871

Molecular mechanisms of cryptococcal meningitis

PubMed Central

Liu, Tong-Bao; Perlin, David; Xue, Chaoyang

2012-01-01

Fungal meningitis is a serious disease caused by a fungal infection of the central nervous system (CNS) mostly in individuals with immune system deficiencies. Fungal meningitis is often fatal without proper treatment, and the mortality rate remains unacceptably high even with antifungal drug interventions. Currently, cryptococcal meningitis is the most common fungal meningitis in HIV-1/AIDS, and its disease mechanism has been extensively studied. The key steps for fungi to infect brain and cause meningitis after establishment of local infection are the dissemination of fungal cells to the bloodstream and invasion through the blood brain barrier to reach the CNS. In this review, we use cryptococcal CNS infection as an example to describe the current molecular understanding of fungal meningitis, including the establishment of the infection, dissemination, and brain invasion. Host and microbial factors that contribute to these infection steps are also discussed. PMID:22460646

The hidden side of drug action: Brain temperature changes induced by neuroactive drugs

PubMed Central

Kiyatkin, Eugene A.

2013-01-01

Rationale Most neuroactive drugs affect brain metabolism as well as systemic and cerebral blood flow, thus altering brain temperature. Although this aspect of drug action usually remains in the shadows, drug-induced alterations in brain temperature reflect their metabolic neural effects and affect neural activity and neural functions. Objectives Here, I review brain temperature changes induced by neuroactive drugs, which are used therapeutically (general anesthetics), as a research tool (dopamine agonists and antagonists), and self-administered to induce desired psychic effects (cocaine, methamphetamine, ecstasy). I consider the mechanisms underlying these temperature fluctuations and their influence on neural, physiological, and behavioral effects of these drugs. Results By interacting with neural mechanisms regulating metabolic activity and heat exchange between the brain and the rest of the body, neuroactive drugs either increase or decrease brain temperatures both within (35-39°C) and exceeding the range of physiological fluctuations. These temperature effects differ drastically depending upon the environmental conditions and activity state during drug administration. This state-dependence is especially important for drugs of abuse that are usually taken by humans during psycho-physiological activation and in environments that prevent proper heat dissipation from the brain. Under these conditions, amphetamine-like stimulants induce pathological brain hyperthermia (>40°C) associated with leakage of the blood-brain barrier and structural abnormalities of brain cells. Conclusions The knowledge on brain temperature fluctuations induced by neuroactive drugs provides new information to understand how they influence metabolic neural activity, why their effects depend upon the behavioral context of administration, and the mechanisms underlying adverse drug effects including neurotoxicity PMID:23274506

The Blood–Brain Barrier

PubMed Central

Daneman, Richard; Prat, Alexandre

2015-01-01

Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood–brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease. PMID:25561720

Brain MRI analysis for Alzheimer's disease diagnosis using an ensemble system of deep convolutional neural networks.

PubMed

Islam, Jyoti; Zhang, Yanqing

2018-05-31

Alzheimer's disease is an incurable, progressive neurological brain disorder. Earlier detection of Alzheimer's disease can help with proper treatment and prevent brain tissue damage. Several statistical and machine learning models have been exploited by researchers for Alzheimer's disease diagnosis. Analyzing magnetic resonance imaging (MRI) is a common practice for Alzheimer's disease diagnosis in clinical research. Detection of Alzheimer's disease is exacting due to the similarity in Alzheimer's disease MRI data and standard healthy MRI data of older people. Recently, advanced deep learning techniques have successfully demonstrated human-level performance in numerous fields including medical image analysis. We propose a deep convolutional neural network for Alzheimer's disease diagnosis using brain MRI data analysis. While most of the existing approaches perform binary classification, our model can identify different stages of Alzheimer's disease and obtains superior performance for early-stage diagnosis. We conducted ample experiments to demonstrate that our proposed model outperformed comparative baselines on the Open Access Series of Imaging Studies dataset.

What happens to your brain on the way to Mars.

PubMed

Parihar, Vipan K; Allen, Barrett; Tran, Katherine K; Macaraeg, Trisha G; Chu, Esther M; Kwok, Stephanie F; Chmielewski, Nicole N; Craver, Brianna M; Baulch, Janet E; Acharya, Munjal M; Cucinotta, Francis A; Limoli, Charles L

2015-05-01

As NASA prepares for the first manned spaceflight to Mars, questions have surfaced concerning the potential for increased risks associated with exposure to the spectrum of highly energetic nuclei that comprise galactic cosmic rays. Animal models have revealed an unexpected sensitivity of mature neurons in the brain to charged particles found in space. Astronaut autonomy during long-term space travel is particularly critical as is the need to properly manage planned and unanticipated events, activities that could be compromised by accumulating particle traversals through the brain. Using mice subjected to space-relevant fluences of charged particles, we show significant cortical- and hippocampal-based performance decrements 6 weeks after acute exposure. Animals manifesting cognitive decrements exhibited marked and persistent radiation-induced reductions in dendritic complexity and spine density along medial prefrontal cortical neurons known to mediate neurotransmission specifically interrogated by our behavioral tasks. Significant increases in postsynaptic density protein 95 (PSD-95) revealed major radiation-induced alterations in synaptic integrity. Impaired behavioral performance of individual animals correlated significantly with reduced spine density and trended with increased synaptic puncta, thereby providing quantitative measures of risk for developing cognitive decrements. Our data indicate an unexpected and unique susceptibility of the central nervous system to space radiation exposure, and argue that the underlying radiation sensitivity of delicate neuronal structure may well predispose astronauts to unintended mission-critical performance decrements and/or longer-term neurocognitive sequelae.

Perinatal choline deficiency delays brain development and alters metabolite concentrations in the young pig.

PubMed

Mudd, Austin T; Getty, Caitlyn M; Sutton, Brad P; Dilger, Ryan N

2016-12-01

Adequate choline supply during the perinatal period is critical for proper brain formation, when robust neurogenesis and neuronal maturation occur. Therefore, the objective of this study was to examine the impact of perinatal choline status on neurodevelopment. Sows were fed a choline-deficient (CD) or choline-sufficient (CS) diet during the last half of the gestational period. At 2 days of age, piglets from sows within each prenatal treatment group were further stratified into postnatal treatment groups and provided either a CD or CS milk replacer, resulting in four treatment groups. At 30 days of age, piglets underwent magnetic resonance imaging (MRI) procedures to analyze structural and metabolite differences. Single-voxel spectroscopy (SVS) analysis revealed postnatally CS piglets had higher (P < 0.001) concentrations of glycerophosphocholine-phosphocholine than postnatally CD piglets. Volumetric analysis indicated smaller (P < 0.006) total brain volumes in prenatally CD piglets compared with prenatally CS piglets. Differences (P < 0.05) in the corpus callosum, pons, midbrain, thalamus, and right hippocampus, were observed as larger region-specific volumes proportional to total brain size in prenatally CD piglets compared with CS piglets. Diffusion tensor imaging (DTI) suggested interactions (P < 0.05) between prenatal and postnatal choline status in fractional anisotropy values of the thalamus and right hippocampus. Prenatally CS piglets had lower cerebellar radial diffusivity (P = 0.045) compared with prenatally CD piglets. This study demonstrates that prenatal choline deficiency has profound effects by delaying neurodevelopment as evidenced by structural and metabolic MRI assessments.

The Korean Spinal Neurosurgery Society ; Are We Reimbursed Properly for Spinal Neurosurgical Practices under the Korean Resource Based Relative Value Scale Service?

PubMed Central

Kwon, Woo-Keun; Kim, Joo Han; Moon, Hong Joo; Park, Youn-Kwan

2017-01-01

Objectives The Korean Resource Based Relative Value Scale (K-RBRVS) was introduced in 2001 as an alternative of the previous medical fee schedule. Unfortunately, most neurosurgeons are unfamiliar with the details of the K-RBRVS and how it affects the reimbursement rates for the surgical procedures we perform. We summarize the K-RBRVS in brief, and discuss on how the relative value (RV) of the spinal neurosurgical procedures have changed since the introduction in 2001. Methods We analyzed the change of spinal procedure RVs since 2001, and compared it with the change of values in the brain neurosurgical procedures. RVs of 88 neurospinal procedures on the list of K-RBRVS were analyzed, while 24 procedures added during annual revisions were excluded. Results During the past 15 years, RVs for spinal procedures have increased 62.8%, which is not so different with the cumulative increase of consumer prices during this time period or the increase rate of 92.3% for brain surgeries. When comparing the change of RVs in more complex procedures between spinal and brain neurosurgery, the increase rate was 125.3% and 133%, respectively. Conclusion More effort of the society of spinal surgeons seems to be needed to get adequate reimbursement, as there have been some discrimination compared to brain surgeons in the increase of RVs. And considering the relative underestimation of spinal neurosurgeons’ labor, more objective measures of neurospinal surgeons’ work and productivity should be developed for impartial reimbursement. PMID:28061492

TMOD-05. MOLECULAR CHARACTERIZATION OF ORTHOTOPIC PATIENT-DERIVED XENOGRAFT MODELS OF PEDIATRIC BRAIN TUMORS AND THEIR USE IN PRECLINICAL EXPERIMENTS

PubMed Central

Brabetz, Sebastian; Schmidt, Christin; Groebner, Susanne N.; Mack, Norman; Seker-Cin, Huriye; Jones, David T.W.; Chavez, Lukas; Milde, Till; Witt, Olaf; Leary, Sarah E.; Li, Xiao-Nan; Wechsler-Reya, Robert J.; Olson, James M.; Pfister, Stefan M.; Kool, Marcel

2017-01-01

Abstract Genomic studies have shown that multiple molecular subtypes of pediatric brain tumors exist that are biologically and clinically highly distinct. These findings ask for novel subtype specific treatments. To develop these we need more and better preclinical models that correctly reflect the proper tumor (sub)type. Orthotopic patient-derived xenograft (PDX) models generated by intracranial injection of primary patient material into the brain of NSG mice offer the unique possibility to test novel substances in primary patient tissue in an in vivo environment. Prior to drug selection and testing, extensive molecular characterizations of PDX and matching primary tumor/blood (DNA methylation, DNA sequencing, and gene expression) are needed to see how the PDX represents the original disease and to learn about targetable oncogenic drivers in each model. In collaboration with several groups around the world we have generated and fully characterized thus far 75 PDX models reflecting 15 distinct subtypes of pediatric brain cancer. PDX models always retain their molecular subtype and in the vast majority of cases also mutations and copy number alterations compared to matching primary tumors. Most aggressive tumors, harboring MYC(N) amplifications, are overrepresented in the cohort, but also subtypes which have not been available for preclinical testing before due to lack of genetically engineered mouse models or suitable cell lines, such as Group 4 medulloblastoma, are included. All models and corresponding molecular data will become available for the community for preclinical research. Examples of such preclinical experiments will be presented. PDX models of pediatric brain tumors are still quite rare. Our repertoire of PDX models and corresponding molecular characterizations allow researchers all over the world to find the right models for their specific scientific questions. It will provide an unprecedented resource to study tumor biology and pave the way for improving treatment strategies for children with malignant brain tumors.

Say It with Flowers! An fMRI Study of Object Mediated Communication

ERIC Educational Resources Information Center

Tylen, Kristian; Wallentin, Mikkel; Roepstorff, Andreas

2009-01-01

Human communicational interaction can be mediated by a host of expressive means from words in a natural language to gestures and material symbols. Given the proper contextual setting even an everyday object can gain a mediating function in a communicational situation. In this study we used event-related fMRI to study the brain activity caused by…

BAD Modulates Counterregulatory Responses to Hypoglycemia and Protective Glucoprivic Feeding

PubMed Central

Osundiji, Mayowa A.; Godes, Marina L.; Evans, Mark L.; Danial, Nika N.

2011-01-01

Hypoglycemia or glucoprivation triggers protective hormonal counterregulatory and feeding responses to aid the restoration of normoglycemia. Increasing evidence suggests pertinent roles for the brain in sensing glucoprivation and mediating counterregulation, however, the precise nature of the metabolic signals and molecular mediators linking central glucose sensing to effector functions are not fully understood. Here, we demonstrate that protective hormonal and feeding responses to hypoglycemia are regulated by BAD, a BCL-2 family protein with dual functions in apoptosis and metabolism. BAD-deficient mice display impaired glycemic and hormonal counterregulatory responses to systemic glucoprivation induced by 2-deoxy-D-glucose. BAD is also required for proper counterregulatory responses to insulin-induced hypoglycemia as evident from significantly higher glucose infusion rates and lower plasma epinephrine levels during hyperinsulinemic hypoglycemic clamps. Importantly, RNA interference-mediated acute knockdown of Bad in the brain provided independent genetic evidence for its relevance in central glucose sensing and proper neurohumoral responses to glucoprivation. Moreover, BAD deficiency is associated with impaired glucoprivic feeding, suggesting that its role in adaptive responses to hypoglycemia extends beyond hormonal responses to regulation of feeding behavior. Together, these data indicate a previously unappreciated role for BAD in the control of central glucose sensing. PMID:22162752

Maintaining the proper connection between the centrioles and the pericentriolar matrix requires Drosophila centrosomin.

PubMed

Lucas, Eliana P; Raff, Jordan W

2007-08-27

Centrosomes consist of two centrioles surrounded by an amorphous pericentriolar matrix (PCM), but it is unknown how centrioles and PCM are connected. We show that the centrioles in Drosophila embryos that lack the centrosomal protein Centrosomin (Cnn) can recruit PCM components but cannot maintain a proper attachment to the PCM. As a result, the centrioles "rocket" around in the embryo and often lose their connection to the nucleus in interphase and to the spindle poles in mitosis. This leads to severe mitotic defects in embryos and to errors in centriole segregation in somatic cells. The Cnn-related protein CDK5RAP2 is linked to microcephaly in humans, but cnn mutant brains are of normal size, and we observe only subtle defects in the asymmetric divisions of mutant neuroblasts. We conclude that Cnn maintains the proper connection between the centrioles and the PCM; this connection is required for accurate centriole segregation in somatic cells but is not essential for the asymmetric division of neuroblasts.

Dissecting out conscious and unconscious memory (sub)processes within the human medial temporal lobe.

PubMed

Grunwald, T; Pezer, N; Münte, T F; Kurthen, M; Lehnertz, K; Van Roost, D; Fernández, G; Kutas, M; Elger, C E

2003-11-01

The human medial temporal lobe (MTL) system mediates memories that can be consciously recollected. However, the specific natures of the individual contributions of its various subregions to conscious memory processes remain equivocal. Here we show a functional dissociation between the hippocampus proper and the parahippocampal region in conscious and unconscious memory as revealed by invasive recordings of limbic event-related brain potentials recorded during explicit and implicit word recognition: Only hippocampal and not parahippocampal neural activity exhibits a sensitivity to the implicit versus explicit nature of the recognition memory task. Moreover, only within the hippocampus proper do the neural responses to repeated words differ not only from those to new words but also from each other as a function of recognition success. By contrast parahippocampal (rhinal) responses are sensitive to repetition independent of conscious recognition. These findings thus demonstrate that it is the hippocampus proper among the MTL structures that is specifically engaged during conscious memory processes.

Maternal Dietary Choline Status Influences Brain Gray and White Matter Development in Young Pigs

PubMed Central

Mudd, Austin T; Getty, Caitlyn M; Dilger, Ryan N

2018-01-01

Abstract Background Choline is an essential nutrient that is pivotal to proper brain development. Research in animal models suggests that perinatal choline deficiency influences neuron development in the hippocampus and cortex, yet these observations require invasive techniques. Objective This study aimed to characterize the effects of perinatal choline deficiency on gray and white matter development with the use of noninvasive neuroimaging techniques in young pigs. Methods During the last 64 d of the 114-d gestation period Yorkshire sows were provided with a choline-sufficient (CS) or choline-deficient (CD) diet, analyzed to contain 1214 mg or 483 mg total choline/kg diet, respectively. Upon farrowing, pigs (Sus scrofa domesticus) were allowed colostrum consumption for ≤48 h, were further stratified into postnatal treatment groups, and were provided either CS or CD milk replacers, analyzed to contain 1591 or 518 mg total choline/kg diet, respectively, for 28 d. At 30 d of age, pigs were subjected to MRI procedures to assess brain development. Gray and white matter development was assessed through voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) to assess the effects of prenatal and postnatal dietary choline status. Results VBM analysis indicated that prenatally CS pigs exhibited increased (P < 0.01) gray matter in the left and right cortex compared with prenatally CD pigs. Analysis of white matter indicated that prenatally CS pigs exhibited increased (P < 0.01) white matter in the internal capsule, putamen–globus pallidus, and right cortex compared with prenatally CD pigs. No postnatal effects (P > 0.05) of choline status were noted for VBM analyses of gray and white matter. TBSS also showed no significant effects (P > 0.05) of prenatal or postnatal choline status for diffusion values along white matter tracts. Conclusions Observations from this study suggest that prenatal choline deficiency results in altered cortical gray matter and reduced white matter in the internal capsule and putamen of young pigs. With the use of noninvasive neuroimaging techniques, results from our study indicate that prenatal choline deficiency greatly alters gray and white matter development in pigs, thereby providing a translational assessment that may be used in clinical populations.

Optimized optical clearing method for imaging central nervous system

NASA Astrophysics Data System (ADS)

Yu, Tingting; Qi, Yisong; Gong, Hui; Luo, Qingming; Zhu, Dan

2015-03-01

The development of various optical clearing methods provides a great potential for imaging entire central nervous system by combining with multiple-labelling and microscopic imaging techniques. These methods had made certain clearing contributions with respective weaknesses, including tissue deformation, fluorescence quenching, execution complexity and antibody penetration limitation that makes immunostaining of tissue blocks difficult. The passive clarity technique (PACT) bypasses those problems and clears the samples with simple implementation, excellent transparency with fine fluorescence retention, but the passive tissue clearing method needs too long time. In this study, we not only accelerate the clearing speed of brain blocks but also preserve GFP fluorescence well by screening an optimal clearing temperature. The selection of proper temperature will make PACT more applicable, which evidently broaden the application range of this method.

Human Cytomegalovirus IE2 Protein Disturbs Brain Development by the Dysregulation of Neural Stem Cell Maintenance and the Polarization of Migrating Neurons.

PubMed

Han, Dasol; Byun, Sung-Hyun; Kim, Juwan; Kwon, Mookwang; Pleasure, Samuel J; Ahn, Jin-Hyun; Yoon, Keejung

2017-09-01

Despite the high incidence of severe defects in the central nervous system caused by human cytomegalovirus (HCMV) congenital infection, the mechanism of HCMV neuropathogenesis and the roles of individual viral genes have not yet been fully determined. In this study, we show that the immediate-early 2 (IE2) protein may play a key role in HCMV-caused neurodevelopmental disorders. IE2-transduced neural progenitor cells gave rise to neurospheres with a lower frequency and produced smaller neurospheres than control cells in vitro , indicating reduction of self-renewal and expansion of neural progenitors by IE2. At 2 days after in utero electroporation into the ventricle of the developing brain, a dramatically lower percentage of IE2-expressing cells was detected in the ventricular zone (VZ) and cortical plate (CP) compared to control cells, suggesting that IE2 concurrently dysregulates neural stem cell maintenance in the VZ and neuronal migration to the CP. In addition, most IE2 + cells in the lower intermediate zone either showed multipolar morphology with short neurites or possessed nonradially oriented processes, whereas control cells had long, radially oriented monopolar or bipolar neurites. IE2 + callosal axons also failed to cross the midline to form the corpus callosum. Furthermore, we provide molecular evidence that the cell cycle arrest and DNA binding activities of IE2 appear to be responsible for the increased neural stem cell exit from the VZ and cortical migrational defects, respectively. Collectively, our results demonstrate that IE2 disrupts the orderly process of brain development in a stepwise manner to further our understanding of neurodevelopmental HCMV pathogenesis. IMPORTANCE HCMV brain pathogenesis has been studied in limited experimental settings, such as in vitro HCMV infection of neural progenitor cells or in vivo murine CMV infection of the mouse brain. Here, we show that IE2 is a pivotal factor that contributes to HCMV-induced abnormalities in the context of the embryonic brain using an in utero gene transfer tool. Surprisingly, IE2, but not HCMV IE1 or murine CMV ie3, interferes pleiotropically with key neurodevelopmental processes, including neural stem cell regulation, proper positioning of migrating neurons, and the callosal axon projections important for communication between the hemispheres. Our data suggest that the wide spectrum of clinical outcomes, ranging from mental retardation to microcephaly, caused by congenital HCMV infection can be sufficiently explained in terms of IE2 action alone. Copyright © 2017 American Society for Microbiology.

A probabilistic framework to infer brain functional connectivity from anatomical connections.

PubMed

Deligianni, Fani; Varoquaux, Gael; Thirion, Bertrand; Robinson, Emma; Sharp, David J; Edwards, A David; Rueckert, Daniel

2011-01-01

We present a novel probabilistic framework to learn across several subjects a mapping from brain anatomical connectivity to functional connectivity, i.e. the covariance structure of brain activity. This prediction problem must be formulated as a structured-output learning task, as the predicted parameters are strongly correlated. We introduce a model selection framework based on cross-validation with a parametrization-independent loss function suitable to the manifold of covariance matrices. Our model is based on constraining the conditional independence structure of functional activity by the anatomical connectivity. Subsequently, we learn a linear predictor of a stationary multivariate autoregressive model. This natural parameterization of functional connectivity also enforces the positive-definiteness of the predicted covariance and thus matches the structure of the output space. Our results show that functional connectivity can be explained by anatomical connectivity on a rigorous statistical basis, and that a proper model of functional connectivity is essential to assess this link.

Brain temperature: heat production, elimination and clinical relevance.

PubMed

Bertolizio, Gianluca; Mason, Linda; Bissonnette, Bruno

2011-04-01

Neurological insults are a leading cause of morbidity and mortality, both in adults and especially in children. Among possible therapeutic strategies to limit clinical cerebral damage and improve outcomes, hypothermia remains a promising and beneficial approach. However, its advantages are still debated after decades of use. Studies in adults have generated conflicting results, whereas in children recent data even suggest that hypothermia may be detrimental. Is it because brain temperature physiology is not well understood and/or not applied properly, that hypothermia fails to convince clinicians of its potential benefits? Or is it because hypothermia is not, as believed, the optimal strategy to improve outcome in patients affected with an acute neurological insult? This review article should help to explain the fundamental physiological principles of brain heat production, distribution and elimination under normal conditions and discuss why hypothermia cannot yet be recommended routinely in the management of children affected with various neurological insults. © 2011 Blackwell Publishing Ltd.

Cortical Development Requires Mesodermal Expression of Tbx1, a Gene Haploinsufficient in 22q11.2 Deletion Syndrome.

PubMed

Flore, Gemma; Cioffi, Sara; Bilio, Marchesa; Illingworth, Elizabeth

2017-03-01

In mammals, proper temporal control of neurogenesis and neural migration during embryonic development ensures correct formation of the cerebral cortex. Changes in the distribution of cortical projection neurons and interneurons are associated with behavioral disorders and psychiatric diseases, including schizophrenia and autism, suggesting that disrupted cortical connectivity contributes to the brain pathology. TBX1 is the major candidate gene for 22q11.2 deletion syndrome (22q11.2DS), a chromosomal deletion disorder characterized by a greatly increased risk for schizophrenia. We have previously shown that Tbx1 heterozygous mice have reduced prepulse inhibition, a behavioral abnormality that is associated with 22q11.2DS and nonsyndromic schizophrenia. Here, we show that loss of Tbx1 disrupts corticogenesis in mice by promoting premature neuronal differentiation in the medio-lateral embryonic cortex, which gives rise to the somatosensory cortex (S1). In addition, we found altered polarity in both radially migrating excitatory neurons and tangentially migrating inhibitory interneurons. Together, these abnormalities lead to altered lamination in the S1 at the terminal stages of corticogenesis in Tbx1 null mice and similar anomalies in Tbx1 heterozygous adult mice. Finally, we show that mesoderm-specific inactivation of Tbx1 is sufficient to recapitulate the brain phenotype indicating that Tbx1 exerts a cell nonautonomous role in cortical development from the mesoderm. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Brain Training in Children and Adolescents: Is It Scientifically Valid?

PubMed

Rossignoli-Palomeque, Teresa; Perez-Hernandez, Elena; González-Marqués, Javier

2018-01-01

Background: Brain training products are becoming increasingly popular for children and adolescents. Despite the marketing aimed at their use in the general population, these products may provide more benefits for specific neurologically impaired populations. A review of Brain Training (BT) products analyzing their efficacy while considering the methodological limitations of supporting research is required for practical applications. Method: searches were made of the PubMed database (until March 2017) for studies including: (1) empirical data on the use of brain training for children or adolescents and any effects on near transfer (NT) and/or far transfer (FT) and/or neuroplasticity, (2) use of brain training for cognitive training purposes, (3) commercially available training applications, (4) computer-based programs for children developed since the 1990s, and (5) relevant printed and peer-reviewed material. Results: Database searches yielded a total of 16,402 references, of which 70 met the inclusion criteria for the review. We classified programs in terms of neuroplasticity, near and far transfer, and long-term effects and their applied methodology. Regarding efficacy, only 10 studies (14.2%) have been found that support neuroplasticity, and the majority of brain training platforms claimed to be based on such concepts without providing any supporting scientific data. Thirty-six studies (51.4%) have shown far transfer (7 of them are non-independent) and only 11 (15.7%) maintained far transfer at follow-up. Considering the methodology, 40 studies (68.2%) were not randomized and controlled; for those randomized, only 9 studies (12.9%) were double-blind, and only 13 studies (18.6%) included active controls in their trials. Conclusion: Overall, few independent studies have found far transfer and long-term effects. The majority of independent results found only near transfer. There is a lack of double-blind randomized trials which include an active control group as well as a passive control to properly control for contaminant variables. Based on our results, Brain Training Programs as commercially available products are not as effective as first expected or as they promise in their advertisements.

Brain Training in Children and Adolescents: Is It Scientifically Valid?

PubMed Central

Rossignoli-Palomeque, Teresa; Perez-Hernandez, Elena; González-Marqués, Javier

2018-01-01

Background: Brain training products are becoming increasingly popular for children and adolescents. Despite the marketing aimed at their use in the general population, these products may provide more benefits for specific neurologically impaired populations. A review of Brain Training (BT) products analyzing their efficacy while considering the methodological limitations of supporting research is required for practical applications. Method: searches were made of the PubMed database (until March 2017) for studies including: (1) empirical data on the use of brain training for children or adolescents and any effects on near transfer (NT) and/or far transfer (FT) and/or neuroplasticity, (2) use of brain training for cognitive training purposes, (3) commercially available training applications, (4) computer-based programs for children developed since the 1990s, and (5) relevant printed and peer-reviewed material. Results: Database searches yielded a total of 16,402 references, of which 70 met the inclusion criteria for the review. We classified programs in terms of neuroplasticity, near and far transfer, and long-term effects and their applied methodology. Regarding efficacy, only 10 studies (14.2%) have been found that support neuroplasticity, and the majority of brain training platforms claimed to be based on such concepts without providing any supporting scientific data. Thirty-six studies (51.4%) have shown far transfer (7 of them are non-independent) and only 11 (15.7%) maintained far transfer at follow-up. Considering the methodology, 40 studies (68.2%) were not randomized and controlled; for those randomized, only 9 studies (12.9%) were double-blind, and only 13 studies (18.6%) included active controls in their trials. Conclusion: Overall, few independent studies have found far transfer and long-term effects. The majority of independent results found only near transfer. There is a lack of double-blind randomized trials which include an active control group as well as a passive control to properly control for contaminant variables. Based on our results, Brain Training Programs as commercially available products are not as effective as first expected or as they promise in their advertisements. PMID:29780336

[Some ethical considerations, especially identity, during xenotransplantation].

PubMed

Cüer, P

2000-05-01

Provided that a pandemic due to retroviruses or prions eventually transmitted by animals is under control, in accordance with the fundamental ethical rule to serve the best interest of the patient, any organ xenotransplantation raises an important ethical dilemma: how to deliver proper and adapted information to the patient on the preservation of his identity. Xenotransplantation of any part of the brain seems to us unethical.

Fully automated tumor segmentation based on improved fuzzy connectedness algorithm in brain MR images.

PubMed

Harati, Vida; Khayati, Rasoul; Farzan, Abdolreza

2011-07-01

Uncontrollable and unlimited cell growth leads to tumor genesis in the brain. If brain tumors are not diagnosed early and cured properly, they could cause permanent brain damage or even death to patients. As in all methods of treatments, any information about tumor position and size is important for successful treatment; hence, finding an accurate and a fully automated method to give information to physicians is necessary. A fully automatic and accurate method for tumor region detection and segmentation in brain magnetic resonance (MR) images is suggested. The presented approach is an improved fuzzy connectedness (FC) algorithm based on a scale in which the seed point is selected automatically. This algorithm is independent of the tumor type in terms of its pixels intensity. Tumor segmentation evaluation results based on similarity criteria (similarity index (SI), overlap fraction (OF), and extra fraction (EF) are 92.89%, 91.75%, and 3.95%, respectively) indicate a higher performance of the proposed approach compared to the conventional methods, especially in MR images, in tumor regions with low contrast. Thus, the suggested method is useful for increasing the ability of automatic estimation of tumor size and position in brain tissues, which provides more accurate investigation of the required surgery, chemotherapy, and radiotherapy procedures. Copyright © 2011 Elsevier Ltd. All rights reserved.

Deep Independence Network Analysis of Structural Brain Imaging: Application to Schizophrenia

PubMed Central

Castro, Eduardo; Hjelm, R. Devon; Plis, Sergey M.; Dinh, Laurent; Turner, Jessica A.; Calhoun, Vince D.

2016-01-01

Linear independent component analysis (ICA) is a standard signal processing technique that has been extensively used on neuroimaging data to detect brain networks with coherent brain activity (functional MRI) or covarying structural patterns (structural MRI). However, its formulation assumes that the measured brain signals are generated by a linear mixture of the underlying brain networks and this assumption limits its ability to detect the inherent nonlinear nature of brain interactions. In this paper, we introduce nonlinear independent component estimation (NICE) to structural MRI data to detect abnormal patterns of gray matter concentration in schizophrenia patients. For this biomedical application, we further addressed the issue of model regularization of nonlinear ICA by performing dimensionality reduction prior to NICE, together with an appropriate control of the complexity of the model and the usage of a proper approximation of the probability distribution functions of the estimated components. We show that our results are consistent with previous findings in the literature, but we also demonstrate that the incorporation of nonlinear associations in the data enables the detection of spatial patterns that are not identified by linear ICA. Specifically, we show networks including basal ganglia, cerebellum and thalamus that show significant differences in patients versus controls, some of which show distinct nonlinear patterns. PMID:26891483

A Consensus Network of Gene Regulatory Factors in the Human Frontal Lobe

PubMed Central

Berto, Stefano; Perdomo-Sabogal, Alvaro; Gerighausen, Daniel; Qin, Jing; Nowick, Katja

2016-01-01

Cognitive abilities, such as memory, learning, language, problem solving, and planning, involve the frontal lobe and other brain areas. Not much is known yet about the molecular basis of cognitive abilities, but it seems clear that cognitive abilities are determined by the interplay of many genes. One approach for analyzing the genetic networks involved in cognitive functions is to study the coexpression networks of genes with known importance for proper cognitive functions, such as genes that have been associated with cognitive disorders like intellectual disability (ID) or autism spectrum disorders (ASD). Because many of these genes are gene regulatory factors (GRFs) we aimed to provide insights into the gene regulatory networks active in the human frontal lobe. Using genome wide human frontal lobe expression data from 10 independent data sets, we first derived 10 individual coexpression networks for all GRFs including their potential target genes. We observed a high level of variability among these 10 independently derived networks, pointing out that relying on results from a single study can only provide limited biological insights. To instead focus on the most confident information from these 10 networks we developed a method for integrating such independently derived networks into a consensus network. This consensus network revealed robust GRF interactions that are conserved across the frontal lobes of different healthy human individuals. Within this network, we detected a strong central module that is enriched for 166 GRFs known to be involved in brain development and/or cognitive disorders. Interestingly, several hubs of the consensus network encode for GRFs that have not yet been associated with brain functions. Their central role in the network suggests them as excellent new candidates for playing an essential role in the regulatory network of the human frontal lobe, which should be investigated in future studies. PMID:27014338

Cdk5 Regulates Activity-Dependent Gene Expression and Dendrite Development.

PubMed

Liang, Zhuoyi; Ye, Tao; Zhou, Xiaopu; Lai, Kwok-On; Fu, Amy K Y; Ip, Nancy Y

2015-11-11

The proper growth and arborization of dendrites in response to sensory experience are essential for neural connectivity and information processing in the brain. Although neuronal activity is important for sculpting dendrite morphology, the underlying molecular mechanisms are not well understood. Here, we report that cyclin-dependent kinase 5 (Cdk5)-mediated transcriptional regulation is a key mechanism that controls activity-dependent dendrite development in cultured rat neurons. During membrane depolarization, Cdk5 accumulates in the nucleus to regulate the expression of a subset of genes, including that of the neurotrophin brain-derived neurotrophic factor, for subsequent dendritic growth. Furthermore, Cdk5 function is mediated through the phosphorylation of methyl-CpG-binding protein 2, a key transcriptional repressor that is mutated in the mental disorder Rett syndrome. These findings collectively suggest that the nuclear import of Cdk5 is crucial for activity-dependent dendrite development by regulating neuronal gene transcription during neural development. Neural activity directs dendrite development through the regulation of gene transcription. However, how molecular signals link extracellular stimuli to the transcriptional program in the nucleus remains unclear. Here, we demonstrate that neuronal activity stimulates the translocation of the kinase Cdk5 from the cytoplasmic compartment into the nucleus; furthermore, the nuclear localization of Cdk5 is required for dendrite development in cultured neurons. Genome-wide transcriptome analysis shows that Cdk5 deficiency specifically disrupts activity-dependent gene transcription of bdnf. The action of Cdk5 is mediated through the modulation of the transcriptional repressor methyl-CpG-binding protein 2. Therefore, this study elucidates the role of nuclear Cdk5 in the regulation of activity-dependent gene transcription and dendritic growth. Copyright © 2015 the authors 0270-6474/15/3515127-08$15.00/0.

Fiber-based tissue identification for electrode placement in deep brain stimulation neurosurgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

DePaoli, Damon T.; Lapointe, Nicolas; Goetz, Laurent; Parent, Martin; Prudhomme, Michel; Cantin, Léo.; Galstian, Tigran; Messaddeq, Younès.; Côté, Daniel C.

2016-03-01

Deep brain stimulation's effectiveness relies on the ability of the stimulating electrode to be properly placed within a specific target area of the brain. Optical guidance techniques that can increase the accuracy of the procedure, without causing any additional harm, are therefore of great interest. We have designed a cheap optical fiber-based device that is small enough to be placed within commercially available DBS stimulating electrodes' hollow cores and that is capable of sensing biological information from the surrounding tissue, using low power white light. With this probe we have shown the ability to distinguish white and grey matter as well as blood vessels, in vitro, in human brain samples and in vivo, in rats. We have also repeated the in vitro procedure with the probe inserted in a DBS stimulating electrode and found the results were in good agreement. We are currently validating a second fiber optic device, with micro-optical components, that will result in label free, molecular level sensing capabilities, using CARS spectroscopy. The final objective will be to use this data in real time, during deep brain stimulation neurosurgery, to increase the safety and accuracy of the procedure.

Current technical approaches to brain energy metabolism.

PubMed

Barros, L Felipe; Bolaños, Juan P; Bonvento, Gilles; Bouzier-Sore, Anne-Karine; Brown, Angus; Hirrlinger, Johannes; Kasparov, Sergey; Kirchhoff, Frank; Murphy, Anne N; Pellerin, Luc; Robinson, Michael B; Weber, Bruno

2018-06-01

Neuroscience is a technology-driven discipline and brain energy metabolism is no exception. Once satisfied with mapping metabolic pathways at organ level, we are now looking to learn what it is exactly that metabolic enzymes and transporters do and when, where do they reside, how are they regulated, and how do they relate to the specific functions of neurons, glial cells, and their subcellular domains and organelles, in different areas of the brain. Moreover, we aim to quantify the fluxes of metabolites within and between cells. Energy metabolism is not just a necessity for proper cell function and viability but plays specific roles in higher brain functions such as memory processing and behavior, whose mechanisms need to be understood at all hierarchical levels, from isolated proteins to whole subjects, in both health and disease. To this aim, the field takes advantage of diverse disciplines including anatomy, histology, physiology, biochemistry, bioenergetics, cellular biology, molecular biology, developmental biology, neurology, and mathematical modeling. This article presents a well-referenced synopsis of the technical side of brain energy metabolism research. Detail and jargon are avoided whenever possible and emphasis is given to comparative strengths, limitations, and weaknesses, information that is often not available in regular articles. © 2017 Wiley Periodicals, Inc.

Post-Activation Brain Warming: A 1-H MRS Thermometry Study

PubMed Central

Rango, Mario; Bonifati, Cristiana; Bresolin, Nereo

2015-01-01

Purpose Temperature plays a fundamental role for the proper functioning of the brain. However, there are only fragmentary data on brain temperature (Tbr) and its regulation under different physiological conditions. Methods We studied Tbr in the visual cortex of 20 normal subjects serially with a wide temporal window under different states including rest, activation and recovery by a visual stimulation-Magnetic Resonance Spectroscopy Thermometry combined approach. We also studied Tbr in a control region, the centrum semiovale, under the same conditions. Results Visual cortex mean baseline Tbr was higher than mean body temperature (37.38 vs 36.60, P<0.001). During activation Tbr remained unchanged at first and then showed a small decrease (-0.20 C°) around the baseline value. After the end of activation Tbr increased consistently (+0.60 C°) and then returned to baseline values after some minutes. Centrum semiovale Tbr remained unchanged through rest, visual stimulation and recovery. Conclusion These findings have several implications, among them that neuronal firing itself is not a major source of heat release in the brain and that there is an aftermath of brain activation that lasts minutes before returning to baseline conditions. PMID:26011731

Prediction of brain-computer interface aptitude from individual brain structure.

