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Sample records for adjacent normal brain

  1. Divergent viral presentation among human tumors and adjacent normal tissues.

    PubMed

    Cao, Song; Wendl, Michael C; Wyczalkowski, Matthew A; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J; Gay, Hiram; Chen, Ken; Rader, Janet S; Dipersio, John F; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  2. Divergent viral presentation among human tumors and adjacent normal tissues

    PubMed Central

    Cao, Song; Wendl, Michael C.; Wyczalkowski, Matthew A.; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J.; Gay, Hiram; Chen, Ken; Rader, Janet S.; Dipersio, John F.; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  3. [Comparative proteomic analysis of cancerous and adjacent normal lung tissues].

    PubMed

    Lee, Ki Beom; Pi, Kyung Bae

    2010-01-01

    Lung cancer is the leading cause of cancer-related mortality in industrialized countries. Unfortunately, most lung cancers are found too late for a cure, therefore early detection and treatment is very important. We have applied proteomic analysis by using two-dimensional gel electrophoresis and peptide mass fingerprinting techniques for examination of cancerous and adjacent non-cancerous lung tissues from the same patient. The aim of the study was to find proteins, which could be used as biomarkers for diagnosis and monitoring of this disease. Indeed, we found differences in expression of several proteins, related to various cellular activities, such as, chaperoning (e.g., GRP96, GRP78, HSP27), metabolism and oxidation stress (e.g., L-fucose, GST), cytoskeleton (e.g., tubulin beta 2/3, beta actin), cell adhesion (e.g., annexin A5/3), binding proteins (e.g., 14-3-3 theta) and signal transduction. These changes may be important for progression of carcinogenesis; they may be used as the molecular-support for future diagnostic markers. PMID:21395069

  4. Effects of photoradiation therapy on normal rat brain

    SciTech Connect

    Cheng, M.K.; McKean, J.; Boisvert, D.; Tulip, J.; Mielke, B.W.

    1984-12-01

    Laser photoradiation of the brain via an optical fiber positioned 5 mm above a burr hole was performed after the injection of hematoporphyrin derivative (HpD) in 33 normal rats and 6 rats with an intracerebral glioma. Normal rats received HpD, 5 or 10 mg/kg of body weight, followed by laser exposure at various doses or were exposed to a fixed laser dose after the administration of HpD, 2.5 to 20 mg/kg. One control group received neither HpD nor laser energy, and another was exposed to laser energy only. The 6 rats bearing an intracranial 9L glioma were treated with HpD, 5 mg/kg, followed by laser exposure at various high doses. The temperature in the cortex or tumor was measured with a probe during laser exposure. The rats were killed 72 hours after photoradiation, and the extent of necrosis of cerebral tissue was measured microscopically. In the normal rats, the extent of brain damage correlated with increases in the dose of both the laser and the HpD. In all 6 glioma-bearing rats, the high laser doses produced some focal necrosis in the tumors but also damaged adjacent normal brain tissue. The authors conclude that damage to normal brain tissue may be a significant complication of high dose photoradiation therapy for intracranial tumors.

  5. Normal Development of Brain Circuits

    PubMed Central

    Tau, Gregory Z; Peterson, Bradley S

    2010-01-01

    Spanning functions from the simplest reflex arc to complex cognitive processes, neural circuits have diverse functional roles. In the cerebral cortex, functional domains such as visual processing, attention, memory, and cognitive control rely on the development of distinct yet interconnected sets of anatomically distributed cortical and subcortical regions. The developmental organization of these circuits is a remarkably complex process that is influenced by genetic predispositions, environmental events, and neuroplastic responses to experiential demand that modulates connectivity and communication among neurons, within individual brain regions and circuits, and across neural pathways. Recent advances in neuroimaging and computational neurobiology, together with traditional investigational approaches such as histological studies and cellular and molecular biology, have been invaluable in improving our understanding of these developmental processes in humans in both health and illness. To contextualize the developmental origins of a wide array of neuropsychiatric illnesses, this review describes the development and maturation of neural circuits from the first synapse through critical periods of vulnerability and opportunity to the emergent capacity for cognitive and behavioral regulation, and finally the dynamic interplay across levels of circuit organization and developmental epochs. PMID:19794405

  6. Differentially Expressed miRNAs in Tumor, Adjacent, and Normal Tissues of Lung Adenocarcinoma

    PubMed Central

    Tian, Fei; Li, Rui; Chen, Zhenzhu; Shen, Yanting; Lu, Jiafeng; Xie, Xueying; Ge, Qinyu

    2016-01-01

    Lung cancer is the leading cause of cancer deaths. Non-small-cell lung cancer (NSCLC) is the major type of lung cancer. The aim of this study was to characterize the expression profiles of miRNAs in adenocarcinoma (AC), one major subtype of NSCLC. In this study, the miRNAs were detected in normal, adjacent, and tumor tissues by next-generation sequencing. Then the expression levels of differential miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the results, 259, 401, and 389 miRNAs were detected in tumor, adjacent, and normal tissues of pooled AC samples, respectively. In addition, for the first time we have found that miR-21-5p and miR-196a-5p were gradually upregulated from normal to adjacent to tumor tissues; miR-218-5p was gradually downregulated with 2-fold or greater change in AC tissues. These 3 miRNAs were validated by qRT-PCR. Lastly, we predicted target genes of these 3 miRNAs and enriched the potential functions and regulatory pathways. The aberrant miR-21-5p, miR-196a-5p, and miR-218-5p may become biomarkers for diagnosis and prognosis of lung adenocarcinoma. This research may be useful for lung adenocarcinoma diagnosis and the study of pathology in lung cancer. PMID:27247934

  7. Spatial normalization of brain images and beyond.

    PubMed

    Mangin, J-F; Lebenberg, J; Lefranc, S; Labra, N; Auzias, G; Labit, M; Guevara, M; Mohlberg, H; Roca, P; Guevara, P; Dubois, J; Leroy, F; Dehaene-Lambertz, G; Cachia, A; Dickscheid, T; Coulon, O; Poupon, C; Rivière, D; Amunts, K; Sun, Z Y

    2016-10-01

    The deformable atlas paradigm has been at the core of computational anatomy during the last two decades. Spatial normalization is the variant endowing the atlas with a coordinate system used for voxel-based aggregation of images across subjects and studies. This framework has largely contributed to the success of brain mapping. Brain spatial normalization, however, is still ill-posed because of the complexity of the human brain architecture and the lack of architectural landmarks in standard morphological MRI. Multi-atlas strategies have been developed during the last decade to overcome some difficulties in the context of segmentation. A new generation of registration algorithms embedding architectural features inferred for instance from diffusion or functional MRI is on the verge to improve the architectural value of spatial normalization. A better understanding of the architectural meaning of the cortical folding pattern will lead to use some sulci as complementary constraints. Improving the architectural compliance of spatial normalization may impose to relax the diffeomorphic constraint usually underlying atlas warping. A two-level strategy could be designed: in each region, a dictionary of templates of incompatible folding patterns would be collected and matched in a way or another using rare architectural information, while individual subjects would be aligned using diffeomorphisms to the closest template. Manifold learning could help to aggregate subjects according to their morphology. Connectivity-based strategies could emerge as an alternative to deformation-based alignment leading to match the connectomes of the subjects rather than images. PMID:27344104

  8. Non-target adjacent stimuli classification improves performance of classical ERP-based brain computer interface

    NASA Astrophysics Data System (ADS)

    Ceballos, G. A.; Hernández, L. F.

    2015-04-01

    Objective. The classical ERP-based speller, or P300 Speller, is one of the most commonly used paradigms in the field of Brain Computer Interfaces (BCI). Several alterations to the visual stimuli presentation system have been developed to avoid unfavorable effects elicited by adjacent stimuli. However, there has been little, if any, regard to useful information contained in responses to adjacent stimuli about spatial location of target symbols. This paper aims to demonstrate that combining the classification of non-target adjacent stimuli with standard classification (target versus non-target) significantly improves classical ERP-based speller efficiency. Approach. Four SWLDA classifiers were trained and combined with the standard classifier: the lower row, upper row, right column and left column classifiers. This new feature extraction procedure and the classification method were carried out on three open databases: the UAM P300 database (Universidad Autonoma Metropolitana, Mexico), BCI competition II (dataset IIb) and BCI competition III (dataset II). Main results. The inclusion of the classification of non-target adjacent stimuli improves target classification in the classical row/column paradigm. A gain in mean single trial classification of 9.6% and an overall improvement of 25% in simulated spelling speed was achieved. Significance. We have provided further evidence that the ERPs produced by adjacent stimuli present discriminable features, which could provide additional information about the spatial location of intended symbols. This work promotes the searching of information on the peripheral stimulation responses to improve the performance of emerging visual ERP-based spellers.

  9. Intelligence and Regional Brain Volumes in Normal Controls.

    ERIC Educational Resources Information Center

    Flashman, Laura A.; Andreasen, Nancy C.; Flaum, Michael; Swayze, Victor W., II

    1998-01-01

    The relationship between brain size and intelligence was examined in 90 normal volunteers. Results support the notion of a modest relationship between brain size and measures of global intelligence and suggest diffuse brain involvement on performance tasks that require integration and use of multiple cognitive domains. (Author/SLD)

  10. Distinctive Glycerophospholipid Profiles of Human Seminoma and Adjacent Normal Tissues by Desorption Electrospray Ionization Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Masterson, Timothy A.; Dill, Allison L.; Eberlin, Livia S.; Mattarozzi, Monica; Cheng, Liang; Beck, Stephen D. W.; Bianchi, Federica; Cooks, R. Graham

    2011-08-01

    Desorption electrospray ionization mass spectrometry (DESI-MS) has been successfully used to discriminate between normal and cancerous human tissue from different anatomical sites. On the basis of this, DESI-MS imaging was used to characterize human seminoma and adjacent normal tissue. Seminoma and adjacent normal paired human tissue sections (40 tissues) from 15 patients undergoing radical orchiectomy were flash frozen in liquid nitrogen and sectioned to 15 μm thickness and thaw mounted to glass slides. The entire sample was two-dimensionally analyzed by the charged solvent spray to form a molecular image of the biological tissue. DESI-MS images were compared with formalin-fixed, hematoxylin and eosin (H&E) stained slides of the same material. Increased signal intensity was detected for two seminolipids [seminolipid (16:0/16:0) and seminolipid (30:0)] in the normal tubule testis tissue; these compounds were undetectable in seminoma tissue, as well as from the surrounding fat, muscle, and blood vessels. A glycerophosphoinositol [PI(18:0/20:4)] was also found at increased intensity in the normal testes tubule tissue when compared with seminoma tissue. Ascorbic acid (i.e., vitamin C) was found at increased amounts in seminoma tissue when compared with normal tissue. DESI-MS analysis was successfully used to visualize the location of several types of molecules across human seminoma and normal tissues. Discrimination between seminoma and adjacent normal testes tubules was achieved on the basis of the spatial distributions and varying intensities of particular lipid species as well as ascorbic acid. The increased presence of ascorbic acid within seminoma compared with normal seminiferous tubules was previously unknown.

  11. Adolescent brain development in normality and psychopathology

    PubMed Central

    LUCIANA, MONICA

    2014-01-01

    Since this journal’s inception, the field of adolescent brain development has flourished, as researchers have investigated the underpinnings of adolescent risk-taking behaviors. Explanations based on translational models initially attributed such behaviors to executive control deficiencies and poor frontal lobe function. This conclusion was bolstered by evidence that the prefrontal cortex and its interconnections are among the last brain regions to structurally and functionally mature. As substantial heterogeneity of prefrontal function was revealed, applications of neuroeconomic theory to adolescent development led to dual systems models of behavior. Current epidemiological trends, behavioral observations, and functional magnetic resonance imaging based brain activity patterns suggest a quadratic increase in limbically mediated incentive motivation from childhood to adolescence and a decline thereafter. This elevation occurs in the context of immature prefrontal function, so motivational strivings may be difficult to regulate. Theoretical models explain this patterning through brain-based accounts of subcortical–cortical integration, puberty-based models of adolescent sensation seeking, and neurochemical dynamics. Empirically sound tests of these mechanisms, as well as investigations of biology–context interactions, represent the field’s most challenging future goals, so that applications to psychopathology can be refined and so that developmental cascades that incorporate neurobiological variables can be modeled. PMID:24342843

  12. Normal brain ageing: models and mechanisms

    PubMed Central

    Toescu, Emil C

    2005-01-01

    Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria–reactive oxygen species (ROS)–intracellular Ca2+. The perturbation in the relationship between the members of this metabolic triad generate a state of decreased homeostatic reserve, in which the aged neurons could maintain adequate function during normal activity, as demonstrated by the fact that normal ageing is not associated with widespread neuronal loss, but become increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischaemia or neurodegenerative processes. This review will concentrate on some of the evidence showing altered mitochondrial function with ageing and also discuss some of the functional consequences that would result from such events, such as alterations in mitochondrial Ca2+ homeostasis, ATP production and generation of ROS. PMID:16321805

  13. The autistic brain in the context of normal neurodevelopment.

    PubMed

    Ziats, Mark N; Edmonson, Catherine; Rennert, Owen M

    2015-01-01

    The etiology of autism spectrum disorders (ASDs) is complex and largely unclear. Among various lines of inquiry, many have suggested convergence onto disruptions in both neural circuitry and immune regulation/glial cell function pathways. However, the interpretation of the relationship between these two putative mechanisms has largely focused on the role of exogenous factors and insults, such as maternal infection, in activating immune pathways that in turn result in neural network abnormalities. Yet, given recent insights into our understanding of human neurodevelopment, and in particular the critical role of glia and the immune system in normal brain development, it is important to consider these putative pathological processes in their appropriate normal neurodevelopmental context. In this review, we explore the hypothesis that the autistic brain cellular phenotype likely represents intrinsic abnormalities of glial/immune processes constitutively operant in normal brain development that result in the observed neural network dysfunction. We review recent studies demonstrating the intercalated role of neural circuit development, the immune system, and glial cells in the normal developing brain, and integrate them with studies demonstrating pathological alterations in these processes in autism. By discussing known abnormalities in the autistic brain in the context of normal brain development, we explore the hypothesis that the glial/immune component of ASD may instead be related to intrinsic exaggerated/abnormal constitutive neurodevelopmental processes such as network pruning. Moreover, this hypothesis may be relevant to other neurodevelopmental disorders that share genetic, pathologic, and clinical features with autism. PMID:26379512

  14. Telomere length variation in normal epithelial cells adjacent to tumor: potential biomarker for breast cancer local recurrence

    PubMed Central

    Zhou, Xin; Meeker, Alan K.; Makambi, Kepher H.; Kosti, Ourania; Kallakury, Bhaskar V.S.; Sidawy, Mary K.; Loffredo, Christopher A.; Zheng, Yun-Ling

    2012-01-01

    A better understanding of the risk of local recurrence (LR) will facilitate therapeutic decision making in the management of early breast cancers. In the present study, we investigated whether telomere length in the normal breast epithelial cells surrounding the tumor is predictive of breast cancer LR; 152 women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this nested case–control study. Cases (patients had LR) and controls (patients had no LR) were matched on year of surgery, age at diagnosis and type of surgery. Telomere fluorescent in situ hybridization was used to determine the telomere length using formalin fixed paraffin-embedded breast tissues. Small telomere length variation (TLV), defined as the coefficient variation of telomere lengths among examined cells, in normal epithelial cells adjacent to the tumor was significantly associated with a 5-fold (95% confidence interval = 1.2–22.2) increased risk of breast cancer LR. When the subjects were categorized into quartiles, a significant inverse dose–response relationship was observed with lowest versus highest quartile odds ratio of 15.3 (Ptrend = 0.012). Patients who had large TLV had significantly better 10 year recurrence free survival rate compared with patients who had small TLV (80 versus 33%). The present study revealed that TLV in normal epithelial cells adjacent to tumor is a strong predictor of breast cancer LR. If confirmed by future studies, TLV in normal epithelial cells adjacent to tumor has the potential to become a promising biomarker for predicting breast cancer LR after breast conserving surgery. PMID:22072619

  15. Normal Variations of Sphenoid Sinus and the Adjacent Structures Detected in Cone Beam Computed Tomography

    PubMed Central

    Rahmati, Azadeh; Ghafari, Roshanak; AnjomShoa, Maryam

    2016-01-01

    Statement of the Problem The sphenoid sinus is a common target of paranasal surgery. Functional endoscopic sinus surgery is likely to endanger the anatomic variations of vital structures adjacent to the sphenoid sinus. Purpose The aim of this study was to determine the variations of sphenoid sinus and the related structures by using cone-beam computed tomography (CBCT). Materials and Method In this descriptive-analytic study, CBCT images of 103 patients aged above 20-years were selected (206 sides). Degree of pneumatization of sphenoid sinus, pneumatization of the anterior clinoid process, pterygoid process, protrusion of optic canal, vidian canal, and foramen rotundum, as well as prevalence of sinus septa were recorded. Examinations were performed using On-Demand software (Version 1); data were analyzed by using chi-square test. Results There was a statistically significant correlation between the pterygoid pneumatization and vidian canal protrusion (p< 0.001), and foramen rotundum protrusion (p< 0.001). The optic canal protrusion was found to be significantly associated with the anterior clinoid pneumatization and pterygoid process (p< 0.001). Statistically significant relationship was also observed between the carotid canal protrusion and pterygoid process pneumatization (p< 0.001). Conclusion The anatomical variations of the sphenoid sinus tend to give rise to a complexity of symptoms and potentially serious complications. This variability necessitates a comprehensive understanding of the regional sphenoid sinus anatomy by a detailed CBCT sinus examination. PMID:26966706

  16. Histomorphometric study to compare histological changes between oral squamous cell carcinoma and apparently normal adjacent oral mucosa.

    PubMed

    Babji, Deepa V; Kale, Alka D; Hallikerimath, Seema R; Kotrashetti, Vijayalakshmi S

    2015-03-01

    Despite the advances in surgery, radiotherapy and chemotherapy the annual death for oral squamous cell carcinoma (OSCC) is rising rapidly. The carcinoma has propensity to develop in a field of cancerization. Clinically may it be apparently normal mucosa (ANM) adjacent to squamous cell carcinoma which harbours certain discrete molecular alteration which ultimately reflects in cellular morphology. Hence the aim of the study is to assess histomorphometric changes in ANM adjacent to OSCC. A prospective study was done on 30 each of histologically diagnosed cases OSCC, ANM at least 1 cm away from OSCC, and normal oral mucosa (NOM). Cellular and nuclear morphometric measurements were assessed on hematoxylin and eosin sections using image analysis software. Statistical analysis was done using analysis of variance test and Tukey's post hoc test. The present study showed significant changes in cellular and nuclear area in superficial and invasive island of OSCC compared to ANM. The basal cells of ANM showed significant decrease in cellular and nuclear areas and nuclear cytoplasmic ratio when compared to NOM. Histomorphometry definitely can differentiate OSCC form ANM and NOM. The basal cells of ANM showed significant alterations in cellular area, nuclear area and nuclear cytoplasmic area when compared to NOM suggesting change in the field and have high risk of malignant transformation. These parameters can be used as indicator of field cancerization. PMID:25621249

  17. Normalization of brain morphology after surgery in sagittal craniosynostosis.

    PubMed

    Brooks, Eric D; Yang, Jenny; Beckett, Joel S; Lacadie, Cheryl; Scheinost, Dustin; Persing, Sarah; Zellner, Elizabeth G; Oosting, Devon; Keifer, Cara; Friedman, Hannah E; Wyk, Brent Vander; Jou, Roger J; Sun, Haosi; Gary, Cyril; Duncan, Charles C; Constable, R Todd; Pelphrey, Kevin A; Persing, John A

    2016-04-01

    OBJECT Nonsyndromic craniosynostosis (NSC) is associated with significant learning disability later in life. Surgical reconstruction is typically performed before 1 year of age to correct the cranial vault morphology and to allow for normalized brain growth with the goal of improving cognitive function. Yet, no studies have assessed to what extent normalized brain growth is actually achieved. Recent advances in MRI have allowed for automated methods of objectively assessing subtle and pronounced brain morphological differences. The authors used one such technique, deformation-based morphometry (DBM) Jacobian mapping, to determine how previously treated adolescents with sagittal NSC (sNSC) significantly differ in brain anatomy compared with healthy matched controls up to 11.5 years after surgery. METHODS Eight adolescent patients with sNSC, previously treated via whole-vault cranioplasty at a mean age of 7 months, and 8 age- and IQ-matched control subjects without craniosynostosis (mean age for both groups = 12.3 years), underwent functional 3-T MRI. Statistically significant group tissue-volume differences were assessed using DBM, a whole-brain technique that estimates morphological differences between 2 groups at each voxel (p < 0.01). Group-wise Jacobian volume maps were generated using a spacing of 1.5 mm and a resolution of 1.05 × 1.05 × 1.05 mm(3). RESULTS There were no significant areas of volume reduction or expansion in any brain areas in adolescents with sNSC compared with controls at a significance level of p < 0.01. At the more liberal threshold of p < 0.05, two areas of brain expansion extending anteroposteriorly in the right temporooccipital and left frontoparietal regions appeared in patients with sNSC compared with controls. CONCLUSIONS Compared with previous reports on untreated infants with sNSC, adolescents with sNSC in this cohort had few areas of brain dysmorphology many years after surgery. This result suggests that comprehensive cranioplasty

  18. Modelling convection-enhanced delivery in normal and oedematous brain.

    PubMed

    Haar, P J; Chen, Z-J; Fatouros, P P; Gillies, G T; Corwin, F D; Broaddus, W C

    2014-03-01

    Convection-enhanced delivery (CED) could have clinical applications in the delivery of neuroprotective agents in brain injury states, such as ischaemic stroke. For CED to be safe and effective, a physician must have accurate knowledge of how concentration distributions will be affected by catheter location, flow rate and other similar parameters. In most clinical applications of CED, brain microstructures will be altered by pathological injury processes. Ischaemic stroke and other acute brain injury states are complicated by formation of cytotoxic oedema, in which cellular swelling decreases the fractional volume of the extracellular space (ECS). Such changes would be expected to significantly alter the distribution of neuroprotective agents delivered by CED. Quantitative characterization of these changes will help confirm this prediction and assist in efforts to model the distribution of therapeutic agents. Three-dimensional computational models based on a Nodal Point Integration (NPI) scheme were developed to model infusions in normal brain and brain with cytotoxic oedema. These models were compared to experimental data in which CED was studied in normal brain and in a middle cerebral artery (MCA) occlusion model of cytotoxic oedema. The computational models predicted concentration distributions with reasonable accuracy. PMID:24446800

  19. Lactotransferrin immunocytochemistry in Alzheimer and normal human brain.

    PubMed Central

    Kawamata, T.; Tooyama, I.; Yamada, T.; Walker, D. G.; McGeer, P. L.

    1993-01-01

    Lactotransferrin (LF) expression was investigated immunocytochemically in postmortem brain tissues of normal controls and patients with Alzheimer's disease (AD). The antibody to LF stained some neurons weakly in young adult brains, but it stained many neurons as well as the glia of all types in elderly brains. LF expression was greatly up-regulated in both neurons and glia in affected AD tissue. It was very strongly associated with such extracellular pathological entities as diffuse and consolidated amyloid deposits and extracellular neurofibrillary tangles. In addition, it was identified in a minority of intracellular neurofibrillary tangles, neuropil threads, and degenerative neurites. LF is an iron scavenger and a complement inhibitor. Up-regulation may be a defense mechanism in AD-affected brain tissue. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8494052

  20. Determinants of iron accumulation in the normal aging brain.

    PubMed

    Pirpamer, Lukas; Hofer, Edith; Gesierich, Benno; De Guio, François; Freudenberger, Paul; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Duchesnay, Edouard; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2016-07-01

    In a recent postmortem study, R2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p ≤ 0.0001). Further associations to R2* values were found in deep GM for age and smoking. No significant associations were found for gender, GM volume, serum levels of iron, or iron-associated genetic polymorphisms. In conclusion, besides age, the BMI and smoking are the only significant determinants of brain iron accumulation in normally aging subjects. Smoking relates to iron deposition in the basal ganglia, whereas higher BMI is associated with iron content in the neocortex following an Alzheimer-like distribution. PMID:27255824

  1. In vitro synthesis of immunoglobulins, secretory component and complement in normal and pathological skin and the adjacent mucous membranes

    PubMed Central

    Lai A Fat, R. F. M.; Suurmond, D.; Van Furth, R.

    1973-01-01

    A study on the synthesis of immunoglobulins (IgG, IgA, IgM, IgD, and IgE), secretory component and complement in normal and pathological skin and in the adjacent mucous membranes (i.e. conjunctiva, nasal, oral and vaginal mucosa) is reported. The results are based on the culture of tissue samples in a medium with two radioactive amino acids and the detection of synthesized proteins by autoradiography of the immunoelectrophoretic pattern of the culture fluid, except in the case of IgE for which the Ouchterlony technique was used. The results indicate that the normal skin does not synthesize immunoglobulins, whereas normal mucous membranes produce IgG and IgA. In the lesions of various skin diseases immunoglobulins are synthesized, mainly IgG but sometimes also IgA and IgE. The cells responsible for the production of immunoglobulins are plasma cells and lymphoid cells present in the skin lesions and mucous membranes. Synthesis of the free secretory component could be demonstrated only in certain mucous membranes (i.e. conjunctiva, nasal mucosa, and oral mucosa). Complement (C3) synthesis was found in normal skin, mucous membranes (i.e. conjunctiva, nasal and oral mucosa), and in the lesions of such skin diseases as discoid lupus erythematosus, (bullous) pemphigoid, dermatitis herpetiformis, malignant reticulosis, eczema and lichen planus. Complement production was also demonstrated in allergic skin reactions (i.e. tissue from allergic-positive patch tests, positive Mantoux tests and drug eruptions), but no immunoglobulin synthesis was detected in these lesions. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:4199092

  2. Normal feline brain: clinical anatomy using magnetic resonance imaging.

    PubMed

    Mogicato, G; Conchou, F; Layssol-Lamour, C; Raharison, F; Sautet, J

    2012-04-01

    The purpose of this study was to provide a clinical anatomy atlas of the feline brain using magnetic resonance imaging (MRI). Brains of twelve normal cats were imaged using a 1.5 T magnetic resonance unit and an inversion/recovery sequence (T1). Fourteen relevant MRI sections were chosen in transverse, dorsal, median and sagittal planes. Anatomic structures were identified and labelled using anatomical texts and Nomina Anatomica Veterinaria, sectioned specimen heads, and previously published articles. The MRI sections were stained according to the major embryological and anatomical subdivisions of the brain. The relevant anatomical structures seen on MRI will assist clinicians to better understand MR images and to relate this neuro-anatomy to clinical signs. PMID:21919951

  3. Glycerol dehydrates oedematous as well as normal brain in dogs.

    PubMed

    Wang, J Y; Chen, J L

    1994-04-01

    1. Although the effect of glycerol on reducing intracranial pressure has been widely investigated, only a few studies have reported its dehydrating effect on brain oedema caused by infarction, ischaemia, microembolism and cold injury, but none on traumatic oedema. In this study the effects of glycerol (1 g/kg, i.v. bolus infusion at a rate of 0.04 g/kg per min) on traumatic and cryogenic cerebral oedema and on normal brain were compared in the anaesthetized dog. The tissue water content was measured with the gravimetric method. 2. Oedema resulting from mechanical trauma was initiated 4 h prior to treatment with glycerol (8 dogs) or vehicle (5 dogs) by closed head contusion with fixed force under general anaesthesia. Tissue samples underneath the region of contusion were taken, before and 1 h after infusion of glycerol or vehicle, for the measurement of water content. 3. Glycerol infusion decreased the water content in white matter of the traumatic brain model from 76.54 +/- 1.70% to 70.73 +/- 1.54% (P < 0.001). In normal brain the reduction was from 68.42 +/- 0.48% to 65.36 +/- 0.39% (P < 0.001). Neither vehicle nor glycerol infusion resulted in significant changes in specific gravity of the gray matter. 4. Cryogenic oedema was initiated 3 h prior to the infusion of glycerol or vehicle by applying unilaterally a brass conical cup (bottom diameter 1 cm) filled with dry ice-acetone (-65 degrees C) to the exposed dura for 1 min. The contralateral hemisphere, which was not subjected to cold injury, was used for determination of water content of normal gray and white matter. 5. Glycerol infusion decreased the water content in the white matter of the cold-injured region from 75.38 +/- 0.69% to 72.57 +/- 0.58% (P < 0.001). In the normal white matter the reduction was from 68.63 +/- 0.34% to 65.48 +/- 0.49% (P < 0.001). 6. Our data indicate that glycerol decreases water content of the white matter in traumatic and cold-injured oedematous brain as well as in normal brain

  4. The Associated Venous Anomalies Variant and Adjacent Brain Function on Iron Sensitive Image Indicate Surgical Risk of Cavernous Malformation.

    PubMed

    Ma, Li; Chen, Xiao-Lin; Ma, Jun; Zhao, Yuan-Li

    2016-01-01

    The cavernous malformations (CMs) associated with venous anomalies (VAs) are now being described with increasing frequency. Assessment of the associated VAs is overlooked in surgical management of the CM. The clinical profiles of CMs with VAs were reviewed to investigate the value of T2* gradient echo (GRE)/susceptibility weighted imaging (SWI) in surgical risk evaluation. Twenty-six patients with symptomatic CMs associated with VAs between 2008 and 2013 were identified. Demographic, clinical, and radiological data were reviewed and functional outcomes were assessed using the modified Rankin Scale (mRS). The T2* GRE/SWI could allow more accurate evaluation of the boundary and drainage vicinity of VAs than contrast-enhanced images (6 vs. 2 patients with VAs on the eloquent region). Patients with VAs adjacent to eloquent brain showed poorer outcomes than those who had VAs in non-eloquent areas (P = 0.005), while the CMs adjacent to eloquent brain did not correlated with poor outcomes (P = 0.15). Type I and III variants of VAs were also significantly associated with poor outcomes, compared with type II variant (P = 0.002). Careful evaluation of VAs variant type and the association between VAs and eloquent brain is helpful for the management of CMs associated with VAs. We recommend T2* GRE/SWI in patients with CMs to assess the associated VAs. The evaluation of VA drainage vicinity on T2* GRE/SWI would be more useful for designing treatment strategies and risk stratification. PMID:26489407

  5. Regional distributions of brain glutamate and glutamine in normal subjects.

    PubMed

    Goryawala, Mohammed Z; Sheriff, Sulaiman; Maudsley, Andrew A

    2016-08-01

    Glutamate (Glu) and glutamine (Gln) play an important role in neuronal regulation and are of value as MRS-observable diagnostic biomarkers. In this study the relative concentrations of these metabolites have been measured in multiple regions in the normal brain using a short-TE whole-brain MRSI measurement at 3 T combined with a modified data analysis approach that used spatial averaging to obtain high-SNR spectra from atlas-registered anatomic regions or interest. By spectral fitting of high-SNR spectra this approach yielded reliable measurements across a wide volume of the brain. Spectral averaging also demonstrated increased SNR and improved fitting accuracy for the sum of Glu and Gln (Glx) compared with individual voxel fitting. Results in 26 healthy controls showed relatively constant Glu/Cr and Gln/Cr throughout the cerebrum, although with increased values in the anterior cingulum and paracentral lobule, and increased Gln/Cr in the superior motor area. The deep gray-matter regions of thalamus, putamen, and pallidum show lower Glu/Cr compared with cortical white-matter regions. Lobar measurements demonstrated reduced Glu/Cr and Gln/Cr in the cerebellum as compared with the cerebrum, where white-matter regions show significantly lower Glu/Cr and Gln/Cr as compared with gray-matter regions across multiple brain lobes. Regression analysis showed no significant effect of gender on Glu/Cr or Gln/Cr measurement; however, Glx/Cr ratio was found to be significantly negatively correlated with age in some lobar brain regions. In summary, this methodology provides the spectral quality necessary for reliable separation of Glu and Gln at 3 T from a single MRSI acquisition enabling generation of regional distributions of metabolites over a large volume of the brain, including cortical regions. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27351339

  6. Brain cholinesterase activity of apparently normal wild birds

    USGS Publications Warehouse

    Hill, E.F.

    1988-01-01

    Organophosphorus and carbamate pesticides are potent anticholinesterase substances that have killed large numbers of wild birds of various species. Cause of death is diagnosed by demonstration of depressed brain cholinesterase (ChE) activity in combination with chemical detection of anticholinesterase residue in the affected specimen. ChE depression is determined by comparison of the affected specimen to normal ChE activity for a sample of control specimens of the same species, but timely procurement of controls is not always possible. Therefore, a reference file of normal whole brain ChE activity is provided for 48 species of wild birds from North America representing 11 orders and 23 families for use as emergency substitutes in diagnosis of anticholinesterase poisoning. The ChE values, based on 83 sets of wild control specimens from across the United States, are reproducible provided the described procedures are duplicated. Overall, whole brain ChE activity varied nearly three-fold among the 48 species represented, but it was usually similar for closely related species. However, some species were statistically separable in most families and some species of the same genus differed as much as 50%.

  7. Normal gut microbiota modulates brain development and behavior.

    PubMed

    Diaz Heijtz, Rochellys; Wang, Shugui; Anuar, Farhana; Qian, Yu; Björkholm, Britta; Samuelsson, Annika; Hibberd, Martin L; Forssberg, Hans; Pettersson, Sven

    2011-02-15

    Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior. PMID:21282636

  8. Cell migration in the normal and pathological postnatal mammalian brain

    PubMed Central

    Canoll, Peter; Goldman, James E.

    2009-01-01

    In the developing brain, cell migration is a crucial process for structural organization, and is therefore highly regulated to allow the correct formation of complex networks, wiring neurons, and glia. In the early postnatal brain, late developmental processes such as the production and migration of astrocyte and oligodendrocyte progenitors still occur. Although the brain is completely formed and structured few weeks after birth, it maintains a degree of plasticity throughout life, including axonal remodeling, synaptogenesis, but also neural cell birth, migration and integration. The subventricular zone (SVZ) and the dentate gyrus of the hippocampus (DG) are the two main neurogenic niches in the adult brain. Neural stem cells reside in these structures and produce progenitors that migrate toward their ultimate location: the olfactory bulb and granular cell layer of the DG respectively. The aim of this review is to synthesize the increasing information concerning the organization, regulation and function of cell migration in a mature brain. In a normal brain, protein involved in cell-cell or cell-matrix interactions together with secreted proteins acting as chemoattractant or chemorepellant play key roles in the regulation of neural progenitor cell migration. In addition, recent data suggest that gliomas arise from the transformation of neural stem cells or progenitor cells and that glioma cell infiltration recapitulates key aspects of glial progenitor migration. Thus, we will consider glioma migration in the context of progenitor migration. Finally, many observations show that brain lesions and neurological diseases trigger neural stem/progenitor cell activation and migration towards altered structures. The factors involved in such cell migration/recruitment are just beginning to be understood. Inflammation which has long been considered as thoroughly disastrous for brain repair is now known to produce some positive effects on stem/progenitor cell recruitment via

  9. 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.