PubMed

Halder, S; Varkuti, B; Bogdan, M; Kübler, A; Rosenstiel, W; Sitaram, R; Birbaumer, N

2013-01-01

Brain-computer interface (BCI) provide a non-muscular communication channel for patients with impairments of the motor system. A significant number of BCI users is unable to obtain voluntary control of a BCI-system in proper time. This makes methods that can be used to determine the aptitude of a user necessary. We hypothesized that integrity and connectivity of involved white matter connections may serve as a predictor of individual BCI-performance. Therefore, we analyzed structural data from anatomical scans and DTI of motor imagery BCI-users differentiated into high and low BCI-aptitude groups based on their overall performance. Using a machine learning classification method we identified discriminating structural brain trait features and correlated the best features with a continuous measure of individual BCI-performance. Prediction of the aptitude group of each participant was possible with near perfect accuracy (one error). Tissue volumetric analysis yielded only poor classification results. In contrast, the structural integrity and myelination quality of deep white matter structures such as the Corpus Callosum, Cingulum, and Superior Fronto-Occipital Fascicle were positively correlated with individual BCI-performance. This confirms that structural brain traits contribute to individual performance in BCI use.

Prediction of brain-computer interface aptitude from individual brain structure

PubMed Central

Halder, S.; Varkuti, B.; Bogdan, M.; Kübler, A.; Rosenstiel, W.; Sitaram, R.; Birbaumer, N.

2013-01-01

Objective: Brain-computer interface (BCI) provide a non-muscular communication channel for patients with impairments of the motor system. A significant number of BCI users is unable to obtain voluntary control of a BCI-system in proper time. This makes methods that can be used to determine the aptitude of a user necessary. Methods: We hypothesized that integrity and connectivity of involved white matter connections may serve as a predictor of individual BCI-performance. Therefore, we analyzed structural data from anatomical scans and DTI of motor imagery BCI-users differentiated into high and low BCI-aptitude groups based on their overall performance. Results: Using a machine learning classification method we identified discriminating structural brain trait features and correlated the best features with a continuous measure of individual BCI-performance. Prediction of the aptitude group of each participant was possible with near perfect accuracy (one error). Conclusions: Tissue volumetric analysis yielded only poor classification results. In contrast, the structural integrity and myelination quality of deep white matter structures such as the Corpus Callosum, Cingulum, and Superior Fronto-Occipital Fascicle were positively correlated with individual BCI-performance. Significance: This confirms that structural brain traits contribute to individual performance in BCI use. PMID:23565083

A topological approach unveils system invariances and broken symmetries in the brain.

PubMed

Tozzi, Arturo; Peters, James F

2016-05-01

Symmetries are widespread invariances underscoring countless systems, including the brain. A symmetry break occurs when the symmetry is present at one level of observation but is hidden at another level. In such a general framework, a concept from algebraic topology, namely, the Borsuk-Ulam theorem (BUT), comes into play and sheds new light on the general mechanisms of nervous symmetries. The BUT tells us that we can find, on an n-dimensional sphere, a pair of opposite points that have the same encoding on an n - 1 sphere. This mapping makes it possible to describe both antipodal points with a single real-valued vector on a lower dimensional sphere. Here we argue that this topological approach is useful for the evaluation of hidden nervous symmetries. This means that symmetries can be found when evaluating the brain in a proper dimension, although they disappear (are hidden or broken) when we evaluate the same brain only one dimension lower. In conclusion, we provide a topological methodology for the evaluation of the most general features of brain activity, i.e., the symmetries, cast in a physical/biological fashion that has the potential to be operationalized. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Implanted Miniaturized Antenna for Brain Computer Interface Applications: Analysis and Design

PubMed Central

Zhao, Yujuan; Rennaker, Robert L.; Hutchens, Chris; Ibrahim, Tamer S.

2014-01-01

Implantable Brain Computer Interfaces (BCIs) are designed to provide real-time control signals for prosthetic devices, study brain function, and/or restore sensory information lost as a result of injury or disease. Using Radio Frequency (RF) to wirelessly power a BCI could widely extend the number of applications and increase chronic in-vivo viability. However, due to the limited size and the electromagnetic loss of human brain tissues, implanted miniaturized antennas suffer low radiation efficiency. This work presents simulations, analysis and designs of implanted antennas for a wireless implantable RF-powered brain computer interface application. The results show that thin (on the order of 100 micrometers thickness) biocompatible insulating layers can significantly impact the antenna performance. The proper selection of the dielectric properties of the biocompatible insulating layers and the implantation position inside human brain tissues can facilitate efficient RF power reception by the implanted antenna. While the results show that the effects of the human head shape on implanted antenna performance is somewhat negligible, the constitutive properties of the brain tissues surrounding the implanted antenna can significantly impact the electrical characteristics (input impedance, and operational frequency) of the implanted antenna. Three miniaturized antenna designs are simulated and demonstrate that maximum RF power of up to 1.8 milli-Watts can be received at 2 GHz when the antenna implanted around the dura, without violating the Specific Absorption Rate (SAR) limits. PMID:25079941

Towards the utilization of EEG as a brain imaging tool.

PubMed

Michel, Christoph M; Murray, Micah M

2012-06-01

Recent advances in signal analysis have engendered EEG with the status of a true brain mapping and brain imaging method capable of providing spatio-temporal information regarding brain (dys)function. Because of the increasing interest in the temporal dynamics of brain networks, and because of the straightforward compatibility of the EEG with other brain imaging techniques, EEG is increasingly used in the neuroimaging community. However, the full capability of EEG is highly underestimated. Many combined EEG-fMRI studies use the EEG only as a spike-counter or an oscilloscope. Many cognitive and clinical EEG studies use the EEG still in its traditional way and analyze grapho-elements at certain electrodes and latencies. We here show that this way of using the EEG is not only dangerous because it leads to misinterpretations, but it is also largely ignoring the spatial aspects of the signals. In fact, EEG primarily measures the electric potential field at the scalp surface in the same way as MEG measures the magnetic field. By properly sampling and correctly analyzing this electric field, EEG can provide reliable information about the neuronal activity in the brain and the temporal dynamics of this activity in the millisecond range. This review explains some of these analysis methods and illustrates their potential in clinical and experimental applications. Copyright © 2011 Elsevier Inc. All rights reserved.

The blood-brain barrier: structure, function and therapeutic approaches to cross it.

PubMed

Tajes, Marta; Ramos-Fernández, Eva; Weng-Jiang, Xian; Bosch-Morató, Mònica; Guivernau, Biuse; Eraso-Pichot, Abel; Salvador, Bertrán; Fernàndez-Busquets, Xavier; Roquer, Jaume; Muñoz, Francisco J

2014-08-01

The blood-brain barrier (BBB) is constituted by a specialized vascular endothelium that interacts directly with astrocytes, neurons and pericytes. It protects the brain from the molecules of the systemic circulation but it has to be overcome for the proper treatment of brain cancer, psychiatric disorders or neurodegenerative diseases, which are dramatically increasing as the population ages. In the present work we have revised the current knowledge on the cellular structure of the BBB and the different procedures utilized currently and those proposed to cross it. Chemical modifications of the drugs, such as increasing their lipophilicity, turn them more prone to be internalized in the brain. Other mechanisms are the use of molecular tools to bind the drugs such as small immunoglobulins, liposomes or nanoparticles that will act as Trojan Horses favoring the drug delivery in brain. This fusion of the classical pharmacology with nanotechnology has opened a wide field to many different approaches with promising results to hypothesize that BBB will not be a major problem for the new generation of neuroactive drugs. The present review provides an overview of all state-of-the-art of the BBB structure and function, as well as of the classic strategies and these appeared in recent years to deliver drugs into the brain for the treatment of Central Nervous System (CNS) diseases.

Investigating Neuromagnetic Brain Responses against Chromatic Flickering Stimuli by Wavelet Entropies

PubMed Central

Bhagat, Mayank; Bhushan, Chitresh; Saha, Goutam; Shimjo, Shinsuke; Watanabe, Katsumi; Bhattacharya, Joydeep

2009-01-01

Background Photosensitive epilepsy is a type of reflexive epilepsy triggered by various visual stimuli including colourful ones. Despite the ubiquitous presence of colorful displays, brain responses against different colour combinations are not properly studied. Methodology/Principal Findings Here, we studied the photosensitivity of the human brain against three types of chromatic flickering stimuli by recording neuromagnetic brain responses (magnetoencephalogram, MEG) from nine adult controls, an unmedicated patient, a medicated patient, and two controls age-matched with patients. Dynamical complexities of MEG signals were investigated by a family of wavelet entropies. Wavelet entropy is a newly proposed measure to characterize large scale brain responses, which quantifies the degree of order/disorder associated with a multi-frequency signal response. In particular, we found that as compared to the unmedicated patient, controls showed significantly larger wavelet entropy values. We also found that Renyi entropy is the most powerful feature for the participant classification. Finally, we also demonstrated the effect of combinational chromatic sensitivity on the underlying order/disorder in MEG signals. Conclusions/Significance Our results suggest that when perturbed by potentially epileptic-triggering stimulus, healthy human brain manages to maintain a non-deterministic, possibly nonlinear state, with high degree of disorder, but an epileptic brain represents a highly ordered state which making it prone to hyper-excitation. Further, certain colour combination was found to be more threatening than other combinations. PMID:19779630

Investigating neuromagnetic brain responses against chromatic flickering stimuli by wavelet entropies.

PubMed

Bhagat, Mayank; Bhushan, Chitresh; Saha, Goutam; Shimjo, Shinsuke; Watanabe, Katsumi; Bhattacharya, Joydeep

2009-09-25

Photosensitive epilepsy is a type of reflexive epilepsy triggered by various visual stimuli including colourful ones. Despite the ubiquitous presence of colorful displays, brain responses against different colour combinations are not properly studied. Here, we studied the photosensitivity of the human brain against three types of chromatic flickering stimuli by recording neuromagnetic brain responses (magnetoencephalogram, MEG) from nine adult controls, an unmedicated patient, a medicated patient, and two controls age-matched with patients. Dynamical complexities of MEG signals were investigated by a family of wavelet entropies. Wavelet entropy is a newly proposed measure to characterize large scale brain responses, which quantifies the degree of order/disorder associated with a multi-frequency signal response. In particular, we found that as compared to the unmedicated patient, controls showed significantly larger wavelet entropy values. We also found that Renyi entropy is the most powerful feature for the participant classification. Finally, we also demonstrated the effect of combinational chromatic sensitivity on the underlying order/disorder in MEG signals. Our results suggest that when perturbed by potentially epileptic-triggering stimulus, healthy human brain manages to maintain a non-deterministic, possibly nonlinear state, with high degree of disorder, but an epileptic brain represents a highly ordered state which making it prone to hyper-excitation. Further, certain colour combination was found to be more threatening than other combinations.

What we know and would like to know about CDKL5 and its involvement in epileptic encephalopathy.

PubMed

Kilstrup-Nielsen, Charlotte; Rusconi, Laura; La Montanara, Paolo; Ciceri, Dalila; Bergo, Anna; Bedogni, Francesco; Landsberger, Nicoletta

2012-01-01

In the last few years, the X-linked serine/threonine kinase cyclin-dependent kinase-like 5 (CDKL5) has been associated with early-onset epileptic encephalopathies characterized by the manifestation of intractable epilepsy within the first weeks of life, severe developmental delay, profound hypotonia, and often the presence of some Rett-syndrome-like features. The association of CDKL5 with neurodevelopmental disorders and its high expression levels in the maturing brain underscore the importance of this kinase for proper brain development. However, our present knowledge of CDKL5 functions is still rather limited. The picture that emerges from the molecular and cellular studies suggests that CDKL5 functions are important for regulating both neuronal morphology through cytoplasmic signaling pathways and activity-dependent gene expression in the nuclear compartment. This paper surveys the current state of CDKL5 research with emphasis on the clinical symptoms associated with mutations in CDKL5, the different mechanisms regulating its functions, and the connected molecular pathways. Finally, based on the available data we speculate that CDKL5 might play a role in neuronal plasticity and we adduce and discuss some possible arguments supporting this hypothesis.

What We Know and Would Like to Know about CDKL5 and Its Involvement in Epileptic Encephalopathy

PubMed Central

Kilstrup-Nielsen, Charlotte; Rusconi, Laura; La Montanara, Paolo; Ciceri, Dalila; Bergo, Anna; Bedogni, Francesco; Landsberger, Nicoletta

2012-01-01

In the last few years, the X-linked serine/threonine kinase cyclin-dependent kinase-like 5 (CDKL5) has been associated with early-onset epileptic encephalopathies characterized by the manifestation of intractable epilepsy within the first weeks of life, severe developmental delay, profound hypotonia, and often the presence of some Rett-syndrome-like features. The association of CDKL5 with neurodevelopmental disorders and its high expression levels in the maturing brain underscore the importance of this kinase for proper brain development. However, our present knowledge of CDKL5 functions is still rather limited. The picture that emerges from the molecular and cellular studies suggests that CDKL5 functions are important for regulating both neuronal morphology through cytoplasmic signaling pathways and activity-dependent gene expression in the nuclear compartment. This paper surveys the current state of CDKL5 research with emphasis on the clinical symptoms associated with mutations in CDKL5, the different mechanisms regulating its functions, and the connected molecular pathways. Finally, based on the available data we speculate that CDKL5 might play a role in neuronal plasticity and we adduce and discuss some possible arguments supporting this hypothesis. PMID:22779007

Blood-brain barrier and its function during inflammation and autoimmunity.

PubMed

Sonar, Sandip Ashok; Lal, Girdhari

2018-05-01

The blood-brain barrier (BBB) is an important physiologic barrier that separates CNS from soluble inflammatory mediators and effector immune cells from peripheral circulation. The optimum function of the BBB is necessary for the homeostasis, maintenance, and proper neuronal function. The clinical and experimental findings have shown that BBB dysfunction is an early hallmark of various neurologic disorders ranging from inflammatory autoimmune, neurodegenerative, and traumatic diseases to neuroinvasive infections. Significant progress has been made in the understanding of the regulation of BBB function under homeostatic and neuroinflammatory conditions. Several neurologic disease-modifying drugs have shown to improve the BBB function. However, they have a broad-acting immunomodulatory function and can increase the risk of life-threatening infections. The recent development of in vitro multicomponent 3-dimensional BBB models coupled with fluidics chamber as well as a cell-type specific reporter and knockout mice gave a new boost to our understanding of the dynamics of the BBB. In the review, we discuss the current understanding of BBB composition and recent findings that illustrate the critical regulatory elements of the BBB function under physiologic and inflammatory conditions, and also suggested the strategies to control BBB structure and function. ©2018 Society for Leukocyte Biology.

Resting state activity in patients with disorders of consciousness

PubMed Central

Soddu, Andrea; Vanhaudenhuyse, Audrey; Demertzi, Athena; Bruno, Marie-Aurélie; Tshibanda, Luaba; Di, Haibo; Boly, Mélanie; Papa, Michele; Laureys, Steven; Noirhomme, Quentin

Summary Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of higher-order associative network functionality. Additionally, such advances are argued to be relevant in pathological states, such as disorders of consciousness (DOC), i.e., coma, vegetative and minimally conscious states. Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network. However, the two main approaches employed in the analysis of resting state functional connectivity data (i.e., hypothesis-driven seed-voxel and data-driven independent component analysis) present multiple methodological difficulties, especially in non-collaborative DOC patients. Improvements in motion artifact removal and spatial normalization are needed before fMRI resting state data can be used as proper biomarkers in severe brain injury. However, we anticipate that such developments will boost clinical resting state fMRI studies, allowing for easy and fast acquisitions and ultimately improve the diagnosis and prognosis in the absence of DOC patients’ active collaboration in data acquisition. PMID:21693087

Cellular immunotherapy for malignant gliomas.

PubMed

Lin, Yi; Okada, Hideho

2016-10-01

Cancer immunotherapy has made much progress in recent years. Clinical trials evaluating a variety of immunotherapeutic approaches are underway in patients with malignant gliomas. Thanks to recent advancements in cell engineering technologies, infusion of ex vivo prepared immune cells have emerged as promising strategies of cancer immunotherapy. Herein, the authors review recent and current studies using cellular immunotherapies for malignant gliomas. Specifically, they cover the following areas: a) cellular vaccine approaches using tumor cell-based or dendritic cell (DC)-based vaccines, and b) adoptive cell transfer (ACT) approaches, including lymphokine-activated killer (LAK) cells, γδ T cells, tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR)-T cells and T-cell receptor (TCR) transduced T cells. While some of the recent studies have shown promising results, the ultimate success of cellular immunotherapy in brain tumor patients would require improvements in the following areas: 1) feasibility in producing cellular therapeutics; 2) identification and characterization of targetable antigens given the paucity and heterogeneity of tumor specific antigens; 3) the development of strategies to promote effector T-cell trafficking; 4) overcoming local and systemic immune suppression, and 5) proper interpretation of imaging data for brain tumor patients receiving immunotherapy.

Cellular immunotherapy for malignant gliomas

PubMed Central

Lin, Yi

2016-01-01

Introduction Cancer immunotherapy has made much progress in recent years. Clinical trials evaluating a variety of immunotherapeutic approaches are underway in patients with malignant gliomas. Thanks to recent advancements in cell engineering technologies, infusion of ex vivo prepared immune cells have emerged as promising strategies of cancer immunotherapy. Areas covered Herein, the authors review recent and current studies using cellular immunotherapies for malignant gliomas. Specifically, they cover the following areas: a) cellular vaccine approaches using tumor cell-based or dendritic cell (DC)-based vaccines, and b) adoptive cell transfer (ACT) approaches, including lymphokine-activated killer (LAK) cells, γδ T cells, tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR)-T cells and T-cell receptor (TCR) transduced T cells. Expert opinion While some of the recent studies have shown promising results, the ultimate success of cellular immunotherapy in brain tumor patients would require improvements in the following areas: 1) feasibility in producing cellular therapeutics; 2) identification and characterization of targetable antigens given the paucity and heterogeneity of tumor specific antigens; 3) the development of strategies to promote effector T-cell trafficking; 4) overcoming local and systemic immune suppression, and 5) proper interpretation of imaging data for brain tumor patients receiving immunotherapy. PMID:27434205

In vivo voltammetry: from wire to wireless measurements.

PubMed

Crespi, Francesco; Dalessandro, Davide; Annovazzi-Lodi, Valerio; Heidbreder, Christian; Norgia, Michele

2004-12-30

A novel telemetric system based on either differential pulse voltammetry (DPV) or direct current amperometry (DCA) by using a diffused infrared transmission channel is presented. Unlike similar pre-existing instruments based on infrared transmission, the present system works on a single-way communication, thus avoiding problems related to cross-talking between two-way channels. The infrared channel is also immune from electromagnetic interferences from the surrounding environment. Further advancement is the development of an original miniaturised system (dimension 1cm x 1.2 cm x 0.5 cm) with reduced weight (5-6 g), suitable for affixing to the rat head and allowing real time telemetric monitoring using DCA sampling of neurotransmitters such as dopamine or serotonin every 100 ms. The set-up is based on a transmitter (TX) circuit mounted on the animal's head and connected to the electrodes inserted into its brain. The TX circuit generates the proper electrical signals for DPV or DCA, collects the electrical response of the brain and transmits it, via an infrared channel, to a receiving station (RX) interfaced with a personal computer. The PC performs the sampling and elaboration of polarographic traces in a flexible and programmable way.

DR-TAMAS: Diffeomorphic Registration for Tensor Accurate alignMent of Anatomical Structures

PubMed Central

Irfanoglu, M. Okan; Nayak, Amritha; Jenkins, Jeffrey; Hutchinson, Elizabeth B.; Sadeghi, Neda; Thomas, Cibu P.; Pierpaoli, Carlo

2016-01-01

In this work, we propose DR-TAMAS (Diffeomorphic Registration for Tensor Accurate alignMent of Anatomical Structures), a novel framework for intersubject registration of Diffusion Tensor Imaging (DTI) data sets. This framework is optimized for brain data and its main goal is to achieve an accurate alignment of all brain structures, including white matter (WM), gray matter (GM), and spaces containing cerebrospinal fluid (CSF). Currently most DTI-based spatial normalization algorithms emphasize alignment of anisotropic structures. While some diffusion-derived metrics, such as diffusion anisotropy and tensor eigenvector orientation, are highly informative for proper alignment of WM, other tensor metrics such as the trace or mean diffusivity (MD) are fundamental for a proper alignment of GM and CSF boundaries. Moreover, it is desirable to include information from structural MRI data, e.g., T1-weighted or T2-weighted images, which are usually available together with the diffusion data. The fundamental property of DR-TAMAS is to achieve global anatomical accuracy by incorporating in its cost function the most informative metrics locally. Another important feature of DR-TAMAS is a symmetric time-varying velocity-based transformation model, which enables it to account for potentially large anatomical variability in healthy subjects and patients. The performance of DR-TAMAS is evaluated with several data sets and compared with other widely-used diffeomorphic image registration techniques employing both full tensor information and/or DTI-derived scalar maps. Our results show that the proposed method has excellent overall performance in the entire brain, while being equivalent to the best existing methods in WM. PMID:26931817

DR-TAMAS: Diffeomorphic Registration for Tensor Accurate Alignment of Anatomical Structures.

PubMed

Irfanoglu, M Okan; Nayak, Amritha; Jenkins, Jeffrey; Hutchinson, Elizabeth B; Sadeghi, Neda; Thomas, Cibu P; Pierpaoli, Carlo

2016-05-15

In this work, we propose DR-TAMAS (Diffeomorphic Registration for Tensor Accurate alignMent of Anatomical Structures), a novel framework for intersubject registration of Diffusion Tensor Imaging (DTI) data sets. This framework is optimized for brain data and its main goal is to achieve an accurate alignment of all brain structures, including white matter (WM), gray matter (GM), and spaces containing cerebrospinal fluid (CSF). Currently most DTI-based spatial normalization algorithms emphasize alignment of anisotropic structures. While some diffusion-derived metrics, such as diffusion anisotropy and tensor eigenvector orientation, are highly informative for proper alignment of WM, other tensor metrics such as the trace or mean diffusivity (MD) are fundamental for a proper alignment of GM and CSF boundaries. Moreover, it is desirable to include information from structural MRI data, e.g., T1-weighted or T2-weighted images, which are usually available together with the diffusion data. The fundamental property of DR-TAMAS is to achieve global anatomical accuracy by incorporating in its cost function the most informative metrics locally. Another important feature of DR-TAMAS is a symmetric time-varying velocity-based transformation model, which enables it to account for potentially large anatomical variability in healthy subjects and patients. The performance of DR-TAMAS is evaluated with several data sets and compared with other widely-used diffeomorphic image registration techniques employing both full tensor information and/or DTI-derived scalar maps. Our results show that the proposed method has excellent overall performance in the entire brain, while being equivalent to the best existing methods in WM. Copyright © 2016 Elsevier Inc. All rights reserved.

[Components of plastic disrupt the function of the nervous system].

PubMed

Szychowski, Konrad Andrzej; Wójtowicz, Anna Katarzyna

2013-05-27

Development of the chemical industry leads to the development of new chemical compounds, which naturally do not exist in the environment. These chemicals are used to reduce flammability, increase plasticity, or improve solubility of other substances. Many of these compounds, which are components of plastic, the new generation of cosmetics, medical devices, food packaging and other everyday products, are easily released into the environment. Many studies have shown that a major lipophilicity characterizes substances such as phthalates, BPA, TBBPA and PCBs. This feature allows them to easily penetrate into living cells, accumulate in the tissues and the organs, and affect human and animal health. Due to the chemical structures, these compounds are able to mimic some endogenous hormones such as estradiol and to disrupt the hormone homeostasis. They can also easily pass the placental barrier and the blood-brain barrier. As numerous studies have shown, these chemicals disturb the proper functions of the nervous system from the earliest moments of life. It has been proven that these compounds affect neurogenesis as well as the synaptic transmission process. As a consequence, they interfere with the formation of the sex of the brain, as well as with the learning processes, memory and behavior. Additionally, the cytotoxic and pro-apoptotic effect may cause neurodegenerative diseases. This article presents the current state of knowledge about the effects of phthalates, BPA, TBBPA, and PCBs on the nervous system.

Determination of head conductivity frequency response in vivo with optimized EIT-EEG.

PubMed

Dabek, Juhani; Kalogianni, Konstantina; Rotgans, Edwin; van der Helm, Frans C T; Kwakkel, Gert; van Wegen, Erwin E H; Daffertshofer, Andreas; de Munck, Jan C

2016-02-15

Electroencephalography (EEG) benefits from accurate head models. Dipole source modelling errors can be reduced from over 1cm to a few millimetres by replacing generic head geometry and conductivity with tailored ones. When adequate head geometry is available, electrical impedance tomography (EIT) can be used to infer the conductivities of head tissues. In this study, the boundary element method (BEM) is applied with three-compartment (scalp, skull and brain) subject-specific head models. The optimal injection of small currents to the head with a modular EIT current injector, and voltage measurement by an EEG amplifier is first sought by simulations. The measurement with a 64-electrode EEG layout is studied with respect to three noise sources affecting EIT: background EEG, deviations from the fitting assumption of equal scalp and brain conductivities, and smooth model geometry deviations from the true head geometry. The noise source effects were investigated depending on the positioning of the injection and extraction electrode and the number of their combinations used sequentially. The deviation from equal scalp and brain conductivities produces rather deterministic errors in the three conductivities irrespective of the current injection locations. With a realistic measurement of around 2 min and around 8 distant distinct current injection pairs, the error from the other noise sources is reduced to around 10% or less in the skull conductivity. The analysis of subsequent real measurements, however, suggests that there could be subject-specific local thinnings in the skull, which could amplify the conductivity fitting errors. With proper analysis of multiplexed sinusoidal EIT current injections, the measurements on average yielded conductivities of 340 mS/m (scalp and brain) and 6.6 mS/m (skull) at 2 Hz. From 11 to 127 Hz, the conductivities increased by 1.6% (scalp and brain) and 6.7% (skull) on the average. The proper analysis was ensured by using recombination of the current injections into virtual ones, avoiding problems in location-specific skull morphology variations. The observed large intersubject variations support the need for in vivo measurement of skull conductivity, resulting in calibrated subject-specific head models. Copyright © 2015 Elsevier Inc. All rights reserved.

The L1-CAM, Neuroglian, functions in glial cells for Drosophila antennal lobe development.

PubMed

Chen, Weitao; Hing, Huey

2008-07-01

Although considerable progress has been made in understanding the roles of olfactory receptor neurons (ORNs) and projection neurons (PNs) in Drosophila antennal lobe (AL) development, the roles of glia have remained largely mysterious. Here, we show that during Drosophila metamorphosis, a population of midline glial cells in the brain undergoes extensive cellular remodeling and is closely associated with the collateral branches of ORN axons. These glial cells are required for ORN axons to project across the midline and establish the contralateral wiring in the ALs. We find that Neuroglian (Nrg), the Drosophila homolog of the vertebrate cell adhesion molecule, L1, is expressed and functions in the midline glial cells to regulate their proper development. Loss of Nrg causes the disruption in glial morphology and the agenesis of the antennal commissural tract. Our genetic analysis further demonstrates that the functions of Nrg in the midline glia require its ankyrin-binding motif. We propose that Nrg is an important regulator of glial morphogenesis and axon guidance in AL development. (Copyright) 2008 Wiley Periodicals, Inc.

Functional Polarity of Microvascular Brain Endothelial Cells Supported by Neurovascular Unit Computational Model of Large Neutral Amino Acid Homeostasis

PubMed Central

Taslimifar, Mehdi; Buoso, Stefano; Verrey, Francois; Kurtcuoglu, Vartan

2018-01-01

The homeostatic regulation of large neutral amino acid (LNAA) concentration in the brain interstitial fluid (ISF) is essential for proper brain function. LNAA passage into the brain is primarily mediated by the complex and dynamic interactions between various solute carrier (SLC) transporters expressed in the neurovascular unit (NVU), among which SLC7A5/LAT1 is considered to be the major contributor in microvascular brain endothelial cells (MBEC). The LAT1-mediated trans-endothelial transport of LNAAs, however, could not be characterized precisely by available in vitro and in vivo standard methods so far. To circumvent these limitations, we have incorporated published in vivo data of rat brain into a robust computational model of NVU-LNAA homeostasis, allowing us to evaluate hypotheses concerning LAT1-mediated trans-endothelial transport of LNAAs across the blood brain barrier (BBB). We show that accounting for functional polarity of MBECs with either asymmetric LAT1 distribution between membranes and/or intrinsic LAT1 asymmetry with low intraendothelial binding affinity is required to reproduce the experimentally measured brain ISF response to intraperitoneal (IP) L-tyrosine and L-phenylalanine injection. On the basis of these findings, we have also investigated the effect of IP administrated L-tyrosine and L-phenylalanine on the dynamics of LNAAs in MBECs, astrocytes and neurons. Finally, the computational model was shown to explain the trans-stimulation of LNAA uptake across the BBB observed upon ISF perfusion with a competitive LAT1 inhibitor. PMID:29593549

Brain MRI findings in patients with idiopathic hypersomnia.

PubMed

Trotti, Lynn Marie; Bliwise, Donald L

2017-06-01

Proper diagnosis of idiopathic hypersomnia necessitates the exclusion of neurologic or medical causes of sleepiness that better explain the clinical syndrome. However, there are no formal guidelines regarding the use of neuroimaging to identify such secondary causes of symptoms. We sought to characterize brain MRI findings in a series of patients with idiopathic hypersomnia. We reviewed medical records on a consecutive series of 61 patients diagnosed with idiopathic hypersomnia to determine the frequency and results of brain magnetic resonance imaging (MRI). One-third of patients had undergone brain MRI, with focal neurologic signs or symptoms being the most common indication for neuroimaging. Although seven patients had an identifiable finding on neuroimaging (e.g., chronic microvascular ischemic changes), clinical management was changed as a result of imaging in only three cases. In all three, the imaging finding was predated by clear clinical abnormalities. Neuroimaging may be a complementary part of an idiopathic hypersomnia evaluation, but the decision to pursue imaging should be made on a case-by-case basis. Copyright © 2017 Elsevier B.V. All rights reserved.

Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods

PubMed Central

Fantini, Sergio; Sassaroli, Angelo; Tgavalekos, Kristen T.; Kornbluth, Joshua

2016-01-01

Abstract. Cerebral blood flow (CBF) and cerebral autoregulation (CA) are critically important to maintain proper brain perfusion and supply the brain with the necessary oxygen and energy substrates. Adequate brain perfusion is required to support normal brain function, to achieve successful aging, and to navigate acute and chronic medical conditions. We review the general principles of CBF measurements and the current techniques to measure CBF based on direct intravascular measurements, nuclear medicine, X-ray imaging, magnetic resonance imaging, ultrasound techniques, thermal diffusion, and optical methods. We also review techniques for arterial blood pressure measurements as well as theoretical and experimental methods for the assessment of CA, including recent approaches based on optical techniques. The assessment of cerebral perfusion in the clinical practice is also presented. The comprehensive description of principles, methods, and clinical requirements of CBF and CA measurements highlights the potentially important role that noninvasive optical methods can play in the assessment of neurovascular health. In fact, optical techniques have the ability to provide a noninvasive, quantitative, and continuous monitor of CBF and autoregulation. PMID:27403447

The Revised Neurobehavioral Severity Scale (NSS-R) for Rodents.

PubMed

Yarnell, Angela M; Barry, Erin S; Mountney, Andrea; Shear, Deborah; Tortella, Frank; Grunberg, Neil E

2016-04-08

Motor and sensory deficits are common following traumatic brain injury (TBI). Although rodent models provide valuable insight into the biological and functional outcomes of TBI, the success of translational research is critically dependent upon proper selection of sensitive, reliable, and reproducible assessments. Published literature includes various observational scales designed to evaluate post-injury functionality; however, the heterogeneity in TBI location, severity, and symptomology can complicate behavioral assessments. The importance of choosing behavioral outcomes that can be reliably and objectively quantified in an efficient manner is becoming increasingly important. The Revised Neurobehavioral Severity Scale (NSS-R) is a continuous series of specific, sensitive, and standardized observational tests that evaluate balance, motor coordination, and sensorimotor reflexes in rodents. The tasks follow a specific order designed to minimize interference: balance, landing, tail raise, dragging, righting reflex, ear reflex, eye reflex, sound reflex, tail pinch, and hindpaw pinch. The NSS-R has proven to be a reliable method differentiating brain-injured rodents from non-brain-injured rodents across many brain injury models. Copyright © 2016 John Wiley & Sons, Inc.

Effects of rutin supplementation on antioxidant status and iron, copper, and zinc contents in mouse liver and brain.

PubMed

Gao, Zhonghong; Xu, Huibi; Huang, Kaixun

2002-09-01

The effect of rutin on total antioxidant status as well as on trace elements such as iron, copper, and zinc in mouse liver and brain were studied. Mice were administrated with 0.75 g/kg or 2.25 g/kg P. O. of rutin for 30 d consecutively. Following the treatment, the activity of total antioxidant status, catalase, Cu,Zn-superoxide dismutase, Mn-superoxide dismutase, zinc, copper, and iron were measured in mouse liver and brain. The results showed that rutin significantly increased the antioxidant status and Mn-superoxide dismutase activities in mouse liver, but it had no effect on these variables in the brain. Treatment with a higher concentration of rutin significantly decreased catalase activity and iron, zinc, and copper contents in mouse liver; it also resulted in a slower weight gain for the first 20 d. These results indicate that rutin taken in proper amount can effectively improve antioxidant status, whereas at an increased dosage, it may cause trace element (such as iron, zinc, and copper) deficiencies and a decrease in the activities of related metal-containing enzymes.

Mild traumatic brain injury: a midwest survey about the assessment and documentation practices of emergency department nurses.

PubMed

Bay, Esther

2011-01-01

Research reported that mild traumatic brain injury (MTBI), the most common neurological condition in the world, is often undetected in the emergency department. Failure to properly detect and offer treatment therapies has been linked to chronic complications such as, mood disorders and postconcussion syndrome. This descriptive study used a tailored survey (25.0% response rate) to determine emergency department nurses' practices for the assessment and documentation of persons with MTBI. The primary purpose was to determine the extent to which these practices were aligned with the Centers for Disease Control and Prevention guidelines contained within the Acute Concussion Evaluation care plan. Results indicated that physical and cognitive symptoms were assessed and documented more than emotional or sleep symptoms. Still, some cognitive and physical symptoms were rarely assessed or documented. Focus seemed to be on ruling out more severe brain injury versus detection of a mild brain injury. Aligning the systematic assessment and documentation of persons with suspected concussion MTBI with recommendations from the Centers for Disease Control and Prevention is suggested.

Real-time monitoring of human blood-brain barrier disruption

PubMed Central

Kiviniemi, Vesa; Korhonen, Vesa; Kortelainen, Jukka; Rytky, Seppo; Keinänen, Tuija; Tuovinen, Timo; Isokangas, Matti; Sonkajärvi, Eila; Siniluoto, Topi; Nikkinen, Juha; Alahuhta, Seppo; Tervonen, Osmo; Turpeenniemi-Hujanen, Taina; Myllylä, Teemu; Kuittinen, Outi; Voipio, Juha

2017-01-01

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery. PMID:28319185

Early-Life Nutrition and Neurodevelopment: Use of the Piglet as a Translational Model12

PubMed Central

Mudd, Austin T

2017-01-01

Optimal nutrition early in life is critical to ensure proper structural and functional development of infant organ systems. Although pediatric nutrition historically has emphasized research on the relation between nutrition, growth rates, and gastrointestinal maturation, efforts increasingly have focused on how nutrition influences neurodevelopment. The provision of human milk is considered the gold standard in pediatric nutrition; thus, there is interest in understanding how functional nutrients and bioactive components in milk may modulate developmental processes. The piglet has emerged as an important translational model for studying neurodevelopmental outcomes influenced by pediatric nutrition. Given the comparable nutritional requirements and strikingly similar brain developmental patterns between young pigs and humans, the piglet is being used increasingly in developmental nutritional neuroscience studies. The piglet primarily has been used to assess the effects of dietary fatty acids and their accretion in the brain throughout neurodevelopment. However, recent research indicates that other dietary components, including choline, iron, cholesterol, gangliosides, and sialic acid, among other compounds, also affect neurodevelopment in the pig model. Moreover, novel analytical techniques, including but not limited to MRI, behavioral assessments, and molecular quantification, allow for a more holistic understanding of how nutrition affects neurodevelopmental patterns. By combining early-life nutritional interventions with innovative analytical approaches, opportunities abound to quantify factors affecting neurodevelopmental trajectories in the neonate. This review discusses research using the translational pig model with primary emphasis on early-life nutrition interventions assessing neurodevelopment outcomes, while also discussing nutritionally-sensitive methods to characterize brain maturation. PMID:28096130

User-friendly cognitive training for the elderly: a technical report.

PubMed

Boquete, Luciano; Rodríguez-Ascariz, José Manuel; Amo-Usanos, Carlos; Martínez-Arribas, Alejandro; Amo-Usanos, Javier; Otón, Salvador

2011-01-01

This article presents a system that implements a cognitive training program in users' homes. The system comprises various applications designed to create a daily brain-fitness regime. The proposed mental training system uses television and a remote control specially designed for the elderly. This system integrates Java applications to promote brain-fitness training in three areas: arithmetic, memory, and idea association. The system comprises the following: Standard television set, simplified wireless remote control, black box (system's core hardware and software), brain-fitness games (language Java), and Wi-Fi-enabled Internet-connected router. All data from the user training sessions are monitored through a control center. This control center analyzes the evolution of the user and the proper performance of the system during the test. The implemented system has been tested by six healthy volunteers. The results for this user group demonstrated the accessibility and usability of the system in a controlled real environment. The impressions of the users were very favorable, and they reported high adaptability to the system. The mean score for usability and accessibility assigned by the users was 3.56 out of 5 points. The operation stress test (over 200 h) was successful. The proposed system was used to implement a cognitive training program in users' homes, which was developed to be a low-cost tool with a high degree of user interactivity. The results of this preliminary study indicate that this user-friendly system could be adopted as a form of cognitive training for the elderly.