  10. Higher FOXP3-TSDR demethylation rates in adjacent normal tissues in patients with colon cancer were associated with worse survival

    PubMed Central

    2014-01-01

    Background The influence of natural regulatory T cells (nTregs) on the patients with colon cancer is unclear. Demethylated status of the Treg-specific demethylated region (TSDR) of the FOXP3 gene was reported to be a potential biomarker for the identification of nTregs. Methods The demethylation rate of the TSDR (TSDR-DMR) was calculated by using methylation-specific quantitative polymerase chain reaction (MS-qPCR) assay. The expression of TSDR-DMR and FOXP3 mRNA was investigated in various colorectal cancer cell lines. A total of 130 colon carcinoma samples were utilized to study the DMR at tumor sites (DMRT) and adjacent normal tissue (DMRN). The correlations between DMRs and clinicopathological variables of patients with colon cancer were studied. Results The TSDR-DMRs varied dramatically among nTregs (97.920 ± 0.466%) and iTregs (3.917 ± 0.750%). Significantly, DMRT (3.296 ± 0.213%) was higher than DMRN (1.605 ± 0.146%) (n = 130, p = 0.000). Higher DMRN levels were found in female patients (p = 0.001) and those with distant metastases (p = 0.017), and were also associated with worse recurrence-free survival in non-stage IV patients (low vs. high, p = 0.022). However, further Cox multivariate analysis revealed that the FOXP3-TSDR status does not have prognostic value. Conclusion MS-qPCR assays of FOXP3-TSDR can efficiently distinguish nTregs from non-nTregs. Abnormal recruitment of nTregs occurs in the local tumor microenvironment. Infiltration of tissue-resident nTregs may have a negative role in anti-tumor effects in patients with colon cancer; however, this role is limited and complicated. PMID:24938080

  11. Compelling Evidence that Exposure Therapy for PTSD Normalizes Brain Function.

    PubMed

    Roy, Michael J; Costanzo, Michelle E; Blair, James R; Rizzo, Albert A

    2014-01-01

    Functional magnetic resonance imaging (fMRI) is helping us better understand the neurologic pathways involved in posttraumatic stress disorder (PTSD). We previously reported that military service members with PTSD after deployment to Iraq or Afghanistan demonstrated significant improvement, or normalization, in the fMRI-measured activation of the amygdala, prefrontal cortex and anterior cingulate gyrus following exposure therapy for PTSD. However, our original study design did not include repeat scans of control participants, rendering it difficult to discern how much of the observed normalization in brain activity is attributable to treatment, rather than merely a practice effect. Using the same Affective Stroop task paradigm, we now report on a larger sample of PTSD-positive combat veterans that we treated with exposure therapy, as well as a combat-exposed control group of service members who completed repeat scans at 3-4 month intervals. Findings from the treatment group are similar to our prior report. Combat controls showed no significant change on repeat scanning, indicating that the observed differences in the intervention group were in fact due to treatment. We continue to scan additional study participants, in order to determine whether virtual reality exposure therapy has a different impact on regional brain activation than other therapies for PTSD. PMID:24875691

  12. Normal findings on brain FLAIR MRI scans at 3T

    PubMed Central

    Neema, Mohit; Guss, Zachary D.; Stankiewicz, James M.; Arora, Ashish; Healy, Brian C.; Bakshi, Rohit

    2010-01-01

    BACKGROUND AND PURPOSE Fluid attenuated inversion recovery (FLAIR) MR imaging of the brain has become a routine tool for assessing lesions in patients with suspected neurologic disorders. There is growing interest in 3T brain FLAIR MR imaging but little normative data are available. The purpose of this study was to evaluate the frequency and topography of cerebral hyperintensities seen with FLAIR MR imaging of the brain at 3T in a normal population and compare those findings to 1.5T. MATERIALS AND METHODS Whole-brain 2D FLAIR MR imaging was performed in 22 healthy controls (mean age, 44 ± 8 years; range, 30–53 years) at 3T. Fifteen of these subjects also underwent 2D FLAIR at 1.5T, with similar optimized parameters and voxel size. Cerebral hyperintense areas, including discrete foci, anterior and posterior periventricular capping, diffuse parenchymal hyperintensity, septal hyperintensity, corticospinal tract hyperintensity, and CSF flow artifacts were assessed. The Spearman rank test assessed the correlation between discrete hyperintense foci and age. The Wilcoxon signed rank test compared foci detectability at 3T versus 1.5T. RESULTS FLAIR at 3T commonly showed hyperintensities such as discrete foci (mean, 10.68 per subject; at least 1 present in 68% of subjects), anterior and posterior periventricular capping, diffuse posterior white matter hyperintensity, septal hyperintensity, corticospinal tract hyperintensity, and ventricular CSF flow artifacts. FLAIR at 3T showed a higher hyperintense foci volume (170 ± 243 versus 93 ± 152 mm3, P < .01) and number (9.4 ± 13 versus 5.5 ± 9.2, P < .01) than at 1.5T. No significant differences (P = .68) in the length/diameter of individual discrete hyperintense foci were seen between 3T and 1.5T. Discrete foci volume (r = 0.72 at 3T, r = 0.70 at 1.5T) and number (r = 0.74 at 3T; r = 0.69 at 1.5T) correlated with age to a similar degree on both platforms. All discrete foci were confined to the noncallosal supratentorial

  13. Identification of reliable reference genes for quantitative gene expression studies in oral squamous cell carcinomas compared to adjacent normal tissues in the F344 rat model.

    PubMed

    Peng, Xinjian; McCormick, David L

    2016-08-01

    Oral squamous cell carcinomas (OSCCs) induced in F344 rats by 4-nitroquinoline-1-oxide (4-NQO) demonstrate considerable phenotypic similarity to human oral cancers and the model has been widely used for carcinogenesis and chemoprevention studies. Molecular characterization of this model needs reliable reference genes (RGs) to avoid false- positive and -negative results for proper interpretation of gene expression data between tumor and adjacent normal tissues. Microarray analysis of 11 pairs of OSCC and site-matched phenotypically normal oral tissues from 4-NQO-treated rats identified 10 stably expressed genes in OSCC compared to adjacent normal tissues (p>0.5, CV<15%) that could serve as potential RGs in this model. The commonly used 27 RGs in the rat were also analyzed based on microarray data and most of them were found unsuitable for RGs in this model. Traditional RGs such as ACTB and GAPDH were significantly altered in OSCC compared to adjacent normal tissues (p<0.01, n=11); however, the Hsp90ab1 was ranked as the best RG candidate and the combination of Hsp90ab1 and HPRT1 was identified by NormFinder to be a superior reference for gene normalization among the commonly used RGs. This result was also validated by RT-PCR based on the selected top RG candidate pool. These data suggest that there are no common RGs suitable for different models and RG(s) should be identified before gene expression analysis. We successfully identified Hsp90ab1 as a stable RG in 4-NQO-induced OSCC compared to adjacent normal tissues in F344 rats. The combination of two stably expressed genes may be a better option for gene normalization in tissue samples. PMID:27375172

  14. Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function.

    PubMed

    Antoniades, Chrystalina A; FitzGerald, James J

    2016-01-01

    The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology. PMID:27501123

  15. Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium

    NASA Technical Reports Server (NTRS)

    Shim, Veronica; Gauthier, Mona L.; Sudilovsky, Daniel; Mantei, Kristin; Chew, Karen L.; Moore, Dan H.; Cha, Imok; Tlsty, Thea D.; Esserman, Laura J.

    2003-01-01

    Cyclooxygenase-2 (COX-2) is emerging as an important cancer biomarker and is now an experimental target for solid tumor treatment.However, no study has exclusively focused on COX-2 expression in early lesions such as ductal carcinoma in situ (DCIS). We examined COX-2 expression by immunohistochemistry in 46 cases of women undergoing surgical resection for DCIS. We found that COX-2 expression was detected in 85% of all DCIS specimens, with increased COX-2 staining correlating with higher nuclear grade. Strikingly, COX-2 staining intensity in the normal adjacent epithelium was stronger than in the DCIS lesion itself. Our observations demonstrate that COX-2 is up-regulated in the normal adjacent epithelium and supports the hypothesis that the surrounding epithelial tissue is part of the disease process in DCIS.

  16. Brain connectivity in normally developing children and adolescents.

    PubMed

    Khundrakpam, Budhachandra S; Lewis, John D; Zhao, Lu; Chouinard-Decorte, François; Evans, Alan C

    2016-07-01

    The developing human brain undergoes an astonishing sequence of events that continuously shape the structural and functional brain connectivity. Distinct regional variations in the timelines of maturational events (synaptogenesis and synaptic pruning) occurring at the synaptic level are reflected in brain measures at macroscopic resolution (cortical thickness and gray matter density). Interestingly, the observed brain changes coincide with cognitive milestones suggesting that the changing scaffold of brain circuits may subserve cognitive development. Recent advances in connectivity analysis propelled by graph theory have allowed, on one hand, the investigation of maturational changes in global organization of structural and functional brain networks; and on the other hand, the exploration of specific networks within the context of global brain networks. An emerging picture from several connectivity studies is a system-level rewiring that constantly refines the connectivity of the developing brain. PMID:27054487

  17. Isolation and characterization of human malignant glioma cells from histologically normal brain.

    PubMed

    Silbergeld, D L; Chicoine, M R

    1997-03-01

    Brain invasion prevents complete surgical extirpation of malignant gliomas; however, invasive cells from distant, histologically normal brain previously have not been isolated, cultured, and characterized. To evaluate invasive human malignant glioma cells, the authors established cultures from gross tumor and histologically normal brain. Three men and one woman, with a mean age of 67 years, underwent two frontal and two temporal lobectomies for tumors, which yielded specimens of both gross tumor and histologically normal brain. Each specimen was acquired a minimum of 4 cm from the gross tumor. The specimens were split: a portion was sent for neuropathological evaluation (three glioblastomas multiforme and one oligodendroglioma) and a portion was used to establish cell lines. Morphologically, the specimens of gross tumor and histologically normal brain were identical in three of the four cell culture pairs. Histochemical staining characteristics were consistent both within each pair and when compared with the specimens sent for neuropathological evaluation. Cultures demonstrated anchorage-independent growth in soft agarose and neoplastic karyotypes. Growth rates in culture were greater for histologically normal brain than for gross tumor in three of the four culture pairs. Although the observed increases in growth rates of histologically normal brain cultures do not correlate with in vivo behavior, these findings corroborate the previously reported stem cell potential of invasive glioma cells. Using the radial dish assay, no significant differences in motility between cultures of gross tumor and histologically normal brain were found. In summary, tumor cells were cultured from histologically normal brain acquired from a distance greater than 4 cm from the gross tumor, indicating the relative insensitivity of standard histopathological identification of invasive glioma cells (and hence the inadequacy of frozen-section evaluation of resection margins). Cell lines

  18. Tumor-induced solid stress activates β-catenin signaling to drive malignant behavior in normal, tumor-adjacent cells

    PubMed Central

    Ou, Guanqing; Weaver, Valerie Marie

    2016-01-01

    Recent work by Fernández-Sánchez and coworkers examining the impact of applied pressure on the malignant phenotype of murine colon tissue in vivo revealed that mechanical perturbations can drive malignant behavior in genetically normal cells. Their findings build upon an existing understanding of how the mechanical cues experienced by cells within a tissue become progressively modified as the tissue transforms. Using magnetically stimulated ultra-magnetic liposomes to mimic tumor growth -induced solid stress, Fernández-Sánchez and coworkers were able to stimulate β-catenin to promote the cancerous behavior of both a normal and genetically modified colon epithelium. In this perspective, we discuss their findings in the context of what is currently known regarding the role of the mechanical landscape in cancer progression and β-catenin as a mechanotransducer. We review data that suggest that mechanically regulated activation of β-catenin fosters development of a malignant phenotype in tissue and predict that mechanical cues may contribute to tumor heterogeneity. PMID:26439949

  19. Contrast medium accumulation and washout in canine brain tumors and irradiated normal brain: a CT study of kinetics

    SciTech Connect

    Fike, J.R.; Cann, C.E.

    1984-04-01

    Kinetics of an iodinated contrast medium were evaluated quantitatively as a function of time up to one hour after intravenous infusion in the brains of dogs with experimentally induced radiation damage and dogs with spontaneous brain tumor. Radiation damage was characterized by an increase in iodine accumulation soon after the infusion, while tumor concentration of iodine either showed no change or decreased with time. These results suggest that contrast kinetic studies may be useful in differentiating radiation damage to normal brain tissue from a malignant brain tumor.

  20. Immunohistochemical quantification of the cobalamin transport protein, cell surface receptor and Ki-67 in naturally occurring canine and feline malignant tumors and in adjacent normal tissues

    PubMed Central

    Sysel, Annette M.; Valli, Victor E.; Bauer, Joseph A.

    2015-01-01

    Cancer cells have an obligate need for cobalamin (vitamin B12) to enable DNA synthesis necessary for cellular replication. This study quantified the immunohistochemical expression of the cobalamin transport protein (transcobalamin II; TCII), cell surface receptor (transcobalamin II-R; TCII-R) and proliferation protein (Ki-67) in naturally occurring canine and feline malignant tumors, and compared these results to expression in corresponding adjacent normal tissues. All malignant tumor tissues stained positively for TCII, TCII-R and Ki-67 proteins; expression varied both within and between tumor types. Expression of TCII, TCII-R and Ki-67 was significantly higher in malignant tumor tissues than in corresponding adjacent normal tissues in both species. There was a strong correlation between TCII and TCII-R expression, and a modest correlation between TCII-R and Ki-67 expression in both species; a modest association between TCII and Ki-67 expression was present in canine tissues only. These results demonstrate a quantifiable, synchronous up-regulation of TCII and TCII-R expression by proliferating canine and feline malignant tumors. The potential to utilize these proteins as biomarkers to identify neoplastic tissues, streamline therapeutic options, evaluate response to anti-tumor therapy and monitor for recurrent disease has important implications in the advancement of cancer management for both human and companion animal patients. PMID:25633912

  1. The neuroanatomy of prematurity: normal brain development and the impact of preterm birth.

    PubMed

    Ortinau, Cynthia; Neil, Jeffrey

    2015-03-01

    Brain development is a complex process of micro- and macrostructural events that include neuronal and glial proliferation and migration, myelination, and organizational development of cortical layers and circuitry. Recent progress in understanding these processes has provided insight into the pathophysiology of brain injury and alterations of cerebral development in preterm infants. A key factor of abnormalities in the preterm infant is the maturational stage of the brain at the time of birth. This review summarizes current data on normal brain development, patterns of brain injury in the preterm infant, and the associated axonal/neuronal disturbances that occur in the setting of this injury, often termed encephalopathy of prematurity. PMID:25043926

  2. Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain

    NASA Astrophysics Data System (ADS)

    Rendon, Cesar A.; Lilge, Lothar

    2004-10-01

    In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

  3. Lipid Profiles of Canine Invasive Transitional Cell Carcinoma of the Urinary Bladder and Adjacent Normal Tissue by Desorption Electrospray Ionization Imaging Mass Spectrometry

    PubMed Central

    Dill, Allison L.; Ifa, Demian R.; Manicke, Nicholas E.; Costa, Anthony B.; Ramos-Vara, José A.; Knapp, Deborah W.; Cooks, R. Graham

    2009-01-01

    Desorption electrospray ionization (DESI) mass spectrometry (MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of canine spontaneous invasive transitional cell carcinoma (TCC) of the urinary bladder (a model of human invasive bladder cancer) as well as adjacent normal tissue from four different dogs. The glycerophospholipids and sphingolipids that appear as intense signals in both the negative ion and positive ion modes were identified by tandem mass spectrometry (MS/MS) product ion scans using collision-induced dissociation. Differences in the relative distributions of the lipid species were present between the tumor and adjacent normal tissue in both the negative and positive ion modes. DESI-MS images showing the spatial distributions of particular glycerophospholipids, sphinoglipids and free fatty acids in both the negative and positive ion modes were compared to serial tissue sections that were stained with hematoxylin and eosin (H&E). Increased absolute and relative intensities for at least five different glycerophospholipids and three free fatty acids in the negative ion mode and at least four different lipid species in the positive ion mode were seen in the tumor region of the samples in all four dogs. In addition, one sphingolipid species exhibited increased signal intensity in the positive ion mode in normal tissue relative to the diseased tissue. Principal component analysis (PCA) was also used to generate unsupervised statistical images from the negative ion mode data and these images are in excellent agreement with the DESI images obtained from the selected ions and also the H&E stained tissue PMID:19810710

  4. High-field proton magnetic resonance spectroscopy reveals metabolic effects of normal brain aging

    PubMed Central

    Harris, Janna L.; Yeh, Hung-Wen; Swerdlow, Russell H.; Choi, In-Young; Lee, Phil; Brooks, William M.

    2014-01-01

    Altered brain metabolism is likely to be an important contributor to normal cognitive decline and brain pathology in elderly individuals. To characterize the metabolic changes associated with normal brain aging, we used high-field proton magnetic resonance spectroscopy in vivo to quantify 20 neurochemicals in the hippocampus and sensorimotor cortex of young adult and aged rats. We found significant differences in the neurochemical profile of the aged brain when compared with younger adults, including lower aspartate, ascorbate, glutamate, and macromolecules, and higher glucose, myo-inositol, N-acetylaspartylglutamate, total choline, and glutamine. These neurochemical biomarkers point to specific cellular mechanisms that are altered in brain aging, such as bioenergetics, oxidative stress, inflammation, cell membrane turnover, and endogenous neuroprotection. Proton magnetic resonance spectroscopy may be a valuable translational approach for studying mechanisms of brain aging and pathology, and for investigating treatments to preserve or enhance cognitive function in aging. PMID:24559659

  5. Diffusion of radiotracers in normal and ischemic brain slices.

    PubMed

    Patlak, C S; Hospod, F E; Trowbridge, S D; Newman, G C

    1998-07-01

    Diffusion in the extracellular space (ECS) is important in physiologic and pathologic brain processes but remains poorly understood. To learn more about factors influencing tissue diffusion and the role of diffusion in solute-tissue interactions, particularly during cerebral ischemia, we have studied the kinetics of several radiotracers in control and hypoxic 450-microm hippocampal slices and in 1,050-microm thick slices that model the ischemic penumbra. Kinetics were analyzed by nonlinear least squares methods using models that combine extracellular diffusion with tissue compartments in series or in parallel. Studies with 14C-polyethylene glycol confirmed prior measurements of extracellular volume and that ECS shrinks during ischemia. Separating diffusion from transport also revealed large amounts of 45Ca that bind to or enter brain as well as demonstrating a small, irreversibly bound compartment during ischemia. The rapidity of 3H2O entry into cells made it impossible for us to distinguish intracellular from extracellular diffusion. The diffusion-compartment analysis of 3-O-methylglucose data appears to indicate that 5 mmol/L glucose is inadequate to support glycolysis fully in thick slices. Unexpectedly, the diffusion coefficient for all four tracers rose in thick slices compared with thin slices, suggesting that ECS becomes less tortuous in the penumbra. PMID:9663508

  6. Discovery and verification of protein differences between Er positive/Her2/neu negative breast tumor tissue and matched adjacent normal breast tissue.

    PubMed

    Weitzel, Lindsay-Rae B; Byers, Tim; Allen, Jenna; Finlayson, Christina; Helmke, Steve M; Hokanson, John E; Hunsucker, Stephen W; Murphy, James R; Newell, Keri; Queensland, Kelly M; Singh, Meenakshi; Wischmeyer, Paul E; Duncan, Mark W; Elias, Anthony

    2010-11-01

    This study was designed to quantify and identify differences in protein levels between tumor and adjacent normal breast tissue from the same breast in 18 women with stage I/II ER positive/Her2/neu negative invasive breast cancer. Eighteen separate difference gel electrophoresis (DIGE) gels were run (1 gel per patient). Relative quantification was based on DIGE analysis. After excision and tryptic digestion, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and peptide mass mapping were used to identify protein spots. Two hundred and forty-three spots were differentially abundant between normal and cancer tissues. Fifty spots were identified: 41 were over abundant and nine were less abundant in cancers than in normal breast tissue. Western blotting provided independent confirmation for three of the most biologically and statistically interesting proteins. All 18 gels were replicated by another technician and 32% of the differentially abundant proteins were verified by the duplicate analysis. Follow-up studies are now examining these proteins as biomarkers in blood. PMID:20087651

  7. Human lung and bladder carcinoma tumors as compared to their adjacent normal tissue have elevated AP-1 activity associated with the retinoblastoma gene promoter.

    PubMed

    Linardopoulos, S; Papadakis, E; Delakas, D; Theodosiou, V; Cranidis, A; Spandidos, D A

    1993-01-01

    Examination of the nucleotide sequence of the retinoblastoma (Rb) promoter revealed the presence of a DNA region highly homologous to the recognition site for the cellular transcription factor AP-1. A pair of complementary oligonucleotides containing the AP-1 site was synthesized and used in gel retardation assays to determine the role of the AP-1 protein in the regulation of the Rb gene expression. Using nuclear extracts from Hela cells as well as from lung and bladder tumors, we found specific binding of the AP-1 protein to this oligonucleotide. This binding is elevated in Hela cells, in 10/13 lung and 3/8 bladder tumors as compared to adjacent normal tissue. These results suggest that AP-1 could be implicated in Rb gene transcriptional regulation through its interaction with the AP-1 binding site of the Rb gene promoter. PMID:8476221

  8. Clinicopathological outcomes of prospectively followed normal elderly brain bank volunteers.

    PubMed

    Dugger, Brittany N; Hentz, Joseph G; Adler, Charles H; Sabbagh, Marwan N; Shill, Holly A; Jacobson, Sandra; Caviness, John N; Belden, Christine; Driver-Dunckley, Erika; Davis, Kathryn J; Sue, Lucia I; Beach, Thomas G

    2014-03-01

    Existing reports on the frequencies of neurodegenerative diseases are typically based on clinical diagnoses. We sought to determine these frequencies in a prospectively assessed, community-based autopsy series. Included subjects had normal cognitive and movement disorder assessments at study entry. Of the 119 cases meeting these criteria, 52% were women; the median age of study entry was 83.5 years (range, 67-99 years), and the median duration from the first visit until death was 4.3 years (range, 0-10 years). At autopsy, clinicopathological diagnoses were made in 30 cases (25%). These diagnoses included 20 with Alzheimer disease (AD) (17%), 7 with vascular dementia (6%), 4 with progressive supranuclear palsy (3%), 3 with Parkinson disease and 1 each with dementia with Lewy bodies, corticobasal degeneration, or multiple system atrophy (0.8% each). Of the 87 subjects still clinically normal at death (73%), 33 had extensive AD pathology (preclinical AD) (38%), 17 had incidental Lewy bodies (20%), and 4 had incidental pathology consistent with progressive supranuclear palsy (5%). The diagnoses were not mutually exclusive. Although limited by a relatively small sample size, the neuropathological outcome of these initially normal elderly subjects represents a rough estimate of the incidence of these neurodegenerative conditions over a defined time period. PMID:24487796

  9. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  10. Brain gray and white matter differences in healthy normal weight and obese children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To compare brain gray and white matter development in healthy normal weight and obese children. Twenty-four healthy 8- to 10-year-old children whose body mass index was either <75th percentile (normal weight) or >95th percentile (obese) completed an MRI examination which included T1-weighted three-d...

  11. Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

    PubMed Central

    Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María

    2014-01-01

    Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition. PMID:25767303

  12. Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

    NASA Astrophysics Data System (ADS)

    Yang, SH.; Ballmann, C.; Quarles, C. A.

    2009-03-01

    The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixed in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.

  13. Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

    SciTech Connect

    Yang, SH.; Ballmann, C.; Quarles, C. A.

    2009-03-10

    The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixed in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.

  14. Patterns of brain activity in normals and schizophrenics with positron emission tomography

    SciTech Connect

    Volkow, N.D.; Wolf, A.P.; Gomez-Mont, F.; Brodie, J.D.; Canero, R.; Van Gelder, P.; Russell, J.A.G.

    1985-05-01

    The authors investigated the functional interaction among brain areas under baseline and upon activation by a visual task to compare the response of normal subjects from the ones of chronic schizophrenics. Cerebral metabolic images were obtained on twelve healthy volunteers an eighteen schizophrenics with positron emission tomography and 11-C-Deoxyglucose. Correlation coefficients among the relative metabolic values (region of interest divided by the average of whole brain gray matter) of 11 brain regions; frontal, parietal, temporal and occipital left and right lobes, left and right basal ganglia and thalamus were computed for the baseline and for the task. Under baseline, normals showed more functional correlations than schizophrenics. Both groups showed a thalamo-occipital (positive) and thalamo-frontal (negative) interaction. The highest correlations among homologous brain areas were the frontal, occipital and basal ganglia.

  15. Computed tomography of the brain stem with intrathecal metrizamide. Part 1: the normal brain stem

    SciTech Connect

    Mawad, M.E.; Silver, A.J.; Hilal, S.K.; Ganti, S.R.

    1983-03-01

    Detailed anatomy of the brain stem and cervicomedullary junction can be accurately demonstrated with metrizamide computed tomographic cisternography. Specifically surface anatomy is unusually well outlined. Nine distinct and easily recognizable levels of section are described: four levels in the medulla, three in the pons, and two in the mesencephalon. Surface features of the brain stem, fine details in the floor of the fourth ventricle, cranial nerves, and vascular structures are shown and discussed.

  16. Aneuploidy in the normal, Alzheimer's disease and ataxia-telangiectasia brain: differential expression and pathological meaning.

    PubMed

    Iourov, Ivan Y; Vorsanova, Svetlana G; Liehr, Thomas; Yurov, Yuri B

    2009-05-01

    Recently it has been suggested that the human brain contains aneuploid cells; however the nature and magnitude of neural aneuploidy in health and disease remain obscure. Here, we have monitored aneuploidy in the cerebral cortex of the normal, Alzheimer's disease (AD) and ataxia telangiectasia (AT) brain by molecular cytogenetic approaches scoring more than 480,000 neural cells. Using arbitrarily selected set of DNA probes for chromosomes 1, 7, 11, 13, 14, 17, 18, 21, X and Y we have determined the mean rate of stochastic aneuploidy per chromosome as 0.5% in the normal human brain (95%CI 0.2-0.7%; SD 0.2%). The overall proportion of aneuploid cells in the normal brain has been estimated at approximately 10%. In the AT brain, we observed a 2-to-5 fold increase of stochastic aneuploidy randomly affecting different chromosomes (mean 2.1%; 95%CI - 1.5-2.6%; SD 0.8%). The overall proportion of aneuploid cells in the brain of AT individuals was estimated at approximately 20-50%. Compared with sex- and age-matched controls, the level of stochastic aneuploidy in the AD brain was not significantly increased. However, a dramatic 10-fold increase of chromosome 21-specific aneuploidy (both hypoploidy and hyperploidy) was detected in the AD cerebral cortex (6-15% versus 0.8-1.8% in control). We conclude that somatic mosaic aneuploidy differentially contributes to intercellular genomic variation in the normal, AD and AT brain. Neural aneuploidy leading to altered cellular physiology may significantly contribute to the pathogenesis of neurodegenerative diseases. These data indicate neural aneuploidy to be a newly identified feature of neurodegenerative diseases, similar to other devastative disorders hallmarked by aneuploidy such as chromosome syndromes and cancer. PMID:19344645

  17. Effects of brain amyloid deposition and reduced glucose metabolism on the default mode of brain function in normal aging.

    PubMed

    Kikuchi, Mitsuru; Hirosawa, Tetsu; Yokokura, Masamichi; Yagi, Shunsuke; Mori, Norio; Yoshikawa, Etsuji; Yoshihara, Yujiro; Sugihara, Genichi; Takebayashi, Kiyokazu; Iwata, Yasuhide; Suzuki, Katsuaki; Nakamura, Kazuhiko; Ueki, Takatoshi; Minabe, Yoshio; Ouchi, Yasuomi

    2011-08-01

    Brain β-amyloid (Aβ) deposition during normal aging is highlighted as an initial pathogenetic event in the development of Alzheimer's disease. Many recent brain imaging studies have focused on areas deactivated during cognitive tasks [the default mode network (DMN), i.e., medial frontal gyrus/anterior cingulate cortex and precuneus/posterior cingulate cortex], where the strength of functional coordination was more or less affected by cerebral Aβ deposits. In the present positron emission tomography study, to investigate whether regional glucose metabolic alterations and Aβ deposits seen in nondemented elderly human subjects (n = 22) are of pathophysiological importance in changes of brain hemodynamic coordination in DMN during normal aging, we measured cerebral glucose metabolism with [(18)F]FDG, Aβ deposits with [(11)C]PIB, and regional cerebral blood flow during control and working memory tasks by H(2)(15)O on the same day. Data were analyzed using both region of interest and statistical parametric mapping. Our results indicated that the amount of Aβ deposits was negatively correlated with hemodynamic similarity between medial frontal and medial posterior regions, and the lower similarity was associated with poorer working memory performance. In contrast, brain glucose metabolism was not related to this medial hemodynamic similarity. These findings suggest that traceable Aβ deposition, but not glucose hypometabolism, in the brain plays an important role in occurrence of neuronal discoordination in DMN along with poor working memory in healthy elderly people. PMID:21813680

  18. Blood-brain barrier and blood-cerebrospinal fluid barrier in normal and pathological conditions.

    PubMed

    Ueno, Masaki; Chiba, Yoichi; Murakami, Ryuta; Matsumoto, Koichi; Kawauchi, Machi; Fujihara, Ryuji

    2016-04-01

    Blood-borne substances can invade into the extracellular spaces of the brain via endothelial cells in sites without the blood-brain barrier (BBB), and can travel through the interstitial fluid (ISF) of the brain parenchyma adjacent to non-BBB sites. It has been shown that cerebrospinal fluid (CSF) drains directly into the blood via the arachnoid villi and also into lymph nodes via the subarachnoid spaces of the brain, while ISF drains into the cervical lymph nodes through perivascular drainage pathways. In addition, the glymphatic pathway of fluids, characterized by para-arterial pathways, aquaporin4-dependent passage through astroglial cytoplasm, interstitial spaces, and paravenous routes, has been established. Meningeal lymphatic vessels along the superior sagittal sinus were very recently discovered. It is known that, in mice, blood-borne substances can be transferred to areas with intact BBB function, such as the medial regions of the hippocampus, presumably through leaky vessels in non-BBB sites. In the present paper, we review the clearance mechanisms of interstitial substances, such as amyloid-β peptides, as well as summarize models of BBB deterioration in response to different types of insults, including acute ischemia followed by reperfusion, hypertension, and chronic hypoperfusion. Lastly, we discuss the relationship between perivascular clearance and brain disorders. PMID:26920424

  19. Uptake of radiolabeled ions in normal and ischemia-damaged brain.

    PubMed

    Dienel, G A; Pulsinelli, W A

    1986-05-01

    The regional concentrations of nine radiochemicals were measured in rat brain after induction of cerebral ischemia to identify tracers concentrated by brain undergoing selective neuronal necrosis. Transient (30 minute) forebrain ischemia was produced in the rat; 24 hours after cerebral recirculation the radiochemicals were injected intravenously and allowed to circulate for 5 hours. The brain concentrations of the radiochemicals in dissected regions were determined by scintillation counting. Forebrain ischemia of this nature will produce extensive injury to striatal neurons but will spare the great majority of neocortical neurons at 24 hours. The regional concentrations of these radiochemicals varied considerably in both control and ischemic animals. In postischemic animals, 4 radionuclides (63Ni, 99TcO4, 22Na, and [3H]tetracycline) were concentrated in the irreversibly damaged striatum in amounts ranging from 1.4 to 2.4 times greater than in normal tissue. The concentrations of 65Zn, 59Fe, 32PO4, and 147Pm in postischemic brain were similar to or less than those in normal brain. The concentration of [14C]EDTA was increased in injured and uninjured brain of postischemic rats. Autoradiographic analysis of the distribution patterns of some of these ions in normal animals showed that 99TcO4, 22Na, 65Zn, and 59Fe were distributed more uniformly throughout the brain than were 32PO4, 63Ni, and 147Pm. At 24 or 48 hours after ischemia, 63Ni, 99TcO4, and 22Na were preferentially concentrated in the damaged striatum and hippocampus, whereas 65Zn, 59Fe, 32PO4, and 147Pm did not accumulate in irreversibly injured tissue. Of the radiochemicals tested to date, Ni, TcO4, and tetracycline may be useful for diagnosing ischemic brain injury in humans, using positron emission tomography. PMID:3013076

  20. Regional brain perfusion in 10 normal dogs measured using Technetium-99m ethyl cysteinate dimer spect.

    PubMed

    Peremans, K; De Bondt, P; Audenaert, K; Van Laere, K; Gielen, I; Koole, M; Versijpt, J; Van Bree, H; Verschooten, F; Dierckx, R

    2001-01-01

    Single photon emission computed tomography (SPECT) of the brain using perfusion tracers allows estimation of regional brain perfusion. This allows in vivo examination of brain function in the setting of neuropsychologic and pathophysiologic changes. However functional imaging data on brain perfusion in dogs are limited. Hence, the aim of this study was to determine the scintigraphic regional perfusion pattern of the normal canine brain. Ten healthy shepherd type dogs were injected with 925 MBq Technetium-99m ethyl cysteinate (ECD) 20 minutes before the examination. Acquisition was performed using a triple head gamma camera equipped with fanbeam collimators. Uniform attenuation correction and triple energy window correction were applied. Computed tomographic images were obtained from the same dogs, reoriented along the orbito-meatal axis and SPECT perfusion data were coregistered to the CT-volume data. Based on morphological and suggested brain divisions, regions-of-interest (ROIs) were defined for the bilateral frontocerebral, temporocerebral, parietocerebral, occipitocerebral, cerebellar, thalamic, and striatal area. Regional count density was normalized on total counts. All dogs had the highest uptake in the thalamic/striatal area compared to a rather homogeneous cerebral uptake. No significant left/right count differences were found, but a rostro-caudal gradient (+12-13%) was present. In this group, age and gender did not influence the perfusion pattern. PMID:11768526

  1. Neuroimaging Studies of Normal Brain Development and Their Relevance for Understanding Childhood Neuropsychiatric Disorders

    PubMed Central

    Marsh, Rachel; Gerber, Andrew J.; Peterson, Bradley S.

    2009-01-01

    Objective To review the maturational events that occur during prenatal and postnatal brain development and to present neuroimaging findings from studies of healthy individuals that identify the trajectories of normal brain development. Method Histological and postmortem findings of early brain development are presented, followed by a discussion of anatomical, diffusion tensor, proton spectroscopy, and functional imaging findings from studies of healthy individuals, with special emphasis on longitudinal data. Results Early brain development occurs through a sequence of major events, beginning with the formation of the neural tube and ending with myelination. Brain development at a macroscopic level typically proceeds first in sensorimotor areas, spreading subsequently and progressively into dorsal and parietal, superior temporal, and dorsolateral prefrontal cortices throughout later childhood and adolescence. These patterns of anatomical development parallel increasing activity in frontal cortices that subserves the development of higher-order cognitive functions during late childhood and adolescence. Disturbances in these developmental patterns seem to be involved centrally in the pathogenesis of various childhood psychiatric disorders including childhood-onset schizophrenia, attention-deficit/hyperactivity disorder, developmental dyslexia, Tourette’s syndrome, and bipolar disorder. Conclusions Advances in imaging techniques have enhanced our understanding of normal developmental trajectories in the brain, which may improve insight into the abnormal patterns of development in various childhood psychiatric disorders. PMID:18833009

  2. Confirmation of Correlation between Brain Nerve Conduction Velocity and Intelligence Level in Normal Adults

    ERIC Educational Resources Information Center

    Reed, T. Edward; Vernon, Philip A.; Johnson, Andrew M.

    2004-01-01

    In 1992, Reed and Jensen ["Intelligence" 16 (1992) 259-272] reported a positive correlation (0.26; "p"= 0.002; 0.37 after correcting for restricted intelligence range) between a brain nerve conduction velocity (NCV) and intelligence level in 147 normal male students. In the first follow-up of their study, we report on a study using similar NCV…

  3. Brain gray and white matter differences in healthy normal weight and obese children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To compare brain gray and white matter development in healthy normal weight and obese children. Twenty-four healthy 8- to 10-year-old children whose body mass index was either 95th percentile (obese) completed an MRI examination which included T1-weighted three-d...

  4. Trajectories of cortical surface area and cortical volume maturation in normal brain development

    PubMed Central

    Ducharme, Simon; Albaugh, Matthew D.; Nguyen, Tuong-Vi; Hudziak, James J.; Mateos-Pérez, J.M.; Labbe, Aurelie; Evans, Alan C.; Karama, Sherif

    2015-01-01

    This is a report of developmental trajectories of cortical surface area and cortical volume in the NIH MRI Study of Normal Brain Development. The quality-controlled sample included 384 individual typically-developing subjects with repeated scanning (1–3 per subject, total scans n=753) from 4.9 to 22.3 years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models, with statistical correction for multiple comparisons using random field theory. Analyses were performed with and without controlling for total brain volume. These data are provided for reference and comparison with other databases. Further discussion and interpretation on cortical developmental trajectories can be found in the associated Ducharme et al.׳s article “Trajectories of cortical thickness maturation in normal brain development – the importance of quality control procedures” (Ducharme et al., 2015) [1]. PMID:26702424

  5. Evidence of extensive RNA oxidation in normal appearing cortex of multiple sclerosis brain.

    PubMed

    Kharel, Prakash; McDonough, Jennifer; Basu, Soumitra

    2016-01-01

    The role of reactive oxygen species (ROS) in the progression of neurodegenerative and neuroinflammatory disorders such as multiple sclerosis (MS) has been highlighted in recent years. Due to the debilitated cellular antioxidant defense mechanism in the neurons in MS, and their vulnerability to ROS effects, the cellular components in neuronal cells are susceptible to oxidative damage. The damage due to ROS in various biomolecules including proteins and DNA has already been shown in MS lesions. Using an in situ approach we have detected hitherto unidentified RNA oxidative damage in the neuronal cells of normal appearing cortex of postmortem MS brains. We analyzed the presence of oxidative damage marker nucleoside 8-hydroxyguanosine (8-OHG) to determine the presence of oxidized RNA in MS brain. Immunohistochemical analyses with anti 8-OHG antibody showed significant oxidation in the cytoplasm and to a conspicuously lesser extent in the nucleus of neuronal cells within the normal appearing cortex of MS brain, whereas similar areas were weakly immunopositive in control brain tissues. Pretreatment with RNase 1 greatly reduced the immune reaction with anti 8-OHG antibody while it was only slightly diminished by DNase I pre-treatment, indicating extensive oxidative damage in the RNA pool of MS brain. The abundance of 8-OHG, hence the high extent of RNA oxidative damage was further confirmed by immunoprecipitation and HPLC analyses of total RNA isolated from MS brain. To our knowledge, this is the first evidence of increased RNA oxidation in normal appearing cortex of MS brain. The current study begins to define the link of RNA oxidation to MS pathophysiology. PMID:26706235

  6. Normal-appearing brain tissue analysis in radiologically isolated syndrome using 3 T MRI.

    PubMed

    Labiano-Fontcuberta, Andrés; Mato-Abad, Virginia; Álvarez-Linera, Juan; Hernández-Tamames, Juan Antonio; Martínez-Ginés, María Luisa; Aladro, Yolanda; Ayuso, Lucía; Domingo-Santos, Ángela; Benito-León, Julián

    2016-07-01

    To date, it remains largely unknown whether there is in radiologically isolated syndrome (RIS) brain damage beyond visible T2 white matter lesions. We used single- voxel proton magnetic resonance spectroscopy and diffusion tensor imaging (3 T MRI) to analyze normal-appearing brain tissue regions in 18 RIS patients and 18 matched healthy controls. T2-hyperintense lesion volumes and structural brain volumes were also measured. The absolute metabolite concentrations and ratios of total N-acetylaspartate+N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamine-glutamate complex to creatine were calculated. Spectral analysis was performed by LCModel. Voxelwise morphometry analysis was performed to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Compared with healthy controls, RIS patients did not show any significant differences in either the absolute concentration of NAA or NAA/Cr ratio in mid-parietal gray matter. A trend toward lower NAA concentrations (-3.35%) was observed among RIS patients with high risk for conversion to multiple sclerosis. No differences in the other metabolites or their ratios were observed. RIS patients showed lower fractional anisotropy only in clusters overlapping lesional areas, namely in the cingulate gyrus bilaterally and the frontal lobe subgyral bilaterally (P < 0.001). Normalized brain and cortical volumes were significantly lower in RIS patients than in controls (P = 0.01 and P = 0.03, respectively). Our results suggest that in RIS, global brain and cortical atrophy are not primarily driven by significant occult microstructural normal appearing brain damage. Longitudinal MRI studies are needed to better understand the pathological processes underlying this novel entity. PMID:27399108

  7. Multi-Contrast Human Neonatal Brain Atlas: Application to Normal Neonate Development Analysis

    PubMed Central

    Oishi, Kenichi; Mori, Susumu; Donohue, Pamela K.; Ernst, Thomas; Anderson, Lynn; Buchthal, Steven; Faria, Andreia; Jiang, Hangyi; Li, Xin; Miller, Michael I.; van Zijl, Peter C.M.; Chang, Linda

    2011-01-01

    MRI is a sensitive method for detecting subtle anatomic abnormalities in the neonatal brain. To optimize the usefulness for neonatal and pediatric care, systematic research, based on quantitative image analysis and functional correlation, is required. Normalization-based image analysis is one of the most effective methods for image quantification and statistical comparison. However, the application of this methodology to neonatal brain MRI scans is rare. Some of the difficulties are the rapid changes in T1 and T2 contrasts and the lack of contrast between brain structures, which prohibits accurate cross-subject image registration. Diffusion tensor imaging (DTI), which provides rich and quantitative anatomical contrast in neonate brains, is an ideal technology for normalization–based neonatal brain analysis. In this paper, we report the development of neonatal brain atlases with detailed anatomic information derived from DTI and co-registered anatomical MRI. Combined with a diffeomorphic transformation, we were able to normalize neonatal brain images to the atlas space and three-dimensionally parcellate images into 122 regions. The accuracy of the normalization was comparable to the reliability of human raters. This method was then applied to babies of 37 to 53 post-conceptional weeks to characterize developmental changes of the white matter, which indicated a posterior-to-anterior and a central-to-peripheral direction of maturation. We expect that future applications of this atlas will include investigations of the effect of prenatal events and the effects of preterm birth or low birth weights, as well as clinical applications, such as determining imaging biomarkers for various neurological disorders. PMID:21276861

  8. R2* mapping for brain iron: associations with cognition in normal aging.

    PubMed

    Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2015-02-01

    Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined. PMID:25443291

  9. Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

    2007-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time

  10. Lactate: Brain Fuel in Human Traumatic Brain Injury: A Comparison with Normal Healthy Control Subjects

    PubMed Central

    Martin, Neil A.; Horning, Michael A.; McArthur, David L.; Hovda, David A.; Vespa, Paul; Brooks, George A.

    2015-01-01

    Abstract We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-2H2]glucose, that is, D2-glucose, and [3-13C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives. Written and informed consent was obtained from control volunteers (n=6). Patients were studied 5.7±2.2 (mean±SD) days post-injury; during periods when arterial glucose concentration tended to be higher in TBI patients. As in previous investigations, the cerebral metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly suppressed following TBI (p<0.001). However, lactate fractional extraction, an index of cerebral lactate uptake related to systemic lactate supply, approximated 11% in both healthy control subjects and TBI patients. Further, neither the CMR for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral lactate uptake differed between healthy controls and TBI patients. The percentages of lactate tracer taken up and released as 13CO2 into the JB accounted for 92% and 91% for control and TBI conditions, respectively, suggesting that most cerebral lactate uptake was oxidized following TBI. Comparisons of isotopic enrichments of lactate oxidation from infused [3-13C]lactate tracer and 13C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75–80% of 13CO2 released into the JB was from lactate and that the remainder was from the oxidation of glucose secondarily labeled from lactate. Hence, either directly as lactate uptake, or indirectly via GNG, peripheral lactate production accounted for ∼70% of carbohydrate (direct lactate uptake+uptake of glucose from lactate) consumed by the

  11. Diffusion-weighted magnetic resonance imaging of the normal canine brain.

    PubMed

    Hartmann, Antje; Söffler, Charlotte; Failing, Klaus; Schaubmar, Andreas; Kramer, Martin; Schmidt, Martin J

    2014-01-01

    Diffusion-weighted imaging (DWI) MRI has been primarily reported as a method for diagnosing cerebrovascular disease in veterinary patients. In humans, clinical applications for diffusion-weighted MRI have also included epilepsy, Alzheimer's, and Creutzfeld-Jakob disease. Before these applications can be developed in veterinary patients, more data on brain diffusion characteristics are needed. Therefore, the aim of this study was to evaluate the distribution of diffusion in the normal canine brain. Magnetic resonance imaging of the brain was performed in ten, clinically normal, purpose-bred beagle dogs. On apparent diffusion coefficient maps, regions of interest were drawn around the caudate nucleus, thalamus, piriform lobe, hippocampus, semioval center, and cerebral cortex. Statistically significant differences in mean apparent diffusion coefficient were found for the internal capsule, hippocampus, and thalamus. The highest apparent diffusion coefficient (1044.29 ± 165.21 μm(2)/s (mean ± SD (standard deviation)) was detected in the hippocampus. The lowest apparent diffusion coefficient was measured in the semioval center (721.39 ± 126.28 μm(2)/s (mean ± SD)). Significant differences in mean apparent diffusion coefficients of the caudate nucleus, thalamus, and piriform lobe were found by comparing right and left sides. Differences between brain regions may occur due to differences in myelination, neural density, or fiber orientation. The reason for the differences between right and left sides remains unclear. Data from the current study provide background for further studies of diffusion changes in dogs with brain disease. PMID:24798796

  12. Doses delivered to normal brain under different treatment protocols at Brookhaven National Laboratory

    SciTech Connect

    Capala, J.; Coderre, J.A.; Liu, H.B.

    1996-12-31

    As of October 31, 1996, 23 glioblastoma multiforme patients underwent BNCT under several treatment protocols at the Brookhaven Medical Research Reactor. For treatment planning and dosimetry purposes, these protocols may be divided into four groups. The first group comprises protocols that used an 8-cm collimator and allowed a peak normal brain dose of 10.5 Gy-Eq to avolume of 1 cm{sup 3} were the thermal neutron flux was maximal (even if it happened to be in the tumor volume). The second group differs from the first in that it allowed a peak normal brain dose of 12.6 Gy-Eq. The protocols of the third and fourth groups allowed the prescribed peak normal brain dose of 12.6 Gy-Eq to be outside of the tumor volume, used a 12-cm collimator and, respectively, uni- or bilateral irradiations. We describe the treatment planning procedures and report the doses delivered to various structures of the brain.

  13. Patterns of brain structural connectivity differentiate normal weight from overweight subjects

    PubMed Central

    Gupta, Arpana; Mayer, Emeran A.; Sanmiguel, Claudia P.; Van Horn, John D.; Woodworth, Davis; Ellingson, Benjamin M.; Fling, Connor; Love, Aubrey; Tillisch, Kirsten; Labus, Jennifer S.

    2015-01-01

    Background Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. Aim To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. Methods Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. Results 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42

  14. SOX2+ Cell Population from Normal Human Brain White Matter Is Able to Generate Mature Oligodendrocytes

    PubMed Central

    Oliver-De La Cruz, Jorge; Carrión-Navarro, Josefa; García-Romero, Noemí; Gutiérrez-Martín, Antonio; Lázaro-Ibáñez, Elisa; Escobedo-Lucea, Carmen; Perona, Rosario; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel

    2014-01-01

    Objectives A number of neurodegenerative diseases progress with a loss of myelin, which makes them candidate diseases for the development of cell-replacement therapies based on mobilisation or isolation of the endogenous neural/glial progenitor cells, in vitro expansion, and further implantation. Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial progenitor cells in the subcortical white matter of the normal adult human brain, all of which demonstrate glial progenitor features. However, the heterogeneity and differentiation potential of this pool of cells is not yet well established. Methods We used diffusion tensor images, histopathology, and immunostaining analysis to demonstrate normal cytoarchitecture and the absence of abnormalities in human temporal lobe samples from patients with mesial temporal sclerosis. These samples were used to isolate and enrich glial progenitor cells in vitro, and later to detect such cells in vivo. Results We have identified a subpopulation of SOX2+ cells, most of them co-localising with OLIG2, in the white matter of the normal adult human brain in vivo. These cells can be isolated and enriched in vitro, where they proliferate and generate immature (O4+) and mature (MBP+) oligodendrocytes and, to a lesser extent, astrocytes (GFAP+). Conclusion Our results demonstrate the existence of a new glial progenitor cell subpopulation that expresses SOX2 in the white matter of the normal adult human brain. These cells might be of use for tissue regeneration procedures. PMID:24901457

  15. Long-term influence of normal variation in neonatal characteristics on human brain development

    PubMed Central

    Walhovd, Kristine B.; Fjell, Anders M.; Brown, Timothy T.; Kuperman, Joshua M.; Chung, Yoonho; Hagler, Donald J.; Roddey, J. Cooper; Erhart, Matthew; McCabe, Connor; Akshoomoff, Natacha; Amaral, David G.; Bloss, Cinnamon S.; Libiger, Ondrej; Schork, Nicholas J.; Darst, Burcu F.; Casey, B. J.; Chang, Linda; Ernst, Thomas M.; Frazier, Jean; Gruen, Jeffrey R.; Kaufmann, Walter E.; Murray, Sarah S.; van Zijl, Peter; Mostofsky, Stewart; Dale, Anders M.; Jernigan, Terry L.; McCabe, Connor; Chang, Linda; Akshoomoff, Natacha; Newman, Erik; Dale, Anders M.; Ernst, Thomas; Dale, Anders M.; Van Zijl, Peter; Kuperman, Joshua; Murray, Sarah; Bloss, Cinnamon; Schork, Nicholas J.; Appelbaum, Mark; Gamst, Anthony; Thompson, Wesley; Bartsch, Hauke; Jernigan, Terry L.; Dale, Anders M.; Akshoomoff, Natacha; Chang, Linda; Ernst, Thomas; Keating, Brian; Amaral, David; Sowell, Elizabeth; Kaufmann, Walter; Van Zijl, Peter; Mostofsky, Stewart; Casey, B.J.; Ruberry, Erika J.; Powers, Alisa; Rosen, Bruce; Kenet, Tal; Frazier, Jean; Kennedy, David; Gruen, Jeffrey

    2012-01-01

    It is now recognized that a number of cognitive, behavioral, and mental health outcomes across the lifespan can be traced to fetal development. Although the direct mediation is unknown, the substantial variance in fetal growth, most commonly indexed by birth weight, may affect lifespan brain development. We investigated effects of normal variance in birth weight on MRI-derived measures of brain development in 628 healthy children, adolescents, and young adults in the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics study. This heterogeneous sample was recruited through geographically dispersed sites in the United States. The influence of birth weight on cortical thickness, surface area, and striatal and total brain volumes was investigated, controlling for variance in age, sex, household income, and genetic ancestry factors. Birth weight was found to exert robust positive effects on regional cortical surface area in multiple regions as well as total brain and caudate volumes. These effects were continuous across birth weight ranges and ages and were not confined to subsets of the sample. The findings show that (i) aspects of later child and adolescent brain development are influenced at birth and (ii) relatively small differences in birth weight across groups and conditions typically compared in neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder, schizophrenia, and personality disorders) may influence group differences observed in brain parameters of interest at a later stage in life. These findings should serve to increase our attention to early influences. PMID:23169628

  16. Regional Blood Flow in the Normal and Ischemic Brain Is Controlled by Arteriolar Smooth Muscle Cell Contractility and Not by Capillary Pericytes.

    PubMed

    Hill, Robert A; Tong, Lei; Yuan, Peng; Murikinati, Sasidhar; Gupta, Shobhana; Grutzendler, Jaime

    2015-07-01

    The precise regulation of cerebral blood flow is critical for normal brain function, and its disruption underlies many neuropathologies. The extent to which smooth muscle-covered arterioles or pericyte-covered capillaries control vasomotion during neurovascular coupling remains controversial. We found that capillary pericytes in mice and humans do not express smooth muscle actin and are morphologically and functionally distinct from adjacent precapillary smooth muscle cells (SMCs). Using optical imaging we investigated blood flow regulation at various sites on the vascular tree in living mice. Optogenetic, whisker stimulation, or cortical spreading depolarization caused microvascular diameter or flow changes in SMC but not pericyte-covered microvessels. During early stages of brain ischemia, transient SMC but not pericyte constrictions were a major cause of hypoperfusion leading to thrombosis and distal microvascular occlusions. Thus, capillary pericytes are not contractile, and regulation of cerebral blood flow in physiological and pathological conditions is mediated by arteriolar SMCs. PMID:26119027

  17. A longitudinal study of structural brain network changes with normal aging

    PubMed Central

    Wu, Kai; Taki, Yasuyuki; Sato, Kazunori; Qi, Haochen; Kawashima, Ryuta; Fukuda, Hiroshi

    2013-01-01

    The aim of this study was to investigate age-related changes in the topological organization of structural brain networks by applying a longitudinal design over 6 years. Structural brain networks were derived from measurements of regional gray matter volume and were constructed in age-specific groups from baseline and follow-up scans. The structural brain networks showed economical small-world properties, providing high global and local efficiency for parallel information processing at low connection costs. In the analysis of the global network properties, the local and global efficiency of the baseline scan were significantly lower compared to the follow-up scan. Moreover, the annual rate of change in local and global efficiency showed a positive and negative quadratic correlation with the baseline age, respectively; both curvilinear correlations peaked at approximately the age of 50. In the analysis of the regional nodal properties, significant negative correlations between the annual rate of change in nodal strength and the baseline age were found in the brain regions primarily involved in the visual and motor/control systems, whereas significant positive quadratic correlations were found in the brain regions predominately associated with the default-mode, attention, and memory systems. The results of the longitudinal study are consistent with the findings of our previous cross-sectional study: the structural brain networks develop into a fast distribution from young to middle age (approximately 50 years old) and eventually became a fast localization in the old age. Our findings elucidate the network topology of structural brain networks and its longitudinal changes, thus enhancing the understanding of the underlying physiology of normal aging in the human brain. PMID:23565087

  18. Effect of /sup 125/I interstitial radiotherapy on blood-brain barrier function in normal canine brain

    SciTech Connect

    Groothuis, D.R.; Wright, D.C.; Ostertag, C.B.

    1987-12-01

    Blood-brain barrier (BBB) function was studied in 14 normal dogs at time periods from 7 to 717 days after permanent insertion of 5- to 7-mCi seeds of iodine-125 (/sup 125/I) for interstitial radiation. The BBB function was measured with carbon-14-labeled alpha aminoisobutyric acid (AIB) and quantitative autoradiography, and expressed as a unidirectional blood-to-brain transfer constant, K. The /sup 125/I radiation lesions consisted of three concentric histologically and functionally distinct zones: 1) a central zone of calcified necrosis; 2) a spongy fluid-filled zone; and 3) a narrow rim (2.6 +/- 0.6 mm wide) of viable brain tissue with increased permeability. Within this rim, the mean value of the K of AIB was 5.8 times that of normal cortex. Over the 7- to 392-day time period the value of K remained rather constant, and by 716 days K values had returned to normal. There was moderate regional variation in the value of K; it was highest in the white matter and lowest in the gray matter surrounding the radiation lesion. The radiation lesion progressively increased in size from 7 to 80 days, after which there was little change. This study illustrates that the geographically circumscribed radiation from /sup 125/I seeds is accompanied by similarly well-defined changes in BBB function, which may persist for over 1 year following insertion of the /sup 125/I seed. This altered BBB function is probably responsible for the cerebral edema associated with /sup 125/I interstitial radiotherapy.

  19. Cranial index of children with normal and abnormal brain development in Sokoto, Nigeria: A comparative study

    PubMed Central

    Musa, Muhammad Awwal; Zagga, Abdullahi Daudu; Danfulani, Mohammed; Tadros, Aziz Abdo; Ahmed, Hamid

    2014-01-01

    Background: Abnormal brain development due to neurodevelopmental disorders in children has always been an important concern, but yet has to be considered as a significant public health problem, especially in the low- and middle-income countries including Nigeria. Aims: The aim of this study is to determine whether abnormal brain development in the form of neurodevelopmental disorders causes any deviation in the cranial index of affected children. Materials and Methods: This is a comparative study on the head length, head width, and cranial index of 112 children (72 males and 40 females) diagnosed with at least one abnormal problem in brain development, in the form of a neurodevelopmental disorder (NDD), in comparison with that of 218 normal growing children without any form of NDD (121 males and 97 females), aged 0-18 years old seen at the Usmanu Danfodiyo University Teaching Hospital, Sokoto, over a period of six months, June to December, 2012. The head length and head width of the children was measured using standard anatomical landmarks and cranial index calculated. The data obtained was entered into the Microsoft excel worksheet and analyzed using SPSS version 17. Results: The mean Cephalic Index for normal growing children with normal brain development was 79.82 ± 3.35 and that of the children with abnormal brain development was 77.78 ± 2.95 and the difference between the two groups was not statistically significant (P > 0.05). Conclusion: It can be deduced from this present study that the cranial index does not change in children with neurodevelopmental disorders. PMID:24966551

  20. Classification of normal and pathological aging processes based on brain MRI morphology measures

    NASA Astrophysics Data System (ADS)

    Perez-Gonzalez, J. L.; Yanez-Suarez, O.; Medina-Bañuelos, V.

    2014-03-01

    Reported studies describing normal and abnormal aging based on anatomical MRI analysis do not consider morphological brain changes, but only volumetric measures to distinguish among these processes. This work presents a classification scheme, based both on size and shape features extracted from brain volumes, to determine different aging stages: healthy control (HC) adults, mild cognitive impairment (MCI), and Alzheimer's disease (AD). Three support vector machines were optimized and validated for the pair-wise separation of these three classes, using selected features from a set of 3D discrete compactness measures and normalized volumes of several global and local anatomical structures. Our analysis show classification rates of up to 98.3% between HC and AD; of 85% between HC and MCI and of 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indexes to classify different aging stages.

  1. CSF Flow in the Brain in the Context of Normal Pressure Hydrocephalus.

    PubMed

    Bradley, W G

    2015-05-01

    CSF normally flows back and forth through the aqueduct during the cardiac cycle. During systole, the brain and intracranial vasculature expand and compress the lateral and third ventricles, forcing CSF craniocaudad. During diastole, they contract and flow through the aqueduct reverses. Hyperdynamic CSF flow through the aqueduct is seen when there is ventricular enlargement without cerebral atrophy. Therefore, patients presenting with clinical normal pressure hydrocephalus who have hyperdynamic CSF flow have been found to respond better to ventriculoperitoneal shunting than those with normal or decreased CSF flow. Patients with normal pressure hydrocephalus have also been found to have larger intracranial volumes than sex-matched controls, suggesting that they may have had benign external hydrocephalus as infants. While their arachnoidal granulations clearly have decreased CSF resorptive capacity, it now appears that this is fixed and that the arachnoidal granulations are not merely immature. Such patients appear to develop a parallel pathway for CSF to exit the ventricles through the extracellular space of the brain and the venous side of the glymphatic system. This pathway remains functional until late adulthood when the patient develops deep white matter ischemia, which is characterized histologically by myelin pallor (ie, loss of lipid). The attraction between the bare myelin protein and the CSF increases resistance to the extracellular outflow of CSF, causing it to back up, resulting in hydrocephalus. Thus idiopathic normal pressure hydrocephalus appears to be a "2 hit" disease: benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood. PMID:25355813

  2. Brain regional angiogenic potential at the neurovascular unit during normal aging

    PubMed Central

    Murugesan, Nivetha; Demarest, Tyler G.; Madri, Joseph A.; Pachter, Joel S.

    2011-01-01

    Given strong regional specialization of the brain, cerebral angiogenesis may be regionally modified during normal aging. To test this hypothesis, expression of a broad cadre of angiogenesis-associated genes was assayed at the neurovascular unit (NVU) in discrete brain regions of young vs. aged mice by laser capture microdissection coupled to quantitative real-time PCR. Complementary quantitative capillary density/branching studies were performed as well. Effects of physical exercise were also assayed to determine if age-related trends could be reversed. Additionally, gene response to hypoxia was probed to highlight age-associated weaknesses in adapting to this angiogenic stress. Aging impacted resting expression of angiogenesis-associated genes at the NVU in a region-dependent manner. Physical exercise reversed some of these age-associated gene trends, as well as positively influenced cerebral capillary density/branching in a region-dependent way. Lastly, hypoxia revealed a weaker angiogenic response in aged brain. These results suggest heterogeneous changes in angiogenic capacity of the brain during normal aging, and imply a therapeutic benefit of physical exercise that acts at the level of the NVU. PMID:22019053

  3. Characterizing structural association alterations within brain networks in normal aging using Gaussian Bayesian networks

    PubMed Central

    Guo, Xiaojuan; Wang, Yan; Chen, Kewei; Wu, Xia; Zhang, Jiacai; Li, Ke; Jin, Zhen; Yao, Li

    2014-01-01

    Recent multivariate neuroimaging studies have revealed aging-related alterations in brain structural networks. However, the sensory/motor networks such as the auditory, visual and motor networks, have obtained much less attention in normal aging research. In this study, we used Gaussian Bayesian networks (BN), an approach investigating possible inter-regional directed relationship, to characterize aging effects on structural associations between core brain regions within each of these structural sensory/motor networks using volumetric MRI data. We then further examined the discriminability of BN models for the young (N = 109; mean age =22.73 years, range 20–28) and old (N = 82; mean age =74.37 years, range 60–90) groups. The results of the BN modeling demonstrated that structural associations exist between two homotopic brain regions from the left and right hemispheres in each of the three networks. In particular, compared with the young group, the old group had significant connection reductions in each of the three networks and lesser connection numbers in the visual network. Moreover, it was found that the aging-related BN models could distinguish the young and old individuals with 90.05, 73.82, and 88.48% accuracy for the auditory, visual, and motor networks, respectively. Our findings suggest that BN models can be used to investigate the normal aging process with reliable statistical power. Moreover, these differences in structural inter-regional interactions may help elucidate the neuronal mechanism of anatomical changes in normal aging. PMID:25324771

  4. Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice.

    PubMed

    Smith, Carli J; Emge, Jacob R; Berzins, Katrina; Lung, Lydia; Khamishon, Rebecca; Shah, Paarth; Rodrigues, David M; Sousa, Andrew J; Reardon, Colin; Sherman, Philip M; Barrett, Kim E; Gareau, Mélanie G

    2014-10-15

    The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1(-/-) mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis. PMID:25190473

  5. Periodontal disease associates with higher brain amyloid load in normal elderly

    PubMed Central

    Kamer, Angela R.; Pirraglia, Elizabeth; Tsui, Wai; Rusinek, Henry; Vallabhajosula, Shankar; Mosconi, Lisa; Yi, Li; McHugh, Pauline; Craig, Ronald G.; Svetcov, Spencer; Linker, Ross; Shi, Chen; Glodzik, Lidia; Williams, Schantel; Corby, Patricia; Saxena, Deepak; de Leon, Mony J.

    2015-01-01

    Background The accumulation of amyloid β plaques (Aβ) is a central feature of Alzheimer’s disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory/infectious conditions in humans can promote Aβ brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD. Methods Thirty-eight cognitively normal, healthy, community residing elderly (mean age 61; 68% female) were examined in an Alzheimer’s Disease research center and a University-based Dental School. Linear regression models (adjusted for age, ApoE and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Aβ load using 11C-PIB PET imaging. Results After adjusting for confounders, clinical attachment loss (≥ 3mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased 11C-PIB uptake in Aβ vulnerable brain regions (p=0.002). Conclusion We show for the first time in humans an association between periodontal disease and brain Aβ load. These data are consistent with prior animal studies showing that peripheral inflammation/infections are sufficient to produce brain Aβ accumulations. PMID:25491073

  6. Expression and distribution of carboxypeptidase B in the hippocampal subregions of normal and Alzheimer's disease brain.

    PubMed

    Papp, Henrietta; Török, I; Matsumoto, A; Enomoto, T; Matsuyama, S; Kása, P

    2003-01-01

    Earlier neurochemical studies suggested that human brain carboxypeptidase B may play a significant role in the degradation of amyloid-beta1-42 in the brain. Using an immimohistochemical technique we report here on the neuronal expression and distribution of this enzyme in the segments (CA1a, CA1b and CA1c) of the CA1 subfield and in area CA4 of the hippocampus in normal and Alzheimer's disease brain samples. Its distribution was compared with the appearance of neurofibrillary tangles in the same brain sample. For immunohistochemical localization of carboxypeptidase B, a specific C14-module antibody was applied, together with the Gallyas silver impregnation technique for the demonstration of neurofibrillary tangles. The results revealed that, in the control samples, most of the immunoreactivity appeared in segment CA1a in the pyramidal cells, less in segment CA1b and least in segment CA1c. In the Alzheimer's disease samples, there was no particular immunostaining in the neurons, but, a large number of silver-impregnated degenerated neurons appeared. The results support the suggestion that carboxypeptidase B may play a significant role in elimination of the intracellular accumulation and toxicity of amyloid-beta in the human brain and thereby protect the neurons from degeneration. PMID:12705322

  7. Delineating Normal from Diseased Brain by Aminolevulinic Acid-Induced Fluorescence

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Stummer, Walter

    5-Aminolevulinic acid (5-ALA) as a precursor of protoporphyrin IX (PpIX) has been established as an orally applied drug to guide surgical resection of malignant brain tumors by exciting the red fluorescence of PpIX. The accumulation of PpIX in glioblastoma multiforme (GBM) is highly selective and provides excellent contrast to normal brain when using surgical microscopes with appropriately filtered light sources and cameras. The positive predictive value of fluorescent tissue is very high, enabling safe gross total resection of GBM and other brain tumors and improving prognosis of patients. Compared to other intraoperative techniques that have been developed with the aim of increasing the rate of safe gross total resections of malignant gliomas, PpIX fluorescence is considerably simpler, more cost effective, and comparably reliable. We present the basics of 5-ALA-based fluorescence-guided resection, and discuss the clinical results obtained for GBM and the experience with the fluorescence staining of other primary brain tumors and metastases as well as the results for spinal cord tumors. The phototoxicity of PpIX, increasingly used for photodynamic therapy of brain tumors, is mentioned briefly in this chapter.

  8. Chronic histological effects of ultrasonic hyperthermia on normal feline brain tissue.

    PubMed

    Lyons, B E; Obana, W G; Borcich, J K; Kleinman, R; Singh, D; Britt, R H

    1986-05-01

    The histopathological changes associated with ultrasonic heating of normal cat brain have been correlated with thermal distributions. Ultrasound energy was applied for 50 min at different intensities to generate tissue temperatures from 42 to 48 degrees C. Animals were sacrificed at various intervals from 1 to 56 days. The organization and resolution of thermal damage was characterized by three stages of histopathological changes within the nervous tissue. The acute stage (Days 1-3) was defined by (1) extensive coagulation necrosis, (2) pyknosis of neuronal elements in the gray matter, (3) edema and vacuolation in the white matter, and (4) polymorphonuclear leukocytes. The subacute stage (Days 3-21) was characterized by (1) the appearance of lipid-laden macrophages, (2) liquefaction of the necrotic regions, (3) fibroblastic proliferation, and (4) vascular proliferation with some perivascular inflammatory infiltration (lymphocytes). Lastly, the chronic stage (Days 21-56) was defined by (1) fibrosis (reticulin and collagen formation) and (2) gliosis (reactive astrocytic proliferation) occurring around the fluid-filled necrotic center. Analysis of these data has also included a study of the lesion size versus the dose (temperature for 50 min) of heating. The results demonstrate a significant linear dose-response correlation. The results of this study indicate that the histological appearance and time course of repair of thermal injury in the normal brain tissue are analogous to acute brain necrosis resulting from cerebral infarction, except the thermal damage does not result in significant hemorrhage. PMID:3704114

  9. SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

    SciTech Connect

    Hossain, S; Hildebrand, K; Ahmad, S; Larson, D; Ma, L; Sahgal, A

    2014-06-01

    Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targets were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.

  10. Nonlinear time course of brain volume loss in cognitively normal and impaired elders

    PubMed Central

    Schuff, Norbert; Tosun, Duygu; Insel, Philip S.; Chiang, Gloria C.; Truran, Diana; Aisen, Paul S.; Jack, Clifford R; Weiner, Michael W.

    2010-01-01

    The goal was to elucidate the time course of regional brain atrophy rates relative to age in cognitively normal (CN) aging, mild cognitively impairment (MCI) and Alzheimer’s disease (AD), without a-priori models for atrophy progression. Regional brain volumes from 147 CN subjects, 164 stable MCI, 93 MCI-to-AD converters and 111 AD patients, between 51 to 91 years old and who had repeated 1.5T magnetic resonance imaging (MRI) scans over 30 months, were analyzed. Relations between regional brain volume change and age were determined using generalized additive models, an established non-parametric concept for approximating nonlinear relations. Brain atrophy rates varied nonlinearly with age, predominantly in regions of the temporal lobe. Moreover, the atrophy rates of some regions leveled off with increasing age in control and stable MCI subjects whereas those rates progressed further in MCI-to-AD converters and AD patients. The approach has potential uses for early detection of AD and differentiation between stable and progressing MCI. PMID:20855131

  11. Normal Brain Response to Propofol in Advance of Recovery from Unresponsive Wakefulness Syndrome

    PubMed Central

    Blain-Moraes, Stefanie; Boshra, Rober; Ma, Heung Kan; Mah, Richard; Ruiter, Kyle; Avidan, Michael; Connolly, John F.; Mashour, George A.

    2016-01-01

    Up to 40% of individuals with unresponsive wakefulness syndrome (UWS) actually might be conscious. Recent attempts to detect covert consciousness in behaviorally unresponsive patients via neurophysiological patterns are limited by the need to compare data from brain-injured patients to healthy controls. In this report, we pilot an alternative within-subject approach by using propofol to perturb the brain state of a patient diagnosed with UWS. An auditory stimulation series was presented to the patient before, during, and after exposure to propofol while high-density electroencephalograph (EEG) was recorded. Baseline analysis revealed residual markers in the continuous EEG and event-related potentials (ERPs) that have been associated with conscious processing. However, these markers were significantly distorted by the patient’s pathology, challenging the interpretation of their functional significance. Upon exposure to propofol, changes in EEG characteristics were similar to what is seen in healthy individuals and ERPs associated with conscious processing disappeared. At the 1-month follow up, the patient had regained consciousness. We offer three alternative explanations for these results: (1) the patient was covertly consciousness, and was anesthetized by propofol administration; (2) the patient was unconscious, and the observed EEG changes were a propofol-specific phenomenon; and (3) the patient was unconscious, but his brain networks responded normally in a way that heralded the possibility of recovery. These alternatives will be tested in a larger study, and raise the intriguing possibility of using a general anesthetic as a probe of brain states in behaviorally unresponsive patients. PMID:27313518

  12. Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat

    NASA Technical Reports Server (NTRS)

    Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.

    1986-01-01

    The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.

  13. Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer’s disease

    PubMed Central

    Rosario, Emily R.; Chang, Lilly; Head, Elizabeth H.; Stanczyk, Frank Z.; Pike, Christian J.