Towards a miniaturized brain-machine-spinal cord interface (BMSI) for restoration of function after spinal cord injury.

PubMed

Shahdoost, Shahab; Frost, Shawn; Van Acker, Gustaf; DeJong, Stacey; Dunham, Caleb; Barbay, Scott; Nudo, Randolph; Mohseni, Pedram

2014-01-01

Nearly 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress towards developing a miniaturized brain-machine-spinal cord interface (BMSI) that is envisioned to convert in real time the neural command signals recorded from the brain to electrical stimuli delivered to the spinal cord below the injury level. Specifically, the paper reports on a corticospinal interface integrated circuit (IC) as a core building block for such a BMSI that is capable of low-noise recording of extracellular neural spikes from the cerebral cortex as well as muscle activation using intraspinal microstimulation (ISMS) in a rat with contusion injury to the thoracic spinal cord. The paper further presents results from a neurobiological study conducted in both normal and SCI rats to investigate the effect of various ISMS parameters on movement thresholds in the rat hindlimb. Coupled with proper signal-processing algorithms in the future for the transformation between the cortically recorded data and ISMS parameters, such a BMSI has the potential to facilitate functional recovery after an SCI by re-establishing corticospinal communication channels lost due to the injury.

Partial Tmem106b reduction does not correct abnormalities due to progranulin haploinsufficiency.

PubMed

Arrant, Andrew E; Nicholson, Alexandra M; Zhou, Xiaolai; Rademakers, Rosa; Roberson, Erik D

2018-06-22

Loss of function mutations in progranulin (GRN) are a major cause of frontotemporal dementia (FTD). Progranulin is a secreted glycoprotein that localizes to lysosomes and is critical for proper lysosomal function. Heterozygous GRN mutation carriers develop FTD with TDP-43 pathology and exhibit signs of lysosomal dysfunction in the brain, with increased levels of lysosomal proteins and lipofuscin accumulation. Homozygous GRN mutation carriers develop neuronal ceroid lipofuscinosis (NCL), an earlier-onset lysosomal storage disorder caused by severe lysosomal dysfunction. Multiple genome-wide association studies have shown that risk of FTD in GRN mutation carriers is modified by polymorphisms in TMEM106B, which encodes a lysosomal membrane protein. Risk alleles of TMEM106B may increase TMEM106B levels through a variety of mechanisms. Brains from FTD patients with GRN mutations exhibit increased TMEM106B expression, and protective TMEM106B polymorphisms are associated with decreased TMEM106B expression. Together, these data raise the possibility that reduction of TMEM106B levels may protect against the pathogenic effects of progranulin haploinsufficiency. We crossed Tmem106b +/- mice with Grn +/- mice, which model the progranulin haploinsufficiency of GRN mutation carriers and develop age-dependent social deficits and lysosomal abnormalities in the brain. We tested whether partial Tmem106b reduction could normalize the social deficits and lysosomal abnormalities of Grn +/- mice. Partial reduction of Tmem106b levels did not correct the social deficits of Grn +/- mice. Tmem106b reduction also failed to normalize most lysosomal abnormalities of Grn +/- mice, except for β-glucuronidase activity, which was suppressed by Tmem106b reduction and increased by progranulin insufficiency. These data do not support the hypothesis that Tmem106b reduction protects against the pathogenic effects of progranulin haploinsufficiency, but do show that Tmem106b reduction normalizes some lysosomal phenotypes in Grn +/- mice.

The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of Drosophila melanogaster.

PubMed

Sano, Hiroko; Nakamura, Akira; Texada, Michael J; Truman, James W; Ishimoto, Hiroshi; Kamikouchi, Azusa; Nibu, Yutaka; Kume, Kazuhiko; Ida, Takanori; Kojima, Masayasu

2015-05-01

The coordination of growth with nutritional status is essential for proper development and physiology. Nutritional information is mostly perceived by peripheral organs before being relayed to the brain, which modulates physiological responses. Hormonal signaling ensures this organ-to-organ communication, and the failure of endocrine regulation in humans can cause diseases including obesity and diabetes. In Drosophila melanogaster, the fat body (adipose tissue) has been suggested to play an important role in coupling growth with nutritional status. Here, we show that the peripheral tissue-derived peptide hormone CCHamide-2 (CCHa2) acts as a nutrient-dependent regulator of Drosophila insulin-like peptides (Dilps). A BAC-based transgenic reporter revealed strong expression of CCHa2 receptor (CCHa2-R) in insulin-producing cells (IPCs) in the brain. Calcium imaging of brain explants and IPC-specific CCHa2-R knockdown demonstrated that peripheral-tissue derived CCHa2 directly activates IPCs. Interestingly, genetic disruption of either CCHa2 or CCHa2-R caused almost identical defects in larval growth and developmental timing. Consistent with these phenotypes, the expression of dilp5, and the release of both Dilp2 and Dilp5, were severely reduced. Furthermore, transcription of CCHa2 is altered in response to nutritional levels, particularly of glucose. These findings demonstrate that CCHa2 and CCHa2-R form a direct link between peripheral tissues and the brain, and that this pathway is essential for the coordination of systemic growth with nutritional availability. A mammalian homologue of CCHa2-R, Bombesin receptor subtype-3 (Brs3), is an orphan receptor that is expressed in the islet β-cells; however, the role of Brs3 in insulin regulation remains elusive. Our genetic approach in Drosophila melanogaster provides the first evidence, to our knowledge, that bombesin receptor signaling with its endogenous ligand promotes insulin production.

A follow-up ¹⁸F-FDG brain PET study in a case of Hashimoto's encephalopathy causing drug-resistant status epilepticus treated with plasmapheresis.

PubMed

Pari, Elisa; Rinaldi, Fabrizio; Premi, Enrico; Codella, Maria; Rao, Renata; Paghera, Barbara; Panarotto, Maria Beatrice; De Maria, Giovanni; Padovani, Alessandro

2014-04-01

Hashimoto's encephalopathy (HE) is a rare neuropsychiatric syndrome associated with antithyroid antibodies. It may have an acute onset (episodes of cerebral ischemia, seizure, and psychosis) or it may present as an indolent form (depression, cognitive decline, myoclonus, tremors, and fluctuations in level of consciousness). We here describe a case of encephalopathy presenting as non-convulsive status epilepticus associated with Hashimoto's thyroiditis (HT), unresponsive to corticosteroid therapy, with improvement after plasma exchange treatment. A previously healthy 19-year-old woman, presented generalized tonic-clonic seizures. About a month later, she manifested a speech disorder characterized by difficulties in the production and comprehension of language. Within a few days she also developed confusion and difficulties in recognizing familiar places, with gradual worsening over time. EEG revealed a non-convulsive status epilepticus (NCSE). CSF examination showed slightly elevated cell count and four oligoclonal bands. MRI was unremarkable, and (18)F-FDG brain PET showed widespread hypometabolism, mostly in posterior regions bilaterally. Laboratory and ultrasound findings showed signs of HT. Treatment with steroid was introduced without any improvement. After five sessions of plasma exchange there was a decrease of antithyroid antibodies, as well as EEG and clinical improvement. Three months after discharge (18)F-FDG brain PET showed a complete normalization of the picture, and the patient was asymptomatic. This report emphasizes the successful treatment of HE with plasma exchange in a patient who presented with NCSE. Based on the actual evidence, the term "Encephalopathy associated with Hashimoto's thyroiditis" may be the most proper. Furthermore, to our knowledge, this is the first case of an adult patient studied twice with an (18)F-FDG brain PET: prior to treatment with plasma exchange, and at 3 months follow-up when the patient was clinically completely asymptomatic. Studies in more patients are needed to clarify the relevance of (18)F-FDG brain PET as a possible diagnostic tool for HE.

The biochemical, nanomechanical and chemometric signatures of brain cancer.

PubMed

Abramczyk, Halina; Imiela, Anna

2018-01-05

Raman spectroscopy and imaging combined with AFM topography and mechanical indentation by AFM have been shown to be an effective tool for analysis and discrimination of human brain tumors from normal structures. Raman methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n=5) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma (IV grade), and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational spectra and Raman images we provide a real-time feedback that is label-free method to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, and proteins. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845cm -1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the lipid and protein contents of tumorous brain tissue compared to the non-tumor tissue. Almost all brain tumors have the Raman intensity ratios significantly higher (1.99±0.026) than that found in non-tumor brain tissue, which is 1.456±0.02, and indicates that the relative amount of lipids compared to proteins is significantly higher in the normal brain tissue. Mechanical indentation using AFM on sliced human brain tissues (medulloblastoma, grade IV) revealed that the mechanical properties of this tissue are strongly heterogeneous, between 1.8 and 75.7kPa, and the mean of 27.16kPa. The sensitivity and specificity obtained directly from PLSDA and cross validation gives a sensitivity and specificity of 98.5% and 96% and 96.3% and 92% for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A clinical review on megalencephaly

PubMed Central

Pavone, Piero; Praticò, Andrea Domenico; Rizzo, Renata; Corsello, Giovanni; Ruggieri, Martino; Parano, Enrico; Falsaperla, Raffaele

2017-01-01

Abstract Megalencephaly and macrocephaly present with a head circumference measurement 2 standard deviations above the age-related mean. However, even if pathologic events resulting in both megalencephaly and macrocephaly may coexist, a distinction between these two entities is appropriate, as they represent clinical expression of different disorders with a different approach in clinical work-up, overall prognosis, and treatment. Megalencephaly defines an increased growth of cerebral structures related to dysfunctional anomalies during the various steps of brain development in the neuronal proliferation and/or migration phases or as a consequence of postnatal abnormal events. The disorders associated with megalencephaly are classically defined into 3 groups: idiopathic or benign, metabolic, and anatomic. In this article, we seek to underline the clinical aspect of megalencephaly, emphasizing the main disorders that manifest with this anomaly in an attempt to properly categorize these disorders within the megalencephaly group. PMID:28658095

Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders.

PubMed

Jaiswal, Preeti; Mohanakumar, Kochupurackal P; Rajamma, Usha

2015-08-01

Serotonergic system has long been implicated in the aetiology of autism spectrum disorders (ASD), since platelet hyperserotonemia is consistently observed in a subset of autistic patients, who respond well to selective serotonin reuptake inhibitors. Apart from being a neurotransmitter, serotonin functions as a neurotrophic factor directing brain development and as an immunoregulator modulating immune responses. Serotonin transporter (SERT) regulates serotonin level in lymphoid tissues to ensure its proper functioning in innate and adaptive responses. Immunological molecules such as cytokines in turn regulate the transcription and activity of SERT. Dysregulation of serotonergic system could trigger signalling cascades that affect normal neural-immune interactions culminating in neurodevelopmental and neural connectivity defects precipitating behavioural abnormalities, or the disease phenotypes. Therefore, we suggest that a better understanding of the cross talk between serotonergic genes, immune systems and serotonergic neurotransmission will open wider avenues to develop pharmacological leads for addressing the core ASD behavioural deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Editing the Neuronal Genome: a CRISPR View of Chromatin Regulation in Neuronal Development, Function, and Plasticity.

PubMed

Yang, Marty G; West, Anne E

2016-12-01

The dynamic orchestration of gene expression is crucial for the proper differentiation, function, and adaptation of cells. In the brain, transcriptional regulation underlies the incredible diversity of neuronal cell types and contributes to the ability of neurons to adapt their function to the environment. Recently, novel methods for genome and epigenome editing have begun to revolutionize our understanding of gene regulatory mechanisms. In particular, the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has proven to be a particularly accessible and adaptable technique for genome engineering. Here, we review the use of CRISPR/Cas9 in neurobiology and discuss how these studies have advanced understanding of nervous system development and plasticity. We cover four especially salient applications of CRISPR/Cas9: testing the consequences of enhancer mutations, tagging genes and gene products for visualization in live cells, directly activating or repressing enhancers in vivo , and manipulating the epigenome. In each case, we summarize findings from recent studies and discuss evolving adaptations of the method.

Clinical, Dopaminergic, and Metabolic Correlations in Parkinson Disease: A Dual-Tracer PET Study.

PubMed

Liu, Feng-Tao; Ge, Jing-Jie; Wu, Jian-Jun; Wu, Ping; Ma, Yilong; Zuo, Chuan-Tao; Wang, Jian

2018-05-31

Neuroimaging indicators of Parkinson disease have been developed and applied in clinical practices. Dopaminergic imaging reflects nigrostriatal dopaminergic dysfunction, and metabolic network imaging offers disease-related metabolic changes at a system level. We aimed to elucidate the association between Parkinsonian symptoms and neuroimaging, and interactions between different imaging techniques. We conducted a dual-tracer PET study for the combined assessments of dopaminergic binding (C-CFT) and glucose metabolism (F-FDG) in 103 participants with Parkinson disease (65 male and 38 female subjects). The detailed clinical rating scores were systematically collected in all members. The interactions among dopaminergic bindings, metabolic changes, and clinical manifestations were evaluated at voxel, regional, and network levels. Striatal DAT binding correlated with akinesia-rigidity (P < 0.001) but not with tremor; the metabolic PET imaging, nonspecific to the dopaminergic dysfunction, disclosed a set of brain regions correlating with the cardinal symptoms, including tremor. In addition, the unilateral symptom correlated with the contralateral nigrostriatal dopamine loss, but with bilateral metabolic changes, suggesting their differences in the application of disease-related mechanistic studies. Further imaging-imaging correlation study revealed that dopaminergic dysfunction correlated with widely distributed metabolic changes in Parkinson disease, and the modest correlations supported the findings on the clinical-imaging correlation. In this dual-tracer PET study, we demonstrated the robust interactions among dopaminergic dysfunction, metabolic brain changes and clinical manifestations at voxel, regional, and network levels. Our findings might promote the understanding in the proper application of dopaminergic and metabolic PET imaging in Parkinson disease and offer more evidence in support of Parkinsonian pathophysiological mechanisms.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Brain Hyperglycemia Induced by Heroin: Association with Metabolic Neural Activation.

PubMed

Solis, Ernesto; Bola, R Aaron; Fasulo, Bradley J; Kiyatkin, Eugene A

2017-02-15

Glucose enters the brain extracellular space from arterial blood, and its proper delivery is essential for metabolic activity of brain cells. By using enzyme-based biosensors coupled with high-speed amperometry in freely moving rats, we previously showed that glucose levels in the nucleus accumbens (NAc) display high variability, increasing rapidly following exposure to various arousing stimuli. In this study, the same technology was used to assess NAc glucose fluctuations induced by intravenous heroin. Heroin passively injected at a low dose optimal for maintaining self-administration behavior (100 μg/kg) induces a rapid but moderate glucose rise (∼150-200 μM or ∼15-25% over resting baseline). When the heroin dose was doubled and tripled, the increase became progressively larger in magnitude and longer in duration. Heroin-induced glucose increases also occurred in other brain structures (medial thalamus, lateral striatum, hippocampus), suggesting that brain hyperglycemia is a whole-brain phenomenon but changes were notably distinct in each structure. While local vasodilation appears to be the possible mechanism underlying the rapid rise in extracellular glucose levels, the driving factor for this vasodilation (central vs peripheral) remains to be clarified. The heroin-induced NAc glucose increases positively correlated with increases in intracerebral heat production determined in separate experiments using multisite temperature recordings (NAc, temporal muscle and skin). However, glucose levels rise very rapidly, preceding much slower increases in brain heat production, a measure of metabolic activation associated with glucose consumption.

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents.

PubMed

Jastreboff, Ania M; Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A; Santoro, Nicola; Savoye, Mary; Duran, Elvira J; Pierpont, Bridget; Cline, Gary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia

2016-07-01

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

In Vivo Characterization of an AHR-Dependent Long Noncoding RNA Required for Proper Sox9b Expression

PubMed Central

Garcia, Gloria R.; Goodale, Britton C.; Wiley, Michelle W.; La Du, Jane K.; Hendrix, David A.

2017-01-01

Xenobiotic activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prevents the proper formation of craniofacial cartilage and the heart in developing zebrafish. Downstream molecular targets responsible for AHR-dependent adverse effects remain largely unknown; however, in zebrafish sox9b has been identified as one of the most-reduced transcripts in several target organs and is hypothesized to have a causal role in TCDD-induced toxicity. The reduction of sox9b expression in TCDD-exposed zebrafish embryos has been shown to contribute to heart and jaw malformation phenotypes. The mechanisms by which AHR2 (functional ortholog of mammalian AHR) activation leads to reduced sox9b expression levels and subsequent target organ toxicity are unknown. We have identified a novel long noncoding RNA (slincR) that is upregulated by strong AHR ligands and is located adjacent to the sox9b gene. We hypothesize that slincR is regulated by AHR2 and transcriptionally represses sox9b. The slincR transcript functions as an RNA macromolecule, and slincR expression is AHR2 dependent. Antisense knockdown of slincR results in an increase in sox9b expression during both normal development and AHR2 activation, which suggests relief in repression. During development, slincR was expressed in tissues with sox9 essential functions, including the jaw/snout region, otic vesicle, eye, and brain. Reducing the levels of slincR resulted in altered neurologic and/or locomotor behavioral responses. Our results place slincR as an intermediate between AHR2 activation and the reduction of sox9b mRNA in the AHR2 signaling pathway. PMID:28385905

In Vivo Characterization of an AHR-Dependent Long Noncoding RNA Required for Proper Sox9b Expression.

PubMed

Garcia, Gloria R; Goodale, Britton C; Wiley, Michelle W; La Du, Jane K; Hendrix, David A; Tanguay, Robert L

2017-06-01

Xenobiotic activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) prevents the proper formation of craniofacial cartilage and the heart in developing zebrafish. Downstream molecular targets responsible for AHR-dependent adverse effects remain largely unknown; however, in zebrafish sox9b has been identified as one of the most-reduced transcripts in several target organs and is hypothesized to have a causal role in TCDD-induced toxicity. The reduction of sox9b expression in TCDD-exposed zebrafish embryos has been shown to contribute to heart and jaw malformation phenotypes. The mechanisms by which AHR2 (functional ortholog of mammalian AHR) activation leads to reduced sox9b expression levels and subsequent target organ toxicity are unknown. We have identified a novel long noncoding RNA ( slincR ) that is upregulated by strong AHR ligands and is located adjacent to the sox9b gene. We hypothesize that slincR is regulated by AHR2 and transcriptionally represses sox9b. The slincR transcript functions as an RNA macromolecule, and slincR expression is AHR2 dependent. Antisense knockdown of slincR results in an increase in sox9b expression during both normal development and AHR2 activation, which suggests relief in repression. During development, slincR was expressed in tissues with sox9 essential functions, including the jaw/snout region, otic vesicle, eye, and brain. Reducing the levels of slincR resulted in altered neurologic and/or locomotor behavioral responses. Our results place slincR as an intermediate between AHR2 activation and the reduction of sox9b mRNA in the AHR2 signaling pathway. Copyright © 2017 by The Author(s).

Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.

PubMed

Bonar, Nicolle A; Petersen, Christian P

2017-03-01

Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarian Schmidtea mediterranea as a model, we identify β1-integrin as a crucial regulator of blastema architecture. β1-integrin(RNAi) animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesized in vitro We identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized in β1-integrin(RNAi) animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema. © 2017. Published by The Company of Biologists Ltd.

Brain early infarct detection using gamma correction extreme-level eliminating with weighting distribution.

PubMed

Teh, V; Sim, K S; Wong, E K

2016-11-01

According to the statistic from World Health Organization (WHO), stroke is one of the major causes of death globally. Computed tomography (CT) scan is one of the main medical diagnosis system used for diagnosis of ischemic stroke. CT scan provides brain images in Digital Imaging and Communication in Medicine (DICOM) format. The presentation of CT brain images is mainly relied on the window setting (window center and window width), which converts an image from DICOM format into normal grayscale format. Nevertheless, the ordinary window parameter could not deliver a proper contrast on CT brain images for ischemic stroke detection. In this paper, a new proposed method namely gamma correction extreme-level eliminating with weighting distribution (GCELEWD) is implemented to improve the contrast on CT brain images. GCELEWD is capable of highlighting the hypodense region for diagnosis of ischemic stroke. The performance of this new proposed technique, GCELEWD, is compared with four of the existing contrast enhancement technique such as brightness preserving bi-histogram equalization (BBHE), dualistic sub-image histogram equalization (DSIHE), extreme-level eliminating histogram equalization (ELEHE), and adaptive gamma correction with weighting distribution (AGCWD). GCELEWD shows better visualization for ischemic stroke detection and higher values with image quality assessment (IQA) module. SCANNING 38:842-856, 2016. © 2016 Wiley Periodicals, Inc. © Wiley Periodicals, Inc.

3D virtual histology at the host/parasite interface: visualisation of the master manipulator, Dicrocoelium dendriticum, in the brain of its ant host.

PubMed

Martín-Vega, Daniel; Garbout, Amin; Ahmed, Farah; Wicklein, Martina; Goater, Cameron P; Colwell, Douglas D; Hall, Martin J R

2018-06-05

Some parasites are able to manipulate the behaviour of their hosts to their own advantage. One of the most well-established textbook examples of host manipulation is that of the trematode Dicrocoelium dendriticum on ants, its second intermediate host. Infected ants harbour encysted metacercariae in the gaster and a non-encysted metacercaria in the suboesophageal ganglion (SOG); however, the mechanisms that D. dendriticum uses to manipulate the ant behaviour remain unknown, partly because of a lack of a proper and direct visualisation of the physical interface between the parasite and the ant brain tissue. Here we provide new insights into the potential mechanisms that this iconic manipulator uses to alter its host's behaviour by characterising the interface between D. dendriticum and the ant tissues with the use of non-invasive micro-CT scanning. For the first time, we show that there is a physical contact between the parasite and the ant brain tissue at the anteriormost part of the SOG, including in a case of multiple brain infection where only the parasite lodged in the most anterior part of the SOG was in contact with the ant brain tissue. We demonstrate the potential of micro-CT to further understand other parasite/host systems in parasitological research.

Integrity of the midbrain region is required to maintain the diencephalic-mesencephalic boundary in zebrafish no isthmus/pax2.1 mutants.

PubMed

Scholpp, Steffen; Brand, Michael

2003-11-01

Initial anterior-posterior patterning of the neural tube into forebrain, midbrain, and hindbrain primordia occurs already during gastrulation, in response to signals patterning the gastrula embryo. After the initial establishment, further development within each brain part is thought to proceed largely independently of the others. However, mechanisms should exist that ensure proper delineation of brain subdivisions also at later stages; such mechanisms are, however, poorly understood. In zebrafish no isthmus mutant embryos, inactivation of the pax2.1 gene leads to a failure of the midbrain and isthmus primordium to develop normally from the gastrula stage onward (Lun and Brand [1998] Development 125:3049-3062). Here, we report that, after the initially correct establishment during gastrulation stages, the neighbouring forebrain primordium and, partially, the hindbrain primordium expand into the misspecified midbrain territory in no isthmus mutant embryos. The expansion is particularly evident for the posterior part of the diencephalon and less so for the first rhombomeric segment, the territories immediately abutting the midbrain/isthmus primordium. The nucleus of the posterior commissure is expanded in size, and marker genes of the forebrain and rhombomere 1 expand progressively into the misspecified midbrain primordium, eventually resulting in respecification of the midbrain primordium. We therefore suggest that the genetic program controlled by Pax2.1 is not only involved in initiating but also in maintaining the identity of midbrain and isthmus cells to prevent them from assuming a forebrain or hindbrain fate. Copyright 2003 Wiley-Liss, Inc.

Temporal learning in the cerebellum: The microcircuit model

NASA Technical Reports Server (NTRS)

Miles, Coe F.; Rogers, David

1990-01-01

The cerebellum is that part of the brain which coordinates motor reflex behavior. To perform effectively, it must learn to generate specific motor commands at the proper times. We propose a fundamental circuit, called the MicroCircuit, which is the minimal ensemble of neurons both necessary and sufficient to learn timing. We describe how learning takes place in the MicroCircuit, which then explains the global behavior of the cerebellum as coordinated MicroCircuit behavior.

Globally conditioned Granger causality in brain–brain and brain–heart interactions: a combined heart rate variability/ultra-high-field (7 T) functional magnetic resonance imaging study

PubMed Central

Passamonti, Luca; Wald, Lawrence L.; Barbieri, Riccardo

2016-01-01

The causal, directed interactions between brain regions at rest (brain–brain networks) and between resting-state brain activity and autonomic nervous system (ANS) outflow (brain–heart links) have not been completely elucidated. We collected 7 T resting-state functional magnetic resonance imaging (fMRI) data with simultaneous respiration and heartbeat recordings in nine healthy volunteers to investigate (i) the causal interactions between cortical and subcortical brain regions at rest and (ii) the causal interactions between resting-state brain activity and the ANS as quantified through a probabilistic, point-process-based heartbeat model which generates dynamical estimates for sympathetic and parasympathetic activity as well as sympathovagal balance. Given the high amount of information shared between brain-derived signals, we compared the results of traditional bivariate Granger causality (GC) with a globally conditioned approach which evaluated the additional influence of each brain region on the causal target while factoring out effects concomitantly mediated by other brain regions. The bivariate approach resulted in a large number of possibly spurious causal brain–brain links, while, using the globally conditioned approach, we demonstrated the existence of significant selective causal links between cortical/subcortical brain regions and sympathetic and parasympathetic modulation as well as sympathovagal balance. In particular, we demonstrated a causal role of the amygdala, hypothalamus, brainstem and, among others, medial, middle and superior frontal gyri, superior temporal pole, paracentral lobule and cerebellar regions in modulating the so-called central autonomic network (CAN). In summary, we show that, provided proper conditioning is employed to eliminate spurious causalities, ultra-high-field functional imaging coupled with physiological signal acquisition and GC analysis is able to quantify directed brain–brain and brain–heart interactions reflecting central modulation of ANS outflow. PMID:27044985

Lightning may pose a danger to patients receiving deep brain stimulation: case report.

PubMed

Prezelj, Neža; Trošt, Maja; Georgiev, Dejan; Flisar, Dušan

2018-05-01

Deep brain stimulation (DBS) is an established treatment option for advanced stages of Parkinson's disease and other movement disorders. It is known that DBS is susceptible to strong electromagnetic fields (EMFs) that can be generated by various electrical devices at work, home, and in medical environments. EMFs can interfere with the proper functioning of implantable pulse generators (IPGs). Very strong EMFs can generate induction currents in implanted electrodes and even damage the brain. Manufacturers of DBS devices have issued a list of warnings on how to avoid this danger. Strong EMFs can result from natural forces as well. The authors present the case of a 66-year-old woman who was being treated with a rechargeable DBS system for neck dystonia when her apartment was struck by lightning. Domestic electronic devices that were operating during the event were burned and destroyed. The woman's IPG switched off but remained undamaged, and she suffered no neurological consequences.

A new species of myxozoan (Myxosporea) from the brain and spinal cord of rainbow trout (Oncorhynchus mykiss) from Idaho.

PubMed

Hogge, Carla I; Campbell, Matthew R; Johnson, Keith A

2008-02-01

A new species of Myxosporea, Myxobolus neurotropus n. sp., is described from the brain and spinal cord of rainbow trout (Oncorhynchus mykiss) from Duncan Creek, Owyhee County, Idaho. Spores are oval, have 2 pyriform polar capsules, and possess a thick spore wall (sutural rim) with a short intracapsular offshoot. The mean spore dimensions are length 11.8 microm, width 10.8 microm, and thickness 8.8 microm. This myxozoan is compared to other described Myxobolus species found in cranial tissues of salmonids in terms of spore morphology and phylogenetic analysis. Because it is found in brain and spinal cord, it is encountered while performing screening tests for Myxobolus cerebralis, the causative agent of salmonid whirling disease. Where chronic inflammation and granulomatous lesions are associated with M. cerebralis, histological examination shows no host response to M. neurotropus n. sp. A diagnostic polymerase chain reaction (PCR) test is included as an aid in properly identifying the species.

Adipostatic regulation of motivation and emotion.

PubMed

Davis, Jon F

2010-05-01

The proper maintenance of body weight and mood are two of the most prevalent health issues present in society today. Obese humans display higher levels of mood-related disorders and the causality of such an association is unknown. A common feature of obesity is the imbalance of regulatory hormones which normally act to maintain stable energy balance and body weight. The adiposity hormone leptin is one such signal elevated in obesity with the capacity to dampen feeding behavior through action on brain circuits which regulate appetite and metabolism. Recent evidence suggests that leptin may regulate motivation through its actions within brain reward circuitry. In addition, leptin signaling within central nervous system regions that regulate cognition and emotion elicits anti-depressant like effects. Together, these data indicate that leptin may regulate the decreased motivation and mood present in obesity and depression. This review describes the capacity of leptin to regulate motivation and depression through actions within brain circuits that modulate effort-based behavior and emotion, respectively.

Xenomelia: a social neuroscience view of altered bodily self-consciousness.

PubMed

Brugger, Peter; Lenggenhager, Bigna; Giummarra, Melita J

2013-01-01

Xenomelia, the "foreign limb syndrome," is characterized by the non-acceptance of one or more of one's own extremities and the resulting desire for elective limb amputation or paralysis. Formerly labeled "body integrity identity disorder" (BIID), the condition was originally considered a psychological or psychiatric disorder, but a brain-centered Zeitgeist and a rapidly growing interest in the neural underpinnings of bodily self-consciousness has shifted the focus toward dysfunctional central nervous system circuits. The present article outlays both mind-based and brain-based views highlighting their shortcomings. We propose that full insight into what should be conceived a "xenomelia spectrum disorder" will require interpretation of individual symptomatology in a social context. A proper social neuroscience of xenomelia respects the functional neuroanatomy of corporeal awareness, but also acknowledges the brain's plasticity in response to an individual's history, which is lived against a cultural background. This integrated view of xenomelia will promote the subfield of consciousness research concerned with the unity of body and self.

Osmotherapy for intracranial hypertension: mannitol versus hypertonic saline.

PubMed

Fink, Matthew E

2012-06-01

Hyperosmolar therapy is one of the core medical treatments for brain edema and intracranial hypertension, but controversy exists regarding the use of the most common agents, mannitol, and hypertonic saline. This article describes the relative merits and adverse effects of these agents using the best available clinical evidence. Mannitol is effective and has been used for decades in the treatment of traumatic brain injury, but it may precipitate acute renal failure if serum osmolarity exceeds 320 mOsm/L. Hypertonic saline appears to be safe, and serum sodium has been elevated to as high as 180 mEq/L in clinical settings without significant neurologic, cardiac, or renal injury. In small comparative trials both agents are effective and no clinically significant difference has been noted, but a properly powered trial has not yet been performed. Both mannitol and hypertonic saline are effective and have an acceptable risk profile for use in the treatment of elevated intracranial pressure secondary to brain edema.

Identifying the null subject: evidence from event-related brain potentials.

PubMed

Demestre, J; Meltzer, S; García-Albea, J E; Vigil, A

1999-05-01

Event-related brain potentials (ERPs) were recorded during spoken language comprehension to study the on-line effects of gender agreement violations in controlled infinitival complements. Spanish sentences were constructed in which the complement clause contained a predicate adjective marked for syntactic gender. By manipulating the gender of the antecedent (i.e., the controller) of the implicit subject while holding constant the gender of the adjective, pairs of grammatical and ungrammatical sentences were created. The detection of such a gender agreement violation would indicate that the parser had established the coreference relation between the null subject and its antecedent. The results showed a complex biphasic ERP (i.e., an early negativity with prominence at anterior and central sites, followed by a centroparietal positivity) in the violating condition as compared to the non-violating conditions. The brain reacts to NP-adjective gender agreement violations within a few hundred milliseconds of their occurrence. The data imply that the parser has properly coindexed the null subject of an infinitive clause with its antecedent.

Legal and Ethical Issues of Persons with Special Needs in Nigeria

ERIC Educational Resources Information Center

Asiwe, C. C.; Omiegbe, Odirin

2014-01-01

Persons with special needs have innate abilities and when properly harnessed through proper education would be able to contribute ultimately to their development as well as that of the society they reside in terms of political, social, economic and technological development. Before such group of persons can be properly educated there is the dire…

The Type I Interferon Response Determines Differences in Choroid Plexus Susceptibility between Newborns and Adults in Herpes Simplex Virus Encephalitis.

PubMed

Wilcox, Douglas R; Folmsbee, Stephen S; Muller, William J; Longnecker, Richard

2016-04-12

Newborns are significantly more susceptible to severe viral encephalitis than adults, with differences in the host response to infection implicated as a major factor. However, the specific host signaling pathways responsible for differences in susceptibility and neurologic morbidity have remained unknown. In a murine model of HSV encephalitis, we demonstrated that the choroid plexus (CP) is susceptible to herpes simplex virus 1 (HSV-1) early in infection of the newborn but not the adult brain. We confirmed susceptibility of the CP to HSV infection in a human case of newborn HSV encephalitis. We investigated components of the type I interferon (IFN) response in the murine brain that might account for differences in cell susceptibility and found that newborns have a dampened interferon response and significantly lower basal levels of the alpha/beta interferon (IFN-α/β) receptor (IFNAR) than do adults. To test the contribution of IFNAR to restricting infection from the CP, we infected IFNAR knockout (KO) adult mice, which showed restored CP susceptibility to HSV-1 infection in the adult. Furthermore, reduced IFNAR levels did not account for differences we found in the basal levels of several other innate signaling proteins in the wild-type newborn and the adult, including protein kinase R (PKR), that suggested specific regulation of innate immunity in the developing brain. Viral targeting of the CP, a region of the brain that plays a critical role in neurodevelopment, provides a link between newborn susceptibility to HSV and long-term neurologic morbidity among survivors of newborn HSV encephalitis. Compared to adults, newborns are significantly more susceptible to severe disease following HSV infection. Over half of newborn HSV infections result in disseminated disease or encephalitis, with long-term neurologic morbidity in 2/3 of encephalitis survivors. We investigated differences in host cell susceptibility between newborns and adults that contribute to severe central nervous system disease in the newborn. We found that, unlike the adult brain, the newborn choroid plexus (CP) was susceptible early in HSV-1 infection. We demonstrated that IFN-α/β receptor levels are lower in the newborn brain than in the adult brain and that deletion of this receptor restores susceptibility of the CP in the adult brain. The CP serves as a barrier between the blood and the cerebrospinal fluid and plays a role in proper neurodevelopment. Susceptibility of the newborn choroid plexus to HSV-1 has important implications in viral spread to the brain and, also, in the neurologic morbidity following HSV encephalitis. Copyright © 2016 Wilcox et al.

Surgical bedside master console for neurosurgical robotic system.

PubMed

Arata, Jumpei; Kenmotsu, Hajime; Takagi, Motoki; Hori, Tatsuya; Miyagi, Takahiro; Fujimoto, Hideo; Kajita, Yasukazu; Hayashi, Yuichiro; Chinzei, Kiyoyuki; Hashizume, Makoto

2013-01-01

We are currently developing a neurosurgical robotic system that facilitates access to residual tumors and improves brain tumor removal surgical outcomes. The system combines conventional and robotic surgery allowing for a quick conversion between the procedures. This concept requires a new master console that can be positioned at the surgical bedside and be sterilized. The master console was developed using new technologies, such as a parallel mechanism and pneumatic sensors. The parallel mechanism is a purely passive 5-DOF (degrees of freedom) joystick based on the author's haptic research. The parallel mechanism enables motion input of conventional brain tumor removal surgery with a compact, intuitive interface that can be used in a conventional surgical environment. In addition, the pneumatic sensors implemented on the mechanism provide an intuitive interface and electrically isolate the tool parts from the mechanism so they can be easily sterilized. The 5-DOF parallel mechanism is compact (17 cm width, 19cm depth, and 15cm height), provides a 505,050 mm and 90° workspace and is highly backdrivable (0.27N of resistance force representing the surgical motion). The evaluation tests revealed that the pneumatic sensors can properly measure the suction strength, grasping force, and hand contact. In addition, an installability test showed that the master console can be used in a conventional surgical environment. The proposed master console design was shown to be feasible for operative neurosurgery based on comprehensive testing. This master console is currently being tested for master-slave control with a surgical robotic system.

Tensor decomposition-based and principal-component-analysis-based unsupervised feature extraction applied to the gene expression and methylation profiles in the brains of social insects with multiple castes.

PubMed

Taguchi, Y-H

2018-05-08

Even though coexistence of multiple phenotypes sharing the same genomic background is interesting, it remains incompletely understood. Epigenomic profiles may represent key factors, with unknown contributions to the development of multiple phenotypes, and social-insect castes are a good model for elucidation of the underlying mechanisms. Nonetheless, previous studies have failed to identify genes associated with aberrant gene expression and methylation profiles because of the lack of suitable methodology that can address this problem properly. A recently proposed principal component analysis (PCA)-based and tensor decomposition (TD)-based unsupervised feature extraction (FE) can solve this problem because these two approaches can deal with gene expression and methylation profiles even when a small number of samples is available. PCA-based and TD-based unsupervised FE methods were applied to the analysis of gene expression and methylation profiles in the brains of two social insects, Polistes canadensis and Dinoponera quadriceps. Genes associated with differential expression and methylation between castes were identified, and analysis of enrichment of Gene Ontology terms confirmed reliability of the obtained sets of genes from the biological standpoint. Biologically relevant genes, shown to be associated with significant differential gene expression and methylation between castes, were identified here for the first time. The identification of these genes may help understand the mechanisms underlying epigenetic control of development of multiple phenotypes under the same genomic conditions.