    2009-01-01

    We examined the relationships between normal aging, Alzheimer’s disease (AD), and brain levels of sex steroid hormones in men and women. In postmortem brain tissue from neuropathologically normal, postmenopausal women, we found no age-related changes in brain levels of either androgens or estrogens. In comparing women with and without AD at different ages, brain levels of estrogens and androgens were lower in AD cases aged 80 years and older but not significantly different in the 60–79 year age range. In male brains, we observed that normal aging was associated with significant decreases in androgens but not estrogens. Further, in men aged 60–79 years, brain levels of testosterone but not estrogens were lower in cases with mild neuropathological changes as well as those with advanced AD neuropathology. In male cases over age 80, brain levels hormones did not significantly vary by neuropathological status. To begin investigating the relationships between hormone levels and indices of AD neuropathology, we measured brain levels of soluble β-amyloid (Aβ). In male cases with mild neuropathological changes, we found an inverse relationship between brain levels of testosterone and soluble Aβ. Collectively, these findings demonstrate sex-specific relationships between normal, age-related depletion of androgens and estrogens in men and women, which may be relevant to development of AD. PMID:19428144

  14. Normalization of coagulopathy is associated with improved outcome after isolated traumatic brain injury.

    PubMed

    Epstein, Daniel S; Mitra, Biswadev; Cameron, Peter A; Fitzgerald, Mark; Rosenfeld, Jeffrey V

    2016-07-01

    Acute traumatic coagulopathy (ATC) has been reported in the setting of isolated traumatic brain injury (iTBI) and is associated with poor outcomes. We aimed to evaluate the effectiveness of procoagulant agents administered to patients with ATC and iTBI during resuscitation, hypothesizing that timely normalization of coagulopathy may be associated with a decrease in mortality. A retrospective review of the Alfred Hospital trauma registry, Australia, was conducted and patients with iTBI (head Abbreviated Injury Score [AIS] ⩾3 and all other body AIS <3) and coagulopathy (international normalized ratio ⩾1.3) were selected for analysis. Data on procoagulant agents used (fresh frozen plasma, platelets, cryoprecipitate, prothrombin complex concentrates, tranexamic acid, vitamin K) were extracted. Among patients who had achieved normalization of INR or survived beyond 24hours and were not taking oral anticoagulants, the association of normalization of INR and death at hospital discharge was analyzed using multivariable logistic regression analysis. There were 157 patients with ATC of whom 68 (43.3%) received procoagulant products within 24hours of presentation. The median time to delivery of first products was 182.5 (interquartile range [IQR] 115-375) minutes, and following administration of coagulants, time to normalization of INR was 605 (IQR 274-1146) minutes. Normalization of INR was independently associated with significantly lower mortality (adjusted odds ratio 0.10; 95% confidence interval 0.03-0.38). Normalization of INR was associated with improved mortality in patients with ATC in the setting of iTBI. As there was a substantial time lag between delivery of products and eventual normalization of coagulation, specific management of coagulopathy should be implemented as early as possible. PMID:26947341

  15. Resting-state activity in development and maintenance of normal brain function

    PubMed Central

    Pizoli, Carolyn E.; Snyder, Abraham Z.; Shimony, Joshua S.; Limbrick, David D.; Schlaggar, Bradley L.; Smyth, Matthew D.

    2011-01-01

    One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level–dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization. PMID:21709227

  16. Construction and Validation of Brain MRI Templates from a Korean Normal Elderly Population

    PubMed Central

    Lee, Hyunna; Yoo, Byung Il; Han, Ji Won; Lee, Jung Jae; Oh, San Yeo Wool; Lee, Eun Young; Kim, Jae Hyoung

    2016-01-01

    Objective This study aimed to construct a Korean normal elderly brain template (KNE96) using Korean elderly individuals for use in brain MRI studies and to validate it. Methods We used high-resolution 3.0T T1 structural MR images from 96 Korean normal elderly individuals (M/F=48/48), aged 60 years or older (M=69.5±6.2 years, F=70.1±7.0 years), for constructing the KNE96 template. The KNE96 template was validated by comparing the registration-induced deformations between the KNE96 and ICBM152 templates using different MR images from 48 Korean normal elderly individuals (M/F=24/24), aged 60 years or older (M=71.5±5.9 years, F=72.8±5.1 years). We used the magnitude of displacement vectors (mag-displacement) and log of Jacobian determinants (log-Jacobian) to quantify the deformation produced during registration process to templates. Results The mag-displacement and log-Jacobian of the registration were much smaller using the KNE96 template than with the ICBM152 template in most brain regions. There was a prominent difference in the significant averaged differences (SADs) of the mag-displacement and log-Jacobian between the KNE96 and ICBM152 at the superior, medial, and middle frontal gyrus, the lingual, inferior, middle, and superior occipital gyrus, and the caudate and thalamus. Conclusion This study suggests that templates constructed from Asian populations, such as the KNE96, may be more desirable than those from Caucasian populations, like the ICBM152, in computational neuroimaging studies that measure and compare anatomical features of the frontal and occipital lobe, thalamus and caudate. PMID:26766956

  17. Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.

    PubMed

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban

    2012-06-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. PMID:22484141

  18. Clinical NMR imaging of the brain in children: normal and neurologic disease

    SciTech Connect

    Johnson, M.A,; Pennock, J.M.; Bydder, G.M.; Steiner, R.E.; Thomas, D.J.; Hayward, R.; Bryant, D.R.T.; Payne, J.A.; Levene, M.I.; Whitelaw, A.; Dubowitz, L.M.S.; Dubowitz, V.

    1983-11-01

    The results of initial clinical nuclear magnetic resonance imaging of the brain in eight normal and 52 children with a wide variety of neurologic diseases were reviewed. The high level of gray-white matter contrast available with inversion-recovery sequences provided a basis for visualizing normal myelination as well as delays or deficits in this process. The appearances seen in cases of parenchymal hemorrhage, cerebral infarction, and proencephalic cysts are described. Ventricular enlargement was readily identified and marginal edema was demonstrated with spin-echo sequences. Abnormalities were seen in cerebral palsy, congenital malformations, Hallervorden-Spatz disease, aminoaciduria, and meningitis. Space-occupying lesions were identified by virtue of their increased relaxation times and mass effects. Nuclear magnetic resonance imaging has considerable potential in pediatric neuroradiologic practice, in some conditions supplying information not available by computed tomography or sonography.

  19. Pain perception and brain evoked potentials in patients with angina despite normal coronary angiograms.

    PubMed Central

    Frøbert, O.; Arendt-Nielsen, L.; Bak, P.; Funch-Jensen, P.; Peder Bagger, J.

    1996-01-01

    OBJECTIVE: To evaluate the role of nociception in patients with angina despite normal coronary angiograms and to investigate whether any abnormality is confined to visceral or somatosensory perception. METHODS: Perception, pain threshold, and brain evoked potentials to nociceptive electrical stimuli of the oesophageal mucosa and the sternal skin were investigated in 10 patients who had angina but normal coronary angiograms, no other signs of cardiac disease, and normal upper endoscopy. Controls were 10 healthy volunteers. The peaks of the evoked potential signal were designated N for negative deflections and P for positive. Numbers were given to the peaks in order of appearance after the stimulus. The peak to peak amplitudes (P1/N1, N1/P2) were measured in microV. RESULTS: (1) Angina pectoris was provoked in seven patients following continuous oesophageal stimulation. (2) Distant projection of pain occurred after continuous electrical stimulation of the oesophagus in four patients and in no controls. (3) Patients had higher oesophageal pain thresholds (median 16.3 mA v 7.3 mA, P = 0.02) to repeated stimuli than controls, whereas the values did not differ with respect to the skin. There were no intergroup differences in thresholds to single stimuli. (4) Patients had substantially reduced brain evoked potential amplitudes after both single oesophageal (P1/N1, median values: 7.2 microV, controls: 29.0 microV; N1/P2: 16.5 microV, controls: 66.0 microV; P < 0.001 for both) and skin (N1/P2: 13.5 microV; controls: 76.0 microV; P < 0.001) stimuli despite the similar pain thresholds. CONCLUSION: Central nervous system responses to visceral and somatosensory nociceptive input are altered in patients who have angina despite normal coronary angiograms. PMID:8665332

  20. Quantitation of normal metabolite concentrations in six brain regions by in-vivoH-MR spectroscopy.

    PubMed

    Minati, Ludovico; Aquino, Domenico; Bruzzone, Maria Grazia; Erbetta, Alessandra

    2010-07-01

    This study examined the concentrations of brain metabolites visible to in-vivo(1)H-Magnetic Resonance Spectroscopy ((1)H-MRS) at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal reference and using an external reference; metabolite signal intensity ratios with respect to creatine were also calculated. The inter-individual variability was smaller for absolute concentrations (internal reference) as compared to that for signal intensity ratios. Significant regional variability in concentration was found for all metabolites, indicating that separate normative values are needed for different brain regions. The values obtained in this study can be used as reference in future studies, provided the same methodology is followed; it is confirmed that despite unsuccessful attempts in the past, smaller coefficients of variation can indeed be obtained through absolute quantification. PMID:20927223

  1. Opposite roles of apolipoprotein E in normal brains and in Alzheimer’s disease

    PubMed Central

    Russo, Claudio; Angelini, Giovanna; Dapino, Debora; Piccini, Alessandra; Piombo, Giuseppe; Schettini, Gennaro; Chen, Shu; Teller, Jan K.; Zaccheo, Damiano; Gambetti, Pierluigi; Tabaton, Massimo

    1998-01-01

    We have characterized the interaction between apolipoprotein E (apoE) and amyloid β peptide (Aβ) in the soluble fraction of the cerebral cortex of Alzheimer’s disease (AD) and control subjects. Western blot analysis with specific antibodies identified in both groups a complex composed of the full-length apoE and Aβ peptides ending at residues 40 and 42. The apoE–Aβ soluble aggregate is less stable in AD brains than in controls, when treated with the anionic detergent SDS. The complex is present in significantly higher quantity in control than in AD brains, whereas in the insoluble fraction an inverse correlation has previously been reported. Moreover, in the AD subjects the Aβ bound to apoE is more sensitive to protease digestion than is the unbound Aβ. Taken together, our results indicate that in normal brains apoE efficiently binds and sequesters Aβ, preventing its aggregation. In AD, the impaired apoE–Aβ binding leads to the critical accumulation of Aβ, facilitating plaque formation. PMID:9861015

  2. Opposite roles of apolipoprotein E in normal brains and in Alzheimer's disease.

    PubMed

    Russo, C; Angelini, G; Dapino, D; Piccini, A; Piombo, G; Schettini, G; Chen, S; Teller, J K; Zaccheo, D; Gambetti, P; Tabaton, M

    1998-12-22

    We have characterized the interaction between apolipoprotein E (apoE) and amyloid beta peptide (Abeta) in the soluble fraction of the cerebral cortex of Alzheimer's disease (AD) and control subjects. Western blot analysis with specific antibodies identified in both groups a complex composed of the full-length apoE and Abeta peptides ending at residues 40 and 42. The apoE-Abeta soluble aggregate is less stable in AD brains than in controls, when treated with the anionic detergent SDS. The complex is present in significantly higher quantity in control than in AD brains, whereas in the insoluble fraction an inverse correlation has previously been reported. Moreover, in the AD subjects the Abeta bound to apoE is more sensitive to protease digestion than is the unbound Abeta. Taken together, our results indicate that in normal brains apoE efficiently binds and sequesters Abeta, preventing its aggregation. In AD, the impaired apoE-Abeta binding leads to the critical accumulation of Abeta, facilitating plaque formation. PMID:9861015

  3. Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue

    PubMed Central

    Lilge, L; Portnoy, M; Wilson, B C

    2000-01-01

    The apoptotic response of normal brain and intracranial VX2 tumour following photodynamic therapy (PDT) mediated by 5 different photosensitizers (Photofrin, 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chloroaluminium phthalocyanine (AlCIPc), Tin Ethyl Etiopurpurin (SnET 2), and meta-tetra(hydroxyphenyl)chlorin (m THPC)) was evaluated following a previous analysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apoptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis and determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinkage, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any detectable apoptosis, while the other photosensitizers produced varying numbers of apoptotic cells near the region of coagulative necrosis. The apoptotic response did not appear to be related to photosensitizer dose. These results suggest that at this time point, a minimal and fairly localized apoptotic effect is produced in brain tissues, the extent of which depends largely on the particular photosensitizer. © 2000 Cancer Research Campaign PMID:10993661

  4. Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue.

    PubMed

    Lilge, L; Portnoy, M; Wilson, B C

    2000-10-01

    The apoptotic response of normal brain and intracranial VX2 tumour following photodynamic therapy (PDT) mediated by 5 different photosensitizers (Photofrin, 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chloroaluminium phthalocyanine (AlCIPc), Tin Ethyl Etiopurpurin (SnET(2)), and meta -tetra(hydroxyphenyl)chlorin (m THPC)) was evaluated following a previous analysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apoptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis and determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinkage, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any detectable apoptosis, while the other photosensitizers produced varying numbers of apoptotic cells near the region of coagulative necrosis. The apoptotic response did not appear to be related to photosensitizer dose. These results suggest that at this time point, a minimal and fairly localized apoptotic effect is produced in brain tissues, the extent of which depends largely on the particular photosensitizer. PMID:10993661

  5. Regional distribution of potassium, calcium, and six trace elements in normal human brain

    SciTech Connect

    Duflou, H.; Maenhaut, W.; De Reuck, J. )

    1989-11-01

    Eight elements (i.e. K, Ca, Mn, Fe, Cu, Zn, Se, and Rb) were measured in 50 different regions of 12 normal human brains by particle-induced X-ray emission (PIXE) analysis. The dry weight concentrations of K, Fe, Cu, Zn, Se, and Rb were consistently higher for gray than for white matter areas. The K, Zn and Se concentrations for the regions of mixed composition and, to some extent, also the Rb concentrations, were intermediate between the gray and white matter values, and they tended to decrease with decreasing neuron density. The mean dry weight concentrations of K, Ca, Zn, Se, and Rb in the various brain regions were highly correlated with the mean wet-to-dry weight ratios of these regions. For Mn, Fe, and Cu, however, such a correlation was not observed, and these elements exhibited elevated levels in several structures of the basal ganglia. For K, Fe, and Se the concentrations seemed to change with age. A hierarchical cluster analysis indicated that the structures clustered into two large groups, one comprising gray and mixed matter regions, the other white and mixed matter areas. Brain structures involved in the same physiological function or morphologically similar regions often conglomerated in a single subcluster.

  6. Effects of active music therapy on the normal brain: fMRI based evidence.

    PubMed

    Raglio, Alfredo; Galandra, Caterina; Sibilla, Luisella; Esposito, Fabrizio; Gaeta, Francesca; Di Salle, Francesco; Moro, Luca; Carne, Irene; Bastianello, Stefano; Baldi, Maurizia; Imbriani, Marcello

    2016-03-01

    The aim of this study was to investigate the neurophysiological bases of Active Music Therapy (AMT) and its effects on the normal brain. Twelve right-handed, healthy, non-musician volunteers were recruited. The subjects underwent 2 AMT sessions based on the free sonorous-music improvisation using rhythmic and melodic instruments. After these sessions, each subject underwent 2 fMRI scan acquisitions while listening to a Syntonic (SP) and an A-Syntonic (AP) Production from the AMT sessions. A 3 T Discovery MR750 scanner with a 16-channel phased array head coil was used, and the image analysis was performed with Brain Voyager QX 2.8. The listening to SP vs AP excerpts mainly activated: (1) the right middle temporal gyrus and right superior temporal sulcus, (2) the right middle frontal gyrus and in particular the right precentral gyrus, (3) the bilateral precuneus, (4) the left superior temporal sulcus and (5) the left middle temporal gyrus. These results are consistent with the psychological bases of the AMT approach and with the activation of brain areas involved in memory and autobiographical processes, and also in personal or interpersonal significant experiences. Further studies are required to confirm these findings and to explain possible effects of AMT in clinical settings. PMID:25847861

  7. Voxel-based Morphometry of Brain MRI in Normal Aging and Alzheimer's Disease.

    PubMed

    Matsuda, Hiroshi

    2013-02-01

    Voxel-based morphometry (VBM) using structural brain MRI has been widely used for assessment of normal aging and Alzheimer's disease (AD). VBM of MRI data comprises segmentation into gray matter, white matter, and cerebrospinal fluid partitions, anatomical standardization of all the images to the same stereotactic space using linear affine transformation and further non-linear warping, smoothing, and finally performing a statistical analysis. Two techniques for VBM are commonly used, optimized VBM using statistical parametric mapping (SPM) 2 or SPM5 with non-linear warping based on discrete cosine transforms and SPM8 plus non-linear warping based on diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL). In normal aging, most cortical regions prominently in frontal and insular areas have been reported to show age-related gray matter atrophy. In contrast, specific structures such as amygdala, hippocampus, and thalamus have been reported to be preserved in normal aging. On the other hand, VBM studies have demonstrated progression of atrophy mapping upstream to Braak's stages of neurofibrillary tangle deposition in AD. The earliest atrophy takes place in medial temporal structures. Stand-alone VBM software using SPM8 plus DARTEL running on Windows has been newly developed as an adjunct to the clinical assessment of AD. This software provides a Z-score map as a consequence of comparison of a patient's MRI with a normal database. PMID:23423504

  8. Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain.

    PubMed

    Does, Mark D; Parsons, Edward C; Gore, John C

    2003-02-01

    Oscillating gradients were used to probe the diffusion-time/frequency dependence of water diffusion in the gray matter of normal and globally ischemic rat brain. In terms of a conventional definition of diffusion time, the oscillating gradient measurements provided the apparent diffusion coefficient (ADC) of water with diffusion times between 9.75 ms and 375 micros, an order of magnitude shorter than previously studied in vivo. Over this range, ADCs increased as much as 24% in vivo and 50% postmortem, depending on the nature of the oscillating gradient waveform used. Novel waveforms were employed to sample narrow frequency bands of the so-called diffusion spectrum. This spectral description of ADC includes the effects of restriction and/or flow, and is independent of experimental parameters, such as diffusion time. The results in rat brain were found to be consistent with restricted diffusion and the known micro-anatomy of gray matter. Differences between normal and postmortem data were consistent with an increase in water restriction and/or a decrease in flow, and tentatively suggest that physical changes following the onset of ischemia occur on a scale of about 2 microm, similar to a typical cellular dimension in gray matter. PMID:12541239

  9. A computational model of oxygen transport in the cerebrocapillary levels for normal and pathologic brain function

    PubMed Central

    Safaeian, Navid; David, Tim

    2013-01-01

    The oxygen exchange and correlation between the cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO2) in the cortical capillary levels for normal and pathologic brain functions remain the subject of debate. A 3D realistic mesoscale model of the cortical capillary network (non-tree like) is constructed using a random Voronoi tessellation in which each edge represents a capillary segment. The hemodynamics and oxygen transport are numerically simulated in the model, which involves rheological laws in the capillaries, oxygen diffusion, and non-linear binding of oxygen to hemoglobin, respectively. The findings show that the cerebral hypoxia due to a significant decreased perfusion (as can occur in stroke) can be avoided by a moderate reduction in oxygen demand. Oxygen extraction fraction (OEF) can be an important indicator for the brain oxygen metabolism under normal perfusion and misery-perfusion syndrome (leading to ischemia). The results demonstrated that a disproportionately large increase in blood supply is required for a small increase in the oxygen demand, which, in turn, is strongly dependent on the resting OEF. The predicted flow-metabolism coupling in the model supports the experimental studies of spatiotemporal stimulations in humans by positron emission tomography and functional magnetic resonance imaging. PMID:23921901

  10. Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer's disease

    PubMed Central

    Lipinski, Marta M.; Zheng, Bin; Lu, Tao; Yan, Zhenyu; Py, Bénédicte F.; Ng, Aylwin; Xavier, Ramnik J.; Li, Cheng; Yankner, Bruce A.; Scherzer, Clemens R.; Yuan, Junying

    2010-01-01

    Dysregulation of autophagy, a cellular catabolic mechanism essential for degradation of misfolded proteins, has been implicated in multiple neurodegenerative diseases. However, the mechanisms that lead to the autophagy dysfunction are still not clear. Based on the results of a genome-wide screen, we show that reactive oxygen species (ROS) serve as common mediators upstream of the activation of the type III PI3 kinase, which is critical for the initiation of autophagy. Furthermore, ROS play an essential function in the induction of the type III PI3 kinase and autophagy in response to amyloid β peptide, the main pathogenic mediator of Alzheimer's disease (AD). However, lysosomal blockage also caused by Aβ is independent of ROS. In addition, we demonstrate that autophagy is transcriptionally down-regulated during normal aging in the human brain. Strikingly, in contrast to normal aging, we observe transcriptional up-regulation of autophagy in the brains of AD patients, suggesting that there might be a compensatory regulation of autophagy. Interestingly, we show that an AD drug and an AD drug candidate have inhibitory effects on autophagy, raising the possibility that decreasing input into the lysosomal system may help to reduce cellular stress in AD. Finally, we provide a list of candidate drug targets that can be used to safely modulate levels of autophagy without causing cell death. PMID:20660724

  11. The SRI24 multichannel atlas of normal adult human brain structure.

    PubMed

    Rohlfing, Torsten; Zahr, Natalie M; Sullivan, Edith V; Pfefferbaum, Adolf

    2010-05-01

    This article describes the SRI24 atlas, a new standard reference system of normal human brain anatomy, that was created using template-free population registration of high-resolution magnetic resonance images acquired at 3T in a group of 24 normal control subjects. The atlas comprises anatomical channels (T1, T2, and proton density weighted), diffusion-related channels (fractional anisotropy, mean diffusivity, longitudinal diffusivity, mean diffusion-weighted image), tissue channels (CSF probability, gray matter probability, white matter probability, tissue labels), and two cortical parcellation maps. The SRI24 atlas enables multichannel atlas-to-subject image registration. It is uniquely versatile in that it is equally suited for the two fundamentally different atlas applications: label propagation and spatial normalization. Label propagation, herein demonstrated using diffusion tensor image fiber tracking, is enabled by the increased sharpness of the SRI24 atlas compared with other available atlases. Spatial normalization, herein demonstrated using data from a young-old group comparison study, is enabled by its unbiased average population shape property. For both propagation and normalization, we also report the results of quantitative comparisons with seven other published atlases: Colin27, MNI152, ICBM452 (warp5 and air12), and LPBA40 (SPM5, FLIRT, AIR). Our results suggest that the SRI24 atlas, although based on 3T MR data, allows equally accurate spatial normalization of data acquired at 1.5T as the comparison atlases, all of which are based on 1.5T data. Furthermore, the SRI24 atlas is as suitable for label propagation as the comparison atlases and detailed enough to allow delineation of anatomical structures for this purpose directly in the atlas. PMID:20017133

  12. The SRI24 Multi-Channel Atlas of Normal Adult Human Brain Structure

    PubMed Central

    Rohlfing, Torsten; Zahr, Natalie M.; Sullivan, Edith V.; Pfefferbaum, Adolf

    2010-01-01

    This paper describes the SRI24 atlas, a new standard reference system of normal human brain anatomy, that was created using template-free population registration of high-resolution magnetic resonance images acquired at 3T in a group of 24 normal control subjects. The atlas comprises anatomical channels (T1, T2, and proton density weighted), diffusion-related channels (fractional anisotropy, mean diffusivity, longitudinal diffusivity, mean diffusion-weighted image), tissue channels (CSF probability, gray matter probability, white matter probability, tissue labels), and two cortical parcellation maps. The SRI24 atlas enables multi-channel atlas-to-subject image registration. It is uniquely versatile in that it is equally suited for the two fundamentally different atlas applications: label propagation and spatial normalization. Label propagation, herein demonstrated using DTI fiber tracking, is enabled by the increased sharpness of the SRI24 atlas compared with other available atlases. Spatial normalization, herein demonstrated using data from a young-old group comparison study, is enabled by its unbiased average population shape property. For both propagation and normalization, we also report the results of quantitative comparisons with seven other published atlases: Colin27, MNI152, ICBM452 (warp5 and air12), and LPBA40 (SPM5, FLIRT, AIR). Our results suggest that the SRI24 atlas, although based on 3T MR data, allows equally accurate spatial normalization of data acquired at 1.5T as the comparison atlases, all of which are based on 1.5T data. Furthermore, the SRI24 atlas is as suitable for label propagation as the comparison atlases and detailed enough to allow delineation of anatomical structures for this purpose directly in the atlas. PMID:20017133

  13. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    PubMed Central

    Kennard, John A.; Woodruff-Pak, Diana S.

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE) in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena. PMID:21647305

  14. BDNF-estrogen interactions in hippocampal mossy fiber pathway: implications for normal brain function and disease

    PubMed Central

    Harte-Hargrove, Lauren; MacLusky, Neil J.; Scharfman, Helen E.

    2013-01-01

    The neurotrophin BDNF and the steroid hormone estrogen exhibit potent effects on hippocampal neurons during development and in adulthood. BDNF and estrogen have also been implicated in the etiology of diverse types of neurological disorders or psychiatric illnesses, or have been discussed as potentially important in treatment. Although both are typically studied independently, it has been suggested that BDNF mediates several of the effects of estrogen in hippocampus, and that these interactions play a role in the normal brain as well as disease. Here we focus on the mossy fiber (MF) pathway of the hippocampus, a critical pathway in normal hippocampal function, and a prime example of a location where numerous studies support an interaction between BDNF and estrogen in the rodent brain. We first review the temporal and spatially-regulated expression of BDNF and estrogen in the MFs, as well as their receptors. Then we consider the results of studies that suggest that 17β-estradiol alters hippocampal function by its influence on BDNF expression in the MF pathway. We also address the hypothesis that estrogen influences hippocampus by mechanisms related not only to the mature form of BDNF, acting at trkB receptors, but also by regulating the precursor, proBDNF, acting at p75NTR. We suggest that the interactions between BDNF and 17β-estradiol in the MFs are potentially important in the normal function of the hippocampus, and have implications for sex differences in functions that depend on the MFs and in diseases where MF plasticity has been suggested to play an important role, Alzheimer’s disease, epilepsy and addiction. PMID:23276673

  15. Simulations of exercise and brain effects of acute exposure to carbon monoxide in normal and vascular-diseased persons.

    EPA Science Inventory

    At some level, carboxyhemoglobin (RbCO) due to inhalation of carbon monoxide (CO) reduces maximum exercise duration in normal and ischemic heart patients. At high RbCO levels in normal subjects, brain function is also affected and behavioral performance is impaired. These are fin...

  16. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer.

    PubMed

    Pathak, Sen; Multani, Asha S; Banerji, Pratip; Banerji, Prasanta

    2003-10-01

    Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma. PMID:12963976

  17. Brain gene expression patterns differentiate Mild Cognitive Impairment from normal Aged and Alzheimer Disease

    PubMed Central

    Berchtold, Nicole C.; Sabbagh, Marwan N.; Beach, Thomas G.; Kim, Ronald C.; Cribbs, David H.; Cotman, Carl W.

    2014-01-01

    Mild cognitive impairment (MCI) represents a cognitive state intermediate between normal aging and early Alzheimer Disease (AD). To investigate if the molecular signature of MCI parallels the clinical picture, we use microarrays to extensively profile gene expression in 4 cortical brain regions (entorhinal cortex, hippocampus, superior frontal gyrus, post-central gyrus) using post-mortem tissue from cognitively normal aged controls, MCI, and AD cases. Our data reveal that gene expression patterns in MCI are not an extension of aging, and for the most part, are not intermediate between aged controls and AD. Functional enrichment analysis of significant genes revealed prominent upregulation in MCI brains of genes associated with anabolic and biosynthetic pathways (notably transcription, protein biosynthesis, protein trafficking and turnover) as well as mitochondrial energy generation. In addition, many synaptic genes showed altered expression in MCI, predominantly upregulation, including genes for central components of the vesicle fusion machinery at the synapse, synaptic vesicle trafficking, neurotransmitter receptors, and synaptic structure and stabilization. These data suggest that there is a rebalancing of synaptic transmission in the MCI brain. To investigate if synaptic gene expression levels in MCI were related to cognitive function, Pearson’s correlation coefficient between MMSE and region-specific mRNA expression were computed for MCI cases. A number of synaptic genes showed strong significant correlations (r>0.8, p<0.01) most notably in the EC, with fewer in the HC, and very few in neocortical regions. The synaptic genes with highly significant correlations were predominantly related to synaptic transmission and plasticity, and myelin composition. Unexpectedly, we found that gene expression changes that facilitate synaptic excitability and plasticity were overwhelmingly associated with poorer MMSE, and conversely that gene expression changes that inhibit

  18. Expression of gangliosides on glial and neuronal cells in normal and pathological adult human brain.

    PubMed

    Marconi, Silvia; De Toni, Luca; Lovato, Laura; Tedeschi, Elisa; Gaetti, Luigi; Acler, Michele; Bonetti, Bruno

    2005-12-30

    Few studies have assessed the glycolipid phenotype of glial cells in the human central nervous system (CNS) in situ. We investigated by immunohistochemistry the expression and cellular distribution of a panel of gangliosides (GM1, GM2, acetyl-GM3, GD1a, GD1b, GD2, GD3, GT1b, GQ1b and the A2B5 antibody) in adult, human normal and pathological brain, namely multiple sclerosis (MS) and other neurological diseases (OND). In normal conditions, we found diffuse expression in the white matter of most gangliosides tested, with the exception of acetyl-GM3, GT1b and GQ1b. By double immunofluorescence with phenotypic markers, GM1 and GD1b were preferentially expressed on GFAP+ astrocytes, GD1a on NG2+ oligodendrocyte precursors, A2B5 immunostained both populations, while GD2 was selectively present on mature oligodendrocytes. In the gray matter, only GM1, GD2 and A2B5 were present on neuronal cells. Interestingly, those gangliosides present on astrocytes in normal conditions were preferentially expressed on NG2+ cells in chronic MS lesions and in OND. Selective expression of GT1b upon astrocytes and NG2+ cells was instead observed in MS lesions, but not in OND. The definition of the glycolipid phenotype of CNS glial cells may be useful to identify distinct biological glial subsets and provide insights on the potential autoantigenic role of gangliosides in CNS autoimmune diseases. PMID:16313974

  19. Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain

    PubMed Central

    Seymour, Tracy; Twigger, Alecia-Jane; Kakulas, Foteini

    2015-01-01

    Pluripotent stem cells (PSCs) attracted considerable interest with the successful isolation of embryonic stem cells (ESCs) from the inner cell mass of murine, primate and human embryos. Whilst it was initially thought that the only PSCs were ESCs, in more recent years cells with similar properties have been isolated from organs of the adult, including the breast and brain. Adult PSCs in these organs have been suggested to be remnants of embryonic development that facilitate normal tissue homeostasis during repair and regeneration. They share certain characteristics with ESCs, such as an inherent capacity to self-renew and differentiate into cells of the three germ layers, properties that are regulated by master pluripotency transcription factors (TFs) OCT4 (octamer-binding transcription factor 4), SOX2 (sex determining region Y-box 2), and homeobox protein NANOG. Aberrant expression of these TFs can be oncogenic resulting in heterogeneous tumours fueled by cancer stem cells (CSC), which are resistant to conventional treatments and are associated with tumour recurrence post-treatment. Further to enriching our understanding of the role of pluripotency TFs in normal tissue function, research now aims to develop optimized isolation and propagation methods for normal adult PSCs and CSCs for the purposes of regenerative medicine, developmental biology, and disease modeling aimed at targeted personalised cancer therapies. PMID:26580604

  20. Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain.

    PubMed

    Seymour, Tracy; Twigger, Alecia-Jane; Kakulas, Foteini

    2015-01-01

    Pluripotent stem cells (PSCs) attracted considerable interest with the successful isolation of embryonic stem cells (ESCs) from the inner cell mass of murine, primate and human embryos. Whilst it was initially thought that the only PSCs were ESCs, in more recent years cells with similar properties have been isolated from organs of the adult, including the breast and brain. Adult PSCs in these organs have been suggested to be remnants of embryonic development that facilitate normal tissue homeostasis during repair and regeneration. They share certain characteristics with ESCs, such as an inherent capacity to self-renew and differentiate into cells of the three germ layers, properties that are regulated by master pluripotency transcription factors (TFs) OCT4 (octamer-binding transcription factor 4), SOX2 (sex determining region Y-box 2), and homeobox protein NANOG. Aberrant expression of these TFs can be oncogenic resulting in heterogeneous tumours fueled by cancer stem cells (CSC), which are resistant to conventional treatments and are associated with tumour recurrence post-treatment. Further to enriching our understanding of the role of pluripotency TFs in normal tissue function, research now aims to develop optimized isolation and propagation methods for normal adult PSCs and CSCs for the purposes of regenerative medicine, developmental biology, and disease modeling aimed at targeted personalised cancer therapies. PMID:26580604

  1. Where the brain grows old: decline in anterior cingulate and medial prefrontal function with normal aging.

    PubMed

    Pardo, José V; Lee, Joel T; Sheikh, Sohail A; Surerus-Johnson, Christa; Shah, Hemant; Munch, Kristin R; Carlis, John V; Lewis, Scott M; Kuskowski, Michael A; Dysken, Maurice W

    2007-04-15

    Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimer's disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown. PMID:17321756

  2. A novel POMT2 mutation causes mild congenital muscular dystrophy with normal brain MRI

    PubMed Central

    MURAKAMI, Terumi; HAYASHI, Yukiko K.; OGAWA, Megumu; NOGUCHI, Satoru; CAMPBELL, Kevin P.; TOGAWA, Masami; INOUE, Takehiko; OKA, Akira; OHNO, Kousaku; NONAKA, Ikuya; NISHINO, Ichizo

    2009-01-01

    We report a patient harboring a novel homozygous mutation of c.604T>G (p.F202V) in POMT2. He showed delayed psychomotor development but acquired the ability to walk at the age of 3 years and 10 months. His brain MRI was normal. No ocular abnormalities were seen. Biopsied skeletal muscle revealed markedly decreased but still detectable glycosylated forms of alpha-dystroglycan (α-DG). Our results indicate that mutations in POMT2 can cause a wide spectrum of clinical phenotypes as observed in other genes associated with alpha-dystroglycanopathy. Presence of small amounts of partly glycosylated α-DG may have a role in reducing the clinical symptoms of alpha-dystroglycanopathy. PMID:18804929

  3. Pattern of CXCR7 Gene Expression in Mouse Brain Under Normal and Inflammatory Conditions.

    PubMed

    Banisadr, Ghazal; Podojil, Joseph R; Miller, Stephen D; Miller, Richard J

    2016-03-01

    The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 acting via its G-protein coupled receptor (GPCR) CXCR4 has been implicated in neurogenesis, neuromodulation, brain inflammation, HIV-1 encephalopathy and tumor growth. CXCR7 was identified as an alternate receptor for SDF-1/CXCL12. Characterization of CXCR7-deficient mice demonstrated a role for CXCR7 in fetal endothelial biology, cardiac development, and B-cell localization. Despite its ligand binding properties, CXCR7 does not seem to signal like a conventional GPCR. It has been suggested that CXCR7 may not function alone but in combination with CXCR4. Here, we investigated the regional localization of CXCR7 receptors in adult mouse brain using CXCR7-EGFP transgenic mice. We found that the receptors were expressed in various brain regions including olfactory bulb, cerebral cortex, hippocampus, subventricular zone (SVZ), hypothalamus and cerebellum. Extensive CXCR7 expression was associated with cerebral blood vessels. Using cell type specific markers, CXCR7 expression was found in neurons, astrocytes and oligodendrocyte progenitors. GAD-expressing neurons exhibited CXCR7 expression in the hippocampus. Expression of CXCR7 in the dentate gyrus included cells that expressed nestin, GFAP and cells that appeared to be immature granule cells. In mice with Experimental Autoimmune Encephalomyelitis (EAE), CXCR7 was expressed by migrating oligodendrocyte progenitors in the SVZ. We then compared the distribution of SDF-1/CXCL12 and CXCR7 using bitransgenic mice expressing both CXCR7-EGFP and SDF-1-mRFP. Enhanced expression of SDF-1/CXCL12 and CXCR7 was observed in the corpus callosum, SVZ and cerebellum. Overall, the expression of CXCR7 in normal and pathological nervous system suggests CXCR4-independent functions of SDF-1/CXCL12 mediated through its interaction with CXCR7. PMID:25997895

  4. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

    PubMed Central

    McCoy, Melissa K; Tansey, Malú G

    2008-01-01

    The role of tumor necrosis factor (TNF) as an immune mediator has long been appreciated but its function in the brain is still unclear. TNF receptor 1 (TNFR1) is expressed in most cell types, and can be activated by binding of either soluble TNF (solTNF) or transmembrane TNF (tmTNF), with a preference for solTNF; whereas TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF. Elevation of solTNF is a hallmark of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including ischemic stroke, Alzheimer's (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). The presence of this potent inflammatory factor at sites of injury implicates it as a mediator of neuronal damage and disease pathogenesis, making TNF an attractive target for therapeutic development to treat acute and chronic neurodegenerative conditions. However, new and old observations from animal models and clinical trials reviewed here suggest solTNF and tmTNF exert different functions under normal and pathological conditions in the CNS. A potential role for TNF in synaptic scaling and hippocampal neurogenesis demonstrated by recent studies suggest additional in-depth mechanistic studies are warranted to delineate the distinct functions of the two TNF ligands in different parts of the brain prior to large-scale development of anti-TNF therapies in the CNS. If inactivation of TNF-dependent inflammation in the brain is warranted by additional pre-clinical studies, selective targeting of TNFR1-mediated signaling while sparing TNFR2 activation may lessen adverse effects of anti-TNF therapies in the CNS. PMID:18925972

  5. EEG Oscillatory States: Universality, Uniqueness and Specificity across Healthy-Normal, Altered and Pathological Brain Conditions

    PubMed Central

    Fingelkurts, Alexander A.; Fingelkurts, Andrew A.

    2014-01-01

    For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations’ functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292

  6. Heat loss and blood flow during hyperthermia in normal canine brain. I: Empirical study and analysis.

    PubMed

    Lyons, B E; Samulski, T V; Cox, R S; Fessenden, P

    1989-01-01

    The effects of blood flow and thermal conduction during microwave hyperthermia were investigated in normal canine brain. Heating was accomplished with an external microstrip spiral antenna and temperature measurements were made using a multichannel fluoroptic thermometry system. In order to determine cooling rates, temperature measurements made during cooling were fitted with a model consisting of a constant value and an exponential term. Data from experiments in both perfused and non-perfused brains could be fitted with this simple model. The resulting cooling rates indicated that heat loss by conduction is comparable to that by blood flow. In another series of experiments, temperature measurements were made during several 1 min cooling intervals in which the power was shut off intermittently during a 35 min heating episode. Results were consistent with a 2-3-fold increase in blood flow rate which occurred gradually throughout the course of heating. Parameters that affect the determination of cooling rates are discussed in terms of the bioheat transfer equation. These investigations demonstrate that a simple heat sink model provides a good representation of the cooling data for the thermal distributions obtained. PMID:2926187

  7. An avian retrovirus expressing chicken pp59c-myc possesses weak transforming activity distinct from v-myc that may be modulated by adjacent normal cell neighbors.

    PubMed Central

    Filardo, E J; Humphries, E H

    1991-01-01

    We demonstrate that EF168, an avian retrovirus that expresses the chicken pp59c-myc proto-oncogene, transforms quail embryo fibroblasts in vitro. An EF168-transformed quail clone, EF168-28, containing a single provirus, synthesizes several hundred copies of c-myc RNA and expresses elevated levels of the pp59c-myc gene product. The EF168 provirus in EF168-28 was isolated as a molecular clone, and the nucleotide sequence of its c-myc allele was confirmed as identical to that of exons 2 and 3 of the chicken c-myc proto-oncogene. Extended infection of quail embryo fibroblast cultures with EF168 induced a number of in vitro transformation-associated parameters similar to those elicited by the oncogenic v-myc-encoding retrovirus MC29, including alteration of cellular morphology, anchorage-independent growth, and induction of immortalized cell lines. Despite the fact that EF168 and MC29 shared these biological activities, further analysis revealed that EF168 initiated transformation in quail embryo fibroblasts, bone marrow, or adherent peripheral blood cultures 100- to 1,000-fold less efficiently than did MC29. Further, in contrast to MC29-induced foci, EF168 foci were smaller, morphologically diffuse, and less prominent. Analysis of newly infected cells demonstrated efficient expression of EF168 viral RNA in the absence of transformation. These differences suggest that while the pp59v-myc gene product can exert dominant transforming activity on quail embryo fibroblasts, its ability to initiate transformation is distinct from that of the pp110gag-v-myc gene product encoded by MC29 and may be suppressed by adjacent nontransformed cell neighbors. Images PMID:1942247

  8. Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

    PubMed Central

    Eizayaga, Francisco; Scorticati, Camila; Prestifilippo, Juan P; Romay, Salvador; Fernandez, Maria A; Castro, José L; Lemberg, Abraham; Perazzo, Juan C

    2006-01-01

    AIM: To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 d after ligation when portal pressure is spontaneously normalized. METHODS: Adult male Wistar rats were divided into four groups: Group I: Sham14d , sham operated; Group II: PH14d , portal vein stenosis; (both groups were used 14 days after surgery); Group III: Sham40d, Sham operated and Group IV: PH40d Portal vein stenosis (Groups II and IV used 40 d after surgery). Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS: Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION: The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment. PMID:16552803

  9. The effect of regadenoson-induced transient disruption of the blood–brain barrier on temozolomide delivery to normal rat brain

    PubMed Central

    Jackson, Sadhana; Anders, Nicole M.; Mangraviti, Antonella; Wanjiku, Teresia M.; Sankey, Eric W.; Liu, Ann; Brem, Henry; Tyler, Betty; Rudek, Michelle A.

    2016-01-01

    The blood–brain barrier (BBB) significantly reduces the delivery of many systemically administered agents to the central nervous system. Although temozolomide is the only chemotherapy to improve survival in patients with glioblastoma, its concentration in brain is only 20 % of that in blood. Regadenoson, an FDA approved adenosine receptor agonist used for cardiac stress testing, transiently disrupts rodent BBB allowing high molecular weight dextran (70 kD) to enter the brain. This study was conducted to determine if regadenoson could facilitate entry of temozolomide into normal rodent brain. Temozolomide (50 mg/kg) was administered by oral gavage to non-tumor bearing F344 rats. Two-thirds of the animals received a single dose of intravenous regadenoson 60–90 min later. All animals were sacrificed 120 or 360 min after temozolomide administration. Brain and plasma temozolomide concentrations were determined using HPLC/MS/MS. Brain temozolomide concentrations were significantly higher at 120 min when it was given with regadenoson versus alone (8.1 ± 2.7 and 5.1 ± 3.5 μg/g, P <0.05). A similar trend was noted in brain:plasma ratios (0.45 ± 0.08 and 0.29 ± 0.09, P < 0.05). Brain concentrations and brain:plasma ratios were not significantly different 360 min after temozolomide administration. No differences were seen in plasma temozolomide concentrations with or without regadenoson. These results suggest co-administration of regadenoson with temozolomide results in 60 % higher temozolomide levels in normal brain without affecting plasma concentrations. This novel approach to increasing intracranial concentrations of systemically administered agents has potential to improve the efficacy of chemotherapy in neuro-oncologic disorders. PMID:26626489

  10. Impact of Millimeter-Level Margins on Peripheral Normal Brain Sparing for Gamma Knife Radiosurgery

    SciTech Connect

    Ma, Lijun; Sahgal, Arjun; Larson, David A.; Pinnaduwage, Dilini; Fogh, Shannon; Barani, Igor; Nakamura, Jean; McDermott, Michael; Sneed, Penny

    2014-05-01

    Purpose: To investigate how millimeter-level margins beyond the gross tumor volume (GTV) impact peripheral normal brain tissue sparing for Gamma Knife radiosurgery. Methods and Materials: A mathematical formula was derived to predict the peripheral isodose volume, such as the 12-Gy isodose volume, with increasing margins by millimeters. The empirical parameters of the formula were derived from a cohort of brain tumor and surgical tumor resection cavity cases (n=15) treated with the Gamma Knife Perfexion. This was done by first adding margins from 0.5 to 3.0 mm to each individual target and then creating for each expanded target a series of treatment plans of nearly identical quality as the original plan. Finally, the formula was integrated with a published logistic regression model to estimate the treatment-induced complication rate for stereotactic radiosurgery when millimeter-level margins are added. Results: Confirmatory correlation between the nominal target radius (ie, R{sub T}) and commonly used maximum target size was found for the studied cases, except for a few outliers. The peripheral isodose volume such as the 12-Gy volume was found to increase exponentially with increasing Δ/R{sub T}, where Δ is the margin size. Such a curve fitted the data (logarithmic regression, R{sup 2} >0.99), and the 12-Gy isodose volume was shown to increase steeply with a 0.5- to 3.0-mm margin applied to a target. For example, a 2-mm margin on average resulted in an increase of 55% ± 16% in the 12-Gy volume; this corresponded to an increase in the symptomatic necrosis rate of 6% to 25%, depending on the Δ/R{sub T} values for the target. Conclusions: Millimeter-level margins beyond the GTV significantly impact peripheral normal brain sparing and should be applied with caution. Our model provides a rapid estimate of such an effect, particularly for large and/or irregularly shaped targets.

  11. Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis in Normal and Hyperammonemic Brain.

    PubMed

    Cooper, Arthur J L; Jeitner, Thomas M

    2016-01-01

    Glutamate is present in the brain at an average concentration-typically 10-12 mM-far in excess of those of other amino acids. In glutamate-containing vesicles in the brain, the concentration of glutamate may even exceed 100 mM. Yet because glutamate is a major excitatory neurotransmitter, the concentration of this amino acid in the cerebral extracellular fluid must be kept low-typically µM. The remarkable gradient of glutamate in the different cerebral compartments: vesicles > cytosol/mitochondria > extracellular fluid attests to the extraordinary effectiveness of glutamate transporters and the strict control of enzymes of glutamate catabolism and synthesis in well-defined cellular and subcellular compartments in the brain. A major route for glutamate and ammonia removal is via the glutamine synthetase (glutamate ammonia ligase) reaction. Glutamate is also removed by conversion to the inhibitory neurotransmitter γ-aminobutyrate (GABA) via the action of glutamate decarboxylase. On the other hand, cerebral glutamate levels are maintained by the action of glutaminase and by various α-ketoglutarate-linked aminotransferases (especially aspartate aminotransferase and the mitochondrial and cytosolic forms of the branched-chain aminotransferases). Although the glutamate dehydrogenase reaction is freely reversible, owing to rapid removal of ammonia as glutamine amide, the direction of the glutamate dehydrogenase reaction in the brain in vivo is mainly toward glutamate catabolism rather than toward the net synthesis of glutamate, even under hyperammonemia conditions. During hyperammonemia, there is a large increase in cerebral glutamine content, but only small changes in the levels of glutamate and α-ketoglutarate. Thus, the channeling of glutamate toward glutamine during hyperammonemia results in the net synthesis of 5-carbon units. This increase in 5-carbon units is accomplished in part by the ammonia-induced stimulation of the anaplerotic enzyme pyruvate carboxylase

  12. Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis in Normal and Hyperammonemic Brain

    PubMed Central

    Cooper, Arthur J. L.; Jeitner, Thomas M.

    2016-01-01

    Glutamate is present in the brain at an average concentration—typically 10–12 mM—far in excess of those of other amino acids. In glutamate-containing vesicles in the brain, the concentration of glutamate may even exceed 100 mM. Yet because glutamate is a major excitatory neurotransmitter, the concentration of this amino acid in the cerebral extracellular fluid must be kept low—typically µM. The remarkable gradient of glutamate in the different cerebral compartments: vesicles > cytosol/mitochondria > extracellular fluid attests to the extraordinary effectiveness of glutamate transporters and the strict control of enzymes of glutamate catabolism and synthesis in well-defined cellular and subcellular compartments in the brain. A major route for glutamate and ammonia removal is via the glutamine synthetase (glutamate ammonia ligase) reaction. Glutamate is also removed by conversion to the inhibitory neurotransmitter γ-aminobutyrate (GABA) via the action of glutamate decarboxylase. On the other hand, cerebral glutamate levels are maintained by the action of glutaminase and by various α-ketoglutarate-linked aminotransferases (especially aspartate aminotransferase and the mitochondrial and cytosolic forms of the branched-chain aminotransferases). Although the glutamate dehydrogenase reaction is freely reversible, owing to rapid removal of ammonia as glutamine amide, the direction of the glutamate dehydrogenase reaction in the brain in vivo is mainly toward glutamate catabolism rather than toward the net synthesis of glutamate, even under hyperammonemia conditions. During hyperammonemia, there is a large increase in cerebral glutamine content, but only small changes in the levels of glutamate and α-ketoglutarate. Thus, the channeling of glutamate toward glutamine during hyperammonemia results in the net synthesis of 5-carbon units. This increase in 5-carbon units is accomplished in part by the ammonia-induced stimulation of the anaplerotic enzyme pyruvate

  13. Relationships between brain metabolism decrease in normal aging and changes in structural and functional connectivity.

    PubMed

    Chételat, Gaël; Landeau, Brigitte; Salmon, Eric; Yakushev, Igor; Bahri, Mohamed Ali; Mézenge, Florence; Perrotin, Audrey; Bastin, Christine; Manrique, Alain; Scheurich, Armin; Scheckenberger, Mathias; Desgranges, Béatrice; Eustache, Francis; Fellgiebel, Andreas

    2013-08-01

    Normal aging is characterized by brain glucose metabolism decline predominantly in the prefrontal cortex. The goal of the present study was to assess whether this change was associated with age-related alteration of white matter (WM) structural integrity and/or functional connectivity. FDG-PET data from 40 young and 57 elderly healthy participants from two research centers (n=49/48 in Center 1/2) were analyzed. WM volume from T1-weighted MRI (Center 1), fractional anisotropy from diffusion-tensor imaging (Center 2), and resting-state fMRI data (Center 1) were also obtained. Group comparisons were performed within each imaging modality. Then, positive correlations were assessed, within the elderly, between metabolism in the most affected region and the other neuroimaging modalities. Metabolism decline in the elderly predominated in the left inferior frontal junction (LIFJ). LIFJ hypometabolism was significantly associated with macrostructural and microstructural WM disturbances in long association fronto-temporo-occipital fibers, while no relationship was found with functional connectivity. The findings offer new perspectives to understand normal aging processes and open avenues for future studies to explore causality between age-related metabolism and connectivity changes. PMID:23518010

  14. Diagnosing dementia and normal aging: clinical relevance of brain ratios and cognitive performance in a Brazilian sample.

    PubMed

    Chaves, M L; Ilha, D; Maia, A L; Motta, E; Lehmen, R; Oliveira, L M

    1999-09-01

    The main objective of the present study was to evaluate the diagnostic value (clinical application) of brain measures and cognitive function. Alzheimer and multi-infarct patients (N = 30) and normal subjects over the age of 50 (N = 40) were submitted to a medical, neurological and cognitive investigation. The cognitive tests applied were Mini-Mental, word span, digit span, logical memory, spatial recognition span, Boston naming test, praxis, and calculation tests. The brain ratios calculated were the ventricle-brain, bifrontal, bicaudate, third ventricle, and suprasellar cistern measures. These data were obtained from a brain computer tomography scan, and the cutoff values from receiver operating characteristic curves. We analyzed the diagnostic parameters provided by these ratios and compared them to those obtained by cognitive evaluation. The sensitivity and specificity of cognitive tests were higher than brain measures, although dementia patients presented higher ratios, showing poorer cognitive performances than normal individuals. Normal controls over the age of 70 presented higher measures than younger groups, but similar cognitive performance. We found diffuse losses of tissue from the central nervous system related to distribution of cerebrospinal fluid in dementia patients. The likelihood of case identification by functional impairment was higher than when changes of the structure of the central nervous system were used. Cognitive evaluation still seems to be the best method to screen individuals from the community, especially for developing countries, where the cost of brain imaging precludes its use for screening and initial assessment of dementia. PMID:10464391

  15. In vivo administration of fluorescent dextrans for the specific and sensitive localization of brain vascular pericytes and their characterization in normal and neurotoxin exposed brains.

    PubMed

    Sarkar, Sumit; Schmued, Larry

    2012-06-01

    We have aimed to develop novel histochemical markers for the labeling of brain pericytes and characterize their morphology in the normal and the excitotoxin-exposed brain, as this class of cells has received little attention until recently. Pericyte labeling was accomplished by the intracerebroventricular injection of certain fluorescent dextran conjugates, such as Fluoro-Gold-dextran, FR-dextran, FITC-dextran and Fluoro-Turquoise (FT)-dextran. 1-7 days after the tracer injection, extensive labeling of vascular pericytes was seen throughout the entire brain. These cells were found distal to the endothelial cells and exhibited large dye containing vacuoles. The morphology of the pericytes was somewhat variable, exhibiting round or amoeboid shapes within larger intracellular vesicles, while those wrapping around capillaries exhibited a more elongated appearance with finger-like projections. The use of FG-dextran resulted in bluish yellow fluorescently labeled pericytes, while FR-dextran resulted in red fluorescent labeled pericytes, FITC-dextran exhibited green fluorescent pericytes and FT-dextran showed fluorescent blue pericytes in the brain. We have used these tracers to study possible changes in morphology and pericyte number following kainic acid insult, observing that the number of pericytes in the injured or lesioned areas of the brain is dramatically reduced compared to the non-injured areas. These novel fluorochromes should be of use for studies involving the detection and localization of pericytes in both normal and pathological brain tissues. PMID:22525936

  16. White matter hyperintensities and normal-appearing white matter integrity in the aging brain.

    PubMed

    Maniega, Susana Muñoz; Valdés Hernández, Maria C; Clayden, Jonathan D; Royle, Natalie A; Murray, Catherine; Morris, Zoe; Aribisala, Benjamin S; Gow, Alan J; Starr, John M; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

    2015-02-01

    White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10(-9) m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe. PMID:25457555

  17. Molecular disorganization of axons adjacent to human lacunar infarcts

    PubMed Central

    Lee, Monica D.; Tung, Spencer; Vinters, Harry V.; Carmichael, S. Thomas

    2015-01-01

    Cerebral microvascular disease predominantly affects brain white matter and deep grey matter, resulting in ischaemic damage that ranges from lacunar infarcts to white matter hyperintensities seen on magnetic resonance imaging. These lesions are common and result in both clinical stroke syndromes and accumulate over time, resulting in cognitive deficits and dementia. Magnetic resonance imaging studies suggest that these lesions progress over time, accumulate adjacent to prior lesions and have a penumbral region susceptible to further injury. The pathological correlates of this adjacent injury in surviving myelinated axons have not been previously defined. In this study, we sought to determine the molecular organization of axons in tissue adjacent to lacunar infarcts and in the regions surrounding microinfarcts, by determining critical elements in axonal function: the morphology and length of node of Ranvier segments and adjacent paranodal segments. We examined post-mortem brain tissue from six patients with lacunar infarcts and tissue from two patients with autosomal dominant retinal vasculopathy and cerebral leukoencephalopathy (previously known as hereditary endotheliopathy with retinopathy, nephropathy and stroke) who accumulate progressive white matter ischaemic lesions in the form of lacunar and microinfarcts. In axons adjacent to lacunar infarcts yet extending up to 150% of the infarct diameter away, both nodal and paranodal length increase by ∼20% and 80%, respectively, reflecting a loss of normal cell-cell adhesion and signalling between axons and oligodendrocytes. Using premorbid magnetic resonance images, brain regions from patients with retinal vasculopathy and cerebral leukoencephalopathy that harboured periventricular white matter hyperintensities were selected and the molecular organization of axons was determined within these regions. As in regions adjacent to lacunar infarcts, nodal and paranodal length in white matter of these patients is

  18. Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain stem.

    PubMed

    Jacobs, M A; Horská, A; van Zijl, P C; Barker, P B

    2001-10-01

    Quantitative, multislice proton MR spectroscopic imaging (MRSI) was used to investigate regional metabolite levels and ratios in the normal adult human posterior fossa. Six normal volunteers (36 +/- 3 years, five male, one female) were scanned on a 1.5 T scanner using multislice MRSI at long echo time (TE 280 msec). The entire cerebellum was covered using three oblique-axial slice locations, which also included the pons, mid-brain, insular cortex, and parieto-occipital lobe. Concentrations of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were estimated using the phantom replacement technique. Regional variations of the concentrations were assessed using ANOVA (P < 0.05). High-resolution MRSI data was obtained in all subjects and brain regions examined. Metabolite concentrations (mM) (mean +/- SD) were as follows: cerebellar vermis: 2.3 +/- 0.4, 8.8 +/- 1.7 and 7.6 +/- 1.0 for Cho, Cr, and NAA respectively; cerebellar hemisphere: 2.2 +/- 0.6, 8.9 +/- 2.1, 7.5 +/- 0.8; pons 2.2 +/- 0.5, 4.3 +/- 1.1, 8.3 +/- 0.9; insular cortex, 1.8 +/- 0.5, 7.8 +/- 2, 8.0 +/- 1.1, parieto-occipital gray matter, 1.3 +/- 0.3, 5.7 +/- 1.1, 7.2 +/- 0.9, and occipital white matter, 1.4 +/- 0.3, 5.3 +/- 1.3, 7.5 +/- 0.8. Consistent with previous reports, significantly higher levels of Cr were found in the cerebellum compared to parieto-occipital gray and occipital white matter, and pons (P < 0.0001). NAA was essentially uniformly distributed within the regions chosen for analysis, with the highest level in the pons (P < 0.04). Cho was significantly higher in the cerebellum and pons than parieto-occipital gray and occipital white matter (P < 0.002) and was also higher in the pons than in the insular cortex (P < 0.05). Quantitative multislice MRSI of the posterior fossa is feasible and significant regional differences in metabolite concentrations were found. PMID:11590646

  19. Structural Brain Atlases: Design, Rationale, and Applications in Normal and Pathological Cohorts

    PubMed Central

    Mandal, Pravat K.; Mahajan, Rashima; Dinov, Ivo D.

    2015-01-01

    Structural magnetic resonance imaging (MRI) provides anatomical information about the brain in healthy as well as in diseased conditions. On the other hand, functional MRI (fMRI) provides information on the brain activity during performance of a specific task. Analysis of fMRI data requires the registration of the data to a reference brain template in order to identify the activated brain regions. Brain templates also find application in other neuroimaging modalities, such as diffusion tensor imaging and multi-voxel spectroscopy. Further, there are certain differences (e.g., brain shape and size) in the brains of populations of different origin and during diseased conditions like in Alzheimer’s disease (AD), population and disease-specific brain templates may be considered crucial for accurate registration and subsequent analysis of fMRI as well as other neuroimaging data. This manuscript provides a comprehensive review of the history, construction and application of brain atlases. A chronological outline of the development of brain template design, starting from the Talairach and Tournoux atlas to the Chinese brain template (to date), along with their respective detailed construction protocols provides the backdrop to this manuscript. The manuscript also provides the automated workflow-based protocol for designing a population-specific brain atlas from structural MRI data using LONI Pipeline graphical workflow environment. We conclude by discussing the scope of brain templates as a research tool and their application in various neuroimaging modalities. PMID:22647262

  20. Segmentation and classification of normal-appearing brain: how much is enough?

    NASA Astrophysics Data System (ADS)

    Glass, John O.; Reddick, Wilburn E.; Ji, Qing; Glas, Lauren S.

    2002-05-01

    In this study, subsets of MR slices were examined to assess their ability to optimally predict the total cerebral volume of gray matter, white matter and CSF. Patients underwent a clinical imaging protocol consisting of T1-, T2-, PD-, and FLAIR-weighted images after obtaining informed consent. MR imaging sets were registered, RF-corrected, and then analyzed with a hybrid neural network segmentation and classification algorithm to identify normal brain parenchyma. After processing the data, the correlation between the image subsets and the total cerebral volumes of gray matter, white matter and CSF were examined. The 29 subjects (18F, 11M) assessed in this study were 1.7 ? 18.7 (median = 5.2) years of age. The five subsets accounted for 5%, 15%, 24%, 56%, and 79% of the total cerebral volume. The predictive correlation for gray matter, white matter, and CSF in each of these subsets were: 5% (R= 0.94, 0.92, 0.91), 15% (R= 0.93, 0.95, 0.94), 24% (R= 0.92, 0.95, 0.94), 56% (R= 0.75, 0.95, 0.89), and 79% (R= 0.89, 0.98, 0.99) respectively. All subsets of slices examined were significantly correlated (p<0.001) with the total cerebral volume of gray matter, white matter, and CSF.

  1. Neuroprotective Pathways: Lifestyle activity, brain pathology and cognition in cognitively normal older adults

    PubMed Central

    Wirth, Miranka; Haase, Claudia M.; Villeneuve, Sylvia; Vogel, Jacob; Jagust, William J.

    2014-01-01

    This study used path analysis to examine effects of cognitive activity and physical activity on cognitive functioning in older adults, through pathways involving beta-amyloid (Aβ) burden, cerebrovascular lesions, and neural injury within brain regions affected in Alzheimer’s disease (AD). Ninety-two cognitively normal older adults (75.2±5.6 years) reported lifetime cognitive activity and current physical activity using validated questionnaires. For each participant, we evaluated cortical Aβ burden (using PIB-PET), cerebrovascular lesions (using MRI-defined white matter lesion (WML)), and neural integrity within AD regions (using a multimodal biomarker). Path models (adjusted for age, gender, and education) indicated that higher lifetime cognitive activity and higher current physical activity was associated with fewer WMLs. Lower WML volumes were in turn related to higher neural integrity and higher global cognitive functioning. As shown previously, higher lifetime cognitive activity was associated with lower PIB retention, which itself moderated the impact of neural integrity on cognitive functioning. Lifestyle activity may thus promote cognitive health in aging by protecting against cerebrovascular pathology and Aβ pathology thought to be relevant to AD development. PMID:24656834

  2. Astrocyte activation is suppressed in both normal and injured brain by FGF signaling.

    PubMed

    Kang, Wenfei; Balordi, Francesca; Su, Nan; Chen, Lin; Fishell, Gordon; Hébert, Jean M

    2014-07-22

    In the brain, astrocytes are multifunctional cells that react to insults and contain damage. However, excessive or sustained reactive astrocytes can be deleterious to functional recovery or contribute to chronic inflammation and neuronal dysfunction. Therefore, astrocyte activation in response to damage is likely to be tightly regulated. Although factors that activate astrocytes have been identified, whether factors also exist that maintain astrocytes as nonreactive or reestablish their nonreactive state after containing damage remains unclear. By using loss- and gain-of-function genetic approaches, we show that, in the unperturbed adult neocortex, FGF signaling is required in astrocytes to maintain their nonreactive state. Similarly, after injury, FGF signaling delays the response of astrocytes and accelerates their deactivation. In addition, disrupting astrocytic FGF receptors results in reduced scar size without affecting neuronal survival. Overall, this study reveals that the activation of astrocytes in the normal and injured neocortex is not only regulated by proinflammatory factors, but also by factors such as FGFs that suppress activation, providing alternative therapeutic targets. PMID:25002516

  3. Astrocyte activation is suppressed in both normal and injured brain by FGF signaling

    PubMed Central

    Kang, Wenfei; Balordi, Francesca; Su, Nan; Chen, Lin; Fishell, Gordon; Hébert, Jean M.

    2014-01-01

    In the brain, astrocytes are multifunctional cells that react to insults and contain damage. However, excessive or sustained reactive astrocytes can be deleterious to functional recovery or contribute to chronic inflammation and neuronal dysfunction. Therefore, astrocyte activation in response to damage is likely to be tightly regulated. Although factors that activate astrocytes have been identified, whether factors also exist that maintain astrocytes as nonreactive or reestablish their nonreactive state after containing damage remains unclear. By using loss- and gain-of-function genetic approaches, we show that, in the unperturbed adult neocortex, FGF signaling is required in astrocytes to maintain their nonreactive state. Similarly, after injury, FGF signaling delays the response of astrocytes and accelerates their deactivation. In addition, disrupting astrocytic FGF receptors results in reduced scar size without affecting neuronal survival. Overall, this study reveals that the activation of astrocytes in the normal and injured neocortex is not only regulated by proinflammatory factors, but also by factors such as FGFs that suppress activation, providing alternative therapeutic targets. PMID:25002516

  4. The vasopressinergic innervation of the brain in normal and castrated rats.

    PubMed

    DeVries, G J; Buijs, R M; Van Leeuwen, F W; Caffé, A R; Swaab, D F

    1985-03-01

    A detailed description is given of the distribution of vasopressin-immunoreactive structures in the brain of intact adult male rats. By application of a modified immunocytochemical procedure, vasopressin-immunoreactive fibers were detected in many new areas. In adult male rats which were castrated 15 weeks before death, vasopressin-immunoreactive cell bodies had disappeared from the bed nucleus of the stria terminalis and the medial amygdaloid nucleus. No obvious changes were found in vasopressin-immunoreactive cell bodies in other areas. Furthermore, a very strong reduction was seen in the density of vasopressin-immunoreactive fibers in the olfactory tubercle, nucleus of the diagonal band and its immediate surroundings, ventral pallidum, basal nucleus of Meynert, lateral septum, septofimbrial nucleus, ventral hippocampal formation, amygdaloid area, pre- and supramammillary nucleus, supramammillary decussation, (inter)dorsomedial, parafascicular, and ventral aspect of paraventricular thalamic nuclei, zona incerta, lateral habenular nucleus, ventral tegmental area, substantia nigra, periventricular gray, dorsal and median raphe nucleus, and locus coeruleus. No changes were observed in other areas containing vasopressin-immunoreactive fibers. These changes following gonadectomy were not observed in castrated rats which had been treated with testosterone. The results suggest that vasopressin projections from the bed nucleus of the stria terminalis and possibly from the medial amygdaloid nucleus require the presence of gonadal hormones for their normal appearance. This is in contrast to pathways arising from the hypothalamic vasopressin-producing nuclei, which fail to show obvious changes following castration. PMID:3882778

  5. FMRI Brain Activation in a Finnish Family with Specific Language Impairment Compared with a Normal Control Group

    ERIC Educational Resources Information Center

    Hugdahl, Kenneth; Gundersen, Hilde; Brekke, Cecilie; Thomsen, Tormod; Rimol, Lars Morten; Ersland, Lars; Niemi, Jussi

    2004-01-01

    The aim of the present study was to investigate differences in brain activation in a family with SLI as compared to intact individuals with normally developed language during processing of language stimuli. Functional magnetic resonance imaging (fMRI) was used to monitor changes in neuronal activation in temporal and frontal lobe areas in 5…

  6. NUTRIENT PATTERNS AND BRAIN BIOMARKERS OF ALZHEIMER’S DISEASE IN COGNITIVELY NORMAL INDIVIDUALS

    PubMed Central

    BERTI, V.; MURRAY, J.; DAVIES, M.; SPECTOR, N.; TSUI, W.H.; LI, Y.; WILLIAMS, S.; PIRRAGLIA, E.; VALLABHAJOSULA, S.; MCHUGH, P.; PUPI, A.; DE LEON, M.J.; MOSCONI, L.

    2015-01-01

    Objectives Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer’s disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD. Design Cross-sectional study. Setting Manhattan (broader area). Participants Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-β, Aβ) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined. Measurements Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers. Results None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB&Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ω-3 and ω-6 PUFA, and vitamin E [VitE&PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants&Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12&D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12&D

  7. Normal Organ Weights in Women: Part II-The Brain, Lungs, Liver, Spleen, and Kidneys.

    PubMed

    Molina, D Kimberley; DiMaio, Vincent J M

    2015-09-01

    Organomegaly can be a sign of disease and pathology, although standard tables defining organomegaly have yet to be established and universally accepted. This study was designed to address the issue and to determine a normal weight for the major organs in adult human females. A prospective study was undertaken of healthy females who had sudden, traumatic deaths at age 18 to 35 years. Cases were excluded if there was a history of medical illness including illicit drug use, prolonged medical treatment was performed, there was a prolonged period between the time of injury and death, body length and weight could not be accurately assessed, or if any illness or intoxication was identified after gross and microscopic analysis including evidence of systemic disease. Individual organs were excluded if there was significant injury to the organ that could have affected the weight. A total of 102 cases met criteria for inclusion in the study during the approximately 10-year period of data collection from 2004 to 2014. The decedents had an average age of 24.4 years and ranged in length from 141 to 182 cm (56.4-72.8 inches) with an average length of 160 cm (64 inches). The weight ranged from 35.9 to 152 kg (79-334 lb) with an average weight of 65.3 kg (143 lb). The majority of the decedents (86%) died of either ballistic or blunt force (including craniocerebral) injuries. The mean brain weight was 1233 g (range, 1000-1618 g); liver mean weight, 1288 g (range, 775-2395 g); spleen mean weight, 115 g (range, 51-275 g); right lung mean weight, 340 g (range, 142-835 g); left lung mean, 299 g (range, 108-736 g); right kidney mean weight, 108 g (range, 67-261 g); and the left kidney mean weight, 116 g (range, 55-274 g). Regression analysis was performed and showed that there were insufficient associations between organ weight and body length, body weight, and body mass index to allow for predictability. The authors therefore propose establishing a reference range for organ weights in

  8. Normal organ weights in men: part II-the brain, lungs, liver, spleen, and kidneys.

    PubMed

    Molina, D Kimberley; DiMaio, Vincent J M

    2012-12-01

    Organomegaly can be a sign of disease and pathologic abnormality, although standard tables defining organomegaly have yet to be established and universally accepted. This study was designed to address the issue and to determine a normal weight for the major organs in adult human males. A prospective study of healthy men aged 18 to 35 years who died of sudden, traumatic deaths was undertaken. Cases were excluded if there was a history of medical illness including illicit drug use, if prolonged medical treatment was performed, if there was a prolonged period between the time of injury and death, if body length and weight could not be accurately assessed, or if any illness or intoxication was identified after gross and microscopic analysis including evidence of systemic disease. Individual organs were excluded if there was significant injury to the organ, which could have affected the weight. A total of 232 cases met criteria for inclusion in the study during the approximately 6-year period of data collection from 2005 to 2011. The decedents had a mean age of 23.9 years and ranged in length from 146 to 193 cm, with a mean length of 173 cm. The weight ranged from 48.5 to 153 kg, with a mean weight of 76.4 kg. Most decedents (87%) died of either ballistic or blunt force (including craniocerebral) injuries. The mean weight of the brain was 1407 g (range, 1070-1767 g), that of the liver was 1561 g (range, 838-2584 g), that of the spleen was 139 g (range, 43-344 g), that of the right lung was 445 g (range, 185-967 g), that of the left lung was 395 g (range, 186-885 g), that of the right kidney was 129 g (range, 79-223 g), and that of the left kidney was 137 g (range, 74-235 g). Regression analysis was performed and showed that there were insufficient associations between organ weight and body length, body weight, and body mass index to allow for predictability. The authors, therefore, propose establishing a reference range for organ weights in men, much like those in use

  9. An update of the classical and novel methods used for measuring fast neurotransmitters during normal and brain altered function.

    PubMed

    Cifuentes Castro, Victor Hugo; López Valenzuela, Carmen Lucía; Salazar Sánchez, Juan Carlos; Peña, Kenia Pardo; López Pérez, Silvia J; Ibarra, Jorge Ortega; Villagrán, Alberto Morales

    2014-12-01

    To understand better the cerebral functions, several methods have been developed to study the brain activity, they could be related with morphological, electrophysiological, molecular and neurochemical techniques. Monitoring neurotransmitter concentration is a key role to know better how the brain works during normal or pathological conditions, as well as for studying the changes in neurotransmitter concentration with the use of several drugs that could affect or reestablish the normal brain activity. Immediate response of the brain to environmental conditions is related with the release of the fast acting neurotransmission by glutamate (Glu), γ-aminobutyric acid (GABA) and acetylcholine (ACh) through the opening of ligand-operated ion channels. Neurotransmitter release is mainly determined by the classical microdialysis technique, this is generally coupled to high performance liquid chromatography (HPLC). Detection of neurotransmitters can be done by fluorescence, optical density, electrochemistry or other detection systems more sophisticated. Although the microdialysis method is the golden technique to monitor the brain neurotransmitters, it has a poor temporal resolution. Recently, with the use of biosensor the drawback of temporal resolution has been improved considerably, however other inconveniences have merged, such as stability, reproducibility and the lack of reliable biosensors mainly for GABA. The aim of this review is to show the important advances in the different ways to measure neurotransmitter concentrations; both with the use of classic techniques as well as with the novel methods and alternant approaches to improve the temporal resolution. PMID:25977677

  10. Studies of a nuclear matrix protein restricted to normal brain cells and lead-induced intranuclear inclusion bodies of kidney

    SciTech Connect

    Shelton, K.; Egle, P.; Redford, K.; Bigbee, J.