Characterizing PCDH19 in human induced pluripotent stem cells (iPSCs) and iPSC-derived developing neurons: emerging role of a protein involved in controlling polarity during neurogenesis

PubMed Central

Compagnucci, Claudia; Petrini, Stefania; Higuraschi, Norimichi; Trivisano, Marina; Specchio, Nicola; Hirose, Shinichi; Bertini, Enrico; Terracciano, Alessandra

2015-01-01

PCDH19 (Protocadherin 19), a member of the cadherin superfamily, is involved in the pathogenic mechanism of an X-linked model of neurological disease. The biological function of PCHD19 in human neurons and during neurogenesis is currently unknown. Therefore, we decided to use the model of the induced pluripotent stem cells (iPSCs) to characterize the location and timing of expression of PCDH19 during cortical neuronal differentiation. Our data show that PCDH19 is expressed in pluripotent cells before differentiation in a homogeneous pattern, despite its localization is often limited to one pole of the cell. During neuronal differentiation, positional information on the progenitor cells assumes an important role in acquiring polarization. The proper control of the cell orientation ensures a fine balancing between symmetric (giving rise to two progenitor sister cells) versus asymmetric (giving rise to one progenitor cell and one newborn neuron) division. This process results in the polar organization of the neural tube with a lumen indicating the basal part of the polarized neuronal progenitor cell; in the iPSC model the cells are organized in the ‘neural rosette’ and interestingly, PCDH19 is located at the center of the rosette, with other well-known markers of the lumen (N-cadherin and ZO-1). These data suggest that PCDH19 has a role in instructing the apico-basal polarity of the progenitor cells, thus regulating the development of a properly organized human brain. PMID:26450854

Comparison of water-based foam and inert-gas mass emergency depopulation methods.

PubMed

Alphin, R L; Rankin, M K; Johnson, K J; Benson, E R

2010-03-01

Current control strategies for avian influenza (AI) and other highly contagious poultry diseases include surveillance, quarantine, depopulation, disposal, and decontamination. Selection of the best method of emergency mass depopulation involves maximizing human health and safety while minimizing disease spread and animal welfare concerns. Proper selection must ensure that the method is compatible with the species, age, housing type, and disposal options. No one single method is appropriate for all situations. Gassing is one of the accepted methods for euthanatizing poultry. Whole-house, partial-house, or containerized gassing procedures are currently used. The use of water-based foam was developed for emergency mass depopulation and was conditionally approved by the United States Department of Agriculture in 2006. Research has been done comparing these different methods; parameters such as time to brain death, consistency of time to brain death, and pretreatment and posttreatment corticosterone stress levels were considered. In Europe, the use of foam with carbon dioxide is preferred over conventional water-based foam. A recent experiment comparing CO2 gas, foam with CO2 gas, and foam without CO2 gas depopulation methods was conducted with the use of electroencephalometry results. Foam was as consistent as CO2 gassing and more consistent than argon-CO2 gassing. There were no statistically significant differences between foam methods.

Functional Neuroprotection and Efficient Regulation of GDNF Using Destabilizing Domains in a Rodent Model of Parkinson's Disease

PubMed Central

Quintino, Luis; Manfré, Giuseppe; Wettergren, Erika Elgstrand; Namislo, Angrit; Isaksson, Christina; Lundberg, Cecilia

2013-01-01

Glial cell line–derived neurotrophic factor (GDNF) has great potential to treat Parkinson's disease (PD). However, constitutive expression of GDNF can over time lead to side effects. Therefore, it would be useful to regulate GDNF expression. Recently, a new gene inducible system using destabilizing domains (DD) from E. coli dihydrofolate reductase (DHFR) has been developed and characterized. The advantage of this novel DD is that it is regulated by trimethoprim (TMP), a well-characterized drug that crosses the blood–brain barrier and can therefore be used to regulate gene expression in the brain. We have adapted this system to regulate expression of GDNF. A C-terminal fusion of GDNF and a DD with an additional furin cleavage site was able to be efficiently regulated in vitro, properly processed and was able to bind to canonical GDNF receptors, inducing a signaling cascade response in target cells. In vivo characterization of the protein showed that it could be efficiently induced by TMP and it was only functional when gene expression was turned on. Further characterization in a rodent model of PD showed that the regulated GDNF protected neurons, improved motor behavior of animals and was efficiently regulated in a pathological setting. PMID:23881415

Combinations of Multiple Neuroimaging Markers using Logistic Regression for Auxiliary Diagnosis of Alzheimer Disease and Mild Cognitive Impairment.

PubMed

Mao, Nini; Liu, Yunting; Chen, Kewei; Yao, Li; Wu, Xia

2018-06-05

Multiple neuroimaging modalities have been developed providing various aspects of information on the human brain. Used together and properly, these complementary multimodal neuroimaging data integrate multisource information which can facilitate a diagnosis and improve the diagnostic accuracy. In this study, 3 types of brain imaging data (sMRI, FDG-PET, and florbetapir-PET) were fused in the hope to improve diagnostic accuracy, and multivariate methods (logistic regression) were applied to these trimodal neuroimaging indices. Then, the receiver-operating characteristic (ROC) method was used to analyze the outcomes of the logistic classifier, with either each index, multiples from each modality, or all indices from all 3 modalities, to investigate their differential abilities to identify the disease. With increasing numbers of indices within each modality and across modalities, the accuracy of identifying Alzheimer disease (AD) increases to varying degrees. For example, the area under the ROC curve is above 0.98 when all the indices from the 3 imaging data types are combined. Using a combination of different indices, the results confirmed the initial hypothesis that different biomarkers were potentially complementary, and thus the conjoint analysis of multiple information from multiple sources would improve the capability to identify diseases such as AD and mild cognitive impairment. © 2018 S. Karger AG, Basel.

Attention versus consciousness in the visual brain: differences in conception, phenomenology, behavior, neuroanatomy, and physiology.

PubMed

Baars, B J

1999-07-01

A common confound between consciousness and attention makes it difficult to think clearly about recent advances in the understanding of the visual brain. Visual consciousness involves phenomenal experience of the visual world, but visual attention is more plausibly treated as a function that selects and maintains the selection of potential conscious contents, often unconsciously. In the same sense, eye movements select conscious visual events, which are not the same as conscious visual experience. According to common sense, visual experience is consciousness, and selective processes are labeled as attention. The distinction is reflected in very different behavioral measures and in very different brain anatomy and physiology. Visual consciousness tends to be associated with the "what" stream of visual feature neurons in the ventral temporal lobe. In contrast, attentional selection and maintenance are mediated by other brain regions, ranging from superior colliculi to thalamus, prefrontal cortex, and anterior cingulate. The author applied the common-sense distinction between attention and consciousness to the theoretical positions of M. I. Posner (1992, 1994) and D. LaBerge (1997, 1998) to show how it helps to clarify the evidence. He concluded that clarity of thought is served by calling a thing by its proper name.

Role of mouthguards in reducing mild traumatic brain injury/concussion incidence in high school football athletes.

PubMed

Winters, Jackson; DeMont, Richard

2014-01-01

There is continued speculation on the value of mouthguards (MGs) in preventing mild traumatic brain injury (MTBI)/concussion injuries. The purpose of this randomized prospective study was to compare the impact of pressure-laminated (LM), custom-made, properly fitted MGs to over-the-counter (OTC) MGs on the MTBI/concussion incidence in high school football athletes over a season of play. Four hundred twelve players from 6 high school football teams were included in the study. Twenty-four MTBI/concussion injuries (5.8%) were recorded. When examining the MTBI/concussion injury rate by MG type, there was a significant difference (P = 0.0423) with incidence rates of 3.6% and 8.3% in the LM MG and OTC MG groups, respectively.

[The role of neurologists in deep brain stimulation for Parkinson disease: a neurosurgical perspective].

PubMed

Umemura, Atsushi

2012-01-01

Deep brain stimulation (DBS) has been accepted as an effective treatment for medically refractory Parkinson disease (PD). Appropriate patient selection, safe and precise surgery, and proper postoperative adjustment of stimulation and medication, are essential for the success of DBS. Patient selection is the most important role for the neurologist in DBS treatment. Neurologists treating PD should understand the correct indications and contraindications for DBS, and introduce it in a timely manner to patients who can be expected to benefit substantially from it. For long term treatment of PD, ideally the neurologist in charge of the patient should adjust both the stimulation parameters and medication. Neurologists engaged in this treatment should also have a comprehensive understanding of the probable complications and how to avoid them.

Dendritic protein synthesis in the normal and diseased brain

PubMed Central

Swanger, Sharon A.; Bassell, Gary J.

2015-01-01

Synaptic activity is a spatially-limited process that requires a precise, yet dynamic, complement of proteins within the synaptic micro-domain. The maintenance and regulation of these synaptic proteins is regulated, in part, by local mRNA translation in dendrites. Protein synthesis within the postsynaptic compartment allows neurons tight spatial and temporal control of synaptic protein expression, which is critical for proper functioning of synapses and neural circuits. In this review, we discuss the identity of proteins synthesized within dendrites, the receptor-mediated mechanisms regulating their synthesis, and the possible roles for these locally synthesized proteins. We also explore how our current understanding of dendritic protein synthesis in the hippocampus can be applied to new brain regions and to understanding the pathological mechanisms underlying varied neurological diseases. PMID:23262237

Examining sensory ability, feature matching and assessment-based adaptation for a brain-computer interface using the steady-state visually evoked potential.

PubMed

Brumberg, Jonathan S; Nguyen, Anh; Pitt, Kevin M; Lorenz, Sean D

2018-01-31

We investigated how overt visual attention and oculomotor control influence successful use of a visual feedback brain-computer interface (BCI) for accessing augmentative and alternative communication (AAC) devices in a heterogeneous population of individuals with profound neuromotor impairments. BCIs are often tested within a single patient population limiting generalization of results. This study focuses on examining individual sensory abilities with an eye toward possible interface adaptations to improve device performance. Five individuals with a range of neuromotor disorders participated in four-choice BCI control task involving the steady state visually evoked potential. The BCI graphical interface was designed to simulate a commercial AAC device to examine whether an integrated device could be used successfully by individuals with neuromotor impairment. All participants were able to interact with the BCI and highest performance was found for participants able to employ an overt visual attention strategy. For participants with visual deficits to due to impaired oculomotor control, effective performance increased after accounting for mismatches between the graphical layout and participant visual capabilities. As BCIs are translated from research environments to clinical applications, the assessment of BCI-related skills will help facilitate proper device selection and provide individuals who use BCI the greatest likelihood of immediate and long term communicative success. Overall, our results indicate that adaptations can be an effective strategy to reduce barriers and increase access to BCI technology. These efforts should be directed by comprehensive assessments for matching individuals to the most appropriate device to support their complex communication needs. Implications for Rehabilitation Brain computer interfaces using the steady state visually evoked potential can be integrated with an augmentative and alternative communication device to provide access to language and literacy for individuals with neuromotor impairment. Comprehensive assessments are needed to fully understand the sensory, motor, and cognitive abilities of individuals who may use brain-computer interfaces for proper feature matching as selection of the most appropriate device including optimization device layouts and control paradigms. Oculomotor impairments negatively impact brain-computer interfaces that use the steady state visually evoked potential, but modifications to place interface stimuli and communication items in the intact visual field can improve successful outcomes.

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants

PubMed Central

Ten, Vadim S.

2017-01-01

At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units—alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise. PMID:27901512

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants.

PubMed

Ten, Vadim S

2017-02-01

At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units-alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.

Avoiding hypothermia, an intervention to prevent morbidity and mortality from pneumonia in young children.

PubMed

Pio, Antonio; Kirkwood, Betty R; Gove, Sandy

2010-02-01

Observations and experiments in animals and human beings grant plausibility to the hypothesis that hypothermia is a risk factor for pneumonia. Exposure of body to cold stress causes alterations in the systemic and local defenses against respiratory infections, favoring the infection by inhalation of pathogens normally present in the oropharynx. Neonates and young infants with hypothermia have an increased risk of death; however, there is no strong demonstration that hypothermia leads to pneumonia in these children. Studies that properly addressed the problem of confounding variables have shown an association between cold weather and pneumonia incidence. Probably the strongest evidence that supports the plausibility of the hypothesis is provided by the controlled comparison between patients with traumatic brain injury treated with hypothermia and those treated under normal body temperature. The association between exposure to cold and pneumonia is strong enough to warrant further research focused in young children in developing countries.

The dream in contemporary psychiatry.

PubMed

Reiser, M F

2001-03-01

This article offers selective reviews of cogent sectors of research regarding the dream in contemporary psychiatry. First, the author discusses relatively recent research (1953-1999) on the neurobiology and clinical psychophysiology of dreaming sleep; second, he reviews experimental cognitive neuroscientific studies of perception, emotion, and memory and the putative interrelationships among them in generating dream imagery; and third, he interprets psychoanalytic studies (1900-1999) on related aspects of dreams and the dream process. Exploration for interrelationships among information from these three areas entails discussion of the mind/brain problem. These considerations illuminate some of the logical and interpretive dilemmas that enter into debates about Freud's theory of the dream. The author proposes a preliminary psychobiologic concept of the dream process and discusses, in light of the foregoing considerations, the importance of collaborative research for developing a realistic perspective concerning the proper place of the dream in contemporary psychiatry.

Mechanisms of input and output synaptic specificity: finding partners, building synapses, and fine-tuning communication.

PubMed

Rawson, Randi L; Martin, E Anne; Williams, Megan E

2017-08-01

For most neurons to function properly, they need to develop synaptic specificity. This requires finding specific partner neurons, building the correct types of synapses, and fine-tuning these synapses in response to neural activity. Synaptic specificity is common at both a neuron's input and output synapses, whereby unique synapses are built depending on the partnering neuron. Neuroscientists have long appreciated the remarkable specificity of neural circuits but identifying molecular mechanisms mediating synaptic specificity has only recently accelerated. Here, we focus on recent progress in understanding input and output synaptic specificity in the mammalian brain. We review newly identified circuit examples for both and the latest research identifying molecular mediators including Kirrel3, FGFs, and DGLα. Lastly, we expect the pace of research on input and output specificity to continue to accelerate with the advent of new technologies in genomics, microscopy, and proteomics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cognitive impairment in heart failure patients

PubMed Central

Leto, Laura; Feola, Mauro

2014-01-01

Cognitive damage in heart failure (HF) involves different domains thus interfering with the ability for single patient to self-care and to cope with treatment regimens, modifying symptoms and health behaviours. Many cerebral and functional changes were detected in brain imaging, involving areas of both grey and white matter deputed to cognition. Although various instruments are available to explore cognition, no consensus was obtained on better tools to be used in HF population. Reduction in cerebral blood flow, decreased cardiac output, alterations of cerebrovascular reactivity and modification of blood pressure levels are the main features involved in the etiopathogenetic mechanisms of cognitive deficit. Several cardiac variables, laboratory parameters, demographic and clinical elements were studied for their possible relation with cognition and should be properly evaluated to define patients at increased risk of impairment. The present review gathers available data pointing out assured information and discussing possible areas of research development. PMID:25593581

Models in search of a brain.

PubMed

Love, Bradley C; Gureckis, Todd M

2007-06-01

Mental localization efforts tend to stress the where more than the what. We argue that the proper targets for localization are well-specified cognitive models. We make this case by relating an existing cognitive model of category learning to a learning circuit involving the hippocampus, perirhinal, and prefrontal cortices. Results from groups varying in function along this circuit (e.g., infants, amnesics, and older adults) are successfully simulated by reducing the model's ability to form new clusters in response to surprising events, such as an error in supervised learning or an unfamiliar stimulus in unsupervised learning. Clusters in the model are akin to conjunctive codes that are rooted in an episodic experience (the surprising event) yet can develop to resemble abstract codes as they are updated by subsequent experiences. Thus, the model holds that the line separating episodic and semantic information can become blurred. Dissociations (categorization vs. recognition) are explained in terms of cluster recruitment demands.

Brain Immune Interactions as the Basis of Gulf War Illness: Gulf War Illness Consortium (GWIC)

DTIC Science & Technology

2015-10-01

August to train all clinical staff and to ensure proper quality control measures are in place for the clinical studies. This has been followed up by...clinical and preclinical studies Training for researchers and clinical staff was completed at in-person meeting in Boston in August 2014 and continued to...Catechol-O- methyl transferase ( COMT ). COMT is associated with synaptic catecholamine neurotransmitters. COMT helps regulate cortical dopamine in the

Constructing fMRI connectivity networks: a whole brain functional parcellation method for node definition.

PubMed

Maggioni, Eleonora; Tana, Maria Gabriella; Arrigoni, Filippo; Zucca, Claudio; Bianchi, Anna Maria

2014-05-15

Functional Magnetic Resonance Imaging (fMRI) is used for exploring brain functionality, and recently it was applied for mapping the brain connection patterns. To give a meaningful neurobiological interpretation to the connectivity network, it is fundamental to properly define the network framework. In particular, the choice of the network nodes may affect the final connectivity results and the consequent interpretation. We introduce a novel method for the intra subject topological characterization of the nodes of fMRI brain networks, based on a whole brain parcellation scheme. The proposed whole brain parcellation algorithm divides the brain into clusters that are homogeneous from the anatomical and functional point of view, each of which constitutes a node. The functional parcellation described is based on the Tononi's cluster index, which measures instantaneous correlation in terms of intrinsic and extrinsic statistical dependencies. The method performance and reliability were first tested on simulated data, then on a real fMRI dataset acquired on healthy subjects during visual stimulation. Finally, the proposed algorithm was applied to epileptic patients' fMRI data recorded during seizures, to verify its usefulness as preparatory step for effective connectivity analysis. For each patient, the nodes of the network involved in ictal activity were defined according to the proposed parcellation scheme and Granger Causality Analysis (GCA) was applied to infer effective connectivity. We showed that the algorithm 1) performed well on simulated data, 2) was able to produce reliable inter subjects results and 3) led to a detailed definition of the effective connectivity pattern. Copyright © 2014 Elsevier B.V. All rights reserved.

Large-scale functional brain network changes in taxi drivers: evidence from resting-state fMRI.

PubMed

Wang, Lubin; Liu, Qiang; Shen, Hui; Li, Hong; Hu, Dewen

2015-03-01

Driving a car in the environment is a complex behavior that involves cognitive processing of visual information to generate the proper motor outputs and action controls. Previous neuroimaging studies have used virtual simulation to identify the brain areas that are associated with various driving-related tasks. Few studies, however, have focused on the specific patterns of functional organization in the driver's brain. The aim of this study was to assess differences in the resting-state networks (RSNs) of the brains of drivers and nondrivers. Forty healthy subjects (20 licensed taxi drivers, 20 nondrivers) underwent an 8-min resting-state functional MRI acquisition. Using independent component analysis, three sensory (primary and extrastriate visual, sensorimotor) RSNs and four cognitive (anterior and posterior default mode, left and right frontoparietal) RSNs were retrieved from the data. We then examined the group differences in the intrinsic brain activity of each RSN and in the functional network connectivity (FNC) between the RSNs. We found that the drivers had reduced intrinsic brain activity in the visual RSNs and reduced FNC between the sensory RSNs compared with the nondrivers. The major finding of this study, however, was that the FNC between the cognitive and sensory RSNs became more positively or less negatively correlated in the drivers relative to that in the nondrivers. Notably, the strength of the FNC between the left frontoparietal and primary visual RSNs was positively correlated with the number of taxi-driving years. Our findings may provide new insight into how the brain supports driving behavior. © 2014 Wiley Periodicals, Inc.

The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory.

PubMed

Cicvaric, Ana; Yang, Jiaye; Krieger, Sigurd; Khan, Deeba; Kim, Eun-Jung; Dominguez-Rodriguez, Manuel; Cabatic, Maureen; Molz, Barbara; Acevedo Aguilar, Juan Pablo; Milicevic, Radoslav; Smani, Tarik; Breuss, Johannes M; Kerjaschki, Dontscho; Pollak, Daniela D; Uhrin, Pavel; Monje, Francisco J

2016-12-01

Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology. Key messages Podoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus-dependent learning and memory functions. Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation. Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these grounds, a relevant cross-talk between podoplanin and NGF as well as a role for podoplanin in plasticity-related brain neuronal functions is here proposed.

Clinical trials in mild traumatic brain injury.

PubMed

Hoffer, Michael E; Szczupak, Mikhaylo; Balaban, Carey

2016-10-15

Traumatic brain injury is an increasingly prevalent injury seen in both civilian and military populations. Regardless of the mechanisms of injury, the most common sub-type of injury continues to be mild traumatic brain injury. Within the last decade, there has been tremendous growth in the literature regarding this disease entity. To describe the obstacles necessary to overcome in performing a rigorous and sound clinical research study investigating mild traumatic brain injury. This examination begins by a consideration of changing standards for good faith open and total reporting of any and all conflicts of interest or commitment. This issue is particularly critical in mTBI research. We next examine obstacles that include but are not limited to diagnostic criteria, inclusion/exclusion criteria, source of injury, previous history of injury, presence of comorbid conditions and proper informed consent of participants. Frequently, multi-center studies are necessary for adequate subject accrual with the added challenges of site coordination, data core management and site specific study conduct. We propose a total reversal to the traditional translational research approach where clinical studies drive new concepts for future basic science studies. There have been few mild traumatic brain injury clinical trials in the literature with treatments/interventions that have been able to overcome many of these described obstacles. We look forward to the results of current and ongoing clinical mild traumatic brain injury studies providing the tools necessary for the next generation of basic science projects. Copyright © 2016 Elsevier B.V. All rights reserved.

Impaired brain energy gain upon a glucose load in obesity.

PubMed

Wardzinski, Ewelina K; Kistenmacher, Alina; Melchert, Uwe H; Jauch-Chara, Kamila; Oltmanns, Kerstin M

2018-03-06

There is evidence that the brain's energy status is lowered in obesity despite of chronic hypercaloric nutrition. The underlying mechanisms are unknown. We hypothesized that the brain of obese people does not appropriately generate energy in response to a hypercaloric supply. Glucose was intravenously infused in 17 normal weights and 13 obese participants until blood glucose concentrations reached the postprandial levels of 7 mmol/L and 10 mmol/L. Changes in cerebral adenosine triphosphate (ATP) and phosphocreatine (PCr) content were measured by 31 phosphorus magnetic resonance spectroscopy and stress hormonal measures regulating glucose homeostasis were monitored. Because vitamin C is crucial for a proper neuronal energy synthesis we determined circulating concentrations during the experimental testing. Cerebral high-energy phosphates were increased at blood glucose levels of 7 mmol/L in normal weights, which was completely missing in the obese. Brain energy content moderately raised only at blood glucose levels of 10 mmol/L in obese participants. Vitamin C concentrations generally correlated with the brain energy content at blood glucose concentrations of 7 mmol/L. Our data demonstrate an inefficient cerebral energy gain upon a glucose load in obese men, which may result from a dysfunctional glucose transport across the blood-brain barrier or a downregulated energy synthesis in mitochondrial oxidation processes. Our finding offers an explanation for the chronic neuroenergetic deficiency and respectively missing satiety perception in obesity. Copyright © 2018. Published by Elsevier Inc.

Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier

PubMed Central

Baghirov, Habib; Karaman, Didem; Viitala, Tapani; Duchanoy, Alain; Lou, Yan-Ru; Mamaeva, Veronika; Pryazhnikov, Evgeny; Khiroug, Leonard; de Lange Davies, Catharina; Sahlgren, Cecilia; Rosenholm, Jessica M.

2016-01-01

Drug delivery into the brain is impeded by the blood-brain-barrier (BBB) that filters out the vast majority of drugs after systemic administration. In this work, we assessed the transport, uptake and cytotoxicity of promising drug nanocarriers, mesoporous silica nanoparticles (MSNs), in in vitro models of the BBB. RBE4 rat brain endothelial cells and Madin-Darby canine kidney epithelial cells, strain II, were used as BBB models. We studied spherical and rod-shaped MSNs with the following modifications: bare MSNs and MSNs coated with a poly(ethylene glycol)-poly(ethylene imine) (PEG-PEI) block copolymer. In transport studies, MSNs showed low permeability, whereas the results of the cellular uptake studies suggest robust uptake of PEG-PEI-coated MSNs. None of the MSNs showed significant toxic effects in the cell viability studies. While the shape effect was detectable but small, especially in the real-time surface plasmon resonance measurements, coating with PEG-PEI copolymers clearly facilitated the uptake of MSNs. Finally, we evaluated the in vivo detectability of one of the best candidates, i.e. the copolymer-coated rod-shaped MSNs, by two-photon in vivo imaging in the brain vasculature. The particles were clearly detectable after intravenous injection and caused no damage to the BBB. Thus, when properly designed, the uptake of MSNs could potentially be utilized for the delivery of drugs into the brain via transcellular transport. PMID:27547955

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

PubMed

Fišar, Z; Hroudová, J

2016-01-01

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

Optimization of flow-sensitive alternating inversion recovery (FAIR) for perfusion functional MRI of rodent brain.

PubMed

Nasrallah, Fatima A; Lee, Eugene L Q; Chuang, Kai-Hsiang

2012-11-01

Arterial spin labeling (ASL) MRI provides a noninvasive method to image perfusion, and has been applied to map neural activation in the brain. Although pulsed labeling methods have been widely used in humans, continuous ASL with a dedicated neck labeling coil is still the preferred method in rodent brain functional MRI (fMRI) to maximize the sensitivity and allow multislice acquisition. However, the additional hardware is not readily available and hence its application is limited. In this study, flow-sensitive alternating inversion recovery (FAIR) pulsed ASL was optimized for fMRI of rat brain. A practical challenge of FAIR is the suboptimal global inversion by the transmit coil of limited dimensions, which results in low effective labeling. By using a large volume transmit coil and proper positioning to optimize the body coverage, the perfusion signal was increased by 38.3% compared with positioning the brain at the isocenter. An additional 53.3% gain in signal was achieved using optimized repetition and inversion times compared with a long TR. Under electrical stimulation to the forepaws, a perfusion activation signal change of 63.7 ± 6.3% can be reliably detected in the primary somatosensory cortices using single slice or multislice echo planar imaging at 9.4 T. This demonstrates the potential of using pulsed ASL for multislice perfusion fMRI in functional and pharmacological applications in rat brain. Copyright © 2012 John Wiley & Sons, Ltd.

Oligodendroglial Alterations and the Role of Microglia in White Matter Injury: Relevance to Schizophrenia

PubMed Central

Chew, Li-Jin; Fusar-Poli, Paolo; Schmitz, Thomas

2015-01-01

Schizophrenia is a chronic and debilitating mental illness characterized by a broad range of abnormal behaviors, including delusions and hallucinations, impaired cognitive function, as well as mood disturbances and social withdrawal. Due to the heterogeneous nature of the disease, the causes of schizophrenia are very complex; its etiology is believed to involve multiple brain regions and the connections between them, and includes alterations in both gray and white matter regions. The onset of symptoms varies with age and severity, and there is some debate over a degenerative or developmental etiology. Longitudinal magnetic resonance imaging studies have detected progressive gray matter loss in the first years of disease, suggesting neurodegeneration; but there is also increasing recognition of a temporal association between clinical complications at birth and disease onset that supports a neurodevelopmental origin. Presently, neuronal abnormalities in schizophrenia are better understood than alterations in myelin-producing cells of the brain, the oligodendrocytes, which are the predominant constituents of white matter structures. Proper white matter development and its structural integrity critically impacts brain connectivity, which affects sensorimotor coordination and cognitive ability. Evidence of defective white matter growth and compromised white matter integrity has been found in individuals at high risk of psychosis, and decreased numbers of mature oligodendrocytes are detected in schizophrenia patients. Inflammatory markers, including proinflammatory cytokines and chemokines, are also associated with psychosis. A relationship between risk of psychosis, white matter defects and prenatal inflammation is being established. Animal models of perinatal brain injury are successful in producing white matter damage in the brain, typified by hypomyelination and/or dysmyelination, impaired motor coordination and prepulse inhibition of the acoustic startle reflex, recapitulating structural and functional characteristics observed in schizophrenia. In addition, elevated expression of inflammation-related genes in brain tissue and increased production of cytokines by blood cells from patients with schizophrenia indicate immunological dysfunction and abnormal inflammatory responses, which are also important underlying features in experimental models. Microglia, resident immune defenders of the central nervous system, play important roles in the development and protection of neural cells, but can contribute to injury under pathological conditions. This article discusses oligodendroglial changes in schizophrenia and focuses on microglial activity in the context of the disease, in neonatal brain injury and in various experimental models of white matter damage. These include disorders associated with premature birth, and animal models of perinatal bacterial and viral infection, oxygen deprivation (hypoxia) and excess (hyperoxia), and elevated systemic proinflammatory cytokine levels. We briefly review the effects of treatment with antipsychotic and anti-inflammatory agents in models of perinatal brain injury, and comment on the therapeutic potential of these strategies. By understanding the neurobiological basis of oligodendroglial abnormalities in schizophrenia, it is hoped that patients will benefit from the availability of targeted and more efficacious treatment options. PMID:23446060

Building a neuroscience of pleasure and well-being

PubMed Central

Berridge, Kent C; Kringelbach, Morten L

2012-01-01

Background How is happiness generated via brain function in lucky individuals who have the good fortune to be happy? Conceptually, well-being or happiness has long been viewed as requiring at least two crucial ingredients: positive affect or pleasure (hedonia) and a sense of meaningfulness or engagement in life (eudaimonia). Science has recently made progress in relating hedonic pleasure to brain function, and so here we survey new insights into how brains generate the hedonic ingredient of sustained or frequent pleasure. We also briefly discuss how brains might connect hedonia states of pleasure to eudaimonia assessments of meaningfulness, and so create balanced states of positive well-being. Results Notable progress has been made in understanding brain bases of hedonic processing, producing insights into that brain systems that cause and/or code sensory pleasures. Progress has been facilitated by the recognition that hedonic brain mechanisms are largely shared between humans and other mammals, allowing application of conclusions from animal studies to a better understanding of human pleasures. In the past few years, evidence has also grown to indicate that for humans, brain mechanisms of higher abstract pleasures strongly overlap with more basic sensory pleasures. This overlap may provide a window into underlying brain circuitry that generates all pleasures, including even the hedonic quality of pervasive well-being that detaches from any particular sensation to apply to daily life in a more sustained or frequent fashion. Conclusions Hedonic insights are applied to understanding human well-being here. Our strategy combines new findings on brain mediators that generate the pleasure of sensations with evidence that human brains use many of the same hedonic circuits from sensory pleasures to create the higher pleasures. This in turn may be linked to how hedonic systems interact with other brain systems relevant to self-understanding and the meaning components of eudaimonic happiness. Finally, we speculate a bit about how brains that generate hedonia states might link to eudaimonia assessments to create properly balanced states of positive well-being that approach true happiness. PMID:22328976

Molecular Mechanisms of Cannabis Signaling in the Brain.

PubMed

Ronan, Patrick J; Wongngamnit, Narin; Beresford, Thomas P

2016-01-01

Cannabis has been cultivated and used by humans for thousands of years. Research for decades was focused on understanding the mechanisms of an illegal/addictive drug. This led to the discovery of the vast endocannabinoid system. Research has now shifted to understanding fundamental biological questions related to one of the most widespread signaling systems in both the brain and the body. Our understanding of cannabinoid signaling has advanced significantly in the last two decades. In this review, we discuss the state of knowledge on mechanisms of Cannabis signaling in the brain and the modulation of key brain neurotransmitter systems involved in both brain reward/addiction and psychiatric disorders. It is highly probable that various cannabinoids will be found to be efficacious in the treatment of a number of psychiatric disorders. However, while there is clearly much potential, marijuana has not been properly vetted by the medical-scientific evaluation process and there are clearly a range of potentially adverse side-effects-including addiction. We are at crossroads for research on endocannabinoid function and therapeutics (including the use of exogenous treatments such as Cannabis). With over 100 cannabinoid constituents, the majority of which have not been studied, there is much Cannabis research yet to be done. With more states legalizing both the medicinal and recreational use of marijuana the rigorous scientific investigation into cannabinoid signaling is imperative. Copyright © 2016. Published by Elsevier Inc.

SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis

PubMed Central

Zhou, Ying; Wang, Jian; Tseng, I-Chu; Huang, Timothy; Zhao, Yingjun; Zheng, Qiuyang; Gao, Yue; Luo, Hong; Zhang, Xian; Bu, Guojun; Hong, Wanjin

2016-01-01

Hydrocephalus is a brain disorder derived from CSF accumulation due to defects in CSF clearance. Although dysfunctional apical cilia in the ependymal cell layer are causal to the onset of hydrocephalus, mechanisms underlying proper ependymal cell differentiation are largely unclear. SNX27 is a trafficking component required for normal brain function and was shown previously to suppress γ-secretase-dependent amyloid precursor protein and Notch cleavage. However, it was unclear how SNX27-dependent γ-secretase inhibition could contribute to brain development and pathophysiology. Here, we describe and characterize an Snx27-deleted mouse model for the ependymal layer defects of deciliation and hydrocephalus. SNX27 deficiency results in reductions in ependymal cells and cilia density, as well as severe postnatal hydrocephalus. Inhibition of Notch intracellular domain signaling with γ-secretase inhibitors reversed ependymal cells/cilia loss and dilation of lateral ventricles in Snx27-deficient mice, giving strong indication that Snx27 deletion triggers defects in ependymal layer formation and ciliogenesis through Notch hyperactivation. Together, these results suggest that SNX27 is essential for ependymal cell differentiation and ciliogenesis, and its deletion can promote hydrocephalus pathogenesis. SIGNIFICANCE STATEMENT Down's syndrome (DS) in humans and mouse models has been shown previously to confer a high risk for the development of pathological hydrocephalus. Because we have previously described SNX27 as a component that is consistently downregulated in DS, we present here a robust Snx27-deleted mouse model that produces hydrocephalus and associated ciliary defects with complete penetrance. In addition, we find that γ-secretase/Notch modulation may be a candidate drug target in SNX27-associated hydrocephalus such as that observed in DS. Based on these findings, we anticipate that future study will determine whether modulation of a SNX27/Notch/γ-secretase pathway can also be of therapeutic interest to congenital hydrocephalus. PMID:27974614

SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis.

PubMed

Wang, Xin; Zhou, Ying; Wang, Jian; Tseng, I-Chu; Huang, Timothy; Zhao, Yingjun; Zheng, Qiuyang; Gao, Yue; Luo, Hong; Zhang, Xian; Bu, Guojun; Hong, Wanjin; Xu, Huaxi

2016-12-14

Hydrocephalus is a brain disorder derived from CSF accumulation due to defects in CSF clearance. Although dysfunctional apical cilia in the ependymal cell layer are causal to the onset of hydrocephalus, mechanisms underlying proper ependymal cell differentiation are largely unclear. SNX27 is a trafficking component required for normal brain function and was shown previously to suppress γ-secretase-dependent amyloid precursor protein and Notch cleavage. However, it was unclear how SNX27-dependent γ-secretase inhibition could contribute to brain development and pathophysiology. Here, we describe and characterize an Snx27-deleted mouse model for the ependymal layer defects of deciliation and hydrocephalus. SNX27 deficiency results in reductions in ependymal cells and cilia density, as well as severe postnatal hydrocephalus. Inhibition of Notch intracellular domain signaling with γ-secretase inhibitors reversed ependymal cells/cilia loss and dilation of lateral ventricles in Snx27-deficient mice, giving strong indication that Snx27 deletion triggers defects in ependymal layer formation and ciliogenesis through Notch hyperactivation. Together, these results suggest that SNX27 is essential for ependymal cell differentiation and ciliogenesis, and its deletion can promote hydrocephalus pathogenesis. Down's syndrome (DS) in humans and mouse models has been shown previously to confer a high risk for the development of pathological hydrocephalus. Because we have previously described SNX27 as a component that is consistently downregulated in DS, we present here a robust Snx27-deleted mouse model that produces hydrocephalus and associated ciliary defects with complete penetrance. In addition, we find that γ-secretase/Notch modulation may be a candidate drug target in SNX27-associated hydrocephalus such as that observed in DS. Based on these findings, we anticipate that future study will determine whether modulation of a SNX27/Notch/γ-secretase pathway can also be of therapeutic interest to congenital hydrocephalus. Copyright © 2016 the authors 0270-6474/16/3612586-12$15.00/0.

Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

NASA Technical Reports Server (NTRS)

Quinn, K. J.; Didier, A. J.; Baker, J. F.; Peterson, B. W.

1998-01-01

A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

Perspectives on dyslexia

PubMed Central

Siegel, Linda S

2006-01-01

Dyslexia, or a reading disability, occurs when an individual has significant difficulty with speed and accuracy of word decoding. Comprehension of text and spelling are also affected. The diagnosis of dyslexia involves the use of reading tests, but the continuum of reading performance means that any cutoff point is arbitrary. The IQ score does not play a role in the diagnosis of dyslexia. The cognitive difficulties of dyslexics include problems with speech perception, recognizing and manipulating the basic sounds in a language, language memory, and learning the sounds of letters. Dyslexia is a neurological condition with a genetic basis. There are abnormalities in the brains of dyslexic individuals. There are also differences in the electrophysiological and structural characteristics of the brains of dyslexics. Physicians play a particularly important role in recognizing children who are at risk for dyslexia and helping their parents obtain the proper assessment. PMID:19030329

Regionally Impaired Redox Homeostasis in the Brain of Rats Subjected to Global Perinatal Asphyxia: Sustained Effect up to 14 Postnatal Days.

PubMed

Lespay-Rebolledo, Carolyne; Perez-Lobos, Ronald; Tapia-Bustos, Andrea; Vio, Valentina; Morales, Paola; Herrera-Marschitz, Mario

2018-06-29

The present report evaluates the effect of global perinatal asphyxia on several parameters of oxidative stress and cell viability in rat brain tissue sampled at an extended neonatal period up to 14 days, a period characterised by intensive neuritogenesis, synaptogenesis, synaptic consolidation, pruning and delayed cell death. Perinatal asphyxia was induced by immersing foetus-containing uterine horns removed by a caesarean section from on term rat dams into a water bath at 37 °C for 21 min. Asphyxia-exposed and sibling caesarean-delivered foetuses were manually resucitated and nurtured by surrogate dams for 1 to 14 postnatal (P) days. Brain samples (mesencephalon, telencephalon and hippocampus) were assayed for glutathione (reduced and oxidated levels; spectrophotometry), tissue reducing capacity (potassium ferricyanide reducing assay, FRAP), catalase (the key enzyme protecting against oxidative stress and reactive oxygen species, Western blots and ELISA) and cleaved caspase-3 (the key executioner of apoptosis, Western blots) levels. It was found that global PA produced a regionally specific and sustained increase in GSSG/GSH ratio, a regionally specific decrease in tissue reducing capacity and a regionally and time specific decrease of catalase activity and increase of cleaved caspase-3 levels. The present study provides evidence for regionally impaired redox homeostasis in the brain of rats subjected to global PA, an effect observed up to P14, mainly affecting mesencephalon and hippocampus, suggesting a sustained oxidative stress after the posthypoxia period. The oxidative stress observed postnatally can in part be associated to a respiratory apneic-like deficit, since there was a statistically significant decrease in respiration frequency in AS compared to CS neonates, also up to P14, together with the signs of a decreased peripheral blood perfusion (pink-blue skin colour in AS, compared to the pink colour observed in all CS neonates). It is proposed that PA implies a long-term metabolic insult, triggered by the length of hypoxia, the resuscitation/reoxigenation manoevres, but also by the developmental stage of the affected brain regions, and the integrity of cardiovascular and respiratory physiological functions, which are fundamental for warrantying a proper development.

Encoding of speed and direction of movement in the human supplementary motor area

PubMed Central

Tankus, Ariel; Yeshurun, Yehezkel; Flash, Tamar; Fried, Itzhak

2010-01-01

Object The supplementary motor area (SMA) plays an important role in planning, initiation, and execution of motor acts. Patients with SMA lesions are impaired in various kinematic parameters, such as velocity and duration of movement. However, the relationships between neuronal activity and these parameters in the human brain have not been fully characterized. This is a study of single-neuron activity during a continuous volitional motor task, with the goal of clarifying these relationships for SMA neurons and other frontal lobe regions in humans. Methods The participants were 7 patients undergoing evaluation for epilepsy surgery requiring implantation of intracranial depth electrodes. Single-unit recordings were conducted while the patients played a computer game involving movement of a cursor in a simple maze. Results In the SMA proper, most of the recorded units exhibited a monotonic relationship between the unit firing rate and hand motion speed. The vast majority of SMA proper units with this property showed an inverse relation, that is, firing rate decrease with speed increase. In addition, most of the SMA proper units were selective to the direction of hand motion. These relationships were far less frequent in the pre-SMA, anterior cingulate gyrus, and orbitofrontal cortex. Conclusions The findings suggest that the SMA proper takes part in the control of kinematic parameters of end-effector motion, and thus lend support to the idea of connecting neuroprosthetic devices to the human SMA. PMID:19231930

Assistive technology and home modification for people with neurovisual deficits.

PubMed

Copolillo, Al; Ivanoff, Synneve Dahlin

2011-01-01

People with neurovisual deficits from acquired brain injuries and other neurological disabilities can benefit from the array of assistive technologies and home modifications available to the larger vision impairment population, especially when symptoms are mild and associated neurological conditions are few. Optics, proper lighting, and magnification to increase the perceived size of both objects and reading material and to improve contrast sensitivity have been shown to be beneficial. Innovative technologies, universally designed for safe independent living and community participation are gradually developing and show promise for addressing the needs of this population. This article highlights technologies that may be useful for people with neurovisual deficits and describes the evidence to support their training and use. The use of various types of eyewear to reduce falls; prisms and telescopic lenses to improve visual attention and minimize the impact of visual field deficits; and technologies to improve computer use, wayfinding, and home safety are discussed. While there remains substantial need for further research and development focusing on the needs of people with vision impairments from neurological conditions, practitioners can use technology with caution to improve functional outcomes.

Overview of nano-drugs characteristics for clinical application: the journey from the entry to the exit point

NASA Astrophysics Data System (ADS)

Bose, Tanima; Latawiec, Diane; Mondal, Partha Pratim; Mandal, Subhra

2014-08-01

The ever-increasing number of diseases worldwide requires comprehensive, efficient, and cost-effective modes of treatments. Among various strategies, nanomaterials fulfill most of these criteria. The unique physicochemical properties of nanoparticles have made them a premier choice as a drug or a drug delivery system for the purpose of treatment, and as bio-detectors for disease prognosis. However, the main challenge is the proper consideration of the physical properties of these nanomaterials, while developing them as potential tools for therapeutics and/or diagnostics. In this review, we focus mainly on the characteristics of nanoparticles to develop an effective and sensitive system for clinical purposes. This review will present an overview of the important properties of nanoparticles, through their journey from its route of administration until disposal from the human body after accomplishing targeted functionality. We have chosen cancer as our model disease to explain the potentiality of nano-systems for therapeutics and diagnostics in relation to several organs (intestine, lung, brain, etc.). Furthermore, we have discussed their biodegradability and accumulation probability which can cause unfavorable side effects in healthy human subjects.

Editing the Neuronal Genome: a CRISPR View of Chromatin Regulation in Neuronal Development, Function, and Plasticity

PubMed Central

Yang, Marty G.; West, Anne E.

2016-01-01

The dynamic orchestration of gene expression is crucial for the proper differentiation, function, and adaptation of cells. In the brain, transcriptional regulation underlies the incredible diversity of neuronal cell types and contributes to the ability of neurons to adapt their function to the environment. Recently, novel methods for genome and epigenome editing have begun to revolutionize our understanding of gene regulatory mechanisms. In particular, the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has proven to be a particularly accessible and adaptable technique for genome engineering. Here, we review the use of CRISPR/Cas9 in neurobiology and discuss how these studies have advanced understanding of nervous system development and plasticity. We cover four especially salient applications of CRISPR/Cas9: testing the consequences of enhancer mutations, tagging genes and gene products for visualization in live cells, directly activating or repressing enhancers in vivo, and manipulating the epigenome. In each case, we summarize findings from recent studies and discuss evolving adaptations of the method. PMID:28018138

Classification of stroke disease using convolutional neural network

NASA Astrophysics Data System (ADS)

Marbun, J. T.; Seniman; Andayani, U.

2018-03-01

Stroke is a condition that occurs when the blood supply stop flowing to the brain because of a blockage or a broken blood vessel. A symptoms that happen when experiencing stroke, some of them is a dropped consciousness, disrupted vision and paralyzed body. The general examination is being done to get a picture of the brain part that have stroke using Computerized Tomography (CT) Scan. The image produced from CT will be manually checked and need a proper lighting by doctor to get a type of stroke. That is why it needs a method to classify stroke from CT image automatically. A method proposed in this research is Convolutional Neural Network. CT image of the brain is used as the input for image processing. The stage before classification are image processing (Grayscaling, Scaling, Contrast Limited Adaptive Histogram Equalization, then the image being classified with Convolutional Neural Network. The result then showed that the method significantly conducted was able to be used as a tool to classify stroke disease in order to distinguish the type of stroke from CT image.

Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release.

PubMed

Younts, Thomas J; Monday, Hannah R; Dudok, Barna; Klein, Matthew E; Jordan, Bryen A; Katona, István; Castillo, Pablo E

2016-10-19

Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type 1 cannabinoid receptor (CB 1 )-expressing axons. This long-term depression of inhibitory transmission (iLTD) involves cap-dependent protein synthesis in presynaptic interneuron axons, but not somata. Translation is required during the induction, but not maintenance, of iLTD. Mechanistically, CB 1 activation enhances protein synthesis via the mTOR pathway. Furthermore, using super-resolution STORM microscopy, we revealed eukaryotic ribosomes in CB 1 -expressing axon terminals. These findings suggest that presynaptic local protein synthesis controls neurotransmitter release during long-term plasticity in the mature mammalian brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain Development and Its Relationship to Early Childhood Education.

ERIC Educational Resources Information Center

Slegers, Brenda

New research on brain development has profound implications in the areas of child development and education. This review of the research describes how the brain develops to shape children's growing intelligence, addressing such questions as: (1) What are the brain's functions? (2) What are the critical or sensitive periods in brain development?…

Discovery, characterization and expression of a novel zebrafish gene, znfr, important for notochord formation.

PubMed

Xu, Yan; Zou, Peng; Liu, Yao; Deng, Fengjiao

2010-06-01

Genes specifically expressed in the notochord may be crucial for proper notochord development. Using the digital differential display program offered by the National Center for Biotechnology Information, we identified a novel EST sequence from a zebrafish ovary library (No. XM_701450). The full-length cDNA of this transcript was cloned by performing 3' and 5'-RACE and was further confirmed by PCR and sequencing. The resulting 614 bp gene was found to encode a novel 94 amino acid protein that did not share significant homology with any other known protein. Characterization of the genomic sequence revealed that the gene spanned 4.9 kb and was composed of four exons and three introns. RT-PCR gene expression analysis revealed that our gene of interest was expressed in ovary, kidney, brain, mature oocytes and during the early stages of embryogenesis. During embryonic development, znfr mRNA was found to be expressed in the embryonic shield, chordamesoderm and the vacuolated notochord cells by in situ hybridization. Based on this information, we hypothesize that this novel gene is an important maternal factor required for zebrafish notochord formation during early embryonic development. We have thus named this gene znfr (zebrafish notochord formation related).

Coordinating cell and tissue behavior during zebrafish neural tube morphogenesis.

PubMed

Araya, Claudio; Ward, Laura C; Girdler, Gemma C; Miranda, Miguel

2016-03-01

The development of a vertebrate neural epithelium with well-organized apico-basal polarity and a central lumen is essential for its proper function. However, how this polarity is established during embryonic development and the potential influence of surrounding signals and tissues on such organization has remained less understood. In recent years the combined superior transparency and genetics of the zebrafish embryo has allowed for in vivo visualization and quantification of the cellular and molecular dynamics that govern neural tube structure. Here, we discuss recent studies revealing how co-ordinated cell-cell interactions coupled with adjacent tissue dynamics are critical to regulate final neural tissue architecture. Furthermore, new findings show how the spatial regulation and timing of orientated cell division is key in defining precise lumen formation at the tissue midline. In addition, we compare zebrafish neurulation with that of amniotes and amphibians in an attempt to understand the conserved cellular mechanisms driving neurulation and resolve the apparent differences among animals. Zebrafish neurulation not only offers fundamental insights into early vertebrate brain development but also the opportunity to explore in vivo cell and tissue dynamics during complex three-dimensional animal morphogenesis. © 2015 Wiley Periodicals, Inc.

The Neuropathology of Obesity: Insights from Human Disease

PubMed Central

Lee, Edward B.; Mattson, Mark P.

2013-01-01

Obesity, a pathologic state defined by excess adipose tissue, is a significant public health problem as it affects a large proportion of individuals and is linked with increased risk for numerous chronic diseases. Obesity is the result of fundamental changes associated with modern society including overnutrition and sedentary lifestyles. Proper energy homeostasis is dependent on normal brain function as the master metabolic regulator which integrates peripheral signals, modulates autonomic outflow and controls feeding behavior. Therefore, many human brain diseases are associated with obesity. This review explores the neuropathology of obesity by examining brain diseases which either cause or are influenced by obesity. First, several genetic and acquired brain diseases are discussed as a means to understand the central regulation of peripheral metabolism. These diseases range from monogenetic causes of obesity (leptin deficiency, MC4R deficiency, Bardet-Biedl syndrome and others) to complex neurodevelopmental disorders (Prader-Willi syndrome and Sim1 deficiency) and neurodegenerative conditions (frontotemporal dementia and Gourmand’s syndrome) and serve to highlight the central regulatory mechanisms which have evolved to maintain energy homeostasis. Next, to examine the effect of obesity on the brain, chronic neuropathologic conditions (epilepsy, multiple sclerosis and Alzheimer’s disease) are discussed as examples of obesity leading to maladaptive processes which exacerbate chronic disease. Thus obesity is associated with multiple pathways including abnormal metabolism, altered hormonal signaling and increased inflammation which act in concert to promote downstream neuropathology. Finally, the effect of anti-obesity interventions is discussed in terms of brain structure and function. Together, understanding human diseases and anti-obesity interventions leads to insights into the bidirectional interaction between peripheral metabolism and central brain function, highlighting the need for continued clinicopathologic and mechanistic studies of the neuropathology of obesity. PMID:24096619

Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

PubMed Central

Kim, Albert H.; Wakabayashi, Ken T.; Baumann, Michael H.; Shaham, Yavin

2014-01-01

MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed “rave” parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22−23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ∼1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues. PMID:24899699

Build-Ups in the Supply Chain of the Brain: on the Neuroenergetic Cause of Obesity and Type 2 Diabetes Mellitus

PubMed Central

Peters, Achim; Langemann, Dirk

2009-01-01

Obesity and type 2 diabetes have become the major health problems in many industrialized countries. A few theoretical frameworks have been set up to derive the possible determinative cause of obesity. One concept views that food availability determines food intake, i.e. that obesity is the result of an external energy “push” into the body. Another one views that the energy milieu within the human organism determines food intake, i.e. that obesity is due to an excessive “pull” from inside the organism. Here we present the unconventional concept that a healthy organism is maintained by a “competent brain-pull” which serves systemic homeostasis, and that the underlying cause of obesity is “incompetent brain-pull”, i.e. that the brain is unable to properly demand glucose from the body. We describe the energy fluxes from the environment, through the body, towards the brain with a mathematical “supply chain” model and test whether its predictions fit medical and experimental data sets from our and other research groups. In this way, we show data-based support of our hypothesis, which states that under conditions of food abundance incompetent brain-pull will lead to build-ups in the supply chain culminating in obesity and type 2 diabetes. In the same way, we demonstrate support of the related hypothesis, which states that under conditions of food deprivation a competent brain-pull mechanism is indispensable for the continuance of the brain´s high energy level. In conclusion, we took the viewpoint of integrative physiology and provided evidence for the necessity of brain-pull mechanisms for the benefit of health. Along these lines, our work supports recent molecular findings from the field of neuroenergetics and continues the work on the “Selfish Brain” theory dealing with the maintenance of the cerebral and peripheral energy homeostasis. PMID:19584906

Doxycycline down-regulates DNA-PK and radiosensitizes tumor initiating cells: Implications for more effective radiation therapy

PubMed Central

Lamb, Rebecca; Fiorillo, Marco; Chadwick, Amy; Ozsvari, Bela; Reeves, Kimberly J.; Smith, Duncan L.; Clarke, Robert B.; Howell, Sacha J.; Cappello, Anna Rita; Martinez-Outschoorn, Ubaldo E.; Peiris-Pagès, Maria; Sotgia, Federica; Lisanti, Michael P.

2015-01-01

DNA-PK is an enzyme that is required for proper DNA-repair and is thought to confer radio-resistance in cancer cells. As a consequence, it is a high-profile validated target for new pharmaceutical development. However, no FDA-approved DNA-PK inhibitors have emerged, despite many years of drug discovery and lead optimization. This is largely because existing DNA-PK inhibitors suffer from poor pharmacokinetics. They are not well absorbed and/or are unstable, with a short plasma half-life. Here, we identified the first FDA-approved DNA-PK inhibitor by “chemical proteomics”. In an effort to understand how doxycycline targets cancer stem-like cells (CSCs), we serendipitously discovered that doxycycline reduces DNA-PK protein expression by nearly 15-fold (> 90%). In accordance with these observations, we show that doxycycline functionally radio-sensitizes breast CSCs, by up to 4.5-fold. Moreover, we demonstrate that DNA-PK is highly over-expressed in both MCF7- and T47D-derived mammospheres. Interestingly, genetic or pharmacological inhibition of DNA-PK in MCF7 cells is sufficient to functionally block mammosphere formation. Thus, it appears that active DNA-repair is required for the clonal expansion of CSCs. Mechanistically, doxycycline treatment dramatically reduced the oxidative mitochondrial capacity and the glycolytic activity of cancer cells, consistent with previous studies linking DNA-PK expression to the proper maintenance of mitochondrial DNA integrity and copy number. Using a luciferase-based assay, we observed that doxycycline treatment quantitatively reduces the anti-oxidant response (NRF1/2) and effectively blocks signaling along multiple independent pathways normally associated with stem cells, including STAT1/3, Sonic Hedgehog (Shh), Notch, WNT and TGF-beta signaling. In conclusion, we propose that the efficacy of doxycycline as a DNA-PK inhibitor should be tested in Phase-II clinical trials, in combination with radio-therapy. Doxycycline has excellent pharmacokinetics, with nearly 100% oral absorption and a long serum half-life (18–22 hours), at a standard dose of 200-mg per day. In further support of this idea, we show that doxycycline effectively inhibits the mammosphere-forming activity of primary breast cancer samples, derived from metastatic disease sites (pleural effusions or ascites fluid). Our results also have possible implications for the radio-therapy of brain tumors and/or brain metastases, as doxycycline is known to effectively cross the blood-brain barrier. Further studies will be needed to determine if other tetracycline family members also confer radio-sensitivity. PMID:26087309

Detection of rabies antigen in the saliva and brains of apparently healthy dogs slaughtered for human consumption and its public health implications in abia state, Nigeria.

PubMed

Mshelbwala, P P; Ogunkoya, A B; Maikai, B V

2013-01-01

The study was carried out in eight dogs slaughtering outlets within four Local Government Areas of the State for the determination of rabies antigen in the saliva and brain of apparently healthy dogs slaughtered for human consumption. A total of one hundred (100) samples each of saliva and brain were collected before and after slaughter, respectively, between April to June, 2013, in the selected areas. The saliva was subjected to rapid immune-chromatographic test (RICT) while direct fluorescent antibody test (DFAT) was carried out on the brain samples. Structured questionnaire was administered to nineteen (19) dog meat processors comprising 18 males and 1 female in the selected areas. Sixty four percent of the samples tested were from female dogs while 36% were from males, 5% tested positive for rabies antigen with the use of both tests; there was no statistical association between sex and rabies status of the dogs sampled (P > 0.05). Butchers bitten during the course of slaughtering were 94.7% out of which 72.8% utilized traditional method of treatment and only 27.8% reported to the hospital for proper medical attention. This study has established the presence of rabies antigen in apparently healthy dogs in the study area.

Altered Insula Connectivity under MDMA.

PubMed

Walpola, Ishan C; Nest, Timothy; Roseman, Leor; Erritzoe, David; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L

2017-10-01

Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, double-blind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations-both of which are known to be associated with insular functioning.

Nutritional status, assessment, requirements and adequacy of traumatic brain injury patients.

PubMed

Daradkeh, Ghazi; Essa, Musthafa Mohamed; Al-Adawi, S Samir; Subash, Selvaraju; Mahmood, Lubna; Kumar, Parvathy R

2014-10-01

Traumatic Brain Injury (TBI) has been considered as a serious public health problem. Each year, traumatic brain injuries are contributing to a substantial number of cases of permanent disability and deaths and it can be classified according to the severity into penetrating and closed head injury. Symptoms, beside to be unconscious can be defined as vomiting, nausea, headache, dizziness, lack of motor coordination, difficulty in balancing, blurred vision and lightheadedness, bad taste in the mouth, ringing in the ears, fatigue and lethargy as well as changes in sleep patterns. The brain is known to be the functional regulator for all the metabolic activities inside the body and TBI patients mostly have a complex metabolic alterations including aberrant cellular metabolism, abnormal metabolic processes, changes in hormones functions and inflammatory cascade. The TBI patient's status needed to be assessed medically and nutritionally since the medical status of the patients can affect the nutrition part. Data from the four assessment tools are needed to be correctly used and interpreted in order to make a proper nutritional diagnosis, clinical assessment, biochemistry as well as anthropometric measurements. Regardless the methods used for assessing TBI patients, having adequate intake and medical care can lead to a reduction in hospital costs, numbers of day hospitalized, numbers of hours of mechanical ventilation and in the overall infection rates.

EEG Classification for Hybrid Brain-Computer Interface Using a Tensor Based Multiclass Multimodal Analysis Scheme

PubMed Central

Ji, Hongfei; Li, Jie; Lu, Rongrong; Gu, Rong; Cao, Lei; Gong, Xiaoliang

2016-01-01

Electroencephalogram- (EEG-) based brain-computer interface (BCI) systems usually utilize one type of changes in the dynamics of brain oscillations for control, such as event-related desynchronization/synchronization (ERD/ERS), steady state visual evoked potential (SSVEP), and P300 evoked potentials. There is a recent trend to detect more than one of these signals in one system to create a hybrid BCI. However, in this case, EEG data were always divided into groups and analyzed by the separate processing procedures. As a result, the interactive effects were ignored when different types of BCI tasks were executed simultaneously. In this work, we propose an improved tensor based multiclass multimodal scheme especially for hybrid BCI, in which EEG signals are denoted as multiway tensors, a nonredundant rank-one tensor decomposition model is proposed to obtain nonredundant tensor components, a weighted fisher criterion is designed to select multimodal discriminative patterns without ignoring the interactive effects, and support vector machine (SVM) is extended to multiclass classification. Experiment results suggest that the proposed scheme can not only identify the different changes in the dynamics of brain oscillations induced by different types of tasks but also capture the interactive effects of simultaneous tasks properly. Therefore, it has great potential use for hybrid BCI. PMID:26880873

Streptococcus agalactiae impairs cerebral bioenergetics in experimentally infected silver catfish.

PubMed

Baldissera, Matheus D; Souza, Carine F; Parmeggiani, Belisa S; Santos, Roberto C V; Leipnitz, Guilhian; Moreira, Karen L S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; Baldisserotto, Bernardo

2017-10-01

It is becoming evident that bacterial infectious diseases affect brain energy metabolism, where alterations of enzymatic complexes of the mitochondrial respiratory chain and creatine kinase (CK) lead to an impairment of cerebral bioenergetics which contribute to disease pathogenesis in the central nervous system (CNS). Based on this evidence, the aim of this study was to evaluate whether alterations in the activity of complex IV of the respiratory chain and CK contribute to impairment of cerebral bioenergetics during Streptococcus agalactiae infection in silver catfish (Rhamdia quelen). The activity of complex IV of the respiratory chain in brain increased, while the CK activity decreased in infected animals compared to uninfected animals. Brain histopathology revealed inflammatory demyelination, gliosis of the brain and intercellular edema in infected animals. Based on this evidence, S. agalactiae infection causes an impairment in cerebral bioenergetics through the augmentation of complex IV activity, which may be considered an adaptive response to maintain proper functioning of the electron respiratory chain, as well as to ensure ongoing electron flow through the electron transport chain. Moreover, inhibition of cerebral CK activity contributes to lower availability of ATP, contributing to impairment of cerebral energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

EEG Classification for Hybrid Brain-Computer Interface Using a Tensor Based Multiclass Multimodal Analysis Scheme.

PubMed

Ji, Hongfei; Li, Jie; Lu, Rongrong; Gu, Rong; Cao, Lei; Gong, Xiaoliang

2016-01-01

Electroencephalogram- (EEG-) based brain-computer interface (BCI) systems usually utilize one type of changes in the dynamics of brain oscillations for control, such as event-related desynchronization/synchronization (ERD/ERS), steady state visual evoked potential (SSVEP), and P300 evoked potentials. There is a recent trend to detect more than one of these signals in one system to create a hybrid BCI. However, in this case, EEG data were always divided into groups and analyzed by the separate processing procedures. As a result, the interactive effects were ignored when different types of BCI tasks were executed simultaneously. In this work, we propose an improved tensor based multiclass multimodal scheme especially for hybrid BCI, in which EEG signals are denoted as multiway tensors, a nonredundant rank-one tensor decomposition model is proposed to obtain nonredundant tensor components, a weighted fisher criterion is designed to select multimodal discriminative patterns without ignoring the interactive effects, and support vector machine (SVM) is extended to multiclass classification. Experiment results suggest that the proposed scheme can not only identify the different changes in the dynamics of brain oscillations induced by different types of tasks but also capture the interactive effects of simultaneous tasks properly. Therefore, it has great potential use for hybrid BCI.

Neural Computations in a Dynamical System with Multiple Time Scales.

PubMed

Mi, Yuanyuan; Lin, Xiaohan; Wu, Si

2016-01-01

Neural systems display rich short-term dynamics at various levels, e.g., spike-frequency adaptation (SFA) at the single-neuron level, and short-term facilitation (STF) and depression (STD) at the synapse level. These dynamical features typically cover a broad range of time scales and exhibit large diversity in different brain regions. It remains unclear what is the computational benefit for the brain to have such variability in short-term dynamics. In this study, we propose that the brain can exploit such dynamical features to implement multiple seemingly contradictory computations in a single neural circuit. To demonstrate this idea, we use continuous attractor neural network (CANN) as a working model and include STF, SFA and STD with increasing time constants in its dynamics. Three computational tasks are considered, which are persistent activity, adaptation, and anticipative tracking. These tasks require conflicting neural mechanisms, and hence cannot be implemented by a single dynamical feature or any combination with similar time constants. However, with properly coordinated STF, SFA and STD, we show that the network is able to implement the three computational tasks concurrently. We hope this study will shed light on the understanding of how the brain orchestrates its rich dynamics at various levels to realize diverse cognitive functions.

Spherical Deconvolution of Multichannel Diffusion MRI Data with Non-Gaussian Noise Models and Spatial Regularization

PubMed Central

Canales-Rodríguez, Erick J.; Caruyer, Emmanuel; Aja-Fernández, Santiago; Radua, Joaquim; Yurramendi Mendizabal, Jesús M.; Iturria-Medina, Yasser; Melie-García, Lester; Alemán-Gómez, Yasser; Thiran, Jean-Philippe; Sarró, Salvador; Pomarol-Clotet, Edith; Salvador, Raymond

2015-01-01

Spherical deconvolution (SD) methods are widely used to estimate the intra-voxel white-matter fiber orientations from diffusion MRI data. However, while some of these methods assume a zero-mean Gaussian distribution for the underlying noise, its real distribution is known to be non-Gaussian and to depend on many factors such as the number of coils and the methodology used to combine multichannel MRI signals. Indeed, the two prevailing methods for multichannel signal combination lead to noise patterns better described by Rician and noncentral Chi distributions. Here we develop a Robust and Unbiased Model-BAsed Spherical Deconvolution (RUMBA-SD) technique, intended to deal with realistic MRI noise, based on a Richardson-Lucy (RL) algorithm adapted to Rician and noncentral Chi likelihood models. To quantify the benefits of using proper noise models, RUMBA-SD was compared with dRL-SD, a well-established method based on the RL algorithm for Gaussian noise. Another aim of the study was to quantify the impact of including a total variation (TV) spatial regularization term in the estimation framework. To do this, we developed TV spatially-regularized versions of both RUMBA-SD and dRL-SD algorithms. The evaluation was performed by comparing various quality metrics on 132 three-dimensional synthetic phantoms involving different inter-fiber angles and volume fractions, which were contaminated with noise mimicking patterns generated by data processing in multichannel scanners. The results demonstrate that the inclusion of proper likelihood models leads to an increased ability to resolve fiber crossings with smaller inter-fiber angles and to better detect non-dominant fibers. The inclusion of TV regularization dramatically improved the resolution power of both techniques. The above findings were also verified in human brain data. PMID:26470024

Closing the Mathematical Achievement Gap Through the Heart To the Brain: A Case Study of Urban High School Mathematics Teachers' Perceptions of How Their Emotional Intelligence Facilitates Instruction and Learning in the Classroom

NASA Astrophysics Data System (ADS)

Fang, Chung-Chieh

The purpose of this qualitative case study was to examine urban high school mathematics teachers' perceptions of how they manage their own and their students' emotional intelligence (EI) to facilitate instruction and learning; their reports of how they handle their emotions as urban mathematics teachers; and their reports of how they manage the emotions of their students. The study focused on the voices of sixteen urban mathematics teachers and was undertaken in reaction to the significant mathematics achievement gap between urban students and their suburban counterparts. The conceptual framework undergirding the study was synthesized work by Daniel Goleman, (1995) and Mayer and Salovey (1997); categorizing emotional intelligence in emotional selfawareness, managing emotions, harnessing emotions, empathy, and handling relationships. Research questions addressing each category were created and from these categories an interview guide was developed. Data gathered during individual teacher interviews was transcribed and sorted into emergent categories using open coding. The findings were organized and presented according to the study's research questions. Urban math teachers reported passion for their students, their feelings affect teaching and learning, and that humor is an important tool in mediating emotions. The study concludes with multiple recommendations for further research and practices. Future studies should compare teachers assuming paternal vs. mentor role when dealing with their students. The study can evaluate if either role has a significant impact in student teacher relationships. A recommendation for practice is for teachers to have professional development experiences focusing on the proper use of humor in the classroom. Humor used properly promotes a positive classroom environment. This is a skill that would be especially beneficial to urban teachers.

Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period

PubMed Central

Whiteus, Christina; Freitas, Catarina; Grutzendler, Jaime

2013-01-01

During the neonatal period, activity-dependent neural circuit remodeling coincides with growth and refinement of the cerebral microvasculature1,2. Whether neural activity also influences the patterning of the vascular bed is not known. Here we show in neonatal mice, that neither reduction of sensory input through whisker trimming nor moderately increased activity by environmental enrichment affected cortical microvascular development. Surprisingly however, chronic stimulation by repetitive sounds, whisker deflection, or motor activity led to a near arrest of angiogenesis in barrel, auditory, and motor cortices, respectively. Chemically-induced seizures also caused robust reductions in microvascular density. Altering neural activity in adult mice, however, did not affect the vasculature. Histological analysis and time-lapse in vivo two-photon microscopy revealed that hyperactivity did not lead to cell death or pruning of existing vessels but rather reduced endothelial proliferation and vessel sprouting. This anti-angiogenic effect was prevented by administration of the nitric oxide synthase (NOS) inhibitor L-NAME and in mice with neuronal and inducible NOS deficiency, suggesting that excessive nitric oxide released from hyperactive interneurons and glia inhibited vessel growth. Vascular deficits persisted long after cessation of hyperstimulation, providing evidence for a critical period after which proper microvascular patterning cannot be re-established. Reduced microvascular density diminished the ability of the brain to compensate for hypoxic challenges, leading to dendritic spine loss in regions distant from capillaries. Therefore, excessive sensorimotor stimulation and repetitive neural activation during early childhood may cause lifelong deficits in microvascular reserve, which could have important consequences on brain development, function, and pathology. PMID:24305053

Content and traffic of taurine in hippocampal reactive astrocytes.

PubMed

Junyent, Fèlix; De Lemos, Luisa; Utrera, Juana; Paco, Sonia; Aguado, Fernando; Camins, Antoni; Pallàs, Mercè; Romero, Rafael; Auladell, Carme

2011-02-01

Taurine is one of the most abundant free amino acids in the mammalian central nervous system, where it is crucial to proper development. Moreover, taurine acts as a neuroprotectant in various diseases; in epilepsy, for example, it has the capacity to reduce or abolish seizures. In the present study, taurine levels has been determine in mice treated with Kainic Acid (KA) and results showed an increase of this amino acid in hippocampus but not in whole brain after 3 and 7 days of KA treatment. This increase occurs when gliosis was observed. Moreover, taurine transporter (TAUT) was found in astrocytes 3 and 7 days after KA treatment, together with an increase in cysteine sulfinic acid decarboxylase (csd) mRNA, that codifies for the rate-limiting enzyme of taurine synthesis, in the hippocampus at the same times after KA treatment. Glial cultures enriched in astrocytes were developed to demonstrate that these cells are responsible for changes in taurine levels after an injury to the brain. The cultures were treated with proinflammatory cytokines to reproduce gliosis. In this experimental model, an increase in the immunoreactivity of GFAP was observed, together with an increase in CSD and taurine levels. Moreover, an alteration in the taurine uptake-release kinetics was detected in glial cells treated with cytokine. All data obtained indicate that astrocytes could play a key role in taurine level changes induced by neuronal damage. More studies are, therefore, needed to clarify the role taurine has in relation to neuronal death and repair. Copyright © 2009 Wiley-Liss, Inc.

Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period.

PubMed

Whiteus, Christina; Freitas, Catarina; Grutzendler, Jaime

2014-01-16

During the neonatal period, activity-dependent neural-circuit remodelling coincides with growth and refinement of the cerebral microvasculature. Whether neural activity also influences the patterning of the vascular bed is not known. Here we show in neonatal mice, that neither reduction of sensory input through whisker trimming nor moderately increased activity by environmental enrichment affects cortical microvascular development. Unexpectedly, chronic stimulation by repetitive sounds, whisker deflection or motor activity led to a near arrest of angiogenesis in barrel, auditory and motor cortices, respectively. Chemically induced seizures also caused robust reductions in microvascular density. However, altering neural activity in adult mice did not affect the vasculature. Histological analysis and time-lapse in vivo two-photon microscopy revealed that hyperactivity did not lead to cell death or pruning of existing vessels but rather to reduced endothelial proliferation and vessel sprouting. This anti-angiogenic effect was prevented by administration of the nitric oxide synthase (NOS) inhibitor L-NAME and in mice with neuronal and inducible NOS deficiency, suggesting that excessive nitric oxide released from hyperactive interneurons and glia inhibited vessel growth. Vascular deficits persisted long after cessation of hyperstimulation, providing evidence for a critical period after which proper microvascular patterning cannot be re-established. Reduced microvascular density diminished the ability of the brain to compensate for hypoxic challenges, leading to dendritic spine loss in regions distant from capillaries. Therefore, excessive sensorimotor stimulation and repetitive neural activation during early childhood may cause lifelong deficits in microvascular reserve, which could have important consequences for brain development, function and pathology.

Region-specific effects of developmental exposure to cocaine on fibroblast growth factor-2 expression in the rat brain.

PubMed

Giannotti, Giuseppe; Caffino, Lucia; Mottarlini, Francesca; Racagni, Giorgio; Fumagalli, Fabio

2016-07-01

Adolescence is a period of high vulnerability to drugs of abuse and alterations of the proper developmental trajectory via psychostimulant exposure might change the physiological brain homeostasis. By microdissection of brain areas via punching, we investigated whether repeated exposure to cocaine during adolescence (from postnatal day 28 [PND28] to PND42) has altered fibroblast growth factor-2 (FGF-2) messenger RNA (mRNA) levels in selected brain subregions critical for the action of cocaine. We found a reduction of FGF-2 mRNA levels in ventral tegmental area (VTA), where mesocortical and mesolimbic pathways originate. The analysis of the trophic factor levels in the distal projecting regions revealed a selective reduction of FGF-2 mRNA levels in infralimbic (IL) subregion of the medial prefrontal cortex (the terminal region of the mesocortical pathway) and in the nucleus accumbens core (cNAc) (the terminal region of the mesolimbic pathway). Last, we found reduced FGF-2 mRNA levels also in brain regions which, although in a different manner, contribute to the reward system, i.e., the central nucleus of amygdala (cAmy) and the ventral portion of hippocampus (vHip). The widespread and coordinated reduction of FGF-2 mRNA levels across the brain's reward neurocircuitry might represent a defensive strategy set in motion to oppose to the psychostimulant properties of cocaine. Moreover, given the role of FGF-2 in modulating mood disorders, the reduced trophic support here observed might sustain the negative emotional state set in motion by repeated exposure to cocaine.

Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function.

PubMed

Lenz, Kathryn M; Nelson, Lars H

2018-01-01

Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.

Brain development and the nature versus nurture debate.

PubMed

Stiles, Joan

2011-01-01

Over the past three decades, developmental neurobiologists have made tremendous progress in defining basic principles of brain development. This work has changed the way we think about how brains develop. Thirty years ago, the dominant model was strongly deterministic. The relationship between brain and behavioral development was viewed as unidirectional; that is, brain maturation enables behavioral development. The advent of modern neurobiological methods has provided overwhelming evidence that it is the interaction of genetic factors and the experience of the individual that guides and supports brain development. Brains do not develop normally in the absence of critical genetic signaling, and they do not develop normally in the absence of essential environmental input. The fundamental facts about brain development should be of critical importance to neuropsychologists trying to understand the relationship between brain and behavioral development. However, the underlying assumptions of most contemporary psychological models reflect largely outdated ideas about how the biological system develops and what it means for something to be innate. Thus, contemporary models of brain development challenge the foundational constructs of the nature versus nurture formulation in psychology. The key to understanding the origins and emergence of both the brain and behavior lies in understanding how inherited and environmental factors are engaged in the dynamic and interactive processes that define and guide development of the neurobehavioral system. Copyright © 2011 Elsevier B.V. All rights reserved.

Proper Names a Cognitive-Philosophical Study

ERIC Educational Resources Information Center

Garcia-Ramirez, Eduardo

2010-01-01

Proper Names appear at the heart of several debates in philosophy and the cognitive sciences. These include "reference", "intentionality", and the nature of "belief" as well as "language acquisition", "cognitive development", and "memory". This dissertation follows a cognitive approach to the philosophical problems posed by proper names. It puts…

Mammalian neurogenesis requires Treacle-Plk1 for precise control of spindle orientation, mitotic progression, and maintenance of neural progenitor cells.

PubMed

Sakai, Daisuke; Dixon, Jill; Dixon, Michael J; Trainor, Paul A

2012-01-01

The cerebral cortex is a specialized region of the brain that processes cognitive, motor, somatosensory, auditory, and visual functions. Its characteristic architecture and size is dependent upon the number of neurons generated during embryogenesis and has been postulated to be governed by symmetric versus asymmetric cell divisions, which mediate the balance between progenitor cell maintenance and neuron differentiation, respectively. The mechanistic importance of spindle orientation remains controversial, hence there is considerable interest in understanding how neural progenitor cell mitosis is controlled during neurogenesis. We discovered that Treacle, which is encoded by the Tcof1 gene, is a novel centrosome- and kinetochore-associated protein that is critical for spindle fidelity and mitotic progression. Tcof1/Treacle loss-of-function disrupts spindle orientation and cell cycle progression, which perturbs the maintenance, proliferation, and localization of neural progenitors during cortical neurogenesis. Consistent with this, Tcof1(+/-) mice exhibit reduced brain size as a consequence of defects in neural progenitor maintenance. We determined that Treacle elicits its effect via a direct interaction with Polo-like kinase1 (Plk1), and furthermore we discovered novel in vivo roles for Plk1 in governing mitotic progression and spindle orientation in the developing mammalian cortex. Increased asymmetric cell division, however, did not promote increased neuronal differentiation. Collectively our research has therefore identified Treacle and Plk1 as novel in vivo regulators of spindle fidelity, mitotic progression, and proliferation in the maintenance and localization of neural progenitor cells. Together, Treacle and Plk1 are critically required for proper cortical neurogenesis, which has important implications in the regulation of mammalian brain size and the pathogenesis of congenital neurodevelopmental disorders such as microcephaly.