    1986-05-01

    A nuclear matrix protein, p32/6.3, with an unusual tissue distribution, has been identified. Protein from 21 tissues was surveyed by immunoprobing Western blots. In normal adult rats p32/6.3 is found only in grey matter from the cerebrum and the cerebellum, occurring in both neurons and astrocytes. Other brain cell types have not been examined. The protein appears to be developmentally regulated. It is detectable in the brain within a few days after birth and reaches adult levels within one to two weeks. Brain p32/6.3 has been found in all animals tested including rat, mouse, dog, cow, pig, chicken and human. This conservation indicates a fundamental role for p32/6.3 in the nucleus of brain cells. Possible functions for p32/6.3 may be indicated by a second novel occurrence. Chronic lead poisoning characteristically induces intranuclear inclusion bodies in the cells lining kidney proximal tubules. p32/6.3 is a major constituent of these inclusion bodies. They are also rich in lead and other metals including calcium, iron, zinc, copper and cadmium. These diverse observations suggest that p32/6.3 may have a role in metal homeostasis in the brain of normal animals.

  11. An Update of the Classical and Novel Methods Used for Measuring Fast Neurotransmitters During Normal and Brain Altered Function

    PubMed Central

    Cifuentes Castro, Victor Hugo; López Valenzuela, Carmen Lucía; Salazar Sánchez, Juan Carlos; Peña, Kenia Pardo; López Pérez, Silvia J.; Ibarra, Jorge Ortega; Villagrán, Alberto Morales

    2014-01-01

    To understand better the cerebral functions, several methods have been developed to study the brain activity, they could be related with morphological, electrophysiological, molecular and neurochemical techniques. Monitoring neurotransmitter concentration is a key role to know better how the brain works during normal or pathological conditions, as well as for studying the changes in neurotransmitter concentration with the use of several drugs that could affect or reestablish the normal brain activity. Immediate response of the brain to environmental conditions is related with the release of the fast acting neurotransmission by glutamate (Glu), γ-aminobutyric acid (GABA) and acetylcholine (ACh) through the opening of ligand-operated ion channels. Neurotransmitter release is mainly determined by the classical microdialysis technique, this is generally coupled to high performance liquid chromatography (HPLC). Detection of neurotransmitters can be done by fluorescence, optical density, electrochemistry or other detection systems more sophisticated. Although the microdialysis method is the golden technique to monitor the brain neurotransmitters, it has a poor temporal resolution. Recently, with the use of biosensor the drawback of temporal resolution has been improved considerably, however other inconveniences have merged, such as stability, reproducibility and the lack of reliable biosensors mainly for GABA. The aim of this review is to show the important advances in the different ways to measure neurotransmitter concentrations; both with the use of classic techniques as well as with the novel methods and alternant approaches to improve the temporal resolution. PMID:25977677

  12. Expression pattern and cellular origin of cytokines in the normal and Toxoplasma gondii-infected murine brain.

    PubMed Central

    Schlüter, D.; Kaefer, N.; Hof, H.; Wiestler, O. D.; Deckert-Schlüter, M.

    1997-01-01

    In the normal brain, low levels of cytokines are observed, whereas inflammatory disorders of the central nervous system are characterized by an up-regulation of cytokine production. The cellular sources for cytokines in the central nervous system are largely undefined. In the present study, we have analyzed intracerebral cytokine production in normal and Toxoplasma gondii-infected mice using immunohistochemistry, in situ hybridization, flow cytometry of brain-derived leukocytes, and reverse transcriptase polymerase chain reaction detection in various subpopulations of inflammatory cells. In the normal brain, neurons and choroid plexus epithelia expressed interleukin (IL)-1 beta and IL-10. Microglia/macrophages produced IL-1 beta, IL-10, and tumor necrosis factor-alpha In Toxoplasma encephalitis, these cell types exhibited increased levels of the respective cytokines. In addition, microglia/macrophages showed a de novo expression of inducible nitric oxide synthase. CD4+ and CD8+ T cells, which were recruited to the brain, produced IL-2, IL-10, tumor necrosis factor-alpha, and interferon-gamma. IL-4 was exclusively detectable in CD4+ T cells, whereas CD8+ T cells showed expression of IL-1 beta. As chronic Toxoplasma encephalitis was not associated with neuronal degeneration and an up-regulation of neurotrophic factors, some cytokines may also exert neurotrophic and/or neuroprotective properties. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:9060839

  13. Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity.

    PubMed

    Schmidt, André; Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Borgwardt, Stefan

    2015-01-01

    Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of

  14. The diffusion tensor imaging (DTI) component of the NIH MRI study of normal brain development (PedsDTI).

    PubMed

    Walker, Lindsay; Chang, Lin-Ching; Nayak, Amritha; Irfanoglu, M Okan; Botteron, Kelly N; McCracken, James; McKinstry, Robert C; Rivkin, Michael J; Wang, Dah-Jyuu; Rumsey, Judith; Pierpaoli, Carlo

    2016-01-01

    The NIH MRI Study of normal brain development sought to characterize typical brain development in a population of infants, toddlers, children and adolescents/young adults, covering the socio-economic and ethnic diversity of the population of the United States. The study began in 1999 with data collection commencing in 2001 and concluding in 2007. The study was designed with the final goal of providing a controlled-access database; open to qualified researchers and clinicians, which could serve as a powerful tool for elucidating typical brain development and identifying deviations associated with brain-based disorders and diseases, and as a resource for developing computational methods and image processing tools. This paper focuses on the DTI component of the NIH MRI study of normal brain development. In this work, we describe the DTI data acquisition protocols, data processing steps, quality assessment procedures, and data included in the database, along with database access requirements. For more details, visit http://www.pediatricmri.nih.gov. This longitudinal DTI dataset includes raw and processed diffusion data from 498 low resolution (3 mm) DTI datasets from 274 unique subjects, and 193 high resolution (2.5 mm) DTI datasets from 152 unique subjects. Subjects range in age from 10 days (from date of birth) through 22 years. Additionally, a set of age-specific DTI templates are included. This forms one component of the larger NIH MRI study of normal brain development which also includes T1-, T2-, proton density-weighted, and proton magnetic resonance spectroscopy (MRS) imaging data, and demographic, clinical and behavioral data. PMID:26048622

  15. CD163 Identifies Perivascular Macrophages in Normal and Viral Encephalitic Brains and Potential Precursors to Perivascular Macrophages in Blood

    PubMed Central

    Kim, Woong-Ki; Alvarez, Xavier; Fisher, Jeanne; Bronfin, Benjamin; Westmoreland, Susan; McLaurin, JoAnne; Williams, Kenneth

    2006-01-01

    Perivascular macrophages are uniquely situated at the intersection between the nervous and immune systems. Although combined myeloid marker detection differentiates perivascular from resident brain macrophages (parenchymal microglia), no single marker distinguishes perivascular macrophages in humans and mice. Here, we present the macrophage scavenger receptor CD163 as a marker for perivascular macrophages in humans, monkeys, and mice. CD163 was primarily confined to perivascular macrophages and populations of meningeal and choroid plexus macrophages in normal brains and in brains of humans and monkeys with human immunodeficiency virus or simian immunodeficiency virus (SIV) encephalitis. Scattered microglia in SIV encephalitis lesions and multinucleated giant cells were also CD163 positive. Consistent with prior findings that perivascular macrophages are primary targets of human immunodeficiency virus and SIV, all SIV-infected cells in the brain were CD163 positive. Using fluorescent dyes that definitively and selectively label perivascular macrophages in vivo, we confirmed that dye-labeled simian perivascular macrophages were CD163 positive and able to repopulate the central nervous system within 24 hours. Flow cytometric studies demonstrated a subset of monocytes (CD163+CD14+CD16+) that were immunophenotypically similar to brain perivascular macrophages. These findings recognize CD163+ blood monocytes/macrophages as a source of brain perivascular macrophages and underscore the utility of this molecule in studying the biology of perivascular macrophages and their precursors in humans, monkeys, and mice. PMID:16507898

  16. Biondi ring tangles in the choroid plexus of Alzheimer's disease and normal aging brains: a quantitative study.

    PubMed

    Wen, G Y; Wisniewski, H M; Kascsak, R J

    1999-06-19

    The choroid plexus (CP) performs the vital function of producing up to 90% (450-1000 ml/day) of cerebrospinal fluid (CSF) to nourish and to protect the brain in the CSF suspension. The CP also acts as a selective barrier between blood and CSF to regulate ions and other essential molecules. However, the accumulation of intracellular inclusions called Biondi ring tangles (BRTs) in CP cells of Alzheimer's disease (AD)/aging brains may affect these vital functions of the CP. Statistical analysis of quantitative data on the numbers of CP cells containing BRTs from 54 brains (29 AD and 25 normal control), age range 1-100 years, indicated a significant difference (p<0.00004) between AD and control brains, using analysis of covariance (ANCOVA) with age as covariate. This study compiled the first set of archives to reveal the distribution pattern of BRTs in the CP of AD brains at various ages. Electron microscopy of negatively stained isolated BRTs revealed that these tangles are made of tightly packed bundles of long filaments with diameter around 10 nm that are morphologically distinct from the more loosely packed/shorter bundles of 6-8 nm amyloid fibrils of neuritic plaques (NPs) and from the 24 nm paired helical filaments of neurofibrillary tangles (NFTs) in AD brain. These data suggest that BRTs may represent a significant and measurable biomarker for AD in addition to NPs and NFTs. PMID:10375650

  17. Searching for Factors Underlying Cerebral Plasticity in the Normal and Injured Brain

    ERIC Educational Resources Information Center

    Kolb, Bryan; Muhammad, Arif; Gibb, Robbin

    2011-01-01

    Brain plasticity refers to the capacity of the nervous system to change its structure and ultimately its function over a lifetime. There have been major advances in our understanding of the principles of brain plasticity and behavior in laboratory animals and humans. Over the past decade there have been advances in the application of these…

  18. Total and Regional Brain Volumes in a Population-Based Normative Sample from 4 to 18 Years: The NIH MRI Study of Normal Brain Development

    PubMed Central

    2012-01-01

    Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5–18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents. PMID:21613470

  19. Total and regional brain volumes in a population-based normative sample from 4 to 18 years: the NIH MRI Study of Normal Brain Development.

    PubMed

    2012-01-01

    Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents. PMID:21613470

  20. Diffusional anisotropy of the human brain assessed with diffusion-weighted MR: Relation with normal brain development and aging

    SciTech Connect

    Nomura, Toshiyuki; Sakuma, Hajime; Takeda, Kan; Tagami, Tomoyasu; Okuda, Yasuyuki; Nakagawa, Tsuyoshi )

    1994-02-01

    To analyze diffusional anisotropy in frontal and occipital white matter of human brain quantitatively as a function of age by using diffusion-weighted MR imaging. Ten neonates (<1 month), 13 infants (1-10 months), 9 children (1-11 years), and 16 adults (20-79 years) were examined. After taking axial spin-echo images of the brain, diffusion-sensitive gradients were added parallel or perpendicular to the orientation of nerve fibers. The apparent diffusion coefficient parallel to the nerve fibers (0) and that perpendicular to the fibers (90) were computed. The anisotropic ratio (90/0) was calculated as a function of age. Anisotropic ratios of frontal white matter were significantly larger in neonates as compared with infants, children, or adults. The ratios showed rapid decrease until 6 months and thereafter were identical in all subjects. In the occipital lobe, the ratios were also greater in neonates, but the differences from other age groups were not so prominent as in the frontal lobe. Comparing anisotropic ratios between frontal and occipital lobes, a significant difference was observed only in neonates. Diffusion-weighted images demonstrated that the myelination process starts earlier in the occipital lobe than in the frontal lobe. The changes of diffusional anisotropy in white matter are completed within 6 months after birth. Diffusion-weighted imaging provides earlier detection of brain myelination compared with the conventional T1- and T2-weighted images. 18 refs., 6 figs., 1 tab.

  1. Oxygen at 2 atmospheres absolute pressure does not increase the radiation sensitivity of normal brain in rats

    SciTech Connect

    Routh, A.; Kapp, J.P.; Smith, E.E.; Bebin, J.; Barnes, T.; Hickman, B.T.

    1984-07-01

    Cranial radiation was administered to CD Fisher rats at 1.0, 1.5 and 2.0 atmospheres oxygen pressure. Life span following radiation was recorded. Surviving animals were killed at 28 weeks and the brains were examined independently by two neuropathologists. Survival time was significantly less in animals receiving higher doses of radiation but showed no relationship to the oxygen pressure in the environment of the animal at the time radiation was administered. Microscopic examination of the brain did not reveal any differences in animals radiated in a normobaric or hyperbaric oxygen environment. It is concluded that hyperbaric oxygen does not sensitize the normal brain to the effects of ionizing radiation.

  2. Distribution of PSA-NCAM in normal, Alzheimer's and Parkinson's disease human brain.

    PubMed

    Murray, Helen C; Low, Victoria F; Swanson, Molly E V; Dieriks, Birger V; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2016-08-25

    Polysialated neural cell adhesion molecule (PSA-NCAM) is a membrane bound glycoprotein widely expressed during nervous system development. While commonly described in the neurogenic niches of the adult human brain, there is limited evidence of its distribution in other brain regions. PSA-NCAM is an important regulator of cell-cell interactions and facilitates cell migration and plasticity. Recent evidence suggests these functions may be altered in neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD). This study provides a detailed description of the PSA-NCAM distribution throughout the human brain and quantitatively compares the staining load in cortical regions and sub-cortical structures between the control, AD and PD brain. Our results provide evidence of widespread, yet specific, PSA-NCAM expression throughout the human brain including regions devoid of PSA-NCAM in the rodent brain such as the caudate nucleus (CN) and cerebellum (CB). We also detected a significant reduction in PSA-NCAM load in the entorhinal cortex (EC) of cases that was inversely correlated with hyperphosphorylated tau load. These results demonstrate that PSA-NCAM-mediated structural plasticity may not be limited to neurogenic niches and is conserved in the aged brain. We also provide evidence that PSA-NCAM is reduced in the EC, a region severely affected by AD pathology. PMID:27282086

  3. Cortical thinning in cognitively normal elderly cohort of 60 to 89 year old from AIBL database and vulnerable brain areas

    NASA Astrophysics Data System (ADS)

    Lin, Zhongmin S.; Avinash, Gopal; Yan, Litao; McMillan, Kathryn

    2014-03-01

    Age-related cortical thinning has been studied by many researchers using quantitative MR images for the past three decades and vastly differing results have been reported. Although results have shown age-related cortical thickening in elderly cohort statistically in some brain regions under certain conditions, cortical thinning in elderly cohort requires further systematic investigation. This paper leverages our previously reported brain surface intensity model (BSIM)1 based technique to measure cortical thickness to study cortical changes due to normal aging. We measured cortical thickness of cognitively normal persons from 60 to 89 years old using Australian Imaging Biomarkers and Lifestyle Study (AIBL) data. MRI brains of 56 healthy people including 29 women and 27 men were selected. We measured average cortical thickness of each individual in eight brain regions: parietal, frontal, temporal, occipital, visual, sensory motor, medial frontal and medial parietal. Unlike the previous published studies, our results showed consistent age-related thinning of cerebral cortex in all brain regions. The parietal, medial frontal and medial parietal showed fastest thinning rates of 0.14, 0.12 and 0.10 mm/decade respectively while the visual region showed the slowest thinning rate of 0.05 mm/decade. In sensorimotor and parietal areas, women showed higher thinning (0.09 and 0.16 mm/decade) than men while in all other regions men showed higher thinning than women. We also created high resolution cortical thinning rate maps of the cohort and compared them to typical patterns of PET metabolic reduction of moderate AD and frontotemporal dementia (FTD). The results seemed to indicate vulnerable areas of cortical deterioration that may lead to brain dementia. These results validate our cortical thickness measurement technique by demonstrating the consistency of the cortical thinning and prediction of cortical deterioration trend with AIBL database.

  4. Somatostatinergic systems: an update on brain functions in normal and pathological aging

    PubMed Central

    Martel, Guillaume; Dutar, Patrick; Epelbaum, Jacques; Viollet, Cécile

    2012-01-01

    Somatostatin is highly expressed in mammalian brain and is involved in many brain functions such as motor activity, sleep, sensory, and cognitive processes. Five somatostatin receptors have been described: sst1, sst2 (A and B), sst3, sst4, and sst5, all belonging to the G-protein-coupled receptor family. During the recent years, numerous studies contributed to clarify the role of somatostatin systems, especially long-range somatostatinergic interneurons, in several functions they have been previously involved in. New advances have also been made on the alterations of somatostatinergic systems in several brain diseases and on the potential therapeutic target they represent in these pathologies. PMID:23230430

  5. Blood-Brain Barrier Permeability of Normal Appearing White Matter in Relapsing-Remitting Multiple Sclerosis

    PubMed Central

    Lund, Henrik; Krakauer, Martin; Skimminge, Arnold; Sellebjerg, Finn; Garde, Ellen; Siebner, Hartwig R.; Paulson, Olaf B.; Hesse, Dan; Hanson, Lars G.

    2013-01-01

    Background Multiple sclerosis (MS) affects the integrity of the blood-brain barrier (BBB). Contrast-enhanced T1 weighted magnetic resonance imaging (MRI) is widely used to characterize location and extent of BBB disruptions in focal MS lesions. We employed quantitative T1 measurements before and after the intravenous injection of a paramagnetic contrast agent to assess BBB permeability in the normal appearing white matter (NAWM) in patients with relapsing-remitting MS (RR-MS). Methodology/Principal Findings Fifty-nine patients (38 females) with RR-MS undergoing immunomodulatory treatment and nine healthy controls (4 females) underwent quantitative T1 measurements at 3 tesla before and after injection of a paramagnetic contrast agent (0.2 mmol/kg Gd-DTPA). Mean T1 values were calculated for NAWM in patients and total cerebral white matter in healthy subjects for the T1 measurements before and after injection of Gd-DTPA. The pre-injection baseline T1 of NAWM (945±55 [SD] ms) was prolonged in RR-MS relative to healthy controls (903±23 ms, p = 0.028). Gd-DTPA injection shortened T1 to a similar extent in both groups. Mean T1 of NAWM was 866±47 ms in the NAWM of RR-MS patients and 824±13 ms in the white matter of healthy controls. The regional variability of T1 values expressed as the coefficient of variation (CV) was comparable between the two groups at baseline, but not after injection of the contrast agent. After intravenous Gd-DTPA injection, T1 values in NAWM were more variable in RR-MS patients (CV = 0.198±0.046) compared to cerebral white matter of healthy controls (CV = 0.166±0.018, p = 0.046). Conclusions/Significance We found no evidence of a global BBB disruption within the NAWM of RR-MS patients undergoing immunomodulatory treatment. However, the increased variation of T1 values in NAWM after intravenous Gd-DTPA injection points to an increased regional inhomogeneity of BBB function in NAWM in relapsing-remitting MS. PMID:23441184

  6. Mapping metals in Parkinson's and normal brain using rapid-scanning x-ray fluorescence

    NASA Astrophysics Data System (ADS)

    Popescu, Bogdan F. Gh; George, Martin J.; Bergmann, Uwe; Garachtchenko, Alex V.; Kelly, Michael E.; McCrea, Richard P. E.; Lüning, Katharina; Devon, Richard M.; George, Graham N.; Hanson, Akela D.; Harder, Sheri M.; Chapman, L. Dean; Pickering, Ingrid J.; Nichol, Helen

    2009-02-01

    Rapid-scanning x-ray fluorescence (RS-XRF) is a synchrotron technology that maps multiple metals in tissues by employing unique hardware and software to increase scanning speed. RS-XRF was validated by mapping and quantifying iron, zinc and copper in brain slices from Parkinson's disease (PD) and unaffected subjects. Regions and structures in the brain were readily identified by their metal complement and each metal had a unique distribution. Many zinc-rich brain regions were low in iron and vice versa. The location and amount of iron in brain regions known to be affected in PD agreed with analyses using other methods. Sample preparation is simple and standard formalin-fixed autopsy slices are suitable. RS-XRF can simultaneously and non-destructively map and quantify multiple metals and holds great promise to reveal metal pathologies associated with PD and other neurodegenerative diseases as well as diseases of metal metabolism.

  7. Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states.

    PubMed

    Lecrux, C; Hamel, E

    2016-10-01

    Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic- or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574304

  8. Hydroxysteroid sulfotransferase 2B1b expression and localization in normal human brain

    PubMed Central

    Salman, Emily D.; Faye-Petersen, Ona; Falany, Charles N.

    2012-01-01

    Steroid sulfonation in the human brain has not been well characterized. The major sulfotransferase (SULT) isoforms that conjugate steroids in humans are SULT1E1, SULT2A1, and SULT2B1b. SULT2B1b catalyzes the sulfonation of 3β-hydroxysteroids, including neurosteroids dehydroepiandrosterone and pregnenolone, as well as cholesterol and several hydroxycholesterols. SULT2B1b mRNA and protein expression were detected in adult and fetal human brain sections, whereas neither mRNA, nor protein expression were identified for SULT1E1 or SULT2A1. Using immunohistochemical analysis, SULT2B1b expression was detected in neurons and oligodendrocytes in adult brain and in epithelial tissues in 28-week-old fetal brain. Sulfonation of cholesterol, oxysterols, and neurosteroids in the brain is apparently catalyzed by SULT2B1b since expression of neither SULT2A1 nor SULT1E1 was detected in human brain sections. SULT2B1b mRNA and protein were also detected in human U373-MG glioblastoma cells. Both mRNA and protein expression of liver X receptor (LXR)-β, but not LXR-α, were detected in U373-MG cells, and LXR-β activation resulted in a decrease in SULT2B1b protein expression. Since hydroxycholesterols are important physiological LXR activators, this suggests a role for regulation of sterol metabolism by LXR and SULT2B1b. Therefore, elucidating key enzymes in the metabolism of cholesterol and neurosteroids could help define the properties of steroid conjugation in the human brain. PMID:24683427

  9. Graph theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks.

    PubMed

    Guye, Maxime; Bettus, Gaelle; Bartolomei, Fabrice; Cozzone, Patrick J

    2010-12-01

    Graph theoretical analysis of structural and functional connectivity MRI data (ie. diffusion tractography or cortical volume correlation and resting-state or task-related (effective) fMRI, respectively) has provided new measures of human brain organization in vivo. The most striking discovery is that the whole-brain network exhibits "small-world" properties shared with many other complex systems (social, technological, information, biological). This topology allows a high efficiency at different spatial and temporal scale with a very low wiring and energy cost. Its modular organization also allows for a high level of adaptation. In addition, degree distribution of brain networks demonstrates highly connected hubs that are crucial for the whole-network functioning. Many of these hubs have been identified in regions previously defined as belonging to the default-mode network (potentially explaining the high basal metabolism of this network) and the attentional networks. This could explain the crucial role of these hub regions in physiology (task-related fMRI data) as well as in pathophysiology. Indeed, such topological definition provides a reliable framework for predicting behavioral consequences of focal or multifocal lesions such as stroke, tumors or multiple sclerosis. It also brings new insights into a better understanding of pathophysiology of many neurological or psychiatric diseases affecting specific local or global brain networks such as epilepsy, Alzheimer's disease or schizophrenia. Graph theoretical analysis of connectivity MRI data provides an outstanding framework to merge anatomical and functional data in order to better understand brain pathologies. PMID:20349109

  10. The Whole-Brain N-Acetylaspartate Correlates with Education in Normal Adults

    PubMed Central

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

    2012-01-01

    N-acetylaspartate (NAA) is an index of neuronal integrity. We hypothesized that in healthy subjects its whole brain concentration (WBNAA) may be related to formal educational attainment, a common proxy for cognitive reserve. To test this hypothesis 97 middle aged to elderly subjects (51–89 years old, 38% women) underwent brain MRI and non-localizing proton spectroscopy. Their WBNAA was obtained by dividing their whole-head NAA amount with the brain volume. Intracranial volume and fractional brain volume, a metric of brain atrophy, were also determined. Each subject’s educational attainment was the sum of their years of formal education. In the entire group higher education was associated with larger intracranial volume. The relationship between WBNAA and education was observed only in younger (51–70 years old) participants. In this group education explained 21% variance in WBNAA. More WBNAA was related to more years of formal education in adults and younger elders. Prospective studies can determine whether this relationship reflects a true advantage from years of training versus innate characteristic predisposing to higher achievements later in life. We offer that late life WBNAA may be more affected by other like factors acting at midlife and later. PMID:23177924

  11. Label-Free Quantitative LC–MS Proteomics of Alzheimer’s Disease and Normally Aged Human Brains

    SciTech Connect

    Andreev, Victor P.; Petyuk, Vladislav A.; Brewer, Heather M.; Karpievitch, Yuliya V.; Xie, Fang; Clarke, Jennifer; Camp, David; Smith, Richard D.; Lieberman, Andrew P.; Albin, Roger L.; Nawaz, Zafar; El Hokayem, Jimmy; Myers, Amanda J.

    2012-06-01

    Quantitative proteomics analysis of cortical samples of 10 Alzheimer’s disease (AD) brains versus 10 normally aged brains was performed by following the accurate mass and time tag (AMT) approach with the high resolution LTQ Orbitrap mass spectrometer. More than 1400 proteins were identified and quantitated. A conservative approach of selecting only the consensus results of four normalization methods was suggested and used. A total of 197 proteins were shown to be significantly differentially abundant (p-values <0.05, corrected for multiplicity of testing) in AD versus control brain samples. Thirty-seven of these proteins were reported as differentially abundant or modified in AD in previous proteomics and transcriptomics publications. The rest to the best of our knowledge are new. Mapping of the discovered proteins with bioinformatic tools revealed significant enrichment with differentially abundant proteins of pathways and processes known to be important in AD, including signal transduction, regulation of protein phosphorylation, immune response, cytoskeleton organization, lipid metabolism, energy production, and cell death.

  12. Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome

    PubMed Central

    Becerra, Lino; Sava, Simona; Simons, Laura E.; Drosos, Athena M.; Sethna, Navil; Berde, Charles; Lebel, Alyssa A.; Borsook, David

    2014-01-01

    Pediatric complex regional pain syndrome (P-CRPS) offers a unique model of chronic neuropathic pain as it either resolves spontaneously or through therapeutic interventions in most patients. Here we evaluated brain changes in well-characterized children and adolescents with P-CRPS by measuring resting state networks before and following a brief (median = 3 weeks) but intensive physical and psychological treatment program, and compared them to matched healthy controls. Differences in intrinsic brain networks were observed in P-CRPS compared to controls before treatment (disease state) with the most prominent differences in the fronto-parietal, salience, default mode, central executive, and sensorimotor networks. Following treatment, behavioral measures demonstrated a reduction of symptoms and improvement of physical state (pain levels and motor functioning). Correlation of network connectivities with spontaneous pain measures pre- and post-treatment indicated concomitant reductions in connectivity in salience, central executive, default mode and sensorimotor networks (treatment effects). These results suggest a rapid alteration in global brain networks with treatment and provide a venue to assess brain changes in CRPS pre- and post-treatment, and to evaluate therapeutic effects. PMID:25379449

  13. Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain

    PubMed Central

    Egorova, Natalia; Gollub, Randy L.; Kong, Jian

    2015-01-01

    Acupuncture, an ancient East Asian therapy, is aimed at rectifying the imbalance within the body caused by disease. Studies evaluating the efficacy of acupuncture with neuroimaging tend to concentrate on brain regions within the pain matrix, associated with acute pain. We, however, focused on the effect of repeated acupuncture treatment specifically on brain regions known to support functions dysregulated in chronic pain disorders. Transition to chronic pain is associated with increased attention to pain, emotional rumination, nociceptive memory and avoidance learning, resulting in brain connectivity changes, specifically affecting the periaqueductal gray (PAG), medial frontal cortex (MFC) and bilateral hippocampus (Hpc). We demonstrate that the PAG–MFC and PAG–Hpc connectivity in patients with chronic pain due to knee osteoarthritis indeed correlates with clinical severity scores and further show that verum acupuncture-induced improvement in pain scores (compared to sham) is related to the modulation of PAG–MFC and PAG–Hpc connectivity in the predicted direction. This study shows that repeated verum acupuncture might act by restoring the balance in the connectivity of the key pain brain regions, altering pain-related attention and memory. PMID:26594625

  14. Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain.

    PubMed

    Egorova, Natalia; Gollub, Randy L; Kong, Jian

    2015-01-01

    Acupuncture, an ancient East Asian therapy, is aimed at rectifying the imbalance within the body caused by disease. Studies evaluating the efficacy of acupuncture with neuroimaging tend to concentrate on brain regions within the pain matrix, associated with acute pain. We, however, focused on the effect of repeated acupuncture treatment specifically on brain regions known to support functions dysregulated in chronic pain disorders. Transition to chronic pain is associated with increased attention to pain, emotional rumination, nociceptive memory and avoidance learning, resulting in brain connectivity changes, specifically affecting the periaqueductal gray (PAG), medial frontal cortex (MFC) and bilateral hippocampus (Hpc). We demonstrate that the PAG-MFC and PAG-Hpc connectivity in patients with chronic pain due to knee osteoarthritis indeed correlates with clinical severity scores and further show that verum acupuncture-induced improvement in pain scores (compared to sham) is related to the modulation of PAG-MFC and PAG-Hpc connectivity in the predicted direction. This study shows that repeated verum acupuncture might act by restoring the balance in the connectivity of the key pain brain regions, altering pain-related attention and memory. PMID:26594625

  15. Monoaminergic uptake in synaptosomes prepared from frozen brain tissue samples of normal and narcoleptic canines.

    PubMed

    Valtier, D; Dement, W C; Mignot, E

    1992-08-14

    Canine narcolepsy, a model of the human disorder, is associated with altered catecholamine but not serotonin (5-HT) metabolism in some brain areas, particularly the amygdala. A possible explanation for these global changes could be the existence of specific defects in monoamine uptake processes. We have studied the uptake of [3H]norepinephrine (NE), [3H]dopamine (DA) and [3H]5-HT in synaptosomes prepared from cortex and amygdala of narcoleptic and control Doberman pinscher brains. Since narcoleptic canines are relatively few in number, we have used a specific brain freezing procedure that has been reported to allow restoration of metabolically functional tissue upon thawing. Preliminary studies comparing monoamine uptake in fresh and frozen brain samples of both groups of dogs were carried out and demonstrated that this procedure significantly altered serotoninergic but not noradrenergic and dopaminergic uptake. All further investigations were then done on synaptosomes prepared from frozen samples. Our results demonstrate that synaptosomal uptake of [3H]NE, [3H]DA and [3H]5-HT in cortex and amygdala are not altered in narcolepsy. PMID:1393561

  16. Calpain proteolysis of alpha II-spectrin in the normal adult human brain.

    PubMed

    Huh, G Y; Glantz, S B; Je, S; Morrow, J S; Kim, J H

    2001-12-01

    The proteolysis of alphaII-spectrin by calpain may be physiologically involved with synaptic remodeling, long-term potentiation, and memory formation. Calpain activation may also mediate neuronal apoptosis, responses to hypoxic insult, and excitotoxic injury. Surprisingly little is known of the activity of these calpain-mediated processes in the adult human brain. Using an antibody that specifically recognizes calpain-cleaved alphaII-spectrin, we have mapped the topographic distribution of the major alphaII-spectrin break-down product (alphaII-bdp1) in six adult brains examined post-mortem. All brains were from patients without evident neurological disease. Focally positive alphaII-bdp1 was consistently detected in the neuropil of the cortical gray matter, in occasional pyramidal neurons, and in rare reactive astrocytes in the cerebral cortex and hippocampus. Cerebellar Purkinje cells were more frequently, and more intensely, immunopositive. In all fields, staining was most intense in the soma and dendrites of neurons. There was no correlation of the frequency of positive cells with the postmortem interval or clinical condition. While these findings do not rigorously exclude contributions from postmortem calpain activation, they do suggest that a low-level of calpain processing of alphaII-spectrin is likely to be a constitutive process in the adult human brain. PMID:11720774

  17. Rough Sets and Stomped Normal Distribution for Simultaneous Segmentation and Bias Field Correction in Brain MR Images.

    PubMed

    Banerjee, Abhirup; Maji, Pradipta

    2015-12-01

    The segmentation of brain MR images into different tissue classes is an important task for automatic image analysis technique, particularly due to the presence of intensity inhomogeneity artifact in MR images. In this regard, this paper presents a novel approach for simultaneous segmentation and bias field correction in brain MR images. It integrates judiciously the concept of rough sets and the merit of a novel probability distribution, called stomped normal (SN) distribution. The intensity distribution of a tissue class is represented by SN distribution, where each tissue class consists of a crisp lower approximation and a probabilistic boundary region. The intensity distribution of brain MR image is modeled as a mixture of finite number of SN distributions and one uniform distribution. The proposed method incorporates both the expectation-maximization and hidden Markov random field frameworks to provide an accurate and robust segmentation. The performance of the proposed approach, along with a comparison with related methods, is demonstrated on a set of synthetic and real brain MR images for different bias fields and noise levels. PMID:26462197

  18. The INIA19 Template and NeuroMaps Atlas for Primate Brain Image Parcellation and Spatial Normalization

    PubMed Central

    Rohlfing, Torsten; Kroenke, Christopher D.; Sullivan, Edith V.; Dubach, Mark F.; Bowden, Douglas M.; Grant, Kathleen A.; Pfefferbaum, Adolf

    2012-01-01

    The INIA19 is a new, high-quality template for imaging-based studies of non-human primate brains, created from high-resolution, T1-weighted magnetic resonance (MR) images of 19 rhesus macaque (Macaca mulatta) animals. Combined with the comprehensive cortical and sub-cortical label map of the NeuroMaps atlas, the INIA19 is equally suitable for studies requiring both spatial normalization and atlas label propagation. Population-averaged template images are provided for both the brain and the whole head, to allow alignment of the atlas with both skull-stripped and unstripped data, and thus to facilitate its use for skull stripping of new images. This article describes the construction of the template using freely available software tools, as well as the template itself, which is being made available to the scientific community (http://nitrc.org/projects/inia19/). PMID:23230398

  19. Cellular proliferation and infiltration following interstitial irradiation of normal dog brain is altered by an inhibitor of polyamine synthesis

    SciTech Connect

    Fike, J.R.; Gobbel, G.T.; Chou, D.

    1995-07-15

    The objectives of this study were to quantitatively define proliferative and infiltrative cell responses after focal {sup 125}I irradiation of normal brain, and to determine the effects of an intravenous infusion of {alpha}-defluoromethylornithine (DFMO) on those responses. Adult beagle dogs were irradiated using high activity {sup 125}I sources. Cellular responses were quantified using a histomorphometric analysis. After radiation alone, cellular events included a substantial acute inflammatory response followed by increased BrdU labeling and progressive increases in numbers of capillaries and astrocytes. {alpha}-Difluoromethylornithine treatment significantly affected the measured cell responses. As in controls, an early inflammatory response was measured, but after 2 weeks there were more PMNs/unit area than in controls. The onset of measurable BrdU labeling was delayed in DFMO-treated animals, and the magnitude of labeling was significantly reduced. Increases in astrocyte and vessel numbers/mm{sup 2} were observed after a 2-week delay. At the site of implant, astrocytes from DFMO-treated dogs were significantly smaller than those from controls. There is substantial cell proliferation and infiltration in response to interstitial irradiation of normal brain, and these responses are significantly altered by DFMO treatment. Although the precise mechanisms by which DFMO exerts its effects in this model are not known, the results from this study suggest that modification of radiation injury may be possible by manipulating the response of normal cells to injury. 57 refs., 6 figs.

  20. Abnormal regional cerebral blood flow found by technetium-99m ethyl cysteinate dimer brain single photon emission computed tomography in systemic lupus erythematosus patients with normal brain MRI findings.

    PubMed

    Chen, J J-H; Yen, R-F; Kao, A; Lin, C-C; Lee, C-C

    2002-11-01

    In this study, technetium-(99m) ethyl cysteinate dimer ((99m)Tc ECD) brain single photon emission computed tomography (SPECT) was used to detect regional cerebral blood flow (rCBF) of the brain in SLE patients with normal brain magnetic resonance imaging (MRI) findings. Twenty female SLE patients were enrolled in this study, divided into two groups. Group 1 consisted of 10 patients with neuropsychiatric manifestations. Group 2 consisted of 10 patients without neuropsychiatric manifestations. All patients had normal brain MRI findings. Another 10 SLE patients with abnormal MRI findings were included as group 3 for comparison. Meanwhile, 10 healthy female volunteers also underwent brain MRI and (99m)Tc ECD brain SPECT for comparison. The scans revealed hypoperfusion lesions in 9/20 (45%) SLE patients, including 7/10 (70%) cases in group 1 and 2/10 (20%) cases in group 2. In contrast, all 10 patients (100%) in group 3 had abnormal (99m)Tc ECD brain SPECT findings. The parietal lobes were the most commonly involved areas. We conclude that (99m)Tc ECD brain SPECT is more sensitive for detecting rCBF changes than is brain MRI in detecting the brain anatomic changes, and may have a diagnostic value in lupus cerebral involvement. However, (99m)Tc ECD brain SPECT may not be indicated for SLE patients with normal MRI and mild neuropsychiatric symptoms/signs, such headaches and dizziness. PMID:12447638

  1. Zika Brain Damage May Occur in Babies with Normal-Sized Heads

    MedlinePlus

    ... in Babies With Normal-Sized Heads Study suggests microcephaly birth defect isn't always present; cases may ... on infants born with too-small heads, or microcephaly. However, a new report suggests that newborns with ...

  2. The essential role of AMPA receptor GluR2 subunit RNA editing in the normal and diseased brain.

    PubMed

    Wright, Amanda; Vissel, Bryce

    2012-01-01

    α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are comprised of different combinations of GluA1-GluA4 (also known asGluR1-GluR4 and GluR-A to GluR-D) subunits. The GluA2 subunit is subject to RNA editing by the ADAR2 enzyme, which converts a codon for glutamine (Gln; Q), present in the GluA2 gene, to a codon for arginine (Arg; R) found in the mRNA. AMPA receptors are calcium (Ca(2+))-permeable if they contain the unedited GluA2(Q) subunit or if they lack the GluA2 subunit. While most AMPA receptors in the brain contain the edited GluA2(R) subunit and are therefore Ca(2+)-impermeable, recent evidence suggests that Ca(2+)-permeable AMPA receptors are important in synaptic plasticity, learning, and disease. Strong evidence supports the notion that Ca(2+)-permeable AMPA receptors are usually GluA2-lacking AMPA receptors, with little evidence to date for a significant role of unedited GluA2 in normal brain function. However, recent detailed studies suggest that Ca(2+)-permeable AMPA receptors containing unedited GluA2 do in fact occur in neurons and can contribute to excitotoxic cell loss, even where it was previously thought that there was no unedited GluA2.This review provides an update on the role of GluA2 RNA editing in the healthy and diseased brain and summarizes recent insights into the mechanisms that control this process. We suggest that further studies of the role of unedited GluA2 in normal brain function and disease are warranted, and that GluA2 editing should be considered as a possible contributing factor when Ca(2+)-permeable AMPA receptors are observed. PMID:22514516

  3. Immunohistoblot analysis on whole human hemispheres from normal and Alzheimer diseased brains.

    PubMed

    Beliczai, Zsuzsa; Varszegi, Szilvia; Gulyas, Balazs; Halldin, Christer; Kasa, Peter; Gulya, Karoly

    2008-12-01

    We demonstrate the feasibility and usefulness of the histoblot immunostaining of cryosections of whole hemispheres of healthy and Alzheimer diseased (AD) human brains by localizing a neuron-specific marker, the anti-neuronal nuclei (NeuN) antigen. As expected, cortical NeuN-immunopositive regions were generally thinner and lighter in the AD brains than in the controls. The advantages of using whole hemisphere histoblots: (1) they provide a low-resolution overview/outline of the antigen distribution in a large surface area, (2) large, thick, and/or unfixed tissue sections from post-mortem samples (perhaps of inferior tissue quality) can be compared, and (3) subsequent immunohistochemistry can be performed on the tissue sections used for the histoblots. PMID:18832000

  4. Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects.

    PubMed

    Villringer, A; Rosen, B R; Belliveau, J W; Ackerman, J L; Lauffer, R B; Buxton, R B; Chao, Y S; Wedeen, V J; Brady, T J

    1988-02-01

    Using a one-dimensional rapid imaging technique, we have found that injection of lanthanide chelates such as Gd(DTPA)2- leads to a significant decrease (50%) in rat brain signal intensity at 1.45 T using T2-weighted pulse sequences; however, no effect of comparable size is observed with T1-weighted pulse sequences. The transient effect and its kinetics were followed with a temporal resolution of between 1 and 8 s. Experiments with different lanthanide chelates show that the observed decrease in signal intensity correlates with the magnetic moment of each agent but not with their longitudinal relaxivity. Three-dimensional chemical-shift resolved experiments demonstrate significant line broadening in brain during infusion with Dy(DTPA)2-. Our results show that the cause of this effect is the difference in susceptibility between the capillaries, containing the contrast agent, and the surrounding tissue. As a result of these susceptibility differences, field gradients are produced in the tissue and diffusion of water through these gradients leads to a loss of spin phase coherence and thus a decrease in signal intensity. We propose this as a new type of contrast agent mechanism in NMR. The effect and its kinetics are likely to be related to important physiological parameters such as cerebral blood volume and cerebral blood flow, and do not depend on a breakdown of the blood-brain barrier as do conventional contrast agent techniques. PMID:3367774

  5. Regional brain glutamate transport in rats at normal and raised concentrations of circulating glutamate.

    PubMed

    Hawkins, R A; DeJoseph, M R; Hawkins, P A

    1995-08-01

    The permeability of the blood-brain barrier to glutamate was measured by quantitative autoradiography in brains of control rats (average plasma glutamate concentration of 95 microns) and rats infused with glutamate (average plasma glutamate concentration of 837 microns). Measurements of glutamate permeability were initiated by the injection of [14C]glutamate and stopped at 1 min to avoid the accumulation of [14C]glutamate metabolites. Glutamate entered the brain at a slow rate, with an average permeability-surface area product of 7 microliters.min-g-1, except in those areas known to have fenestrated capillaries. Glutamate accumulated in the choroid plexus of ventricles, but did not seem to enter the cerebrospinal fluid in detectable amounts regardless of the circulating concentration. Glutamate accumulated in circumventricular organs, such as the median eminence, where the radioactivity was localized without detectable spread. Infusion of glutamate to create high plasma concentrations did not result in greater spread of [14C]glutamate beyond the immediate vicinity of the circumventricular organs. PMID:7648616

  6. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  7. Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity.

    PubMed

    Karlsson, H K; Tuulari, J J; Tuominen, L; Hirvonen, J; Honka, H; Parkkola, R; Helin, S; Salminen, P; Nuutila, P; Nummenmaa, L

    2016-08-01

    Positron emission tomography (PET) studies suggest opioidergic system dysfunction in morbid obesity, while evidence for the role of the dopaminergic system is less consistent. Whether opioid dysfunction represents a state or trait in obesity remains unresolved, but could be assessed in obese subjects undergoing weight loss. Here we measured brain μ-opioid receptor (MOR) and dopamine D2 receptor (D2R) availability in 16 morbidly obese women twice-before and 6 months after bariatric surgery-using PET with [(11)C]carfentanil and [(11)C]raclopride. Data were compared with those from 14 lean control subjects. Receptor-binding potentials (BPND) were compared between the groups and between the pre- and postoperative scans among the obese subjects. Brain MOR availability was initially lower among obese subjects, but weight loss (mean=26.1 kg, s.d.=7.6 kg) reversed this and resulted in ~23% higher MOR availability in the postoperative versus preoperative scan. Changes were observed in areas implicated in reward processing, including ventral striatum, insula, amygdala and thalamus (P's<0.005). Weight loss did not influence D2R availability in any brain region. Taken together, the endogenous opioid system plays an important role in the pathophysiology of human obesity. Because bariatric surgery and concomitant weight loss recover downregulated MOR availability, lowered MOR availability is associated with an obese phenotype and may mediate excessive energy uptake. Our results highlight that understanding the opioidergic contribution to overeating is critical for developing new treatments for obesity. PMID:26460230

  8. Differences in Brain Information Transmission between Gifted and Normal Children during Scientific Hypothesis Generation

    ERIC Educational Resources Information Center

    Jin, Seung-Hyun; Kwon, Yong-Ju; Jeong, Jin-Su; Kwon, Suk-Won; Shin, Dong-Hoon

    2006-01-01

    The purpose of the present study was to investigate differences in neural information transmission between gifted and normal children involved in scientific hypothesis generation. To investigate changes in the amount of information transmission, the children's averaged-cross mutual information (A-CMI) of EEGs was estimated during their generation…

  9. Developmental Component in Brain Electrical Activity of Normal and Learning Disabled Boys.

    ERIC Educational Resources Information Center

    Naour, Paul J.; Martin, Daniel J.

    The study examined the electrophysiologic organization of cognitive function in 12 normally achieving righthanded boys and 12 reading disabled third and sixth grade boys. Ss were administered reading comprehension and spelling recognition subtests from the Peabody Individual Achievement Test. Electroencephalography (EEG) scores were recorded for…

  10. Quantitation of normal metabolite concentrations in six brain regions by in-vivo 1H-MR spectroscopy

    PubMed Central

    Minati, Ludovico; Aquino, Domenico; Bruzzone, Maria Grazia; Erbetta, Alessandra

    2010-01-01

    This study examined the concentrations of brain metabolites visible to in-vivo 1H-Magnetic Resonance Spectroscopy (1H-MRS) at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal reference and using an external reference; metabolite signal intensity ratios with respect to creatine were also calculated. The inter-individual variability was smaller for absolute concentrations (internal reference) as compared to that for signal intensity ratios. Significant regional variability in concentration was found for all metabolites, indicating that separate normative values are needed for different brain regions. The values obtained in this study can be used as reference in future studies, provided the same methodology is followed; it is confirmed that despite unsuccessful attempts in the past, smaller coefficients of variation can indeed be obtained through absolute quantification. PMID:20927223

  11. Normal development.

    PubMed

    Girard, Nadine; Koob, Meriam; Brunel, Herv

    2016-01-01

    Numerous events are involved in brain development, some of which are detected by neuroimaging. Major changes in brain morphology are depicted by brain imaging during the fetal period while changes in brain composition can be demonstrated in both pre- and postnatal periods. Although ultrasonography and computed tomography can show changes in brain morphology, these techniques are insensitive to myelination that is one of the most important events occurring during brain maturation. Magnetic resonance imaging (MRI) is therefore the method of choice to evaluate brain maturation. MRI also gives insight into the microstructure of brain tissue through diffusion-weighted imaging and diffusion tensor imaging. Metabolic changes are also part of brain maturation and are assessed by proton magnetic resonance spectroscopy. Understanding and knowledge of the different steps in brain development are required to be able to detect morphologic and structural changes on neuroimaging. Consequently alterations in normal development can be depicted. PMID:27430460

  12. Re-evaluating the need for hospital admission and observation of pediatric traumatic brain injury after a normal head CT.

    PubMed

    Plackett, Timothy P; Asturias, Sabrina; Tadlock, Matthew; Wright, Franklin; Ton-That, Hieu; Demetriades, Demetrios; Esposito, Thomas; Inaba, Kenji

    2015-10-01

    There is no consensus on the optimal management of pediatric patients with suspected trauma brain injury and a normal head CT. This study characterizes the clinical outcomes of patients with a normal initial CT scan of the head. A retrospective chart review of pediatric blunt trauma patients who underwent head CT for closed head injury at two trauma centers was performed. Charts were reviewed for demographics, neurologic function, CT findings, and complications. 631 blunt pediatric trauma patients underwent a head CT. 63% had a negative CT, 7% had a non-displaced skull fracture, and 31% had an intracranial hemorrhage and/or displaced skull fracture. For patients without intracranial injury, the mean age was 8 years, mean ISS was 5, and 92% had a GCS of 13-15 on arrival. All patients with an initial GCS of 13-15 and no intracranial injury were eventually discharged to home with a normal neurologic exam and no patient required craniotomy. Not admitting those children with an initial GCS of 13-15, normal CT scan, and no other injuries would have saved 1.8 ± 1.5 hospital days per patient. Pediatric patients who have sustained head trauma, have a negative CT scan, and present with a GCS 13-15 can safely be discharged home without admission. PMID:25957025

  13. Dynamics of large-scale brain activity in normal arousal states and epileptic seizures

    NASA Astrophysics Data System (ADS)

    Robinson, P. A.; Rennie, C. J.; Rowe, D. L.

    2002-04-01

    Links between electroencephalograms (EEGs) and underlying aspects of neurophysiology and anatomy are poorly understood. Here a nonlinear continuum model of large-scale brain electrical activity is used to analyze arousal states and their stability and nonlinear dynamics for physiologically realistic parameters. A simple ordered arousal sequence in a reduced parameter space is inferred and found to be consistent with experimentally determined parameters of waking states. Instabilities arise at spectral peaks of the major clinically observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle-with each instability zone lying near its most common experimental precursor arousal states in the reduced space. Theta, alpha, and spindle instabilities evolve toward low-dimensional nonlinear limit cycles that correspond closely to EEGs of petit mal seizures for theta instability, and grand mal seizures for the other types. Nonlinear stimulus-induced entrainment and seizures are also seen, EEG spectra and potentials evoked by stimuli are reproduced, and numerous other points of experimental agreement are found. Inverse modeling enables physiological parameters underlying observed EEGs to be determined by a new, noninvasive route. This model thus provides a single, powerful framework for quantitative understanding of a wide variety of brain phenomena.

  14. In vivo two-photon microscopy study of short-term effects of microbeam irradiation on normal mouse brain microvasculature

    SciTech Connect

    Serduc, Raphael . E-mail: rserduc@ujf-grenoble.fr; Verant, Pascale; Vial, Jean-Claude; Farion, Regine; Rocas, Linda; Remy, Chantal; Fadlallah, Taoufik M.S.; Brauer, Elke M.S.; Bravin, Alberto; Laissue, Jean; Blattmann, Hans; Sanden, Boudewijn van der

    2006-04-01

    Purpose: The purpose of this study was to assess the early effects of microbeam irradiation on the vascular permeability and volume in the parietal cortex of normal nude mice using two-photon microscopy and immunohistochemistry. Methods and Materials: The upper part of the left hemisphere of 55 mice was irradiated anteroposteriorly using 18 vertically oriented beams (width 25 {mu}m, interdistance 211 {mu}m; peak entrance doses: 312 or 1000 Gy). At different times after microbeam exposure, the microvasculature in the cortex was analyzed using intravital two-photon microscopy after intravascular injection of fluorescein isothiocyanate (FITC)-dextrans and sulforhodamine B (SRB). Changes of the vascular volume were observed at the FITC wavelength over a maximum depth of 650 {mu}m from the dura. The vascular permeability was detected as extravasations of SRB. Results: For all times (12 h to 1 month) after microbeam irradiation and for both doses, the FITC-dextran remained in the vessels. No significant change in vascular volume was observed between 12 h and 3 months after irradiation. Diffusion of SRB was observed in microbeam irradiated regions from 12 h until 12 days only after a 1000 Gy exposure. Conclusion: No radiation damage to the microvasculature was detected in normal brain tissue after a 312 Gy microbeam irradiation. This dose would be more appropriate than 1000 Gy for the treatment of brain tumors using crossfired microbeams.

  15. Adjacent segment disease.

    PubMed

    Virk, Sohrab S; Niedermeier, Steven; Yu, Elizabeth; Khan, Safdar N

    2014-08-01

    EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Understand the forces that predispose adjacent cervical segments to degeneration. 2. Understand the challenges of radiographic evaluation in the diagnosis of cervical and lumbar adjacent segment disease. 3. Describe the changes in biomechanical forces applied to adjacent segments of lumbar vertebrae with fusion. 4. Know the risk factors for adjacent segment disease in spinal fusion. Adjacent segment disease (ASD) is a broad term encompassing many complications of spinal fusion, including listhesis, instability, herniated nucleus pulposus, stenosis, hypertrophic facet arthritis, scoliosis, and vertebral compression fracture. The area of the cervical spine where most fusions occur (C3-C7) is adjacent to a highly mobile upper cervical region, and this contributes to the biomechanical stress put on the adjacent cervical segments postfusion. Studies have shown that after fusion surgery, there is increased load on adjacent segments. Definitive treatment of ASD is a topic of continuing research, but in general, treatment choices are dictated by patient age and degree of debilitation. Investigators have also studied the risk factors associated with spinal fusion that may predispose certain patients to ASD postfusion, and these data are invaluable for properly counseling patients considering spinal fusion surgery. Biomechanical studies have confirmed the added stress on adjacent segments in the cervical and lumbar spine. The diagnosis of cervical ASD is complicated given the imprecise correlation of radiographic and clinical findings. Although radiological and clinical diagnoses do not always correlate, radiographs and clinical examination dictate how a patient with prolonged pain is treated. Options for both cervical and lumbar spine ASD include fusion and/or decompression. Current studies are encouraging regarding the adoption of arthroplasty in spinal surgery, but more long

  16. An MRI-Based Semiquantitative Index for the Evaluation of Brain Atrophy and Lesions in Alzheimer's Disease, Mild Cognitive Impairment and Normal Aging

    PubMed Central

    Chen, Wei; Song, Xiaowei; Zhang, Yunting; Darvesh, Sultan; Zhang, Ningnannan; D'Arcy, Ryan C.N.; Black, Sandra; Rockwood, Kenneth

    2010-01-01

    Background This study investigates how T1-weighted MRI can be used to evaluate brain anatomical changes. We investigated these changes in Alzheimer's disease (AD) and normal aging. Methods A semiquantitative brain atrophy and lesion index (BALI) was constructed by adapting existing visual rating scales and validated in 3 datasets. Results The T1- and T2-weighted-imaging-based scores were highly correlated. They were both closely associated with age and with cognitive test scores. Conclusion The T1-based BALI helps describe brain structural variability in AD, mild cognitive impairment and normal aging. PMID:20733305

  17. White matter maturation of normal human fetal brain. An in vivo diffusion tensor tractography study

    PubMed Central

    Zanin, Emilie; Ranjeva, Jean-Philippe; Confort-Gouny, Sylviane; Guye, Maxime; Denis, Daniele; Cozzone, Patrick J; Girard, Nadine

    2011-01-01

    We demonstrate for the first time the ability to determine in vivo and in utero the transitions between the main stages of white matter (WM) maturation in normal human fetuses using magnetic resonance diffusion tensor imaging (DTI) tractography. Biophysical characteristics of water motion are used as an indirect probe to evaluate progression of the tissue matrix organization in cortico-spinal tracts (CSTs), optic radiations (OR), and corpus callosum (CC) in 17 normal human fetuses explored between 23 and 38 weeks of gestation (GW) and selected strictly on minimal motion artifacts. Nonlinear polynomial (third order) curve fittings of normalized longitudinal and radial water diffusivities (Z-scores) as a function of age identify three different phases of maturation with specific dynamics for each WM bundle type. These phases may correspond to distinct cellular events such as axonal organization, myelination gliosis, and myelination, previously reported by other groups on post-mortem fetuses using immunostaining methods. According to the DTI parameter dynamics, we suggest that myelination (phase 3) appears early in the CSTs, followed by the OR and by the CC, respectively. DTI tractography provides access to a better understanding of fetal WM maturation. PMID:22399089

  18. Segmenting nonenhancing brain tumors from normal tissues in magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Fletcher-Heath, Lynn M.; Hall, Lawrence O.; Goldgof, Dmitry B.

    1998-06-01

    Tumor segmentation from magnetic resonance (MR) images aids in tumor treatment by tracking the progress of tumor growth and/or shrinkage. In this paper we present an automatic segmentation method which separates non-enhancing brain tumors from healthy tissues in MR images. The MR feature images used for the segmentation consist of three weighted images (T1, T2 and proton density) for each axial slice through the head. An initial segmentation is computed using an unsupervised clustering algorithm. Then, integrated domain knowledge and image processing techniques contribute to the final tumor segmentation. The system was trained on two patient volumes and preliminary testing has shown successful tumor segmentations on four patient volumes.

  19. Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains

    SciTech Connect

    Kronfeld, Andrea; Müller-Forell, Wibke; Buchholz, Hans-Georg; Maus, Stephan; Reuss, Stefan; Schreckenberger, Mathias; Miederer, Isabelle; Lutz, Beat

    2015-12-15

    Purpose: Image registration is one prerequisite for the analysis of brain regions in magnetic-resonance-imaging (MRI) or positron-emission-tomography (PET) studies. Diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) is a nonlinear, diffeomorphic algorithm for image registration and construction of image templates. The goal of this small animal study was (1) the evaluation of a MRI and calculation of several cannabinoid type 1 (CB1) receptor PET templates constructed using DARTEL and (2) the analysis of the image registration accuracy of MR and PET images to their DARTEL templates with reference to analytical and iterative PET reconstruction algorithms. Methods: Five male Sprague Dawley rats were investigated for template construction using MRI and [{sup 18}F]MK-9470 PET for CB1 receptor representation. PET images were reconstructed using the algorithms filtered back-projection, ordered subset expectation maximization in 2D, and maximum a posteriori in 3D. Landmarks were defined on each MR image, and templates were constructed under different settings, i.e., based on different tissue class images [gray matter (GM), white matter (WM), and GM + WM] and regularization forms (“linear elastic energy,” “membrane energy,” and “bending energy”). Registration accuracy for MRI and PET templates was evaluated by means of the distance between landmark coordinates. Results: The best MRI template was constructed based on gray and white matter images and the regularization form linear elastic energy. In this case, most distances between landmark coordinates were <1 mm. Accordingly, MRI-based spatial normalization was most accurate, but results of the PET-based spatial normalization were quite comparable. Conclusions: Image registration using DARTEL provides a standardized and automatic framework for small animal brain data analysis. The authors were able to show that this method works with high reliability and validity. Using DARTEL

  20. SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

    SciTech Connect

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

    2015-06-15

    Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

  1. Ischaemic and haemorrhagic brain lesions in newborns with seizures and normal Apgar scores.

    PubMed Central

    Mercuri, E.; Cowan, F.; Rutherford, M.; Acolet, D.; Pennock, J.; Dubowitz, L.

    1995-01-01

    Serial ultrasound scans and conventional and diffusion weighted magnetic resonance imaging (MRI) were performed on 16 neonates who presented with seizures. The Apgar scores were normal and subsequently no metabolic or infective cause could be found. The aim of the study was to evaluate the extent to which early sequential imaging can elucidate the cause of seizures in apparently neurologically normal infants. Fourteen of the infants had haemorrhagic or ischaemic lesions on MRI and these were detected by ultrasound scanning in 11. Early ultrasound scanning detected the haemorrhagic lesions but the ischaemic lesions were often not seen until the end of the first week of life. Early MRI, however, was able to detect all the ischaemic lesions. The evolution of the insult could be timed by using serial ultrasound scans and a combination of diffusion weighted and conventional MRI during the first week of life, confirming a perinatal insult even in the absence of fetal distress. Although the aetiology of these lesions remains obscure, serial ultrasound scans will detect the presence of cerebral lesions in neonates presenting with isolated seizures but additional MRI sequences will give better definition on type, site, and extent of the pathology. Images Figures 5 and 6 Figure 2 Figures 3 and 4 Figure 1 PMID:7583609

  2. MRI-based surface area estimates in the normal adult human brain: evidence for structural organisation.

    PubMed Central

    Sisodiya, S; Free, S; Fish, D; Shorvon, S

    1996-01-01

    There are a number of quantitative relationships between geometric parameters describing the structure of the normal human cerebral cortex examined in vivo using volumetric magnetic resonance imaging. A voxel-counting method is used to estimate grey-white interface surface area. The effects of bias associated with the method are considered. In 33 normal controls, the cerebral hemispheres were symmetric in terms of total volume, irrespective of handedness, but not in terms of surface areas for right-handers. The surface area of the grey matter-white matter interface was directly proportional to the cortical grey matter volume, suggesting that growth of the neocortex is primarily tangential, with repetition of a basic structural element rather than gross alterations in the thickness of the cortex. The majority of the surface area of the grey-white interface lies within gyral white matter cores. The mean thickness of the cortex of the right cerebral hemisphere in vivo was 3.0 mm and that of the left 3.3 mm. There was a relationship between the cross-sectional area of the corpus callosum and grey-white interface surface area, suggesting that a fixed proportion and cortical neurons extend interhemispheric axons. These findings suggest that there are general architectural principles governing the organisation of the complex, but ordered, human cerebral cortex. Images Fig. 1 Fig. 2 PMID:8621342

  3. The IMAGEN study: reinforcement-related behaviour in normal brain function and psychopathology.

    PubMed

    Schumann, G; Loth, E; Banaschewski, T; Barbot, A; Barker, G; Büchel, C; Conrod, P J; Dalley, J W; Flor, H; Gallinat, J; Garavan, H; Heinz, A; Itterman, B; Lathrop, M; Mallik, C; Mann, K; Martinot, J-L; Paus, T; Poline, J-B; Robbins, T W; Rietschel, M; Reed, L; Smolka, M; Spanagel, R; Speiser, C; Stephens, D N; Ströhle, A; Struve, M

    2010-12-01

    A fundamental function of the brain is to evaluate the emotional and motivational significance of stimuli and to adapt behaviour accordingly. The IMAGEN study is the first multicentre genetic-neuroimaging study aimed at identifying the genetic and neurobiological basis of individual variability in impulsivity, reinforcer sensitivity and emotional reactivity, and determining their predictive value for the development of frequent psychiatric disorders. Comprehensive behavioural and neuropsychological characterization, functional and structural neuroimaging and genome-wide association analyses of 2000 14-year-old adolescents are combined with functional genetics in animal and human models. Results will be validated in 1000 adolescents from the Canadian Saguenay Youth Study. The sample will be followed up longitudinally at the age of 16 years to investigate the predictive value of genetics and intermediate phenotypes for the development of frequent psychiatric disorders. This review describes the strategies the IMAGEN consortium used to meet the challenges posed by large-scale multicentre imaging-genomics investigations. We provide detailed methods and Standard Operating Procedures that we hope will be helpful for the design of future studies. These include standardization of the clinical, psychometric and neuroimaging-acquisition protocols, development of a central database for efficient analyses of large multimodal data sets and new analytic approaches to large-scale genetic neuroimaging analyses. PMID:21102431

  4. Dopamine in thelimbic regions of the human brain: normal and abnormal.

    PubMed

    Farley, I J; Price, K S; Hornykiewicz, O

    1977-01-01

    1. In the human brain, DA was found in appreciable amounts in most of the examined basal telencephalic limbic regions, with the nucleus accumbens having the highest mean level (3.38 microgram/g). In the cortical areas of the limbic lobe of Broca, DA could be measured with certainty only in the parolfactory gyrus (0.35 microgram/g). 2. In patients with Parkinson's disease, the DA concentration in the parolfactory gyrus and nucleur accumbens was markedly reduced, whereas little change was seen in the olfactory areas. Quantitatively, the DA decrease in the nucleus accumbens was of the same magnitude as in the caudate nucleus, being, in both regions, distinctly less severe than in the putamen. 3. In three cases of paranoid schizophrenia, there were no statistically significant changes of the mean levels of DA or HVA in the nucleus accumbens. However, the DA/HVA ratio was shifted noticeably in favor of HVA, possibly indicating an increase in DA turnover. This change was less pronounced in the putamen of these cases and was absent in the caudate nucleus. 4. The possibility of the substantia nigra contributing to the dopaminergic innervation of the human nucleus accumbens, as well as the significance of the observations on DA metabolism in the schizophrenic cases, is discussed. PMID:883559

  5. Mice lacking glutamate carboxypeptidase II develop normally, but are less susceptible to traumatic brain injury.

    PubMed

    Gao, Yang; Xu, Siyi; Cui, Zhenwen; Zhang, Mingkun; Lin, Yingying; Cai, Lei; Wang, Zhugang; Luo, Xingguang; Zheng, Yan; Wang, Yong; Luo, Qizhong; Jiang, Jiyao; Neale, Joseph H; Zhong, Chunlong

    2015-07-01

    Glutamate carboxypeptidase II (GCPII) is a transmembrane zinc metallopeptidase found mainly in the nervous system, prostate and small intestine. In the nervous system, glia-bound GCPII mediates the hydrolysis of the neurotransmitter N-acetylaspartylglutamate (NAAG) into glutamate and N-acetylaspartate. Inhibition of GCPII has been shown to attenuate excitotoxicity associated with enhanced glutamate transmission under pathological conditions. However, different strains of mice lacking the GCPII gene are reported to exhibit striking phenotypic differences. In this study, a GCPII gene knockout (KO) strategy involved removing exons 3-5 of GCPII. This generated a new GCPII KO mice line with no overt differences in standard neurological behavior compared to their wild-type (WT) littermates. However, GCPII KO mice were significantly less susceptible to moderate traumatic brain injury (TBI). GCPII gene KO significantly lessened neuronal degeneration and astrocyte damage in the CA2 and CA3 regions of the hippocampus 24 h after moderate TBI. In addition, GCPII gene KO reduced TBI-induced deficits in long-term spatial learning/memory tested in the Morris water maze and motor balance tested via beam walking. Knockout of the GCPII gene is not embryonic lethal and affords histopathological protection with improved long-term behavioral outcomes after TBI, a result that further validates GCPII as a target for drug development consistent with results from studies using GCPII peptidase inhibitors. PMID:25872793

  6. Brain parenchymal density measurements by CT in demented subjects and normal controls

    SciTech Connect

    Gado, M.; Danziger, W.L.; Chi, D.; Hughes, C.P.; Coben, L.A.

    1983-06-01

    Parachymal density measurements of 14 regions of gray and white matter from each cerebral hemisphere were made from CT scans of 25 subjects who had varying degrees of dementia as measured by a global Clinical Dementia Rating, and also from CT scans of 33 normal control subjects. There were few significant differences between the two groups in the mean density value for each of the regions examined, although several individual psychometric tests did correlate with density changes. Moreover, for six regions in the cerebral cortex, and for one region in the thalamus of each hemisphere, we found no significant correlation between the gray-white matter density difference and dementia. There was, however, a loss of the discriminability between the gray and white matter with an increase in the size of the ventricles. These findings may be attributed to the loss of white matter volume.

  7. Stability of regional cerebral glucose metabolism in the normal brain measured by positron emission tomography

    SciTech Connect

    Tyler, J.L.; Strother, S.C.; Zatorre, R.J.; Alivisatos, B.; Worsley, K.J.; Diksic, M.; Yamamoto, Y.L.

    1988-05-01

    Cerebral glucose utilization (LCMRGI) was measured using the (/sup 18/F)fluorodeoxyglucose method with PET in two groups of ten healthy young volunteers, each scanned in a resting state under different methodological conditions. In addition, five subjects had a second scan within 48 hr. Mean hemispheric values averaged 45.8 +/- 3.3 mumol/100 g/min in the right cerebral hemisphere and 47.0 +/- 3.7 mumol/100 g/min in the left hemisphere. A four-way analysis of variance (group, sex, region, hemisphere) was carried out on the results using three different methods of data manipulation: (a) the raw values of glucose utilization, (b) LCMRGI values normalized by the mean hemispheric gray matter LCMRGI value, and (c) log transformed LCMRGI values. For all analysis techniques, significantly higher LCMRGI values were consistently seen in the left mid and posterior temporal area and caudate nucleus relative to the right, and in the right occipital region relative to the left. The coefficient of variation of intrasubject regional differences (9.9%) was significantly smaller than the coefficient of variation for regions between subjects (16.5%). No differences were noted between the sexes and no effect of repeat procedures was seen in subjects having multiple scans. In addition, inter-regional LCMRGI correlations were examined both in values from the 20 normal subjects, as well as in a set of hypothetical abnormal values. Results were compared with those reported from other PET centers; despite certain methodological differences, the intersubject and inter-regional variation of LCMRGI is fairly constant.

  8. Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice

    PubMed Central

    Jung, Yeon Suk; Park, Jung Hwa; Kim, Hyunha; Kim, So Young; Hwang, Ji Young; Hong, Ki Whan; Bae, Sun Sik; Choi, Byung Tae; Lee, Sae-Won; Shin, Hwa Kyoung

    2016-01-01

    Aim: Increasing evidence suggests that probucol, a lipid-lowering agent with anti-oxidant activities, may be useful for the treatment of ischemic stroke with hyperlipidemia via reduction in cholesterol and neuroinflammation. In this study we examined whether probucol could protect against brain ischemic injury via anti-neuroinflammatory action in normal and hyperlipidemic mice. Methods: Primary mouse microglia and murine BV2 microglia were exposed to lipopolysaccharide (LPS) for 3 h, and the release NO, PGE2, IL-1β and IL-6, as well as the changes in NF-κB, MAPK and AP-1 signaling pathways were assessed. ApoE KO mice were fed a high-fat diet containing 0.004%, 0.02%, 0.1% (wt/wt) probucol for 10 weeks, whereas normal C57BL/6J mice received probucol (3, 10, 30 mg·kg-1·d-1, po) for 4 d. Then all the mice were subjected to focal cerebral ischemia through middle cerebral artery occlusion (MCAO). The neurological deficits were scored 24 h after the surgery, and then brains were removed for measuring the cerebral infarct size and the production of pro-inflammatory mediators. Results: In LPS-treated BV2 cells and primary microglial cells, pretreatment with probucol (1, 5, 10 μmol/L) dose-dependently inhibited the release of NO, PGE2, IL-1β and IL-6, which occurred at the transcription levels. Furthermore, the inhibitory actions of probucol were associated with the downregulation of the NF-κB, MAPK and AP-1 signaling pathways. In the normal mice with MCAO, pre-administration of probucol dose-dependently decreased the infarct volume and improved neurological function. These effects were accompanied by the decreased production of pro-inflammatory mediators (iNOS, COX-2, IL-1, IL-6). In ApoE KO mice fed a high-fat diet, pre-administration of 0.1% probucol significantly reduced the infarct volume, improved the neurological deficits following MCAO, and decreased the total- and LDL-cholesterol levels. Conclusion: Probucol inhibits LPS-induced microglia activation and

  9. Brain Tumor Therapy-Induced Changes in Normal-Appearing Brainstem Measured With Longitudinal Diffusion Tensor Imaging

    SciTech Connect

    Hua Chiaho; Merchant, Thomas E.; Gajjar, Amar; Broniscer, Alberto; Zhang, Yong; Li Yimei; Glenn, George R.; Kun, Larry E.; Ogg, Robert J.

    2012-04-01

    Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4-39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54-59.4 Gy). Parametric maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6-5.0 years). The median mean dose to the pons was 56 Gy (range, 7-59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response in

  10. Description and classification of normal and pathological aging processes based on brain magnetic resonance imaging morphology measures.