Mammalian Neurogenesis Requires Treacle-Plk1 for Precise Control of Spindle Orientation, Mitotic Progression, and Maintenance of Neural Progenitor Cells

PubMed Central

Sakai, Daisuke; Dixon, Jill; Dixon, Michael J.; Trainor, Paul A.

2012-01-01

The cerebral cortex is a specialized region of the brain that processes cognitive, motor, somatosensory, auditory, and visual functions. Its characteristic architecture and size is dependent upon the number of neurons generated during embryogenesis and has been postulated to be governed by symmetric versus asymmetric cell divisions, which mediate the balance between progenitor cell maintenance and neuron differentiation, respectively. The mechanistic importance of spindle orientation remains controversial, hence there is considerable interest in understanding how neural progenitor cell mitosis is controlled during neurogenesis. We discovered that Treacle, which is encoded by the Tcof1 gene, is a novel centrosome- and kinetochore-associated protein that is critical for spindle fidelity and mitotic progression. Tcof1/Treacle loss-of-function disrupts spindle orientation and cell cycle progression, which perturbs the maintenance, proliferation, and localization of neural progenitors during cortical neurogenesis. Consistent with this, Tcof1 +/− mice exhibit reduced brain size as a consequence of defects in neural progenitor maintenance. We determined that Treacle elicits its effect via a direct interaction with Polo-like kinase1 (Plk1), and furthermore we discovered novel in vivo roles for Plk1 in governing mitotic progression and spindle orientation in the developing mammalian cortex. Increased asymmetric cell division, however, did not promote increased neuronal differentiation. Collectively our research has therefore identified Treacle and Plk1 as novel in vivo regulators of spindle fidelity, mitotic progression, and proliferation in the maintenance and localization of neural progenitor cells. Together, Treacle and Plk1 are critically required for proper cortical neurogenesis, which has important implications in the regulation of mammalian brain size and the pathogenesis of congenital neurodevelopmental disorders such as microcephaly. PMID:22479190

Does non-invasive brain stimulation modify hand dexterity? Protocol for a systematic review and meta-analysis.

PubMed

O'Brien, Anthony Terrence; Torrealba Acosta, Gabriel; Huerta, Rodrigo; Thibaut, Aurore

2017-06-22

Dexterity is described as coordinated hand and finger movement for precision tasks. It is essential for day-to-day activities like computer use, writing or buttoning a shirt. Integrity of brain motor networks is crucial to properly execute these fine hand tasks. When these networks are damaged, interventions to enhance recovery are frequently accompanied by unwanted side effects or limited in their effect. Non-invasive brain stimulation (NIBS) are postulated to target affected motor areas and improve hand motor function with few side effects. However, the results across studies vary, and the current literature does not allow us to draw clear conclusions on the use of NIBS to promote hand function recovery. Therefore, we developed a protocol for a systematic review and meta-analysis on the effects of different NIBS technologies on dexterity in diverse populations. This study will potentially help future evidence-based research and guidelines that use these NIBS technologies for recovering hand dexterity. This protocol will compare the effects of active versus sham NIBS on precise hand activity. Records will be obtained by searching relevant databases. Included articles will be randomised clinical trials in adults, testing the therapeutic effects of NIBS on continuous dexterity data. Records will be studied for risk of bias. Narrative and quantitative synthesis will be done. No private health information is included; the study is not interventional. Ethical approval is not required. The results will be reported in a peer-review journal. PROSPERO International prospective register of systematic reviews registration number: CRD42016043809. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

High-speed imaging and small-scale explosive characterization techniques to understand effects of primary blast-induced injury on nerve cell structure and function

NASA Astrophysics Data System (ADS)

Piehler, T.; Banton, R.; Zander, N.; Duckworth, J.; Benjamin, R.; Sparks, R.

2018-01-01

Traumatic brain injury (TBI) is often associated with blast exposure. Even in the absence of penetrating injury or evidence of tissue injury on imaging, blast TBI may trigger a series of neural/glial cellular and functional changes. Unfortunately, the diagnosis and proper treatment of mild traumatic brain injury (mTBI) caused by explosive blast is challenging, as it is not easy to clinically distinguish blast from non-blast TBI on the basis of patient symptoms. Damage to brain tissue, cell, and subcellular structures continues to occur slowly and in a manner undetectable by conventional imaging techniques. The threshold shock impulse levels required to induce damage and the cumulative effects upon multiple exposures are not well characterized. Understanding how functional and structural damage from realistic blast impact at cellular and tissue levels at variable timescales after mTBI events may be vital for understanding this injury phenomenon and for linking mechanically induced structural changes with measurable effects on the nervous system. Our working hypothesis is that there is some transient physiological dysfunction occurring at cellular and subcellular levels within the central nervous system due to primary blast exposure. We have developed a novel in vitro indoor experimental system that uses real military explosive charges to more accurately represent military blast exposure and to probe the effects of primary explosive blast on dissociated neurons. We believe this system offers a controlled experimental method to analyze and characterize primary explosive blast-induced cellular injury and to understand threshold injury phenomenon. This paper will also focus on the modeling aspect of our work and how it relates to the experimental work.

The generation of NGF-secreting primary rat monocytes: a comparison of different transfer methods.

PubMed

Hohsfield, Lindsay A; Geley, Stephan; Reindl, Markus; Humpel, Christian

2013-05-31

Nerve growth factor (NGF), a member of the neurotrophin family, is responsible for the maintenance and survival of cholinergic neurons in the basal forebrain. The degeneration of cholinergic neurons and reduced acetycholine levels are hallmarks of Alzheimer's disease (AD) as well as associated with learning and memory deficits. Thus far, NGF has proven the most potent neuroprotective molecule against cholinergic neurodegeneration. However, delivery of this factor into the brain remains difficult. Recent studies have begun to elucidate the potential use of monocytes as vehicles for therapeutic delivery into the brain. In this study, we employed different transfection and transduction methods to generate NGF-secreting primary rat monocytes. Specifically, we compared five methods for generating NGF-secreting monocytes: (1) cationic lipid-mediated transfection (Effectene and FuGene), (2) classical electroporation, (3) nucleofection, (4) protein delivery (Bioporter) and (5) lentiviral vectors. Here, we report that classical transfection methods (lipid-mediated transfection, electroporation, nucleofection) are inefficient tools for proper gene transfer into primary rat monocytes. We demonstrate that lentiviral infection and Bioporter can successfully transduce/load primary rat monocytes and produce effective NGF secretion. Furthermore, our results indicate that NGF is bioactive and that Bioporter-loaded monocytes do not appear to exhibit any functional disruptions (i.e. in their ability to differentiate and phagocytose beta-amyloid). Taken together, our results show that primary monocytes can be effectively loaded or transduced with NGF and provides information on the most effective method for generating NGF-secreting primary rat monocytes. This study also provides a basis for further development of primary monocytes as therapeutic delivery vehicles to the diseased AD brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Developmental abnormalities of the occipital bone in human chondrodystrophies (achondroplasia and thanatophoric dwarfism).

PubMed

Marin-Padilla, M; Marin-Padilla, T M

1977-01-01

Specific developmental malformations have been demonstrated in the occipital bone of two chondrodysplastic disorders (achondroplasia and thanatophoric dwarfism). Analysis of these malformations indicates that the occipital bone is primary affected in these disorders. In both cases, the endochondral-derived components of the occipital bone (the basioccipital, the two lateral parts, and the planum nuchale of the squama occipitalis) have failed to grow properly and are smaller and shorter than normal. On the other hand, the planum occipitalis of the squama, which derives from intramembranous ossification, is unaffected. In addition, the nature of these abnormalities indicates that the occipital synchondroses, together with the epiphyseal plates of other bones, are primarily affected in these two chondrodysplasias. The components of the occipital bone formed between the affected synchondroses failed to grow normally. The resulting malformation of the occipital bone is undoubtedly the cause of the shortening of the posterior cerebral fossa and of the considerable narrowing of the foramen magnum often described in these chondrodysplasias. It is postulated that growth disturbances between the affected occipital bone and the unaffected central nervous system results in the inadequacy of the posterior cerebral fossa and the foramen magnum to accommodate the growing brain. Consequently, compression of the brain at the posterior cerebral fossa or the foramen magnum levels could occur and thus lead to neurologic complications such as hydrocephalus and compression of the brain stem. It is suggested that the surgical removal of the fused posterior border of the lateral parts of the occipital bone (partial nuchalectomy) for the purpose of enlarging the narrow foramen magnum may be indicated in those chondrodysplastic children who develop these types of neurologic complications.

The novel agent phospho-glycerol-ibuprofen-amide (MDC-330) inhibits glioblastoma growth in mice: an effect mediated by cyclin D1

PubMed Central

Bartels, Lauren E.; Mattheolabakis, George; Vaeth, Brandon M.; LaComb, Joseph F.; Wang, Ruixue; Zhi, Jizu; Komninou, Despina; Rigas, Basil; Mackenzie, Gerardo G.

2016-01-01

Given that glioblastoma multiforme (GBM) is associated with poor prognosis, new agents are urgently needed. We developed phospho-glycerol-ibuprofen-amide (PGIA), a novel ibuprofen derivative, and evaluated its safety and efficacy in preclinical models of GBM, and its mechanism of action using human GBM cells and animal tumor models. Furthermore, we explored whether formulating PGIA in polymeric nanoparticles could enhance its levels in the brain. PGIA was 3.7- to 5.1-fold more potent than ibuprofen in suppressing the growth of human GBM cell lines. PGIA 0.75× IC50 inhibited cell proliferation by 91 and 87% in human LN-229 and U87-MG GBM cells, respectively, and induced strong G1/S arrest. In vivo, compared with control, PGIA reduced U118-MG and U87-MG xenograft growth by 77 and 56%, respectively (P < 0.05), and was >2-fold more efficacious than ibuprofen. Normal human astrocytes were resistant to PGIA, indicating selectivity. Mechanistically, PGIA reduced cyclin D1 levels in a time- and concentration-dependent manner in GBM cells and in xenografts. PGIA induced cyclin D1 degradation via the proteasome pathway and induced dephosphorylation of GSK3β, which was required for cyclin D1 turnover. Furthermore, cyclin D1 overexpression rescued GBM cells from the cell growth inhibition by PGIA. Moreover, the formulation of PGIA in poly-(l)-lactic acid poly(ethylene glycol) polymeric nanoparticles improved its pharmacokinetics in mice, delivering PGIA to the brain. PGIA displays strong efficacy against GBM, crosses the blood-brain barrier when properly formulated, reaching the target tissue, and establishes cyclin D1 as an important molecular target. Thus, PGIA merits further evaluation as a potential therapeutic option for GBM. PMID:26905586

Mechanisms and use of neural transplants for brain repair.

PubMed

Dunnett, Stephen B; Björklund, Anders

2017-01-01

Under appropriate conditions, neural tissues transplanted into the adult mammalian brain can survive, integrate, and function so as to influence the behavior of the host, opening the prospect of repairing neuronal damage, and alleviating symptoms associated with neuronal injury or neurodegenerative disease. Alternative mechanisms of action have been postulated: nonspecific effects of surgery; neurotrophic and neuroprotective influences on disease progression and host plasticity; diffuse or locally regulated pharmacological delivery of deficient neurochemicals, neurotransmitters, or neurohormones; restitution of the neuronal and glial environment necessary for proper host neuronal support and processing; promoting local and long-distance host and graft axon growth; formation of reciprocal connections and reconstruction of local circuits within the host brain; and up to full integration and reconstruction of fully functional host neuronal networks. Analysis of neural transplants in a broad range of anatomical systems and disease models, on simple and complex classes of behavioral function and information processing, have indicated that all of these alternative mechanisms are likely to contribute in different circumstances. Thus, there is not a single or typical mode of graft function; rather grafts can and do function in multiple ways, specific to each particular context. Consequently, to develop an effective cell-based therapy, multiple dimensions must be considered: the target disease pathogenesis; the neurodegenerative basis of each type of physiological dysfunction or behavioral symptom; the nature of the repair required to alleviate or remediate the functional impairments of particular clinical relevance; and identification of a suitable cell source or delivery system, along with the site and method of implantation, that can achieve the sought for repair and recovery. © 2017 Elsevier B.V. All rights reserved.

Development of intraoperative electrochemical detection: wireless instantaneous neurochemical concentration sensor for deep brain stimulation feedback

PubMed Central

Van Gompel, Jamie J.; Chang, Su-Youne; Goerss, Stephan J.; Kim, In Yong; Kimble, Christopher; Bennet, Kevin E.; Lee, Kendall H.

2010-01-01

Deep brain stimulation (DBS) is effective when there appears to be a distortion in the complex neurochemical circuitry of the brain. Currently, the mechanism of DBS is incompletely understood; however, it has been hypothesized that DBS evokes release of neurochemicals. Well-established chemical detection systems such as microdialysis and mass spectrometry are impractical if one is assessing changes that are happening on a second-to-second time scale or for chronically used implanted recordings, as would be required for DBS feedback. Electrochemical detection techniques such as fast-scan cyclic voltammetry (FSCV) and amperometry have until recently remained in the realm of basic science; however, it is enticing to apply these powerful recording technologies to clinical and translational applications. The Wireless Instantaneous Neurochemical Concentration Sensor (WINCS) currently is a research device designed for human use capable of in vivo FSCV and amperometry, sampling at subsecond time resolution. In this paper, the authors review recent advances in this electrochemical application to DBS technologies. The WINCS can detect dopamine, adenosine, and serotonin by FSCV. For example, FSCV is capable of detecting dopamine in the caudate evoked by stimulation of the subthalamic nucleus/substantia nigra in pig and rat models of DBS. It is further capable of detecting dopamine by amperometry and, when used with enzyme linked sensors, both glutamate and adenosine. In conclusion, WINCS is a highly versatile instrument that allows near real-time (millisecond) detection of neurochemicals important to DBS research. In the future, the neurochemical changes detected using WINCS may be important as surrogate markers for proper DBS placement as well as the sensor component for a “smart” DBS system with electrochemical feedback that allows automatic modulation of stimulation parameters. Current work is under way to establish WINCS use in humans. PMID:20672923

Exercise-induced neuronal plasticity in central autonomic networks: role in cardiovascular control.

PubMed

Michelini, Lisete C; Stern, Javier E

2009-09-01

It is now well established that brain plasticity is an inherent property not only of the developing but also of the adult brain. Numerous beneficial effects of exercise, including improved memory, cognitive function and neuroprotection, have been shown to involve an important neuroplastic component. However, whether major adaptive cardiovascular adjustments during exercise, needed to ensure proper blood perfusion of peripheral tissues, also require brain neuroplasticity, is presently unknown. This review will critically evaluate current knowledge on proposed mechanisms that are likely to underlie the continuous resetting of baroreflex control of heart rate during/after exercise and following exercise training. Accumulating evidence indicates that not only somatosensory afferents (conveyed by skeletal muscle receptors, baroreceptors and/or cardiopulmonary receptors) but also projections arising from central command neurons (in particular, peptidergic hypothalamic pre-autonomic neurons) converge into the nucleus tractus solitarii (NTS) in the dorsal brainstem, to co-ordinate complex cardiovascular adaptations during dynamic exercise. This review focuses in particular on a reciprocally interconnected network between the NTS and the hypothalamic paraventricular nucleus (PVN), which is proposed to act as a pivotal anatomical and functional substrate underlying integrative feedforward and feedback cardiovascular adjustments during exercise. Recent findings supporting neuroplastic adaptive changes within the NTS-PVN reciprocal network (e.g. remodelling of afferent inputs, structural and functional neuronal plasticity and changes in neurotransmitter content) will be discussed within the context of their role as important underlying cellular mechanisms supporting the tonic activation and improved efficacy of these central pathways in response to circulatory demand at rest and during exercise, both in sedentary and in trained individuals. We hope this review will stimulate more comprehensive studies aimed at understanding cellular and molecular mechanisms within CNS neuronal networks that contribute to exercise-induced neuroplasticity and cardiovascular adjustments.

Distinct sets of FGF receptors sculpt excitatory and inhibitory synaptogenesis.

PubMed

Dabrowski, Ania; Terauchi, Akiko; Strong, Cameron; Umemori, Hisashi

2015-05-15

Neurons in the brain must establish a balanced network of excitatory and inhibitory synapses during development for the brain to function properly. An imbalance between these synapses underlies various neurological and psychiatric disorders. The formation of excitatory and inhibitory synapses requires precise molecular control. In the hippocampus, the structure crucial for learning and memory, fibroblast growth factor 22 (FGF22) and FGF7 specifically promote excitatory or inhibitory synapse formation, respectively. Knockout of either Fgf gene leads to excitatory-inhibitory imbalance in the mouse hippocampus and manifests in an altered susceptibility to epileptic seizures, underscoring the importance of FGF-dependent synapse formation. However, the receptors and signaling mechanisms by which FGF22 and FGF7 induce excitatory and inhibitory synapse differentiation are unknown. Here, we show that distinct sets of overlapping FGF receptors (FGFRs), FGFR2b and FGFR1b, mediate excitatory or inhibitory presynaptic differentiation in response to FGF22 and FGF7. Excitatory presynaptic differentiation is impaired in Fgfr2b and Fgfr1b mutant mice; however, inhibitory presynaptic defects are only found in Fgfr2b mutants. FGFR2b and FGFR1b are required for an excitatory presynaptic response to FGF22, whereas only FGFR2b is required for an inhibitory presynaptic response to FGF7. We further find that FGFRs are required in the presynaptic neuron to respond to FGF22, and that FRS2 and PI3K, but not PLCγ, mediate FGF22-dependent presynaptic differentiation. Our results reveal the specific receptors and signaling pathways that mediate FGF-dependent presynaptic differentiation, and thereby provide a mechanistic understanding of precise excitatory and inhibitory synapse formation in the mammalian brain. © 2015. Published by The Company of Biologists Ltd.

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

A Fast Method for the Segmentation of Synaptic Junctions and Mitochondria in Serial Electron Microscopic Images of the Brain.

PubMed

Márquez Neila, Pablo; Baumela, Luis; González-Soriano, Juncal; Rodríguez, Jose-Rodrigo; DeFelipe, Javier; Merchán-Pérez, Ángel

2016-04-01

Recent electron microscopy (EM) imaging techniques permit the automatic acquisition of a large number of serial sections from brain samples. Manual segmentation of these images is tedious, time-consuming and requires a high degree of user expertise. Therefore, there is considerable interest in developing automatic segmentation methods. However, currently available methods are computationally demanding in terms of computer time and memory usage, and to work properly many of them require image stacks to be isotropic, that is, voxels must have the same size in the X, Y and Z axes. We present a method that works with anisotropic voxels and that is computationally efficient allowing the segmentation of large image stacks. Our approach involves anisotropy-aware regularization via conditional random field inference and surface smoothing techniques to improve the segmentation and visualization. We have focused on the segmentation of mitochondria and synaptic junctions in EM stacks from the cerebral cortex, and have compared the results to those obtained by other methods. Our method is faster than other methods with similar segmentation results. Our image regularization procedure introduces high-level knowledge about the structure of labels. We have also reduced memory requirements with the introduction of energy optimization in overlapping partitions, which permits the regularization of very large image stacks. Finally, the surface smoothing step improves the appearance of three-dimensional renderings of the segmented volumes.

Understanding Educational Neuroscience: A Teacher's Perspective

NASA Astrophysics Data System (ADS)

Morgan, Robbi Jo

The purpose of this project was to determine what teachers know and what they need to know about neuro-education applications in the classroom. Teachers in grades kindergarten through eighth grade from a Midwestern community of approximately 45,000 people. There were sixty-nine respondents with 7.2% of them being male. The question regarding their level of education resulted in 59.4% having their master's degree. It was interesting to note that 40.6% of the teachers responding were between the ages of 51-65 and had been teaching for more than 21 years were asked to complete a survey about their understanding of neuro-myths that effect classroom performance. These implications focus on neuro-myths. The resulting list is to provide possible professional development opportunities for the teachers. This survey was conducted for three weeks. There were a total of forty-five statements that asked the respondent to rank on a 5-point scale whether they disagreed or agreed. There were also four open-ended questions. The results indicated teachers were not correct or not confident in their responses regarding the importance of movement in the classroom, good nutrition, proper amount of sleep, and the importance of a positive relationship between the teacher and student. Some of the neuro-myths that teachers were unsure about were learning with only one hemisphere of the brain, synaptic pruning and learning, students' misbehavior changing with conversation, and regenerating brain cells.

Molecular control of brain size: Regulators of neural stem cell life, death and beyond

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

Joseph, Bertrand; Hermanson, Ola, E-mail: ola.hermanson@ki.se

2010-05-01

The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas membersmore » of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.« less

Counseling Athletes on the Risk of Chronic Traumatic Encephalopathy

PubMed Central

Concannon, Leah G.; Kaufman, Marla S.; Herring, Stanley A.

2014-01-01

Context: Chronic traumatic encephalopathy (CTE) is a rare progressive neurologic disorder that can manifest as a combination of cognitive, mood and behavioral, and neurologic symptoms. Despite clinically apparent symptoms, there is no imaging or other diagnostic test that can confirm diagnosis in living subjects. Diagnosis can only be confirmed postmortem by specific histopathologic features within the brain tissue identified on autopsy. CTE represents a unique tauopathy that is distinct from other neurodegenerative diseases. Evidence Acquisition: PubMed was searched from 1990 to 2013 for sport concussion and chronic traumatic encephalopathy. Articles were also identified from bibliographies of recent reviews and consensus statements. Study Design: Clinical review. Level of Evidence: Level 5. Results: Although CTE is postulated to occur as a result of repetitive mild traumatic brain injury, the specific etiology and risk factors have not yet been elucidated, and postmortem diagnosis makes causality difficult to determine. Conclusion: When counseling athletes and families about the potential association of recurrent concussions and the development of CTE, discussion of proper management of concussion is cornerstone. Unfortunately, to date, there is no equipment that can prevent concussions; however, rule changes and legislation may decrease the risk. It is imperative that return to play is medically supervised by a provider trained in the management of concussion and begins only once symptoms have resolved. In addition, athletes with permanent symptoms should be retired from contact sport. PMID:25177414

Tea, cocoa, coffee, and affective disorders: vicious or virtuous cycle?

PubMed

García-Blanco, Tatiana; Dávalos, Alberto; Visioli, Francesco

2017-12-15

The prevalence of psychiatric disorders is increasing worldwide, which underscores the importance of increasing research in this field, in terms of better detection, prevention based on improvement of lifestyle and diet, and effectiveness of treatment. Increasing evidence suggest that diet and exercise can affect proper neuronal development and physiology and protect the brain from neurological illnesses or injuries. Of note, cocoa, tea, and coffee are being actively investigated because they are rich in (poly)phenolic compounds that can modulate mental health, namely brain plasticity, behavior, mood, depression, and cognition. We here systematically review human studies conducted on tea, cocoa, and coffee as related to affective disorders such as depression and anxiety. We carried out a systematic literature search in April 2016, using MEDLINE, on data from the last 10 years. After screening 955 articles, we selected 17 articles that met the criteria of being human studies and that used whole foods or their components. The results of our systematic review indicate that consumption of tea, cocoa, or coffee might have protective effects against depression. Even though this is encouraging, it should be underscored that the near totality of the current evidence comes from observational studies. Ad-hoc human trials and mechanistic, basic science studies are needed before we can provide sound advice to the public. Copyright © 2016 Elsevier B.V. All rights reserved.

A New Life, A New Brain.

ERIC Educational Resources Information Center

Eliot, Lise

2001-01-01

Discusses the connection between brain development and human educational needs based on neuroscience research. Considers brain development from conception, including cell structure, myelination, and regional development of the brain, stressing the importance of a child's early environment and the prenatal vulnerability of the brain. (JPB)

Developmental implications of children's brain networks and learning.

PubMed

Chan, John S Y; Wang, Yifeng; Yan, Jin H; Chen, Huafu

2016-10-01

The human brain works as a synergistic system where information exchanges between functional neuronal networks. Rudimentary networks are observed in the brain during infancy. In recent years, the question of how functional networks develop and mature in children has been a hotly discussed topic. In this review, we examined the developmental characteristics of functional networks and the impacts of skill training on children's brains. We first focused on the general rules of brain network development and on the typical and atypical development of children's brain networks. After that, we highlighted the essentials of neural plasticity and the effects of learning on brain network development. We also discussed two important theoretical and practical concerns in brain network training. Finally, we concluded by presenting the significance of network training in typically and atypically developed brains.

The Neuroprotective Aspects of Sleep.

PubMed

Eugene, Andy R; Masiak, Jolanta

2015-03-01

Sleep is an important component of human life, yet many people do not understand the relationship between the brain and the process of sleeping. Sleep has been proven to improve memory recall, regulate metabolism, and reduce mental fatigue. A minimum of 7 hours of daily sleep seems to be necessary for proper cognitive and behavioral function. The emotional and mental handicaps associated with chronic sleep loss as well as the highly hazardous situations which can be contributed to the lack of sleep is a serious concern that people need to be aware of. When one sleeps, the brain reorganizes and recharges itself, and removes toxic waste byproducts which have accumulated throughout the day. This evidence demonstrates that sleeping can clear the brain and help maintain its normal functioning. Multiple studies have been done to determine the effects of total sleep deprivation; more recently some have been conducted to show the effects of sleep restriction, which is a much more common occurrence, have the same effects as total sleep deprivation. Each phase of the sleep cycle restores and rejuvenates the brain for optimal function. When sleep is deprived, the active process of the glymphatic system does not have time to perform that function, so toxins can build up, and the effects will become apparent in cognitive abilities, behavior, and judgment. As a background for this paper we have reviewed literature and research of sleep phases, effects of sleep deprivation, and the glymphatic system of the brain and its restorative effect during the sleep cycle.

The Neuroprotective Aspects of Sleep

PubMed Central

Eugene, Andy R.; Masiak, Jolanta

2015-01-01

Sleep is an important component of human life, yet many people do not understand the relationship between the brain and the process of sleeping. Sleep has been proven to improve memory recall, regulate metabolism, and reduce mental fatigue. A minimum of 7 hours of daily sleep seems to be necessary for proper cognitive and behavioral function. The emotional and mental handicaps associated with chronic sleep loss as well as the highly hazardous situations which can be contributed to the lack of sleep is a serious concern that people need to be aware of. When one sleeps, the brain reorganizes and recharges itself, and removes toxic waste byproducts which have accumulated throughout the day. This evidence demonstrates that sleeping can clear the brain and help maintain its normal functioning. Multiple studies have been done to determine the effects of total sleep deprivation; more recently some have been conducted to show the effects of sleep restriction, which is a much more common occurrence, have the same effects as total sleep deprivation. Each phase of the sleep cycle restores and rejuvenates the brain for optimal function. When sleep is deprived, the active process of the glymphatic system does not have time to perform that function, so toxins can build up, and the effects will become apparent in cognitive abilities, behavior, and judgment. As a background for this paper we have reviewed literature and research of sleep phases, effects of sleep deprivation, and the glymphatic system of the brain and its restorative effect during the sleep cycle. PMID:26594659

Imaging brain development: the adolescent brain.

PubMed

Blakemore, Sarah-Jayne

2012-06-01

The past 15 years have seen a rapid expansion in the number of studies using neuroimaging techniques to investigate maturational changes in the human brain. In this paper, I review MRI studies on structural changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence. Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental neuroimaging in the next twenty years. Future studies might focus on complex questions including the development of functional connectivity; how gender and puberty influence adolescent brain development; the effects of genes, environment and culture on the adolescent brain; development of the atypical adolescent brain; and implications for policy of the study of the adolescent brain. Copyright © 2011 Elsevier Inc. All rights reserved.

An All-Sky Search for Wide Binaries in the SUPERBLINK Proper Motion Catalog

NASA Astrophysics Data System (ADS)

Hartman, Zachary; Lepine, Sebastien

2017-01-01

We present initial results from an all-sky search for Common Proper Motion (CPM) binaries in the SUPERBLINK all-sky proper motion catalog of 2.8 million stars with proper motions greater than 40 mas/yr, which has been recently enhanced with data from the GAIA mission. We initially search the SUPERBLINK catalog for pairs of stars with angular separations up to 1 degree and proper motion difference less than 40 mas/yr. In order to determine which of these pairs are real binaries, we develop a Bayesian analysis to calculate probabilities of true companionship based on a combination of proper motion magnitude, angular separation, and proper motion differences. The analysis reveals that the SUPERBLINK catalog most likely contains ~40,000 genuine common proper motion binaries. We provide initial estimates of the distances and projected physical separations of these wide binaries.

High frequency oscillations in brain hemodynamic response

NASA Astrophysics Data System (ADS)

Akin, Ata; Bolay, Hayrunnisa

2007-07-01

Tight autoregulation of vessel tone guarantees proper delivery of nutrients to the tissues. This regulation is maintained at a more delicate level in the brain since any decrease in the supply of glucose and oxygen to neuronal tissues might lead to unrecoverable injury. Functional near infrared spectroscopy has been proposed as a new tool to monitor the cerebrovascular response during cognitive activity. We have observed that during a Stroop task three distinct oscillatory patterns govern the control of the cerebrovascular reactivity: very low frequency (0.02-0.05 Hz), low frequency (0.08-0.12 Hz) and high frequency (0.12-0.18 Hz). High frequency oscillations have been shown to be related to stress level of the subjects. Our findings indicate that as the stress level is increased so does the energy of the high frequency component indicating a higher stimulation from the autonomic nervous system.

Neuropathological and transcriptomic characteristics of the aged brain

PubMed Central

Miller, Jeremy A; Guillozet-Bongaarts, Angela; Gibbons, Laura E; Postupna, Nadia; Renz, Anne; Beller, Allison E; Sunkin, Susan M; Ng, Lydia; Rose, Shannon E; Smith, Kimberly A; Szafer, Aaron; Barber, Chris; Bertagnolli, Darren; Bickley, Kristopher; Brouner, Krissy; Caldejon, Shiella; Chapin, Mike; Chua, Mindy L; Coleman, Natalie M; Cudaback, Eiron; Cuhaciyan, Christine; Dalley, Rachel A; Dee, Nick; Desta, Tsega; Dolbeare, Tim A; Dotson, Nadezhda I; Fisher, Michael; Gaudreault, Nathalie; Gee, Garrett; Gilbert, Terri L; Goldy, Jeff; Griffin, Fiona; Habel, Caroline; Haradon, Zeb; Hejazinia, Nika; Hellstern, Leanne L; Horvath, Steve; Howard, Kim; Howard, Robert; Johal, Justin; Jorstad, Nikolas L; Josephsen, Samuel R; Kuan, Chihchau L; Lai, Florence; Lee, Eric; Lee, Felix; Lemon, Tracy; Li, Xianwu; Marshall, Desiree A; Melchor, Jose; Mukherjee, Shubhabrata; Nyhus, Julie; Pendergraft, Julie; Potekhina, Lydia; Rha, Elizabeth Y; Rice, Samantha; Rosen, David; Sapru, Abharika; Schantz, Aimee; Shen, Elaine; Sherfield, Emily; Shi, Shu; Sodt, Andy J; Thatra, Nivretta; Tieu, Michael; Wilson, Angela M; Montine, Thomas J; Larson, Eric B; Bernard, Amy; Crane, Paul K; Ellenbogen, Richard G

2017-01-01

As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer’s disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging.brain-map.org/). We confirm established associations between AD pathology and dementia, albeit with increased, presumably aging-related variability, and identify sets of co-expressed genes correlated with pathological tau and inflammation markers. Finally, we demonstrate a relationship between dementia and RNA quality, and find common gene signatures, highlighting the importance of properly controlling for RNA quality when studying dementia. PMID:29120328

Medulloblastoma: experimental models and reality.

PubMed

Neumann, Julia E; Swartling, Fredrik J; Schüller, Ulrich

2017-11-01

Medulloblastoma is the most frequent malignant brain tumor in childhood, but it may also affect infants, adolescents, and young adults. Recent advances in the understanding of the disease have shed light on molecular and clinical heterogeneity, which is now reflected in the updated WHO classification of brain tumors. At the same time, it is well accepted that preclinical research and clinical trials have to be subgroup-specific. Hence, valid models have to be generated specifically for every medulloblastoma subgroup to properly mimic molecular fingerprints, clinical features, and responsiveness to targeted therapies. This review summarizes the availability of experimental medulloblastoma models with a particular focus on how well these models reflect the actual disease subgroup. We further describe technical advantages and disadvantages of the models and finally point out how some models have successfully been used to introduce new drugs and why some medulloblastoma subgroups are extraordinary difficult to model.

Deep brain stimulation with a pre-existing cochlear implant: Surgical technique and outcome.

PubMed

Eddelman, Daniel; Wewel, Joshua; Wiet, R Mark; Metman, Leo V; Sani, Sepehr

2017-01-01

Patients with previously implanted cranial devices pose a special challenge in deep brain stimulation (DBS) surgery. We report the implantation of bilateral DBS leads in a patient with a cochlear implant. Technical nuances and long-term interdevice functionality are presented. A 70-year-old patient with advancing Parkinson's disease and a previously placed cochlear implant for sensorineural hearing loss was referred for placement of bilateral DBS in the subthalamic nucleus (STN). Prior to DBS, the patient underwent surgical removal of the subgaleal cochlear magnet, followed by stereotactic MRI, frame placement, stereotactic computed tomography (CT), and merging of imaging studies. This technique allowed for successful computational merging, MRI-guided targeting, and lead implantation with acceptable accuracy. Formal testing and programming of both the devices were successful without electrical interference. Successful DBS implantation with high resolution MRI-guided targeting is technically feasible in patients with previously implanted cochlear implants by following proper precautions.

The basics of preclinical drug development for neurodegenerative disease indications.

PubMed

Steinmetz, Karen L; Spack, Edward G

2009-06-12

Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonization. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and services to assist applicants in preparing the preclinical programs and documentation for their drugs. Increasingly, private foundations are also funding preclinical work. Close interaction with the FDA, including a meeting to prepare for submission of an Investigational New Drug application, is critical to ensure that the preclinical development package properly supports the planned phase I clinical trial.

The basics of preclinical drug development for neurodegenerative disease indications

PubMed Central

Steinmetz, Karen L; Spack, Edward G

2009-01-01

Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonisation. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and services to assist applicants in preparing the preclinical programs and documentation for their drugs. Increasingly, private foundations are also funding preclinical work. Close interaction with the FDA, including a meeting to prepare for submission of an Investigational New Drug application, is critical to ensure that the preclinical development package properly supports the planned phase I clinical trial. PMID:19534731

How Do Fruits Ripen?

ERIC Educational Resources Information Center

Sargent, Steven A.

2005-01-01

A fruit is alive, and for it to ripen normally, many biochemical reactions must occur in a proper order. After pollination, proper nutrition, growing conditions, and certain plant hormones cause the fruit to develop and grow to proper size. During this time, fruits store energy in the form of starch and sugars, called photosynthates because they…

Excessive Astrocyte-Derived Neurotrophin-3 Contributes to the Abnormal Neuronal Dendritic Development in a Mouse Model of Fragile X Syndrome

PubMed Central

Guo, Yan-yan; Liu, Shui-bing; Wu, Yu-mei; Li, Xiao-qiang; Zhao, Ming-gao

2012-01-01

Fragile X syndrome (FXS) is a form of inherited mental retardation in humans that results from expansion of a CGG repeat in the Fmr1 gene. Recent studies suggest a role of astrocytes in neuronal development. However, the mechanisms involved in the regulation process of astrocytes from FXS remain unclear. In this study, we found that astrocytes derived from a Fragile X model, the Fmr1 knockout (KO) mouse which lacks FMRP expression, inhibited the proper elaboration of dendritic processes of neurons in vitro. Furthermore, astrocytic conditioned medium (ACM) from KO astrocytes inhibited proper dendritic growth of both wild-type (WT) and KO neurons. Inducing expression of FMRP by transfection of FMRP vectors in KO astrocytes restored dendritic morphology and levels of synaptic proteins. Further experiments revealed elevated levels of the neurotrophin-3 (NT-3) in KO ACM and the prefrontal cortex of Fmr1 KO mice. However, the levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF) were normal. FMRP has multiple RNA–binding motifs and is involved in translational regulation. RNA–binding protein immunoprecipitation (RIP) showed the NT-3 mRNA interacted with FMRP in WT astrocytes. Addition of high concentrations of exogenous NT-3 to culture medium reduced the dendrites of neurons and synaptic protein levels, whereas these measures were ameliorated by neutralizing antibody to NT-3 or knockdown of NT-3 expression in KO astrocytes through short hairpin RNAs (shRNAs). Prefrontal cortex microinjection of WT astrocytes or NT-3 shRNA infected KO astrocytes rescued the deficit of trace fear memory in KO mice, concomitantly decreased the NT-3 levels in the prefrontal cortex. This study indicates that excessive NT-3 from astrocytes contributes to the abnormal neuronal dendritic development and that astrocytes could be a potential therapeutic target for FXS. PMID:23300470

The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory

PubMed Central

Cicvaric, Ana; Yang, Jiaye; Krieger, Sigurd; Khan, Deeba; Kim, Eun-Jung; Dominguez-Rodriguez, Manuel; Cabatic, Maureen; Molz, Barbara; Acevedo Aguilar, Juan Pablo; Milicevic, Radoslav; Smani, Tarik; Breuss, Johannes M.; Kerjaschki, Dontscho; Pollak, Daniela D.; Uhrin, Pavel; Monje, Francisco J.

2016-01-01

Abstract Introduction: Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Materials and methods: Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Results: Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. Discussion: This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology.Key messagesPodoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus-dependent learning and memory functions.Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation.Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these grounds, a relevant cross-talk between podoplanin and NGF as well as a role for podoplanin in plasticity-related brain neuronal functions is here proposed. PMID:27558977

Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections

PubMed Central

Domm, William; Misra, Ravi S.; O’Reilly, Michael A.

2015-01-01

Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses. Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured. Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity. Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense. This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health. PMID:26322310

Sustaining Health and Performance in the Cold: Environmental Medicine Guidance for Cold-Weather Operation.

DTIC Science & Technology

1992-07-01

or vehicle should be suspected of possible CO poisoning. 4. DO NOT APPLY OINTMENTS , SNOW OR ICE TO THE BURN , 3. Proper field sanitation is very AND DO...susceptible to cold injuries, and the use of indoor stoves may lead to burns or suffocation. Operational problems often arise in cold weather. Heavy...potential for body heat to escape. When the skin is exposed to cold, the brain signals the blood vessels in the skin to tighten, and blood flow to the skin

Non-ketotic hyperglycaemia hemichorea–hemiballismus and acute ischaemic stroke

PubMed Central

Carrion, Diego M; Carrion, Andres F

2013-01-01

Here we describe a patient with a rare movement disorder, hemichorea–hemiballismus, which is described as a complication of non-ketotic hyperglycaemia. This complication may be seen in individuals with poorly controlled long-standing diabetes mellitus. Proper diagnosis is established with CT and MRI of the brain, which typically show classic findings in the basal ganglia. Treatment focuses on improvement of glycaemic control and usually results in rapid resolution of the movement disorder. Nevertheless, recurrent episodes of hemichorea–hemiballismus, and even more ominous complications such as ischaemic stroke may occur. PMID:23470671

An analysis of the circuitry of the visual pathway of the lateral eye of limullus

NASA Technical Reports Server (NTRS)

Sjoestrand, F. S.

1970-01-01

The methodology is discussed for three-dimensional analysis of the nervous system on the basis of electron micrographs of serial sections. An analysis is presented of a part of the circuitry of the rabbit retina. In addition, some exploratory work is reported with respect to the visual cortex of the cat brain. A proper technique for preservation of the visual cortex was worked out and a technique to localize microelectrode tips in the tissue in connection with electron microscopy was partially worked out.

Multiple microRNAs regulate human FOXP2 gene expression by targeting sequences in its 3' untranslated region.

PubMed

Fu, Lijuan; Shi, Zhimin; Luo, Guanzheng; Tu, Weihong; Wang, XiuJie; Fang, Zhide; Li, XiaoChing

2014-10-01

Mutations in the human FOXP2 gene cause speech and language impairments. The FOXP2 protein is a transcription factor that regulates the expression of many downstream genes, which may have important roles in nervous system development and function. An adequate amount of functional FOXP2 protein is thought to be critical for the proper development of the neural circuitry underlying speech and language. However, how FOXP2 gene expression is regulated is not clearly understood. The FOXP2 mRNA has an approximately 4-kb-long 3' untranslated region (3' UTR), twice as long as its protein coding region, indicating that FOXP2 can be regulated by microRNAs (miRNAs). We identified multiple miRNAs that regulate the expression of the human FOXP2 gene using sequence analysis and in vitro cell systems. Focusing on let-7a, miR-9, and miR-129-5p, three brain-enriched miRNAs, we show that these miRNAs regulate human FOXP2 expression in a dosage-dependent manner and target specific sequences in the FOXP2 3' UTR. We further show that these three miRNAs are expressed in the cerebellum of the human fetal brain, where FOXP2 is known to be expressed. Our results reveal novel regulatory functions of the human FOXP2 3' UTR sequence and regulatory interactions between multiple miRNAs and the human FOXP2 gene. The expression of let-7a, miR-9, and miR-129-5p in the human fetal cerebellum is consistent with their roles in regulating FOXP2 expression during early cerebellum development. These results suggest that various genetic and environmental factors may contribute to speech and language development and related neural developmental disorders via the miRNA-FOXP2 regulatory network.

Studying the Brain in a Dish: 3D Cell Culture Models of Human Brain Development and Disease.

PubMed

Brown, Juliana; Quadrato, Giorgia; Arlotta, Paola

2018-01-01

The study of the cellular and molecular processes of the developing human brain has been hindered by access to suitable models of living human brain tissue. Recently developed 3D cell culture models offer the promise of studying fundamental brain processes in the context of human genetic background and species-specific developmental mechanisms. Here, we review the current state of 3D human brain organoid models and consider their potential to enable investigation of complex aspects of human brain development and the underpinning of human neurological disease. © 2018 Elsevier Inc. All rights reserved.

GLUT4 Mobilization Supports Energetic Demands of Active Synapses.

PubMed

Ashrafi, Ghazaleh; Wu, Zhuhao; Farrell, Ryan J; Ryan, Timothy A

2017-02-08

The brain is highly sensitive to proper fuel availability as evidenced by the rapid decline in neuronal function during ischemic attacks and acute severe hypoglycemia. We previously showed that sustained presynaptic function requires activity-driven glycolysis. Here, we provide strong evidence that during action potential (AP) firing, nerve terminals rely on the glucose transporter GLUT4 as a glycolytic regulatory system to meet the activity-driven increase in energy demands. Activity at synapses triggers insertion of GLUT4 into the axonal plasma membrane driven by activation of the metabolic sensor AMP kinase. Furthermore, we show that genetic ablation of GLUT4 leads to an arrest of synaptic vesicle recycling during sustained AP firing, similar to what is observed during acute glucose deprivation. The reliance on this biochemical regulatory system for "exercising" synapses is reminiscent of that occurring in exercising muscle to sustain cellular function and identifies nerve terminals as critical sites of proper metabolic control. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of the supplementary motor area for speech and language processing.

PubMed

Hertrich, Ingo; Dietrich, Susanne; Ackermann, Hermann

2016-09-01

Apart from its function in speech motor control, the supplementary motor area (SMA) has largely been neglected in models of speech and language processing in the brain. The aim of this review paper is to summarize more recent work, suggesting that the SMA has various superordinate control functions during speech communication and language reception, which is particularly relevant in case of increased task demands. The SMA is subdivided into a posterior region serving predominantly motor-related functions (SMA proper) whereas the anterior part (pre-SMA) is involved in higher-order cognitive control mechanisms. In analogy to motor triggering functions of the SMA proper, the pre-SMA seems to manage procedural aspects of cognitive processing. These latter functions, among others, comprise attentional switching, ambiguity resolution, context integration, and coordination between procedural and declarative memory structures. Regarding language processing, this refers, for example, to the use of inner speech mechanisms during language encoding, but also to lexical disambiguation, syntax and prosody integration, and context-tracking. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuroimaging Studies of Normal Brain Development and Their Relevance for Understanding Childhood Neuropsychiatric Disorders

ERIC Educational Resources Information Center

Marsh, Rachel; Gerber, Andrew J.; Peterson, Bradley S.

2008-01-01

Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.

Steroid hormone induction of temporal gene expression in Drosophila brain neuroblasts generates neuronal and glial diversity.

PubMed

Syed, Mubarak Hussain; Mark, Brandon; Doe, Chris Q

2017-04-10

An important question in neuroscience is how stem cells generate neuronal diversity. During Drosophila embryonic development, neural stem cells (neuroblasts) sequentially express transcription factors that generate neuronal diversity; regulation of the embryonic temporal transcription factor cascade is lineage-intrinsic. In contrast, larval neuroblasts generate longer ~50 division lineages, and currently only one mid-larval molecular transition is known: Chinmo/Imp/Lin-28+ neuroblasts transition to Syncrip+ neuroblasts. Here we show that the hormone ecdysone is required to down-regulate Chinmo/Imp and activate Syncrip, plus two late neuroblast factors, Broad and E93. We show that Seven-up triggers Chinmo/Imp to Syncrip/Broad/E93 transition by inducing expression of the Ecdysone receptor in mid-larval neuroblasts, rendering them competent to respond to the systemic hormone ecdysone. Importantly, late temporal gene expression is essential for proper neuronal and glial cell type specification. This is the first example of hormonal regulation of temporal factor expression in Drosophila embryonic or larval neural progenitors.

Lineage-specific effects of Notch/Numb signaling in post-embryonic development of the Drosophila brain.

PubMed

Lin, Suewei; Lai, Sen-Lin; Yu, Huang-Hsiang; Chihara, Takahiro; Luo, Liqun; Lee, Tzumin

2010-01-01

Numb can antagonize Notch signaling to diversify the fates of sister cells. We report here that paired sister cells acquire different fates in all three Drosophila neuronal lineages that make diverse types of antennal lobe projection neurons (PNs). Only one in each pair of postmitotic neurons survives into the adult stage in both anterodorsal (ad) and ventral (v) PN lineages. Notably, Notch signaling specifies the PN fate in the vPN lineage but promotes programmed cell death in the missing siblings in the adPN lineage. In addition, Notch/Numb-mediated binary sibling fates underlie the production of PNs and local interneurons from common precursors in the lAL lineage. Furthermore, Numb is needed in the lateral but not adPN or vPN lineages to prevent the appearance of ectopic neuroblasts and to ensure proper self-renewal of neural progenitors. These lineage-specific outputs of Notch/Numb signaling show that a universal mechanism of binary fate decision can be utilized to govern diverse neural sibling differentiations.

Metabolic alterations in developing brain after injury – knowns and unknowns

PubMed Central

McKenna, Mary C.; Scafidi, Susanna; Robertson, Courtney L.

2016-01-01

Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia-ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed. PMID:26148530

Simulation-based training in brain death determination.

PubMed

MacDougall, Benjamin J; Robinson, Jennifer D; Kappus, Liana; Sudikoff, Stephanie N; Greer, David M

2014-12-01

Despite straightforward guidelines on brain death determination by the American Academy of Neurology (AAN), substantial practice variability exists internationally, between states, and among institutions. We created a simulation-based training course on proper determination based on the AAN practice parameters to address and assess knowledge and practice gaps at our institution. Our intervention consisted of a didactic course and a simulation exercise, and was bookended by before and after multiple-choice tests. The 40-min didactic course, including a video demonstration, covered all aspects of the brain death examination. Simulation sessions utilized a SimMan 3G manikin and involved a complete examination, including an apnea test. Possible confounders and signs incompatible with brain death were embedded throughout. Facilitators evaluated performance with a 26-point checklist based on the most recent AAN guidelines. A senior neurologist conducted all aspects of the course, including the didactic session, simulation, and debriefing session. Ninety physicians from multiple specialties have participated in the didactic session, 38 of whom have completed the simulation. Pre-test scores were poor (41.4 %), with attendings scoring higher than residents (46.6 vs. 40.4 %, p = 0.07), and neurologists and neurosurgeons significantly outperforming other specialists (53.9 vs. 38.9 %, p = 0.003). Post-test scores (73.3 %) were notably higher than pre-test scores (45.4 %). Participant feedback has been uniformly positive. Baseline knowledge of brain death determination among providers was low but improved greatly after the course. Our intervention represents an effective model that can be replicated at other institutions to train clinicians in the determination of brain death according to evidence-based guidelines.

Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders

PubMed Central

Ratajczak, Mariusz Z.; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

2018-01-01

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as “sterile inflammation” when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms. PMID:29541038

Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders.

PubMed

Ratajczak, Mariusz Z; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

2018-01-01

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as "sterile inflammation" when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms.

Nanocarriers for the treatment of glioblastoma multiforme: Current state-of-the-art.

PubMed

Karim, Reatul; Palazzo, Claudio; Evrard, Brigitte; Piel, Geraldine

2016-04-10

Glioblastoma multiforme, a grade IV glioma, is the most frequently occurring and invasive primary tumor of the central nervous system, which causes about 4% of cancer-associated-deaths, making it one of the most fatal cancers. With present treatments, using state-of-the-art technologies, the median survival is about 14 months and 2 year survival rate is merely 3-5%. Hence, novel therapeutic approaches are urgently necessary. However, most drug molecules are not able to cross the blood-brain barrier, which is one of the major difficulties in glioblastoma treatment. This review describes the features of blood-brain barrier, and its anatomical changes with different stages of tumor growth. Moreover, various strategies to improve brain drug delivery i.e. tight junction opening, chemical modification of the drug, efflux transporter inhibition, convection-enhanced delivery, craniotomy-based drug delivery and drug delivery nanosystems are discussed. Nanocarriers are one of the highly potential drug transport systems that have gained huge research focus over the last few decades for site specific drug delivery, including drug delivery to the brain. Properly designed nanocolloids are capable to cross the blood-brain barrier and specifically deliver the drug in the brain tumor tissue. They can carry both hydrophilic and hydrophobic drugs, protect them from degradation, release the drug for sustained period, significantly improve the plasma circulation half-life and reduce toxic effects. Among various nanocarriers, liposomes, polymeric nanoparticles and lipid nanocapsules are the most widely studied, and are discussed in this review. For each type of nanocarrier, a general discussion describing their composition, characteristics, types and various uses is followed by their specific application to glioblastoma treatment. Moreover, some of the main challenges regarding toxicity and standardized evaluation techniques are narrated in brief. Copyright © 2016 Elsevier B.V. All rights reserved.

Organotypic hippocampal slice culture from the adult mouse brain: a versatile tool for translational neuropsychopharmacology.

PubMed

Kim, Hyunjeong; Kim, Eosu; Park, Minsun; Lee, Eun; Namkoong, Kee

2013-03-05

One of the most significant barriers towards translational neuropsychiatry would be an unavailability of living brain tissues. Although organotypic brain tissue culture could be a useful alternative enabling observation of temporal changes induced by various drugs in living brain tissues, a proper method to establish a stable organotypic brain slice culture system using adult (rather than neonatal) hippocampus has been still elusive. In this study, we evaluated our simple method using the serum-free culture medium for successful adult organotypic hippocampal slice culture. Several tens of hippocampal slices from a single adult mouse (3-5 months old) were cultured in serum-free versus serum-containing conventional culture medium for 30 days and underwent various experiments to validate the effects of the existence of serum in the culture medium. Neither the excessive regression of neuronal viability nor metabolic deficiency was observed in the serum-free medium culture in contrast to the serum-containing medium culture. Despite such viability, newly generated immature neurons were scarcely detected in the serum-free culture, suggesting that the original neurons in the brain slice persist rather than being replaced by neurogenesis. Key structural features of in vivo neural tissue constituting astrocytes, neural processes, and pre- and post-synapses were also well preserved in the serum-free culture. In conclusion, using the serum-free culture medium, the adult hippocampal slice culture system will serve as a promising ex vivo tool for various fields of neuroscience, especially for studies on aging-related neuropsychiatric disorders or for high throughput screening of potential agents working against such disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

45 CFR 170.423 - Principles of proper conduct for ONC-ATCBs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Principles of proper conduct for ONC-ATCBs. 170... § 170.423 Principles of proper conduct for ONC-ATCBs. An ONC-ATCB shall: (a) Operate its certification... EHR Module developer conspicuously include the following text on its Web site and in all marketing...

Enthalpy Costs of Making and Breaking Bonds: A Game of Generating Molecules with Proper Lewis Structures

ERIC Educational Resources Information Center

Bell, Peter T.; Adkins, Alyssa D.; Gamble, Rex J.; Schultz, Linda D.

2009-01-01

"Enthalpy Costs" is a simple card game created to assist students in developing proper Lewis structure drawing skills. Score keeping is accomplished by tracking the enthalpy changes associated with bond-making and bond-breaking processes during formation of molecules represented by proper Lewis structures. Playing the game requires the student to…

Brain anatomical networks in early human brain development.

PubMed

Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang

2011-02-01

Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.

Genetically induced abnormal cranial development in human trisomy 18 with holoprosencephaly: comparisons with the normal tempo of osteogenic-neural development.

PubMed

Reid, Shaina N; Ziermann, Janine M; Gondré-Lewis, Marjorie C

2015-07-01

Craniofacial malformations are common congenital defects caused by failed midline inductive signals. These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith-Lemli-Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders. Here we present the first in-depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state-of-the-art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31. Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (CNVII) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes to neural patterning, in the proper development of neural and cranial structures. Our study of a T18 specimen emphasizes the intricate interplay between bone and brain development in midline craniofacial abnormalities in general. © 2015 Anatomical Society.

Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells.

PubMed

Uchida, Yasuo; Ito, Katsuaki; Ohtsuki, Sumio; Kubo, Yoshiyuki; Suzuki, Takashi; Terasaki, Tetsuya

2015-07-01

The purpose of this study was to clarify the expression of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo et al. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [(3) H]biotin and [(3) H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone, and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human blood-brain barrier. In humans, it was unclear (not concluded) about what transport system at the blood-brain barrier (BBB) is responsible for the brain uptakes of two vitamins, biotin and pantothenic acid, which are necessary for brain proper function. This study clarified for the first time that the solute carrier 5A6/Na(+) -dependent multivitamin transporter SLC5A6/SMVT is responsible for the supplies of biotin and pantothenic acid into brain across the BBB in humans. DHA, docosahexaenoic acid; NSAID, non-steroidal anti-inflammatory drug; PGE2, prostaglandin E2. © 2015 International Society for Neurochemistry.

Role of mechanical factors in cortical folding development

NASA Astrophysics Data System (ADS)

Razavi, Mir Jalil; Zhang, Tuo; Li, Xiao; Liu, Tianming; Wang, Xianqiao

2015-09-01

Deciphering mysteries of the structure-function relationship in cortical folding has emerged as the cynosure of recent research on brain. Understanding the mechanism of convolution patterns can provide useful insight into the normal and pathological brain function. However, despite decades of speculation and endeavors the underlying mechanism of the brain folding process remains poorly understood. This paper focuses on the three-dimensional morphological patterns of a developing brain under different tissue specification assumptions via theoretical analyses, computational modeling, and experiment verifications. The living human brain is modeled with a soft structure having outer cortex and inner core to investigate the brain development. Analytical interpretations of differential growth of the brain model provide preliminary insight into the critical growth ratio for instability and crease formation of the developing brain followed by computational modeling as a way to offer clues for brain's postbuckling morphology. Especially, tissue geometry, growth ratio, and material properties of the cortex are explored as the most determinant parameters to control the morphogenesis of a growing brain model. As indicated in results, compressive residual stresses caused by the sufficient growth trigger instability and the brain forms highly convoluted patterns wherein its gyrification degree is specified with the cortex thickness. Morphological patterns of the developing brain predicted from the computational modeling are consistent with our neuroimaging observations, thereby clarifying, in part, the reason of some classical malformation in a developing brain.

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

PubMed

Cunnane, Stephen C; Crawford, Michael A

2014-12-01

The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Nature of Compensatory Response to Low Thyroid Hormone in Developing Brain.

EPA Science Inventory

Abstract Thyroid hormone is essential for normal brain development, but the degree to which the developing brain is sensitive to small perturbations in serum thyroxin is not clear. An important concept related to this is that the developing brain possesses potent mechanisms to co...

Starting Smart: How Early Experiences Affect Brain Development. An Ounce of Prevention Fund Paper.

ERIC Educational Resources Information Center

Ounce of Prevention Fund.

Recent research has provided great insight into the impact of early experience on brain development. It is now believed that brain growth is highly dependent upon early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring…

Slc7a11 (xCT) protein expression is not altered in the depressed brain and system xc- deficiency does not affect depression-associated behaviour in the corticosterone mouse model.

PubMed

Demuyser, Thomas; Deneyer, Lauren; Bentea, Eduard; Albertini, Giulia; Femenia, Teresa; Walrave, Laura; Sato, Hideyo; Danbolt, Niels C; De Bundel, Dimitri; Michotte, Alex; Lindskog, Maria; Massie, Ann; Smolders, Ilse

2017-09-27

The cystine/glutamate antiporter (system xc-) is believed to contribute to nonvesicular glutamate release from glial cells in various brain areas. Although recent investigations implicate system xc- in mood disorders, unambiguous evidence has not yet been established. Therefore, we evaluated the possible role of system xc- in the depressive state. We conducted a protein expression analysis of the specific subunit of system xc- (xCT) in brain regions of the corticosterone mouse model, Flinders Sensitive Line rat model and post-mortem tissue of depressed patients. We next subjected system xc- deficient mice to the corticosterone model and analysed their behaviour in several tests. Lastly, we subjected additional cohorts of xCT-deficient and wild-type mice to N-acetylcysteine treatment to unveil whether the previously reported antidepressant-like effects are dependent upon system xc-. We did not detect any changes in xCT expression levels in the animal models or patients compared to proper controls. Furthermore, loss of system xc- had no effect on depression- and anxiety-like behaviour. Finally, the antidepressant-like effects of N-acetylcysteine are not mediated via system xc-. xCT protein expression is not altered in the depressed brain and system xc- deficiency does not affect depression-associated behaviour in the corticosterone mouse model.

Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia.

PubMed

Park, Ji H; Long, Aaron; Owens, Katrina; Kristian, Tibor

2016-11-01

Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor for multiple cellular metabolic reactions and has a central role in energy production. Brain ischemia depletes NAD(+) pools leading to bioenergetics failure and cell death. Nicotinamide mononucleotide (NMN) is utilized by the NAD(+) salvage pathway enzyme, nicotinamide adenylyltransferase (Nmnat) to generate NAD(+). Therefore, we examined whether NMN could protect against ischemic brain damage. Mice were subjected to transient forebrain ischemia and treated with NMN or vehicle at the start of reperfusion or 30min after the ischemic insult. At 2, 4, and 24h of recovery, the proteins poly-ADP-ribosylation (PAR), hippocampal NAD(+) levels, and expression levels of NAD(+) salvage pathway enzymes were determined. Furthermore, animal's neurologic outcome and hippocampal CA1 neuronal death was assessed after six days of reperfusion. NMN (62.5mg/kg) dramatically ameliorated the hippocampal CA1 injury and significantly improved the neurological outcome. Additionally, the post-ischemic NMN treatment prevented the increase in PAR formation and NAD(+) catabolism. Since the NMN administration did not affect animal's temperature, blood gases or regional cerebral blood flow during recovery, the protective effect was not a result of altered reperfusion conditions. These data suggest that administration of NMN at a proper dosage has a strong protective effect against ischemic brain injury. Published by Elsevier Inc.

A physical multifield model predicts the development of volume and structure in the human brain

NASA Astrophysics Data System (ADS)

Rooij, Rijk de; Kuhl, Ellen

2018-03-01

The prenatal development of the human brain is characterized by a rapid increase in brain volume and a development of a highly folded cortex. At the cellular level, these events are enabled by symmetric and asymmetric cell division in the ventricular regions of the brain followed by an outwards cell migration towards the peripheral regions. The role of mechanics during brain development has been suggested and acknowledged in past decades, but remains insufficiently understood. Here we propose a mechanistic model that couples cell division, cell migration, and brain volume growth to accurately model the developing brain between weeks 10 and 29 of gestation. Our model accurately predicts a 160-fold volume increase from 1.5 cm3 at week 10 to 235 cm3 at week 29 of gestation. In agreement with human brain development, the cortex begins to form around week 22 and accounts for about 30% of the total brain volume at week 29. Our results show that cell division and coupling between cell density and volume growth are essential to accurately model brain volume development, whereas cell migration and diffusion contribute mainly to the development of the cortex. We demonstrate that complex folding patterns, including sinusoidal folds and creases, emerge naturally as the cortex develops, even for low stiffness contrasts between the cortex and subcortex.

Design and Mechanism of Tetrahydrothiophene-based GABA Aminotransferase Inactivators

PubMed Central

Le, Hoang V.; Hawker, Dustin D.; Wu, Rui; Doud, Emma; Widom, Julia; Sanishvili, Ruslan; Liu, Dali; Kelleher, Neil L.; Silverman, Richard B.

2015-01-01

Low levels of γ-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the blood-brain barrier and inhibit the activity of γ-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally-restricted, tetrahydrothiophene-based GABA analogs with a properly-positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is eight times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bond interactions with Arg-192, a π-π interaction with Phe-189, and a weak nonbonded S···O=C interaction with Glu-270, thereby inactivating the enzyme. PMID:25781189

Traumatic Brain and Spinal Cord Fatalities Among High School and College Football Players - United States, 2005-2014.

PubMed

Kucera, Kristen L; Yau, Rebecca K; Register-Mihalik, Johna; Marshall, Stephen W; Thomas, Leah C; Wolf, Susanne; Cantu, Robert C; Mueller, Frederick O; Guskiewicz, Kevin M

2017-01-06

An estimated 1.1 million high school and 75,000 college athletes participate in tackle football annually in the United States. Football is a collision sport; traumatic injuries are frequent (1,2), and can be fatal (3). This report updates the incidence and characteristics of deaths caused by traumatic brain injury and spinal cord injury (4) in high school and college football and presents illustrative case descriptions. Information was analyzed from the National Center for Catastrophic Sport Injury Research (NCCSIR). During 2005-2014, a total of 28 deaths (2.8 deaths per year) from traumatic brain and spinal cord injuries occurred among high school (24 deaths) and college football players (four deaths) combined. Most deaths occurred during competitions and resulted from tackling or being tackled. All four of the college deaths and 14 (58%) of the 24 high school deaths occurred during the last 5 years (2010-2014) of the 10-year study period. These findings support the need for continued surveillance and safety efforts (particularly during competition) to ensure proper tackling techniques, emergency planning for severe injuries, availability of medical care onsite during competitions, and assessment that it is safe to return to play following a concussion.

Diagnostic usefulness of 3 tesla MRI of the brain for cushing disease in a child.

PubMed

Ono, Erina; Ozawa, Ayako; Matoba, Kaori; Motoki, Takanori; Tajima, Asako; Miyata, Ichiro; Ito, Junko; Inoshita, Naoko; Yamada, Syozo; Ida, Hiroyuki

2011-10-01

It is sometimes difficult to confirm the location of a microadenoma in Cushing disease. Recently, we experienced an 11-yr-old female case of Cushing disease with hyperprolactinemia. She was referred to our hospital because of decrease of height velocity with body weight gain. On admission, she had typical symptoms of Cushing syndrome. Although no pituitary microadenomas were detected on 1.5 Tesla MRI of the brain, endocrinological examinations including IPS and CS sampling were consistent with Cushing disease with hyperprolactinemia. Oral administration of methyrapone instead of neurosurgery was started after discharge, but subsequent 3 Tesla MRI of the brain clearly demonstrated a 3-mm less-enhanced lesion in the left side of the pituitary gland. Finally, transsphenoidal surgery was performed, and a 3.5-mm left-sided microadenoma was resected. Compared with 1.5 Tesla MRI, 3 Tesla MRI offers the advantage of a higher signal to noise ratio (SNR), which provides higher resolution and proper image quality. Therefore, 3 Tesla MRI is a very useful tool to localize microadenomas in Cushing disease in children as well as in adults. It will be the first choice of radiological examinations in suspected cases of Cushing disease.

Currents of memory: recent progress, translational challenges, and ethical considerations in fornix deep brain stimulation trials for Alzheimer's disease.

PubMed

Viaña, John Noel M; Vickers, James C; Cook, Mark J; Gilbert, Frederic

2017-08-01

The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation in 2008 paved the way for several phase I and phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzheimer's disease. In this article, we summarize clinical trials and case reports on fornix deep brain stimulation for Alzheimer's disease and review experiments on animal models evaluating the physiological or behavioral effects of this intervention. Based on information from these reports and studies, we identify potential translational challenges of this approach and determine practical and ethical considerations for clinical trials, focusing on issues regarding selection criteria, trial design, and outcome evaluation. Based on initial results suggesting greater benefit for those with milder disease stage, we find it essential that participant expectations are carefully managed to avoid treatment disenchantment and/or frustration from participants and caregivers. Finally, we urge for collaboration between centers to establish proper clinical standards and to promote better trial results comparison. Copyright © 2017 Elsevier Inc. All rights reserved.

Visualising inter-subject variability in fMRI using threshold-weighted overlap maps

NASA Astrophysics Data System (ADS)

Seghier, Mohamed L.; Price, Cathy J.

2016-02-01

Functional neuroimaging studies are revealing the neural systems sustaining many sensory, motor and cognitive abilities. A proper understanding of these systems requires an appreciation of the degree to which they vary across subjects. Some sources of inter-subject variability might be easy to measure (demographics, behavioural scores, or experimental factors), while others are more difficult (cognitive strategies, learning effects, and other hidden sources). Here, we introduce a simple way of visualising whole-brain consistency and variability in brain responses across subjects using threshold-weighted voxel-based overlap maps. The output quantifies the proportion of subjects activating a particular voxel or region over a wide range of statistical thresholds. The sensitivity of our approach was assessed in 30 healthy adults performing a matching task with their dominant hand. We show how overlap maps revealed many effects that were only present in a subsample of our group; we discuss how overlap maps can provide information that may be missed or misrepresented by standard group analysis, and how this information can help users to understand their data. In particular, we emphasize that functional overlap maps can be particularly useful when it comes to explaining typical (or atypical) compensatory mechanisms used by patients following brain damage.

The blood-brain barrier of the chick glycogen body (corpus gelatinosum) and its functional implications.

PubMed

Möller, Wilhelm; Kummer, Wolfgang

2003-07-01

Among recent vertebrates only birds possess a glycogen body (corpus gelatinosum), located in the rhomboidal sinus of the lumbosacral region of the spinal cord and separated from the neural tissue proper. Because of the specific topographical situation of this circumventricular organ, the structure of its vascular system is of special interest with respect to the still unsolved functional problems. The existence of a blood-brain barrier is demonstrated by the exclusion of intravascularly injected tracer (horseradish peroxidase), and immunocytochemical demonstration of glucose transporter-1 as a functional marker and of neurothelin, occludin and ZO-1 as structural markers. Alkaline phosphatase and gamma-glutamyltransferase activities, two enzyme reactions frequently used for demonstration of an established blood-brain barrier in vitro, were localized histochemically on the plasmalemma of glycogen body cells and were absent from the endothelium. In addition, local enlargements of the intercellular space were observed by transmission and scanning electron microscopy. In accordance with the concept of a third circulation the cerebrospinal fluid may be the vehicle for distributing substances originating in the glycogen body to the CNS, while the vascular endothelium maintains the internal milieu by virtue of its dynamic barrier functions.

Design and mechanism of tetrahydrothiophene-based γ-aminobutyric acid aminotransferase inactivators.

PubMed

Le, Hoang V; Hawker, Dustin D; Wu, Rui; Doud, Emma; Widom, Julia; Sanishvili, Ruslan; Liu, Dali; Kelleher, Neil L; Silverman, Richard B

2015-04-08

Low levels of γ-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinson's disease, Alzheimer's disease, Huntington's disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the blood-brain barrier and inhibit the activity of γ-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally restricted tetrahydrothiophene-based GABA analogues with a properly positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is 8 times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bonding interactions with Arg-192, a π-π interaction with Phe-189, and a weak nonbonded S···O═C interaction with Glu-270, thereby inactivating the enzyme.

[Acquired drives. The cortical mechanism responsible to the emergence and development of social existence].

PubMed

József, Knoll

2007-10-01

This paper is a brief interpretation of the theory (J. Knoll: The Brain and Its Self, Springer, 2005) the main message of which is that the appearance of the mammalian brain with the ability to acquire drives ensured the development of social life, and eventually led to the evolution of the human society. In the mammalian brain capable to acquire drives, untrained cortical neurons (Group 1) possess the potentiality to change their functional state in response to practice, training, or experience in three consecutive stages, namely, by getting involved in (a) an extinguishable conditioned reflex (ECR) (Group 2), (b) an inextinguishable conditioned reflex (ICR) (Group 3), or (c)an acquired drive (Group 4). The activity of the cortical neurons belonging to Group 3 and 4 is inseparable from conscious perception. In any moment of life self is the sum of those cortical neurons that have already changed their functional significance and belong to Group 3 or 4. Metaphorically, every human being is born with a telencephalon that resembles a book with over 100 billion empty pages (untrained, naive cortical neurons, Group 1), and with the capacity to inscribe as much as possible in this book throughout life. Whenever a drive is acquired, chains of ICRs are fixed, neurons responsible for emotions are also coupled to the integral whole, thus cognitive/volitional consciousness is necessarily inseparable from an affective state of consciousness. Cortical neurons belonging to Group 3 or 4 continuously synthesize their specific enhancer substance within their capacity. This means that even in the vigilant resting state (leisure), in the absence of a dominant drive, as well as in the non-vigilant resting state (sleeping), the cortical neurons representing the totality of the already fixed ICRs and acquired drives are permanently under the influence of their specific enhancer substance. Although the level of this permanent, undulating activation remains low, it is unpredictable as to when any group of cortical neurons will be influenced by enhancer substances on the level already inseparable from conscious perception. Thus, as the totality of the cortical neurons belonging to Group 3 or 4 works continuously on an unconscious level, there is a steadily operating, chaotic background noise in the human telencephalon. Even in the active state ("fight or flight" behavior, goal-seeking), when the actually dominant drive determines the rational goal to be reached, the noise is suppressed, but cannot cease to exist. But it never endangers the function of the actually dominant innate or acquired drive. From this situation it follows that the rational brain activity is necessarily amalgamated with an irrational brain activity and we live through every moment of our life experiencing the totality of order and chaos in our brain. Human society the maintenance of which has always required the proper manipulation of the brain of its members still finds itself in a state of development. It seeks its final equilibrium: namely, that state in which behavioral modification induced by the home/school/society triad will be based, from birth until death, on the exact knowledge of the natural laws that keep the brain and its self going. In this way, members of the community will understand that simultaneity of order and chaos in their brain is the physiological reality that determines human activity, and will consciously try to find the acquired drives that optimally fit their natural endowments. For the time being those who have been lucky enough to acquire the best fitting drives in due time, in the early uphill period of life, have had fair chances for success and happiness. In contrast, those who for any reason have missed this opportunity will remain frustrated and look for 'ersatz'. It seems reasonable to conclude that order and chaos are of equal importance in our brain. Without the ability to adapt ourselves to the concrete (science), we would not be able to survive; without the ability which allows detachment from the concrete and explorations in the infinite (art), life would not be worth living. Thus, the human society, this most sophisticated form of organized life on earth is still in trial and error phase of its development. It seeks to outgrow the myth-directed era of its history and come to its final state, the reason-directed human society.

Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders.

PubMed

Schubert, D; Martens, G J M; Kolk, S M

2015-07-01

The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies.

Cooing, Crying, Cuddling: Infant Brain Development. [Videotape].

ERIC Educational Resources Information Center

National Association for the Education of Young Children, Washington, DC.

Noting recent neuroscience research findings suggesting that caregivers play a vital role in brain development, this videotape explores the process of brain development during the first 15 months of life and presents implications for infant care. Part 1 of the 28-minute video discusses basic infant development and brain research, focusing on how…

Adolescent Brain and Cognitive Developments: Implications for Clinical Assessment in Traumatic Brain Injury

ERIC Educational Resources Information Center

Ciccia, Angela Hein; Meulenbroek, Peter; Turkstra, Lyn S.

2009-01-01

Adolescence is a time of significant physical, social, and emotional developments, accompanied by changes in cognitive and language skills. Underlying these are significant developments in brain structures and functions including changes in cortical and subcortical gray matter and white matter tracts. Among the brain regions that develop during…

Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells.

PubMed

Li, Yuanyuan; Wang, Ran; Qiao, Nan; Peng, Guangdun; Zhang, Ke; Tang, Ke; Han, Jing-Dong J; Jing, Naihe

2017-12-01

Proper neural commitment is essential for ensuring the appropriate development of the human brain and for preventing neurodevelopmental diseases such as autism spectrum disorders, schizophrenia, and intellectual disorders. However, the molecular mechanisms underlying the neural commitment in humans remain elusive. Here, we report the establishment of a neural differentiation system based on human embryonic stem cells (hESCs) and on comprehensive RNA sequencing analysis of transcriptome dynamics during early hESC differentiation. Using weighted gene co-expression network analysis, we reveal that the hESC neurodevelopmental trajectory has five stages: pluripotency (day 0); differentiation initiation (days 2, 4, and 6); neural commitment (days 8-10); neural progenitor cell proliferation (days 12, 14, and 16); and neuronal differentiation (days 18, 20, and 22). These stages were characterized by unique module genes, which may recapitulate the early human cortical development. Moreover, a comparison of our RNA-sequencing data with several other transcriptome profiling datasets from mice and humans indicated that Module 3 associated with the day 8-10 stage is a critical window of fate switch from the pluripotency to the neural lineage. Interestingly, at this stage, no key extrinsic signals were activated. In contrast, using CRISPR/Cas9-mediated gene knockouts, we also found that intrinsic hub transcription factors, including the schizophrenia-associated SIX3 gene and septo-optic dysplasia-related HESX1 gene, are required to program hESC neural determination. Our results improve the understanding of the mechanism of neural commitment in the human brain and may help elucidate the etiology of human mental disorders and advance therapies for managing these conditions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

On the origins of sex-based differences in respiratory disorders: Lessons and hypotheses from stress neuroendocrinology in developing rats.

PubMed

Rousseau, Jean-Philippe; Tenorio-Lopes, Luana; Baldy, Cécile; Janes, Tara Adele; Fournier, Stéphanie; Kinkead, Richard

2017-11-01

The environment plays a critical role in shaping development and function of the brain. Stress, especially when experienced early in life, can interfere with these processes. In the context of respiratory control, perinatal stress can therefore alter the ability to achieve the "fine-tuning" necessary for proper detection of chemosensory stimuli and production of an adequate motor (respiratory) command. Depending on the timing, intensity, and duration, the detrimental consequences of perinatal exposure to adverse conditions on the respiratory network become manifest at various life stages and can persist into adulthood. During early life, respiratory diseases commonly associated with dysfunction of neural networks include apnea of prematurity (AOP) and cardio-respiratory failure leading to sudden infant death syndrome (SIDS). Sleep disordered breathing (SDB) can occur at various life stages, including adulthood. Regardless of age, a common element of these disorders is their greater prevalence in males. While this sexual dimorphism points to a potential role of sex hormones, our understanding of the neuroendocrine mechanisms remain poorly understood. In addition to their modulatory influence on breathing, gonadal hormones regulate sexual differentiation of the brain. Stress alters these effects, and over the years our laboratory has used various perinatal stress protocols to gain insight into the origins of sex-based differences in respiratory disorders. This review discusses our recent advances with a focus on the sex-specific impact of early life stress on O 2 -chemoreflex function both in newborn and adult rats. We conclude by discussing the basic principles emerging from this work, potential mechanisms, and clinical relevance. Copyright © 2017 Elsevier B.V. All rights reserved.

[Neurobiology and neurogenetics of dyslexia].

PubMed

Benítez-Burraco, A

2010-01-01

Dyslexia is a learning disability in which reading (but not any other) impairment is the most prominent symptom. There seems to be a high comorbidity among dyslexia and other learning disabilities, such as SLI, SSD or ADHD. The nulear deficit in dyslexia appears to correspond to an impairment in phonological processing. Structural and functional studies in dyslexic readers converge to indicate the presence of malformations in the brain areas corresponding to the reading systems, but also a failure of these systems to function properly during reading. Genes linked (or associated) to dyslexia have been shown to be involved in neuronal migration and axon guidance during the formation of the cortex. In the developing cerebral neocortex of rats, local loss of function of most of these genes not only results in abnormal neuronal migration and neocortical and hippocampal malformations, but also in deficits related to auditory processing and learning. While the structural malformations resemble neuronal migration abnormalities observed in the brains of individuals with developmental dyslexia, processing/learning deficits also resemble deficits described in individuals affected by the disease. On the whole, dyslexia seems to be on a continuum with typical reading at different biological levels (genetic, biochemical, physiological, cognitive). Furthermore, certain elements belonging to some of these levels (mainly -some of the- genes linked or associated to the disease, but also -some of the- neuronal structures whose development is regulated by these genes) would simultaneously belong to those of other cognitive abilities, which give rise to diseases of a different nature (i.e. non- dyslexic impairments) when they are impaired. Copyright © 2009 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

A Learning-Style Theory for Understanding Autistic Behaviors

PubMed Central

Qian, Ning; Lipkin, Richard M.

2011-01-01

Understanding autism's ever-expanding array of behaviors, from sensation to cognition, is a major challenge. We posit that autistic and typically developing brains implement different algorithms that are better suited to learn, represent, and process different tasks; consequently, they develop different interests and behaviors. Computationally, a continuum of algorithms exists, from lookup table (LUT) learning, which aims to store experiences precisely, to interpolation (INT) learning, which focuses on extracting underlying statistical structure (regularities) from experiences. We hypothesize that autistic and typical brains, respectively, are biased toward LUT and INT learning, in low- and high-dimensional feature spaces, possibly because of their narrow and broad tuning functions. The LUT style is good at learning relationships that are local, precise, rigid, and contain little regularity for generalization (e.g., the name–number association in a phonebook). However, it is poor at learning relationships that are context dependent, noisy, flexible, and do contain regularities for generalization (e.g., associations between gaze direction and intention, language and meaning, sensory input and interpretation, motor-control signal and movement, and social situation and proper response). The LUT style poorly compresses information, resulting in inefficiency, sensory overload (overwhelm), restricted interests, and resistance to change. It also leads to poor prediction and anticipation, frequent surprises and over-reaction (hyper-sensitivity), impaired attentional selection and switching, concreteness, strong local focus, weak adaptation, and superior and inferior performances on simple and complex tasks. The spectrum nature of autism can be explained by different degrees of LUT learning among different individuals, and in different systems of the same individual. Our theory suggests that therapy should focus on training autistic LUT algorithm to learn regularities. PMID:21886617

Rhinencephalon changes in tuberous sclerosis complex.

PubMed

Manara, Renzo; Brotto, Davide; Bugin, Samuela; Pelizza, Maria Federica; Sartori, Stefano; Nosadini, Margherita; Azzolini, Sara; Iaconetta, Giorgio; Parazzini, Cecilia; Murgia, Alessandra; Peron, Angela; Canevini, Paola; Labriola, Francesca; Vignoli, Aglaia; Toldo, Irene

2018-06-17

Despite complex olfactory bulb embryogenesis, its development abnormalities in tuberous sclerosis complex (TSC) have been poorly investigated. Brain MRIs of 110 TSC patients (mean age 11.5 years; age range 0.5-38 years; 52 female; 26 TSC1, 68 TSC2, 8 without mutation identified in TSC1 or TSC2, 8 not tested) were retrospectively evaluated. Signal and morphological abnormalities consistent with olfactory bulb hypo/aplasia or with olfactory bulb hamartomas were recorded. Cortical tuber number was visually assessed and a neurological severity score was obtained. Patients with and without rhinencephalon abnormalities were compared using appropriate parametric and non-parametric tests. Eight of110 (7.2%) TSC patients presented rhinencephalon MRI changes encompassing olfactory bulb bilateral aplasia (2/110), bilateral hypoplasia (2/110), unilateral hypoplasia (1/110), unilateral hamartoma (2/110), and bilateral hamartomas (1/110); olfactory bulb hypo/aplasia always displayed ipsilateral olfactory sulcus hypoplasia, while no TSC patient harboring rhinencephalon hamartomas had concomitant forebrain sulcation abnormalities. None of the patients showed overt olfactory deficits or hypogonadism, though young age and poor compliance hampered a proper evaluation in most cases. TSC patients with rhinencephalon changes had more cortical tubers (47 ± 29.1 vs 26.2 ± 19.6; p = 0.006) but did not differ for clinical severity (p = 0.45) compared to the other patients of the sample. Olfactory bulb and/or forebrain changes are not rare among TSC subjects. Future studies investigating clinical consequences in older subjects (anosmia, gonadic development etc.) will define whether rhinencephalon changes are simply an imaging feature among the constellation of TSC-related brain changes or a feature to be searched for possible implications in the management of TSC subjects.

Accelerated recruitment of new brain development genes into the human genome.

PubMed

Zhang, Yong E; Landback, Patrick; Vibranovski, Maria D; Long, Manyuan

2011-10-01

How the human brain evolved has attracted tremendous interests for decades. Motivated by case studies of primate-specific genes implicated in brain function, we examined whether or not the young genes, those emerging genome-wide in the lineages specific to the primates or rodents, showed distinct spatial and temporal patterns of transcription compared to old genes, which had existed before primate and rodent split. We found consistent patterns across different sources of expression data: there is a significantly larger proportion of young genes expressed in the fetal or infant brain of humans than in mouse, and more young genes in humans have expression biased toward early developing brains than old genes. Most of these young genes are expressed in the evolutionarily newest part of human brain, the neocortex. Remarkably, we also identified a number of human-specific genes which are expressed in the prefrontal cortex, which is implicated in complex cognitive behaviors. The young genes upregulated in the early developing human brain play diverse functional roles, with a significant enrichment of transcription factors. Genes originating from different mechanisms show a similar expression bias in the developing brain. Moreover, we found that the young genes upregulated in early brain development showed rapid protein evolution compared to old genes also expressed in the fetal brain. Strikingly, genes expressed in the neocortex arose soon after its morphological origin. These four lines of evidence suggest that positive selection for brain function may have contributed to the origination of young genes expressed in the developing brain. These data demonstrate a striking recruitment of new genes into the early development of the human brain.

Brain Structure and Development.

ERIC Educational Resources Information Center

Teyler, T.J.; Chiaia, N.

1983-01-01

Considers basic biology of brain, what is known of how it operates, and something of how it develops. Discusses properties of neurons and specialized regions of the brain in linguistic and higher order processing skills, as well as genetic and environmental influences on brain development. (CMG)

Language and reading development in the brain today: neuromarkers and the case for prediction.

PubMed

Buchweitz, Augusto

2016-01-01

The goal of this article is to provide an account of language development in the brain using the new information about brain function gleaned from cognitive neuroscience. This account goes beyond describing the association between language and specific brain areas to advocate the possibility of predicting language outcomes using brain-imaging data. The goal is to address the current evidence about language development in the brain and prediction of language outcomes. Recent studies will be discussed in the light of the evidence generated for predicting language outcomes and using new methods of analysis of brain data. The present account of brain behavior will address: (1) the development of a hardwired brain circuit for spoken language; (2) the neural adaptation that follows reading instruction and fosters the "grafting" of visual processing areas of the brain onto the hardwired circuit of spoken language; and (3) the prediction of language development and the possibility of translational neuroscience. Brain imaging has allowed for the identification of neural indices (neuromarkers) that reflect typical and atypical language development; the possibility of predicting risk for language disorders has emerged. A mandate to develop a bridge between neuroscience and health and cognition-related outcomes may pave the way for translational neuroscience. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Probabilistic fiber tracking of the language and motor white matter pathways of the supplementary motor area (SMA) in patients with brain tumors.

PubMed

Jenabi, Mehrnaz; Peck, Kyung K; Young, Robert J; Brennan, Nicole; Holodny, Andrei I

2014-12-01

Accurate localization of anatomically and functionally separate SMA tracts is important to improve planning prior to neurosurgery. Using fMRI and probabilistic DTI techniques, we assessed the connectivity between the frontal language area (Broca's area) and the rostral pre-SMA (language SMA) and caudal SMA proper (motor SMA). Twenty brain tumor patients completed motor and language fMRI paradigms and DTI. Peaks of functional activity in the language SMA, motor SMA and Broca's area were used to define seed regions for probabilistic tractography. fMRI and probabilistic tractography identified separate and unique pathways connecting the SMA to Broca's area - the language SMA pathway and the motor SMA pathway. For all subjects, the language SMA pathway had a larger number of voxels (P<0.0001) and higher connectivity (P<0.0001) to Broca's area than did the motor SMA pathway. In each patient, the number of voxels was greater in the language and motor SMA pathways than in background pathways (P<0.0001). No differences were found between patients with ipsilateral and those with contralateral tumors for either the language SMA pathway (degree of connectivity: P<0.36; number of voxels: 0.35) or the motor SMA pathway (degree of connectivity, P<0.28; number of voxels, P<0.74). Probabilistic tractography can identify unique white matter tracts that connect language SMA and motor SMA to Broca's area. The language SMA is more significantly connected to Broca's area than is the motor subdivision of the SMA proper. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Difficulties with diagnosis and consequential poor outcome due to stigma of acquired immunodeficiency syndrome - a case report.

PubMed

Vuletic, Vladimira; Nevajda, Branimir; Spero, Martina; Chudy, Darko

2013-09-01

Low incidence of human immunodeficiency virus (HIV) infections and acquired immunodeficiency syndrome (AIDS) has been detected in Croatia so far. Toxoplasmic encephalitis (TE) is the most common opportunistic cerebral infection in AIDS patients and is highly responsive to antiparasitic chemotherapy, if treated at an early stage. We present the case of the brain biopsy confirmed as TE on a 36-year-old female patient who at admission presented with unconsciousness and a right hemiplegia. A MSCT was performed and two hypodense lesions were diagnosed. The patient's family initially denied the presence or history of any medical problem or infection. An MRI showed multiple ring-enhanced mass lesions. An infectologist required a brain biopsy to exclude cerebral lymphoma and multiple metastases. Pathohistological analysis suggested TE. Meanwhile, patient's blood samples were found to be HIV positive. The patient was transferred to University Hospital for Infectious Diseases in Zagreb, where she died 2 days following admission. The patient's family terminally confessed that the patient had been HIV positive for 10 years and had refused any treatment. Family's denial of infection as well as 'hiding information' concerning patient's health from physicians involved in her treatment caused a delay in proper on-time patient treatment. We would like to emphasize that TE must be considered as a differential diagnosis in patients presenting with multiple cerebral lesions, including patients without acknowledged past history of HIV infection. A stigma towards HIV infection and ignorance of the disease still exist and therefore hinders proper treatment.

Difficulties with diagnosis and consequential poor outcome due to stigma of acquired immunodeficiency syndrome – a case report

PubMed Central

Vuletic, Vladimira; Nevajda, Branimir; Spero, Martina; Chudy, Darko

2013-01-01

Low incidence of human immunodeficiency virus (HIV) infections and acquired immunodeficiency syndrome (AIDS) has been detected in Croatia so far. Toxoplasmic encephalitis (TE) is the most common opportunistic cerebral infection in AIDS patients and is highly responsive to antiparasitic chemotherapy, if treated at an early stage. We present the case of the brain biopsy confirmed as TE on a 36-year-old female patient who at admission presented with unconsciousness and a right hemiplegia. A MSCT was performed and two hypodense lesions were diagnosed. The patient’s family initially denied the presence or history of any medical problem or infection. An MRI showed multiple ring-enhanced mass lesions. An infectologist required a brain biopsy to exclude cerebral lymphoma and multiple metastases. Pathohistological analysis suggested TE. Meanwhile, patient’s blood samples were found to be HIV positive. The patient was transferred to University Hospital for Infectious Diseases in Zagreb, where she died 2 days following admission. The patient’s family terminally confessed that the patient had been HIV positive for 10 years and had refused any treatment. Family’s denial of infection as well as ‘hiding information’ concerning patient’s health from physicians involved in her treatment caused a delay in proper on-time patient treatment. We would like to emphasize that TE must be considered as a differential diagnosis in patients presenting with multiple cerebral lesions, including patients without acknowledged past history of HIV infection. A stigma towards HIV infection and ignorance of the disease still exist and therefore hinders proper treatment. PMID:24091082

Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI

DTIC Science & Technology

2015-09-01

for public release; distribution unlimited Autism spectrum disorder (ASD); biomarker; early brain development; intrinsic functional brain networks...three large neuroimaging/neurobehavioral datasets to identify brain-imaging based biomarkers for Autism Spectrum Disorders (ASD). At Yale, we focus...neurobehavioral!datasets!in!order!to!identify! brainFimaging!based!biomarkers!for! Autism ! Spectrum ! Disorders !(ASD),!including!1)!BrainMap,! developed!and

G-protein-coupled estrogen receptor 1 is involved in brain development during zebrafish (Danio rerio) embryogenesis

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

Shi, Yanan; Liu, Xiaochun; Zhu, Pei

Highlights: •The Gper expression was detected in the developing brain of zebrafish. •Gper morpholino knockdown induced apoptosis of brain cells. •Gper morpholino knockdown reduced expression in neuron markers. •Zebrafish Gper may be involved in neuronal development. -- Abstract: G-protein-coupled estrogen receptor 1 (Gper, formerly known as GPR30) is found to be a trophic and protective factor in mediating action of estrogen in adult brain, while its role in developing brain remains to be elucidated. Here we present the expression pattern of Gper and its functions during embryogenesis in zebrafish. Both the mRNA and protein of Gper were detected throughout embryogenesis.more » Whole mount in situ hybridization (WISH) revealed a wide distribution of gper mRNAs in various regions of the developing brain. Gper knockdown by specific morpholinos resulted in growth retardation in embryos and morphological defects in the developing brain. In addition, induced apoptosis, decreased proliferation of the brain cells and maldevelopment of sensory and motor neurons were also found in the morphants. Our results provide novel insights into Gper functions in the developing brain, revealing that Gper can maintain the survival of the brain cells, and formation and/or differentiation of the sensory and motor neurons.« less

Optimized Motor Imagery Paradigm Based on Imagining Chinese Characters Writing Movement.

PubMed

Qiu, Zhaoyang; Allison, Brendan Z; Jin, Jing; Zhang, Yu; Wang, Xingyu; Li, Wei; Cichocki, Andrzej

2017-07-01

motor imagery (MI) is a mental representation of motor behavior. The MI-based brain computer interfaces (BCIs) can provide communication for the physically impaired. The performance of MI-based BCI mainly depends on the subject's ability to self-modulate electroencephalogram signals. Proper training can help naive subjects learn to modulate brain activity proficiently. However, training subjects typically involve abstract motor tasks and are time-consuming. to improve the performance of naive subjects during motor imagery, a novel paradigm was presented that would guide naive subjects to modulate brain activity effectively. In this new paradigm, pictures of the left or right hand were used as cues for subjects to finish the motor imagery task. Fourteen healthy subjects (11 male, aged 22-25 years, and mean 23.6±1.16) participated in this study. The task was to imagine writing a Chinese character. Specifically, subjects could imagine hand movements corresponding to the sequence of writing strokes in the Chinese character. This paradigm was meant to find an effective and familiar action for most Chinese people, to provide them with a specific, extensively practiced task and help them modulate brain activity. results showed that the writing task paradigm yielded significantly better performance than the traditional arrow paradigm (p < 0.001). Questionnaire replies indicated that most subjects thought that the new paradigm was easier. the proposed new motor imagery paradigm could guide subjects to help them modulate brain activity effectively. Results showed that there were significant improvements using new paradigm, both in classification accuracy and usability.

Cystic kidneys in fetal Walker-Warburg syndrome with POMT2 mutation: Intrafamilial phenotypic variability in four siblings and review of literature.

PubMed

Nabhan, Marwa M; ElKhateeb, Nour; Braun, Daniela A; Eun, Sungho; Saleem, Sahar N; YungGee, Heon; Hildebrandt, Friedhelm; Soliman, Neveen A

2017-10-01

Walker-Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy secondary to α-dystroglycanopathy with muscle, brain, and eye abnormalities often leading to death in the first weeks of life. It is transmitted in an autosomal recessive pattern, and has been linked to at least 15 different genes; including protein O-mannosyltransferase 1 (POMT1), protein O-mannosyltransferase 2 (POMT2), protein O-mannose beta-1,2-N acetylglucosaminyltransferase (POMGNT1), fukutin (FKTN), isoprenoid synthase domain-containing protein (ISPD), and other genes. We report on a consanguineous family with four consecutive siblings affected by this condition with lethal outcome in three (still birth), and termination of the fourth pregnancy based on antenatal MRI identification of brain and kidney anomalies that heralded proper and deep clinical phenotyping. The diagnosis of WWS was suggested based on the unique collective phenotype comprising brain anomalies in the form of lissencephaly, subcortical/subependymal heterotopia, and cerebellar hypoplasia shared by all four siblings; microphthalmia in one sibling; and large cystic kidneys in the fetus and another sibling. Other unshared neurological abnormalities included hydrocephalus and Dandy-Walker malformation. Whole exome sequencing of the fetus revealed a highly conserved missense mutation in POMT2 that is known to cause WWS with brain and eye anomalies.In conclusion, the heterogeneous clinical presentation in the four affected conceptions with POMT2 mutation expands the current clinical spectrum of POMT2-associated WWS to include large cystic kidneys; and confirms intra-familial variability in terms of brain, kidney, and eye anomalies. © 2017 Wiley Periodicals, Inc.

Monte Carlo study for physiological interference reduction in near-infrared spectroscopy based on empirical mode decomposition

NASA Astrophysics Data System (ADS)

Zhang, Yan; Sun, JinWei; Rolfe, Peter

2010-12-01

Near-infrared spectroscopy (NIRS) can be used as the basis of non-invasive neuroimaging that may allow the measurement of haemodynamic changes in the human brain evoked by applied stimuli. Since this technique is very sensitive, physiological interference arising from the cardiac cycle and breathing can significantly affect the signal quality. Such interference is difficult to remove by conventional techniques because it occurs not only in the extracerebral layer but also in the brain tissue itself. Previous work on this problem employing temporal filtering, spatial filtering, and adaptive filtering have exhibited good performance for recovering brain activity data in evoked response studies. However, in this study, we present a time-frequency adaptive method for physiological interference reduction based on the combination of empirical mode decomposition (EMD) and Hilbert spectral analysis (HSA). Monte Carlo simulations based on a five-layered slab model of a human adult head were implemented to evaluate our methodology. We applied an EMD algorithm to decompose the NIRS time series derived from Monte Carlo simulations into a series of intrinsic mode functions (IMFs). In order to identify the IMFs associated with symmetric interference, the extracted components were then Hilbert transformed from which the instantaneous frequencies could be acquired. By reconstructing the NIRS signal by properly selecting IMFs, we determined that the evoked brain response is effectively filtered out with even higher signal-to-noise ratio (SNR). The results obtained demonstrated that EMD, combined with HSA, can effectively separate, identify and remove the contamination from the evoked brain response obtained with NIRS using a simple single source-detector pair.

Brain tumor specifies intermediate progenitor cell identity by attenuating β-catenin/Armadillo activity

PubMed Central

Komori, Hideyuki; Xiao, Qi; McCartney, Brooke M.; Lee, Cheng-Yu

2014-01-01

During asymmetric stem cell division, both the daughter stem cell and the presumptive intermediate progenitor cell inherit cytoplasm from their parental stem cell. Thus, proper specification of intermediate progenitor cell identity requires an efficient mechanism to rapidly extinguish the activity of self-renewal factors, but the mechanisms remain unknown in most stem cell lineages. During asymmetric division of a type II neural stem cell (neuroblast) in the Drosophila larval brain, the Brain tumor (Brat) protein segregates unequally into the immature intermediate neural progenitor (INP), where it specifies INP identity by attenuating the function of the self-renewal factor Klumpfuss (Klu), but the mechanisms are not understood. Here, we report that Brat specifies INP identity through its N-terminal B-boxes via a novel mechanism that is independent of asymmetric protein segregation. Brat-mediated specification of INP identity is critically dependent on the function of the Wnt destruction complex, which attenuates the activity of β-catenin/Armadillo (Arm) in immature INPs. Aberrantly increasing Arm activity in immature INPs further exacerbates the defects in the specification of INP identity and enhances the supernumerary neuroblast mutant phenotype in brat mutant brains. By contrast, reducing Arm activity in immature INPs suppresses supernumerary neuroblast formation in brat mutant brains. Finally, reducing Arm activity also strongly suppresses supernumerary neuroblasts induced by overexpression of klu. Thus, the Brat-dependent mechanism extinguishes the function of the self-renewal factor Klu in the presumptive intermediate progenitor cell by attenuating Arm activity, balancing stem cell maintenance and progenitor cell specification. PMID:24257623

Network diffusion accurately models the relationship between structural and functional brain connectivity networks

PubMed Central

Abdelnour, Farras; Voss, Henning U.; Raj, Ashish

2014-01-01

The relationship between anatomic connectivity of large-scale brain networks and their functional connectivity is of immense importance and an area of active research. Previous attempts have required complex simulations which model the dynamics of each cortical region, and explore the coupling between regions as derived by anatomic connections. While much insight is gained from these non-linear simulations, they can be computationally taxing tools for predicting functional from anatomic connectivities. Little attention has been paid to linear models. Here we show that a properly designed linear model appears to be superior to previous non-linear approaches in capturing the brain’s long-range second order correlation structure that governs the relationship between anatomic and functional connectivities. We derive a linear network of brain dynamics based on graph diffusion, whereby the diffusing quantity undergoes a random walk on a graph. We test our model using subjects who underwent diffusion MRI and resting state fMRI. The network diffusion model applied to the structural networks largely predicts the correlation structures derived from their fMRI data, to a greater extent than other approaches. The utility of the proposed approach is that it can routinely be used to infer functional correlation from anatomic connectivity. And since it is linear, anatomic connectivity can also be inferred from functional data. The success of our model confirms the linearity of ensemble average signals in the brain, and implies that their long-range correlation structure may percolate within the brain via purely mechanistic processes enacted on its structural connectivity pathways. PMID:24384152

Rat model of blood-brain barrier disruption to allow targeted neurovascular therapeutics.

PubMed

Martin, Jacob A; Maris, Alexander S; Ehtesham, Moneeb; Singer, Robert J

2012-11-30

Endothelial cells with tight junctions along with the basement membrane and astrocyte end feet surround cerebral blood vessels to form the blood-brain barrier(1). The barrier selectively excludes molecules from crossing between the blood and the brain based upon their size and charge. This function can impede the delivery of therapeutics for neurological disorders. A number of chemotherapeutic drugs, for example, will not effectively cross the blood-brain barrier to reach tumor cells(2). Thus, improving the delivery of drugs across the blood-brain barrier is an area of interest. The most prevalent methods for enhancing the delivery of drugs to the brain are direct cerebral infusion and blood-brain barrier disruption(3). Direct intracerebral infusion guarantees that therapies reach the brain; however, this method has a limited ability to disperse the drug(4). Blood-brain barrier disruption (BBBD) allows drugs to flow directly from the circulatory system into the brain and thus more effectively reach dispersed tumor cells. Three methods of barrier disruption include osmotic barrier disruption, pharmacological barrier disruption, and focused ultrasound with microbubbles. Osmotic disruption, pioneered by Neuwelt, uses a hypertonic solution of 25% mannitol that dehydrates the cells of the blood-brain barrier causing them to shrink and disrupt their tight junctions. Barrier disruption can also be accomplished pharmacologically with vasoactive compounds such as histamine(5) and bradykinin(6). This method, however, is selective primarily for the brain-tumor barrier(7). Additionally, RMP-7, an analog of the peptide bradykinin, was found to be inferior when compared head-to-head with osmotic BBBD with 25% mannitol(8). Another method, focused ultrasound (FUS) in conjunction with microbubble ultrasound contrast agents, has also been shown to reversibly open the blood-brain barrier(9). In comparison to FUS, though, 25% mannitol has a longer history of safety in human patients that makes it a proven tool for translational research(10-12). In order to accomplish BBBD, mannitol must be delivered at a high rate directly into the brain's arterial circulation. In humans, an endovascular catheter is guided to the brain where rapid, direct flow can be accomplished. This protocol models human BBBD as closely as possible. Following a cut-down to the bifurcation of the common carotid artery, a catheter is inserted retrograde into the ECA and used to deliver mannitol directly into the internal carotid artery (ICA) circulation. Propofol and N2O anesthesia are used for their ability to maximize the effectiveness of barrier disruption(13). If executed properly, this procedure has the ability to safely, effectively, and reversibly open the blood-brain barrier and improve the delivery of drugs that do not ordinarily reach the brain (8,13,14).

Discovery of new candidate genes related to brain development using protein interaction information.

PubMed

Chen, Lei; Chu, Chen; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

2015-01-01

Human brain development is a dramatic process composed of a series of complex and fine-tuned spatiotemporal gene expressions. A good comprehension of this process can assist us in developing the potential of our brain. However, we have only limited knowledge about the genes and gene functions that are involved in this biological process. Therefore, a substantial demand remains to discover new brain development-related genes and identify their biological functions. In this study, we aimed to discover new brain-development related genes by building a computational method. We referred to a series of computational methods used to discover new disease-related genes and developed a similar method. In this method, the shortest path algorithm was executed on a weighted graph that was constructed using protein-protein interactions. New candidate genes fell on at least one of the shortest paths connecting two known genes that are related to brain development. A randomization test was then adopted to filter positive discoveries. Of the final identified genes, several have been reported to be associated with brain development, indicating the effectiveness of the method, whereas several of the others may have potential roles in brain development.

Social buffering of stress responses in nonhuman primates: Maternal regulation of the development of emotional regulatory brain circuits.

PubMed

Sanchez, Mar M; McCormack, Kai M; Howell, Brittany R

2015-01-01

Social buffering, the phenomenon by which the presence of a familiar individual reduces or even eliminates stress- and fear-induced responses, exists in different animal species and has been examined in the context of the mother-infant relationship, in addition to adults. Although it is a well-known effect, the biological mechanisms that underlie it as well as its developmental impact are not well understood. Here, we provide a review of evidence of social and maternal buffering of stress reactivity in nonhuman primates, and some data from our group suggesting that when the mother-infant relationship is disrupted, maternal buffering is impaired. This evidence underscores the critical role that maternal care plays for proper regulation and development of emotional and stress responses of primate infants. Disruptions of the parent-infant bond constitute early adverse experiences associated with increased risk for psychopathology. We will focus on infant maltreatment, a devastating experience not only for humans, but for nonhuman primates as well. Taking advantage of this naturalistic animal model of adverse maternal caregiving, we have shown that competent maternal care is critical for the development of healthy attachment, social behavior, and emotional and stress regulation, as well as of the neural circuits underlying these functions.

Social Buffering of Stress Responses in Nonhuman Primates: Maternal Regulation of the Development of Emotional Regulatory Brain Circuits

PubMed Central

McCormack, Kai M.; Howell, Brittany R.

2015-01-01

Social buffering, the phenomenon by which the presence of a familiar individual reduces or even eliminates stress- and fear-induced responses exists in different animal species, and has been examined in the context of the mother-infant relationship in addition to adults. Although it is a well-known effect, the biological mechanisms, which underlie it, as well as its developmental impact are not well understood. Here we provide a review of evidence of social and maternal buffering of stress reactivity in nonhuman primates, and some data from our group suggesting that when the mother-infant relationship is disrupted maternal buffering is impaired. This evidence underscores the critical role that maternal care plays for proper regulation and development of emotional and stress responses of primate infants. Disruptions of the parent-infant bond constitute early adverse experiences associated with increased risk for psychopathology. We will focus on infant maltreatment, a devastating experience not only for humans, but for nonhuman primates as well. Taking advantage of this naturalistic animal model of adverse maternal caregiving we have shown that competent maternal care is critical for the development of healthy attachment, social behavior and emotional and stress regulation, as well as of neural circuits underlying these functions. PMID:26324227

Coiled-coil domain containing 42 (Ccdc42) is necessary for proper sperm development and male fertility in the mouse.

PubMed

Pasek, Raymond C; Malarkey, Erik; Berbari, Nicolas F; Sharma, Neeraj; Kesterson, Robert A; Tres, Laura L; Kierszenbaum, Abraham L; Yoder, Bradley K

2016-04-15

Spermiogenesis is the differentiation of spermatids into motile sperm consisting of a head and a tail. The head harbors a condensed elongated nucleus partially covered by the acrosome-acroplaxome complex. Defects in the acrosome-acroplaxome complex are associated with abnormalities in sperm head shaping. The head-tail coupling apparatus (HTCA), a complex structure consisting of two cylindrical microtubule-based centrioles and associated components, connects the tail or flagellum to the sperm head. Defects in the development of the HTCA cause sperm decapitation and disrupt sperm motility, two major contributors to male infertility. Here, we provide data indicating that mutations in the gene Coiled-coil domain containing 42 (Ccdc42) is associated with malformation of the mouse sperm flagella. In contrast to many other flagella and motile cilia genes, Ccdc42 expression is only observed in the brain and developing sperm. Male mice homozygous for a loss-of-function Ccdc42 allele (Ccdc42(KO)) display defects in the number and location of the HTCA, lack flagellated sperm, and are sterile. The testes enriched expression of Ccdc42 and lack of other phenotypes in mutant mice make it an ideal candidate for screening cases of azoospermia in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Fetal magnetic resonance imaging (MRI): a tool for a better understanding of normal and abnormal brain development.

PubMed

Saleem, Sahar N

2013-07-01

Knowledge of the anatomy of the developing fetal brain is essential to detect abnormalities and understand their pathogenesis. Capability of magnetic resonance imaging (MRI) to visualize the brain in utero and to differentiate between its various tissues makes fetal MRI a potential diagnostic and research tool for the developing brain. This article provides an approach to understand the normal and abnormal brain development through schematic interpretation of fetal brain MR images. MRI is a potential screening tool in the second trimester of pregnancies in fetuses at risk for brain anomalies and helps in describing new brain syndromes with in utero presentation. Accurate interpretation of fetal MRI can provide valuable information that helps genetic counseling, facilitates management decisions, and guides therapy. Fetal MRI can help in better understanding the pathogenesis of fetal brain malformations and can support research that could lead to disease-specific interventions.

Development and genetics of brain temporal stability related to attention problems in adolescent twins.

PubMed

Smit, Dirk J A; Anokhin, Andrey P

2017-05-01

The brain continuously develops and reorganizes to support an expanding repertoire of behaviors and increasingly complex cognition. These processes may, however, also result in the appearance or disappearance of specific neurodevelopmental disorders such as attention problems. To investigate whether brain activity changed during adolescence, how genetics shape this change, and how these changes were related to attention problems, we measured EEG activity in 759 twins and siblings, assessed longitudinally in four waves (12, 14, 16, and 18years of age). Attention problems were assessed with the SWAN at waves 12, 14, and 16. To characterize functional brain development, we used a measure of temporal stability (TS) of brain oscillations over the recording time of 5min reflecting the tendency of a brain to maintain the same oscillatory state for longer or shorter periods. Increased TS may reflect the brain's tendency to maintain stability, achieve focused attention, and thus reduce "mind wandering" and attention problems. The results indicate that brain TS is increased across the scalp from 12 to 18. TS showed large individual differences that were heritable. Change in TS (alpha oscillations) was heritable between 12 and 14 and between 14 and 16 for the frontal brain areas. Absolute levels of brain TS at each wave were positively correlated with attention problems but not significantly. High and low attention problems subjects showed different developmental trajectories in TS, which was significant in a cluster of frontal leads. These results indicate that trajectories in brain TS development are a biomarker for the developing brain. TS in brain oscillations is highly heritable, and age-related change in TS is also heritable in selected brain areas. These results suggest that high and low attention problems subjects are at different stages of brain development. Copyright © 2016. Published by Elsevier B.V.

A forward-adjoint operator pair based on the elastic wave equation for use in transcranial photoacoustic computed tomography

PubMed Central

Mitsuhashi, Kenji; Poudel, Joemini; Matthews, Thomas P.; Garcia-Uribe, Alejandro; Wang, Lihong V.; Anastasio, Mark A.

2017-01-01

Photoacoustic computed tomography (PACT) is an emerging imaging modality that exploits optical contrast and ultrasonic detection principles to form images of the photoacoustically induced initial pressure distribution within tissue. The PACT reconstruction problem corresponds to an inverse source problem in which the initial pressure distribution is recovered from measurements of the radiated wavefield. A major challenge in transcranial PACT brain imaging is compensation for aberrations in the measured data due to the presence of the skull. Ultrasonic waves undergo absorption, scattering and longitudinal-to-shear wave mode conversion as they propagate through the skull. To properly account for these effects, a wave-equation-based inversion method should be employed that can model the heterogeneous elastic properties of the skull. In this work, a forward model based on a finite-difference time-domain discretization of the three-dimensional elastic wave equation is established and a procedure for computing the corresponding adjoint of the forward operator is presented. Massively parallel implementations of these operators employing multiple graphics processing units (GPUs) are also developed. The developed numerical framework is validated and investigated in computer19 simulation and experimental phantom studies whose designs are motivated by transcranial PACT applications. PMID:29387291

Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies.

PubMed

Luchtman, Dirk W; Song, Cai

2013-01-01

Omega-(n)-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are major components of neuronal membranes and have a wide range of functions, from modulating synaptic plasticity and neurochemistry, to neuroimmune-modulation and neuroprotection. Thus, it is not surprising that n-3 PUFA are widely acknowledged to have cognitive-enhancing effects. Although clinical evidence is somewhat conflicting, probably in large part due to methodological issues, animal studies have consistently demonstrated that n-3 PUFA are indispensable for proper brain development, may enhance cognitive function in healthy, adult individuals and attenuate cognitive impairment in aging and age-related disorders, such as dementia. This review discusses and integrates up to date evidence from clinical and animal studies investigating the cognitive-enhancing effects of n-3 PUFA during development, child- and adult-hood, as well as old-age with associated neurodegenerative diseases, such as Alzheimer's disease. Furthermore, we cover the major underlying biochemical and neurophysiological mechanisms by which n-3 PUFA mediate these effects on cognition. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Iterative image reconstruction in elastic inhomogenous media with application to transcranial photoacoustic tomography

NASA Astrophysics Data System (ADS)

Poudel, Joemini; Matthews, Thomas P.; Mitsuhashi, Kenji; Garcia-Uribe, Alejandro; Wang, Lihong V.; Anastasio, Mark A.

2017-03-01

Photoacoustic computed tomography (PACT) is an emerging computed imaging modality that exploits optical contrast and ultrasonic detection principles to form images of the photoacoustically induced initial pressure distribution within tissue. The PACT reconstruction problem corresponds to a time-domain inverse source problem, where the initial pressure distribution is recovered from the measurements recorded on an aperture outside the support of the source. A major challenge in transcranial PACT brain imaging is to compensate for aberrations in the measured data due to the propagation of the photoacoustic wavefields through the skull. To properly account for these effects, a wave equation-based inversion method should be employed that can model the heterogeneous elastic properties of the medium. In this study, an iterative image reconstruction method for 3D transcranial PACT is developed based on the elastic wave equation. To accomplish this, a forward model based on a finite-difference time-domain discretization of the elastic wave equation is established. Subsequently, gradient-based methods are employed for computing penalized least squares estimates of the initial source distribution that produced the measured photoacoustic data. The developed reconstruction algorithm is validated and investigated through computer-simulation studies.

Diatomite filtration of water for injection

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

Olmsted, B.C. Jr.; Bell, G.R.

1966-01-01

A discussion is presented of the capabilities, problems, and answers, in the performance of diatomite filters. The discussion includes a description of diatomite filtration, new developments, design criteria, and some case histories. Diatomite filters, when properly designed and installed, and when properly applied, can provide effective clarification of waters for injection at low capital and operating costs. Design, installation, and proper application, effectiveness, and capital and operating costs can be placed in the proper perspective in the light of general experience and recent pilot plant tests in the southern California area. (30 refs.)

Brain Malformations

MedlinePlus

Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

Depletion of serotonin synthesis with p-CPA pretreatment alters EEG in urethane anesthetized rats under whole body hyperthermia.

PubMed

Sinha, Rakesh Kumar; Aggarwal, Yogender

2007-01-01

Serotonin is believed as an important factor in brain function. The role of serotonin in cerebral psycho-patho-physiology has already been well established. However, the function of serotonin antagonist in anesthetized subjects under hyperthermia has not been studied properly. Experiments were performed in three groups of urethane-anesthetized rats, such as: (i) control group, (ii) whole body hyperthermia group and (iii) p-CPA (para-Chlorophenylalanine) pretreated hyperthermia group. Hyperthermia was produced by subjecting the rats to high ambient temperature of 38 +/- 1 degrees C (relative humidity 45-50%). Each group was divided for EEG (electroencephalogram) study and for determination of edematous swelling in the brain. Urethane anesthetized rats under hyperthermia show highly significant reduction in their survival time. The body temperature recorded during the hyperthermia was observed with significant and linear rise with marked increase in brain water content, which was analyzed just after the death of the subjects. The results of the electroencephalographic study in urethane-anesthetized rats recorded before death indicate that brain function varies in systematic manner during hyperthermia as sequential changes in EEG patterns were observed. However, a serotonin antagonist, p-CPA pretreatment increases the survival time with significant reduction in edematous swelling in brain but it does not affect the relationship between the core body temperature and the brain cortical potentials as observed in urethane anesthetized subjects exposed to whole body hyperthermia. The core body temperature in p-CPA pretreated rats show non-linear relationship with respect to the exposure time as it was observed in drug untreated subjects. The findings of the present study indicate that although pretreatment of p-CPA in rats has a marked correlation between the extravasations of the blood-brain barrier under hyperthermia but shows minimum effect on the EEG in a model of hyperthermia under irreversible anesthesia.