    PubMed

    Perez-Gonzalez, Jorge Luis; Yanez-Suarez, Oscar; Bribiesca, Ernesto; Cosío, Fernando Arámbula; Jiménez, Juan Ramón; Medina-Bañuelos, Veronica

    2014-10-01

    We present a discrete compactness (DC) index, together with a classification scheme, based both on the size and shape features extracted from brain volumes, to determine different aging stages: healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). A set of 30 brain magnetic resonance imaging (MRI) volumes for each group was segmented and two indices were measured for several structures: three-dimensional DC and normalized volumes (NVs). The discrimination power of these indices was determined by means of the area under the curve (AUC) of the receiver operating characteristic, where the proposed compactness index showed an average AUC of 0.7 for HC versus MCI comparison, 0.9 for HC versus AD separation, and 0.75 for MCI versus AD groups. In all cases, this index outperformed the discrimination capability of the NV. Using selected features from the set of DC and NV measures, three support vector machines were optimized and validated for the pairwise separation of the three classes. Our analysis shows classification rates of up to 98.3% between HC and AD, 85% between HC and MCI, and 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indices to classify different aging stages. PMID:26158061

  11. Description and classification of normal and pathological aging processes based on brain magnetic resonance imaging morphology measures

    PubMed Central

    Perez-Gonzalez, Jorge Luis; Yanez-Suarez, Oscar; Bribiesca, Ernesto; Cosío, Fernando Arámbula; Jiménez, Juan Ramón; Medina-Bañuelos, Veronica

    2014-01-01

    Abstract. We present a discrete compactness (DC) index, together with a classification scheme, based both on the size and shape features extracted from brain volumes, to determine different aging stages: healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). A set of 30 brain magnetic resonance imaging (MRI) volumes for each group was segmented and two indices were measured for several structures: three-dimensional DC and normalized volumes (NVs). The discrimination power of these indices was determined by means of the area under the curve (AUC) of the receiver operating characteristic, where the proposed compactness index showed an average AUC of 0.7 for HC versus MCI comparison, 0.9 for HC versus AD separation, and 0.75 for MCI versus AD groups. In all cases, this index outperformed the discrimination capability of the NV. Using selected features from the set of DC and NV measures, three support vector machines were optimized and validated for the pairwise separation of the three classes. Our analysis shows classification rates of up to 98.3% between HC and AD, 85% between HC and MCI, and 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indices to classify different aging stages. PMID:26158061

  12. EEG coherence studies in the normal brain and after early-onset cortical pathologies.

    PubMed

    Knyazeva, M G; Innocenti, G M

    2001-10-01

    Visual corpus callosum (CC) preferentially interconnects neurons selective for similar stimulus orientation near the representations of the vertical meridian. These properties allow studying the CC functionality with EEG coherence analysis. Iso-oriented and orthogonally-oriented gratings were presented to the two hemifields, either close to the vertical meridian or far from it. In animals with intact CC, and in man, interhemispheric coherence (ICoh) increased only with iso-oriented gratings presented near or crossing the vertical meridian. The increase was localized to occipital electrodes and was specific for the beta-gamma frequency band. Visual-stimulus induced changes in ICoh were studied in patients with early pathologies of the visual areas. From a girl with abnormal vision and severe bilateral lesion of the primary visual areas at 3 weeks, after premature birth at 30 weeks, we obtained no ICoh response until 9 years. In control children visual stimulation increased occipital ICoh at 6-7 years. From a young man having suffered similar lesions when he was 9 months older than the girl, no consistent increase in ICoh could be obtained. In a 14-year-old girl with congenital visual agnosia, no visible lesions, but with a temporal-occipital epileptic focus, ICoh responses were evoked both by iso-oriented, and by orthogonally-oriented gratings. In a young man with bilateral parieto-occipital microgyria extending into the calcarine sulcus, visual stimuli increased ICoh as in normal individuals, but the response was weaker. These cases are discussed in terms of development of CC connections and point to a variety of plastic changes in the cortical connectivity of children. PMID:11690608

  13. Abnormal blood–brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI☆☆☆

    PubMed Central

    Cramer, S.P.; Simonsen, H.; Frederiksen, J.L.; Rostrup, E.; Larsson, H.B.W.

    2013-01-01

    Objectives To investigate whether blood–brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics. Methods Dynamic contrast-enhanced MRI was used to measure BBB permeability in 27 patients with MS and compared to 24 matched healthy controls. Results Permeability measured as Ktrans was significantly higher in periventricular normal appearing white matter (NAWM) and thalamic gray matter in MS patients when compared to healthy controls, with periventricular NAWM showing the most pronounced difference. Recent relapse coincided with significantly higher permeability in periventricular NAWM, thalamic gray matter, and MS lesions. Immunomodulatory treatment and recent relapse were significant predictors of permeability in MS lesions and periventricular NAWM. Our results suggest that after an MS relapse permeability gradually decreases, possibly an effect of immunomodulatory treatment. Conclusions Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS. PMID:24371801

  14. Brain-derived neurotrophic factor is required for normal development of the central respiratory rhythm in mice.

    PubMed

    Balkowiec, A; Katz, D M

    1998-07-15

    1. Molecular mechanisms underlying maturation of the central respiratory rhythm are largely unknown. Previously, we found that brain-derived neurotrophic factor (BDNF) is required for expression of normal breathing behaviour in newborn mice, raising the possibility that maturation of central respiratory output is dependent on BDNF. 2. Respiratory activity was recorded in vitro from cervical ventral roots (C1 or C4) using the isolated brainstem-spinal cord preparation from postnatal day (P) 0.5-2.0 and P4.5 wild-type mice and mice lacking functional bdnf alleles. 3. Loss of one or both bdnf alleles resulted in an approximately 50% depression of central respiratory frequency compared with wild-type controls. In addition, respiratory cycle length variability was 214% higher in bdnf null (bdnf-/-) animals compared with controls at P4.5. In contrast, respiratory burst duration was unaffected by bdnf gene mutation. 4. These derangements of central respiratory rhythm paralleled the ventilatory depression and irregular breathing characteristic of bdnf mutants in vivo, indicating that central deficits can largely account for the abnormalities in resting ventilation produced by genetic loss of BDNF. BDNF is thus the first growth factor identified that is required for normal development of the central respiratory rhythm, including the stabilization of central respiratory output that occurs after birth. PMID:9706001

  15. Brain-derived neurotrophic factor is required for normal development of the central respiratory rhythm in mice

    PubMed Central

    Balkowiec, Agnieszka; Katz, David M

    1998-01-01

    Molecular mechanisms underlying maturation of the central respiratory rhythm are largely unknown. Previously, we found that brain-derived neurotrophic factor (BDNF) is required for expression of normal breathing behaviour in newborn mice, raising the possibility that maturation of central respiratory output is dependent on BDNF. Respiratory activity was recorded in vitro from cervical ventral roots (C1 or C4) using the isolated brainstem–spinal cord preparation from postnatal day (P) 0.5–2.0 and P4.5 wild-type mice and mice lacking functional bdnf alleles. Loss of one or both bdnf alleles resulted in an approximately 50 % depression of central respiratory frequency compared with wild-type controls. In addition, respiratory cycle length variability was 214 % higher in bdnf null (bdnf−/−) animals compared with controls at P4.5. In contrast, respiratory burst duration was unaffected by bdnf gene mutation. These derangements of central respiratory rhythm paralleled the ventilatory depression and irregular breathing characteristic of bdnf mutants in vivo, indicating that central deficits can largely account for the abnormalities in resting ventilation produced by genetic loss of BDNF. BDNF is thus the first growth factor identified that is required for normal development of the central respiratory rhythm, including the stabilization of central respiratory output that occurs after birth. PMID:9706001

  16. Longitudinal Metabolite Profiling of Cerebrospinal Fluid in Normal Pressure Hydrocephalus Links Brain Metabolism with Exercise-Induced VEGF Production and Clinical Outcome.

    PubMed

    Huang, He; Yang, Jun; Luciano, Mark; Shriver, Leah P

    2016-07-01

    Idiopathic normal pressure hydrocephalus is a neurological disease caused by abnormal cerebrospinal fluid flow and presents with symptoms such as dementia. Current therapy involves the removal of excess cerebrospinal fluid by shunting. Not all patients respond to this therapy and biomarkers are needed that could facilitate the characterization of patients likely to benefit from this treatment. Here, we measure brain metabolism in normal pressure hydrocephalus patients by performing a novel longitudinal metabolomic profiling study of cerebrospinal fluid. We find that the levels of brain metabolites correlate with clinical parameters, the amount of vascular endothelial growth factor in the cerebrospinal fluid, and environmental stimuli such as exercise. Metabolomic analysis of normal pressure hydrocephalus patients provides insight into changes in brain metabolism that accompany cerebrospinal fluid disorders and may facilitate the development of new biomarkers for this condition. PMID:27084769

  17. De novo development of gliomas in a child with neurofibromatosis type 1, fragile X and previously normal brain magnetic resonance imaging

    PubMed Central

    Zafar, Rabia; Hsiao, Esther Y.; Botteron, Kelly N.; McKinstry, Robert C.; Gutmann, David H.

    2016-01-01

    Fifteen to 20% of children with neurofibromatosis type 1 develop low-grade glial neoplasms. However, since neuroimaging is not routinely obtained until a child is clinically symptomatic, little is known about presymptomatic radiographic characteristics of gliomas in this at-risk population. Herein, we describe a child with neurofibromatosis type 1 who initially had normal brain imaging before the development of multifocal gliomas. Comparison of these serial images demonstrated that brain tumors can arise de novo in children with this cancer predisposition syndrome, further underscoring the limited prognostic value of normal baseline magnetic resonance imaging. PMID:26973730

  18. Cerebral Blood Flow Changes in Glioblastoma Patients Undergoing Bevacizumab Treatment Are Seen in Both Tumor and Normal Brain

    PubMed Central

    Nagpal, Seema; Hippe, Daniel S; Ravanpay, Ali C; Schmiedeskamp, Heiko; Bammer, Roland; Palagallo, Gerald J; Recht, Lawrence; Zaharchuk, Greg

    2015-01-01

    Bevacizumab (BEV) is increasingly used to treat recurrent glioblastoma (GBM) with some reported improvement in neurocognitive function despite potential neurotoxicities. We examined the effects of BEV on cerebral blood flow (CBF) within recurrent GBM tumor and in the contralateral middle cerebral artery (MCA) territory. Post-chemoradiation patients with histologically confirmed GBM were treated with BEV and underwent routine, serial tumor imaging with additional pseudocontinuous arterial spin labeling (pcASL) following informed consent. Circular regions-of-interest were placed on pcASL images directly over the recurrent tumor and in the contralateral MCA territory. CBF changes before and during BEV treatment were evaluated in tumor and normal tissue. Linear mixed models were used to assess statistical significance. Fifty-three pcASL studies in 18 patients were acquired. Evaluation yielded lower mean tumoral CBF during BEV treatment compared with pre-treatment (45 ± 27 vs. 65 ± 27 ml/100 g/min, p = 0.002), and in the contralateral MCA territory during, compared with pre-BEV treatment (35 ± 8.4 vs. 41 ± 8.4 ml/100 g/min, p = 0.03). The decrease in mean CBF tended to be greater in the tumoral region than in the contralateral MCA, though the difference did not reach statistical significance (31% vs. 13%; p = 0.082). Conclusions BEV administration results in statistically significant global CBF decrease with a potentially preferential decrease in tumor perfusion compared with normal brain tissue. PMID:25923677

  19. Attentional distractor interference may be diminished by concurrent working memory load in normal participants and traumatic brain injury patients.

    PubMed

    Gil-Gómez de Liaño, Beatriz; Umiltà, Carlo; Stablum, Franca; Tebaldi, Francesca; Cantagallo, Anna

    2010-12-01

    A reduction in congruency effects under working memory (WM) load has been previously described using different attentional paradigms (e.g., Kim, Kim, & Chun, 2005; Smilek, Enns, Eastwood, & Merikle, 2006). One hypothesis is that different types of WM load have different effects on attentional selection, depending on whether a specific memory load demands resources in common with target or distractor processing. In particular, if information in WM is related to the distractors in the selective attention task, there is a reduction in distraction (Kim et al., 2005). However, although previous results seem to point to a decrease in interference under high WM load conditions (Kim et al., 2005), the lack of a neutral baseline for the congruency effects makes it difficult to differentiate between a decrease in interference or in facilitation. In the present work we included neutral trials in the task introduced by Kim et al. (2005) and tested normal participants and traumatic brain injury patients. Results support a reduction in the processing of distractors under WM load, at least for incongruent trials in both groups. Theoretical as well as applied implications are discussed. PMID:20846773

  20. Effects of normal aging on event-related potentials and oscillatory brain activity during a haptic repetition priming task.

    PubMed

    Sebastián, Manuel; Ballesteros, Soledad

    2012-03-01

    This study reports neural repetition effects in young and older adults while performing a haptic repetition priming task consisting in the detection of the bilateral symmetry of familiar objects. To examine changes in event-related potentials (ERPs) and induced brain oscillations of object repetition priming with aging, we recorded EEGs of healthy groups of young (n=14; mean age=29.93 years) and older adults (n=15; mean age=66.4). Both groups exhibited similar behavioral haptic priming across repetitions, although young adults responded faster than the older group. Young and older adults showed ERP repetition enhancement at the 500-900 ms time window. In contrast, only the young participants showed ERP repetition suppression at the 1200-1500 ms segment. The results from the induced oscillations showed more positive amplitudes in young than in older adults at theta, alpha and beta frequencies (4-30 Hz). In addition, we found amplitude modulation related to stimulus repetition in the upper alpha and low beta sub-bands only in young adults (1250-1750 ms).The results suggest that although behavioral priming is spared with age, normal aging affects ERPs and oscillatory responses when performing an incidental priming symmetry detection task with haptically explored objects. PMID:22155374

  1. Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume?

    PubMed

    Lemaitre, Herve; Goldman, Aaron L; Sambataro, Fabio; Verchinski, Beth A; Meyer-Lindenberg, Andreas; Weinberger, Daniel R; Mattay, Venkata S

    2012-03-01

    Normal aging is accompanied by global as well as regional structural changes. While these age-related changes in gray matter volume have been extensively studied, less has been done using newer morphological indexes, such as cortical thickness and surface area. To this end, we analyzed structural images of 216 healthy volunteers, ranging from 18 to 87 years of age, using a surface-based automated parcellation approach. Linear regressions of age revealed a concomitant global age-related reduction in cortical thickness, surface area and volume. Cortical thickness and volume collectively confirmed the vulnerability of the prefrontal cortex, whereas in other cortical regions, such as in the parietal cortex, thickness was the only measure sensitive to the pronounced age-related atrophy. No cortical regions showed more surface area reduction than the global average. The distinction between these morphological measures may provide valuable information to dissect age-related structural changes of the brain, with each of these indexes probably reflecting specific histological changes occurring during aging. PMID:20739099

  2. Transfer coefficients for L-valine and the rate of incorporation of L-(1-/sup 14/C) valine into proteins in normal adult rat brain

    SciTech Connect

    Kirikae, M.; Diksic, M.; Yamamoto, Y.L.

    1988-08-01

    An autoradiographic method for the measurement of the rate of valine incorporation into brain proteins is described. The transfer coefficients for valine into and out of the brain and the rate of valine incorporation into normal rat brain proteins are given. The valine incorporation and the transfer constants of valine between different biological compartments are provided for 14 gray matter and 2 white matter structures of an adult rat brain. The rate of valine incorporation varies between 0.52 +/- 0.19 nmol/g/min in white matter and 1.94 +/- 0.47 in inferior colliculus (gray matter). Generally, the rate of valine incorporation is about three to four times higher in the gray matter than in the white matter structures.

  3. Brain Tumors

    MedlinePlus

    ... brain. Brain tumors can be benign, with no cancer cells, or malignant, with cancer cells that grow quickly. Some are primary brain ... targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. Many people get ...

  4. Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer's disease.

    PubMed

    Solé-Padullés, Cristina; Bartrés-Faz, David; Junqué, Carme; Vendrell, Pere; Rami, Lorena; Clemente, Imma C; Bosch, Beatriu; Villar, Amparo; Bargalló, Núria; Jurado, M Angeles; Barrios, Maite; Molinuevo, Jose Luis

    2009-07-01

    Cognitive reserve (CR) is the brain's capacity to cope with cerebral damage to minimize clinical manifestations. The 'passive model' considers head or brain measures as anatomical substrates of CR, whereas the 'active model' emphasizes the use of brain networks effectively. Sixteen healthy subjects, 12 amnestic mild cognitive impairment (MCI) and 16 cases with mild Alzheimer's disease (AD) were included to investigate the relationships between proxies of CR and cerebral measures considered in the 'passive' and 'active' models. CR proxies were inferred premorbid IQ (WAIS Vocabulary test), 'education-occupation', a questionnaire of intellectual and social activities and a composite CR measure. MRI-derived whole-brain volumes and brain activity by functional MRI during a visual encoding task were obtained. Among healthy elders, higher CR was related to larger brains and reduced activity during cognitive processing, suggesting more effective use of cerebral networks. In contrast, higher CR was associated with reduced brain volumes in MCI and AD and increased brain function in the latter, indicating more advanced neuropathology but that active compensatory mechanisms are still at work in higher CR patients. The right superior temporal gyrus (BA 22) and the left superior parietal lobe (BA 7) showed greatest significant differences in direction of slope with CR and activation between controls and AD cases. Finally, a regression analysis revealed that fMRI patterns were more closely related to CR proxies than brain volumes. Overall, inverse relationships for healthy and pathological aging groups emerged between brain structure and function and CR variables. PMID:18053618

  5. Neuroanatomical localization and quantification of amyloid precursor protein mRNA by in situ hybridization in the brains of normal, aneuploid, and lesioned mice

    SciTech Connect

    Bendotti, C.; Forloni, G.L.; Morgan, R.A.; O'Hara, B.F.; Oster-Granite, M.L.; Reeves, R.H.; Gearhart, J.D.; Coyle, J.T. )

    1988-05-01

    Amyloid precursor protein mRNA was localized in frozen sections from normal and experimentally lesioned adult mouse brain and from normal and aneuploid fetal mouse brain by in situ hybridization with a {sup 35}S-labeled mouse cDNA probe. The highest levels of hybridization in adult brain were associated with neurons, primarily in telencephalic structures. The dense labeling associated with hippocampal pyramidal cells was reduced significantly when the cells were eliminated by injection of the neurotoxin ibotenic acid but was not affected when electrolytic lesions were placed in the medial septum. Since the gene encoding amyloid precursor protein has been localized to mouse chromosome 16, the authors also examined the expression of this gene in the brains of mouse embryos with trisomy 16 and trisomy 19 at 15 days of gestation. RNA gel blot analysis and in situ hybridization showed a marked increase in amyloid precursor protein mRNA in the trisomy 16 mouse head and brain when compared with euploid littermates or with trisomy 19 mice.

  6. Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain

    PubMed Central

    Marin-Valencia, Isaac; Good, Levi B; Ma, Qian; Malloy, Craig R; Pascual, Juan M

    2013-01-01

    It has been postulated that triheptanoin can ameliorate seizures by supplying the tricarboxylic acid cycle with both acetyl-CoA for energy production and propionyl-CoA to replenish cycle intermediates. These potential effects may also be important in other disorders associated with impaired glucose metabolism because glucose supplies, in addition to acetyl-CoA, pyruvate, which fulfills biosynthetic demands via carboxylation. In patients with glucose transporter type I deficiency (G1D), ketogenic diet fat (a source only of acetyl-CoA) reduces seizures, but other symptoms persist, providing the motivation for studying heptanoate metabolism. In this work, metabolism of infused [5,6,7-13C3]heptanoate was examined in the normal mouse brain and in G1D by 13C-nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). In both groups, plasma glucose was enriched in 13C, confirming gluconeogenesis from heptanoate. Acetyl-CoA and glutamine levels became significantly higher in the brain of G1D mice relative to normal mice. In addition, brain glutamine concentration and 13C enrichment were also greater when compared with glutamate in both animal groups, suggesting that heptanoate and/or C5 ketones are primarily metabolized by glia. These results enlighten the mechanism of heptanoate metabolism in the normal and glucose-deficient brain and encourage further studies to elucidate its potential antiepileptic effects in disorders of energy metabolism. PMID:23072752

  7. Uniform distributions of glucose oxidation and oxygen extraction in gray matter of normal human brain: No evidence of regional differences of aerobic glycolysis.

    PubMed

    Hyder, Fahmeed; Herman, Peter; Bailey, Christopher J; Møller, Arne; Globinsky, Ronen; Fulbright, Robert K; Rothman, Douglas L; Gjedde, Albert

    2016-05-01

    Regionally variable rates of aerobic glycolysis in brain networks identified by resting-state functional magnetic resonance imaging (R-fMRI) imply regionally variable adenosine triphosphate (ATP) regeneration. When regional glucose utilization is not matched to oxygen delivery, affected regions have correspondingly variable rates of ATP and lactate production. We tested the extent to which aerobic glycolysis and oxidative phosphorylation power R-fMRI networks by measuring quantitative differences between the oxygen to glucose index (OGI) and the oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) in normal human brain (resting awake, eyes closed). Regionally uniform and correlated OEF and OGI estimates prevailed, with network values that matched the gray matter means, regardless of size, location, and origin. The spatial agreement between oxygen delivery (OEF≈0.4) and glucose oxidation (OGI ≈ 5.3) suggests that no specific regions have preferentially high aerobic glycolysis and low oxidative phosphorylation rates, with globally optimal maximum ATP turnover rates (VATP ≈ 9.4 µmol/g/min), in good agreement with (31)P and (13)C magnetic resonance spectroscopy measurements. These results imply that the intrinsic network activity in healthy human brain powers the entire gray matter with ubiquitously high rates of glucose oxidation. Reports of departures from normal brain-wide homogeny of oxygen extraction fraction and oxygen to glucose index may be due to normalization artefacts from relative PET measurements. PMID:26755443

  8. Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain.

    PubMed

    Marin-Valencia, Isaac; Good, Levi B; Ma, Qian; Malloy, Craig R; Pascual, Juan M

    2013-02-01

    It has been postulated that triheptanoin can ameliorate seizures by supplying the tricarboxylic acid cycle with both acetyl-CoA for energy production and propionyl-CoA to replenish cycle intermediates. These potential effects may also be important in other disorders associated with impaired glucose metabolism because glucose supplies, in addition to acetyl-CoA, pyruvate, which fulfills biosynthetic demands via carboxylation. In patients with glucose transporter type I deficiency (G1D), ketogenic diet fat (a source only of acetyl-CoA) reduces seizures, but other symptoms persist, providing the motivation for studying heptanoate metabolism. In this work, metabolism of infused [5,6,7-(13)C(3)]heptanoate was examined in the normal mouse brain and in G1D by (13)C-nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). In both groups, plasma glucose was enriched in (13)C, confirming gluconeogenesis from heptanoate. Acetyl-CoA and glutamine levels became significantly higher in the brain of G1D mice relative to normal mice. In addition, brain glutamine concentration and (13)C enrichment were also greater when compared with glutamate in both animal groups, suggesting that heptanoate and/or C5 ketones are primarily metabolized by glia. These results enlighten the mechanism of heptanoate metabolism in the normal and glucose-deficient brain and encourage further studies to elucidate its potential antiepileptic effects in disorders of energy metabolism. PMID:23072752

  9. The Impact of Pre-Hospital Administration of Lactated Ringer's Solution versus Normal Saline in Patients with Traumatic Brain Injury.

    PubMed

    Rowell, Susan E; Fair, Kelly A; Barbosa, Ronald R; Watters, Jennifer M; Bulger, Eileen M; Holcomb, John B; Cohen, Mitchell J; Rahbar, Mohammad H; Fox, Erin E; Schreiber, Martin A

    2016-06-01

    Lactated Ringer's (LR) and normal saline (NS) are both used for resuscitation of injured patients. NS has been associated with increased resuscitation volume, blood loss, acidosis, and coagulopathy compared with LR. We sought to determine if pre-hospital LR is associated with improved outcome compared with NS in patients with and without traumatic brain injury (TBI). We included patients receiving pre-hospital LR or NS from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Patients with TBI (Abbreviated Injury Scale [AIS] head ≥3) and without TBI (AIS head ≤2) were compared. Cox proportional hazards models including Injury Severity Score (ISS), AIS head, AIS extremity, age, fluids, intubation status, and hospital site were generated for prediction of mortality. Linear regression models were generated for prediction of red blood cell (RBC) and crystalloid requirement, and admission biochemical/physiological parameters. Seven hundred ninety-one patients received either LR (n = 117) or NS (n = 674). Median ISS, AIS head, AIS extremity, and pre-hospital fluid volume were higher in TBI and non-TBI patients receiving LR compared with NS (p < 0.01). In patients with TBI (n = 308), LR was associated with higher adjusted mortality compared with NS (hazard rate [HR] = 1.78, confidence interval [CI] 1.04-3.04, p = 0.035). In patients without TBI (n = 483), no difference in mortality was demonstrated (HR = 1.49, CI 0.757-2.95, p = 0.247). Fluid type had no effect on admission biochemical or physiological parameters, 6-hour RBC, or crystalloid requirement in either group. LR was associated with increased mortality compared with NS in patients with TBI. These results underscore the need for a prospective randomized trial comparing pre-hospital LR with NS in patients with TBI. PMID:26914721

  10. Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

    PubMed

    Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

    2016-02-01

    Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized. PMID:26364049

  11. Sucrose ingestion normalizes central expression of corticotropin-releasing-factor messenger ribonucleic acid and energy balance in adrenalectomized rats: a glucocorticoid-metabolic-brain axis?

    PubMed

    Laugero, K D; Bell, M E; Bhatnagar, S; Soriano, L; Dallman, M F

    2001-07-01

    Both CRF and norepinephrine (NE) inhibit food intake and stimulate ACTH secretion and sympathetic outflow. CRF also increases anxiety; NE increases attention and cortical arousal. Adrenalectomy (ADX) changes CRF and NE activity in brain, increases ACTH secretion and sympathetic outflow and reduces food intake and weight gain; all of these effects are corrected by administration of adrenal steroids. Unexpectedly, we recently found that ADX rats drinking sucrose, but not saccharin, also have normal caloric intake, metabolism, and ACTH. Here, we show that ADX (but not sham-ADX) rats prefer to consume significantly more sucrose than saccharin. Voluntary ingestion of sucrose restores CRF and dopamine-beta-hydroxylase messenger RNA expression in brain, food intake, and caloric efficiency and fat deposition, circulating triglyceride, leptin, and insulin to normal. Our results suggest that the brains of ADX rats, cued by sucrose energy (but not by nonnutritive saccharin) maintain normal activity in systems that regulate neuroendocrine (hypothalamic-pituitary-adrenal), behavioral (feeding), and metabolic functions (fat deposition). We conclude that because sucrose ingestion, like glucocorticoid replacement, normalizes energetic and neuromodulatory effects of ADX, many of the actions of the steroids on the central nervous system under basal conditions may be indirect and mediated by signals that result from the metabolic effects of adrenal steroids. PMID:11415998

  12. Differences in brain functional connectivity at resting-state in neonates born to healthy obese or normal-weight mothers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lo...

  13. The significance of electron spin resonance of the ascorbic acid radical in freeze dried human brain tumours and oedematous or normal periphery.

    PubMed Central

    Mueller, H. W.; Tannert, S.

    1986-01-01

    The ESR spectrum, attributed to the ascorbic acid (ascorbyl) radical and obtained by exposing freeze dried material to air, can not be used as proof for the occurrence of in vivo free radical reactions. Depending on the method of freeze drying, the content of blood or hemolyzed blood is the dominant factor in creating higher than normal ESR signals in brain or related tissue. These findings explain why the signal, though larger in many human brain tumours than in their surroundings, is not indicative of malignancy. No differences are seen between oedematous and normal tissue. The ascorbyl radical is definitely not stable in aqueous solution, which indicates that fresh tissue sections can also not be used to study in vivo radicals by ESR. PMID:3008800

  14. Expression of the human ETS-2 oncogene in normal fetal tissues and in the brain of a fetus with trisomy 21.

    PubMed

    Baffico, M; Perroni, L; Rasore-Quartino, A; Scartezzini, P

    1989-10-01

    The expression of the ETS-2 proto-oncogene, located on chromosome 21, in normal fetal tissues and in neural tissue of a fetus affected by Down syndrome has been investigated. The results show that the ETS-2 proto-oncogene is expressed in almost all the tissues examined and that it is transcribed at constant levels in neural tissue between the 13th and 24th weeks. ETS-2 expression appeared to be slightly increased in Down syndrome brain compared with that of normal controls of the same gestational age. PMID:2529204

  15. In situ demonstration of Fluoro-Turquoise conjugated gelatin for visualizing brain vasculature and endothelial cells and their characterization in normal and kainic acid exposed animals.

    PubMed

    Sarkar, Sumit; Raymick, James; Paule, Merle G; Schmued, Larry

    2013-10-15

    The present study describes a new method for the visualization of the vasculature lumen and endothelial cells and characterizes their morphology in the brains of normal and kainic acid (KA) treated rats. Herein, labeling was accomplished using Fluoro-Turquoise (FT), a novel reactive blue fluorochrome conjugated to gelatin. Strong blue fluorescence was observed throughout the brain vasculature following intra-cardiac perfusion with FT-gel in normal animals. However, in the brains of KA treated rats (hippocampus, midline and ventral thalamus, piriform cortex), the vascular lumen was typically constricted, sclerotic and only faintly stained. The advantages of FT-gel over other markers can be attributed to its unique chemical and spectral properties. Specifically, Fluoro-Turquoise is a very bright blue UV excitable dye that does not bleed through when visualized using other filters, making it ideal for multiple immunofluorescent labeling studies. Its brightness at low magnification also makes it ideal for low magnification whole brain imaging. Compared to alternative techniques for visualizing blood vessels, such as India ink, fluorescent dye-conjugated dextran, the corrosion technique, endothelial cell markers and lectins, the present method results in excellent visualization of blood vessels. PMID:23954779

  16. Automated Spatial Brain Normalization and Hindbrain White Matter Reference Tissue Give Improved [18F]-Florbetaben PET Quantitation in Alzheimer's Model Mice

    PubMed Central

    Overhoff, Felix; Brendel, Matthias; Jaworska, Anna; Korzhova, Viktoria; Delker, Andreas; Probst, Federico; Focke, Carola; Gildehaus, Franz-Josef; Carlsen, Janette; Baumann, Karlheinz; Haass, Christian; Bartenstein, Peter; Herms, Jochen; Rominger, Axel

    2016-01-01

    Preclinical PET studies of β-amyloid (Aβ) accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore, we aimed to evaluate systematically the (1) impact of an automated algorithm for spatial brain normalization, and (2) intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a 6 week longitudinal setting (N = 37) and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40) were investigated by [18F]-florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ). For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX∕REF), relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen's d), and in reference to gold standard histopathological quantitation (Pearson's R). Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ≥0.99) between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX∕REF. All SUVRCTX∕REF methods performed better than SUVCTX both with regard to longitudinal stability (d≥1.21 vs. d = 0.23) and histological gold standard agreement (R≥0.66 vs. R≥0.31). Voxel-wise analysis suggested a physiologically implausible longitudinal decrease by global mean scaling. The hindbrain white matter reference (Rmean = 0.75) was slightly superior to the brainstem (Rmean = 0.74) and the cerebellum (Rmean = 0.73). Automated brain

  17. Mortality of passerines adjacent to a North Carolina corn field treated with granular carbofuran.

    USGS Publications Warehouse

    Augspurger, Tom; Smith, Milton R.; Meteyer, Carol U.; Converse, Kathryn A.

    1996-01-01

    Red-winged blackbirds (Agelaius phoeniceus) were collected during an epizootic in southeastern North Carolina (USA). Activity of brain cholinesterase (ChE) was inhibited by 14 to 48% in three of five specimens, and returned to normal levels after incubation. Gastrointestinal tracts were analyzed for 30 anti-ChE agents. Carbofuran, the only compound detected, was present in all specimens at levels from 5.44 to 72.7 μg/g wet weight. Application of granular carbofuran in an adjacent corn field, results of necropsy examinations, and chemical analyses are consistent with a diagnosis of carbofuran poisoning in these specimens.

  18. Oscillating gradient diffusion MRI reveals unique microstructural information in normal and hypoxia-ischemia injured mouse brains

    PubMed Central

    Wu, Dan; Martin, Lee J.; Northington, Frances J.; Zhang, Jiangyang

    2014-01-01

    Purpose We investigated whether oscillating gradient diffusion MRI (dMRI) can provide information on brain microstructural changes after formaldehyde fixation and after hypoxic-ischemic (HI) injury beyond that provided by conventional dMRI. Methods Pulsed gradient spin echo (PGSE) and oscillating gradient spin echo (OGSE) dMRI of the adult mouse brain was performed in vivo (50-200 Hz, b = 600 mm2/s), and a similar protocol was applied to neonatal mouse brains at 24 hours after unilateral hypoxia-ischemia. Animals were perfusion fixed with 4% paraformaldehyde for ex vivo dMRI and histology. Results Apparent diffusion coefficients (ADCs) measured in the live adult mouse brain presented tissue-dependent frequency-dependence. In vivo OGSE-ADC maps at high oscillating frequencies (>100Hz) showed clear contrast between the molecular layer and granule cell layer in the adult mouse cerebellum. Formaldehyde fixation significantly altered the temporal diffusion spectra in several brain regions. In neonatal mouse brains with HI injury, in vivo ADC measurements from edema regions showed diminished edema contrasts at 200 Hz compared to the PGSE results. Histology showed severe tissue swelling and necrosis in the edema regions. Conclusion The results demonstrate the unique ability of OGSE-dMRI in delineating tissue microstructures at different spatial scales. PMID:25168861

  19. Expression and distribution of amyloid precursor protein-like protein-2 in Alzheimer's disease and in normal brain.

    PubMed Central

    Crain, B. J.; Hu, W.; Sze, C. I.; Slunt, H. H.; Koo, E. H.; Price, D. L.; Thinakaran, G.; Sisodia, S. S.

    1996-01-01

    Amyloid precursor-like protein-2 (APLP-2) belongs to a family of homologous amyloid precursor-like proteins. In the present study we report on the expression and distribution of APLP-2 in fetal and adult human brain and in brains of patients with Alzheimer's disease. We demonstrate that APLP-2 mRNAs encoding isoforms predicted to undergo post-translational modification by chondroitin sulfate glycosaminoglycans are elevated in fetal and aging brains relative to the brains of young adults. Immunocytochemical labeling with APLP-2-specific antibodies demonstrates APLP-2 immunoreactivity in cytoplasmic compartments in neurons and astrocytes, in large part overlapping the distribution of the amyloid precursor protein. In Alzheimer's disease brain, APLP-2 antibodies also label a subset of neuritic plaques. APLP-2 immunoreactivity is particularly conspicuous in large dystrophic neurites that also label with antibodies specific for APP and chromogranin A. In view of the age-dependent increase in levels of chondroitin sulfate glycosaminoglycan-modified forms of APLP-2 in aging brain and the accumulation of APLP-2 in dystrophic presynaptic elements, we suggest that APLP-2 may play roles in neuronal sprouting or in the aggregation, deposition, and/or persistence of beta-amyloid deposits. Images Figure 1 Figure 2 Figure 3 PMID:8863657

  20. Annual Research Review: Growth connectomics – the organization and reorganization of brain networks during normal and abnormal development

    PubMed Central

    Vértes, Petra E; Bullmore, Edward T

    2015-01-01

    Background We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). Synthesis We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. Conclusions We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. PMID:25441756

  1. A longitudinal study of the long-term consequences of drinking during pregnancy: heavy in utero alcohol exposure disrupts the normal processes of brain development.

    PubMed

    Lebel, Catherine; Mattson, Sarah N; Riley, Edward P; Jones, Kenneth L; Adnams, Colleen M; May, Philip A; Bookheimer, Susan Y; O'Connor, Mary J; Narr, Katherine L; Kan, Eric; Abaryan, Zvart; Sowell, Elizabeth R

    2012-10-31

    Exposure to alcohol in utero can cause birth defects, including face and brain abnormalities, and is the most common preventable cause of intellectual disabilities. Here we use structural magnetic resonance imaging to measure cortical volume change longitudinally in a cohort of human children and youth with prenatal alcohol exposure (PAE) and a group of unexposed control subjects, demonstrating that the normal processes of brain maturation are disrupted in individuals whose mothers drank heavily during pregnancy. Trajectories of cortical volume change within children and youth with PAE differed from those of unexposed control subjects in posterior brain regions, particularly in the parietal cortex. In these areas, control children appear to show a particularly plastic cortex with a prolonged pattern of cortical volume increases followed by equally vigorous volume loss during adolescence, while the alcohol-exposed participants showed primarily volume loss, demonstrating decreased plasticity. Furthermore, smaller volume changes between scans were associated with lower intelligence and worse facial morphology in both groups, and were related to the amount of PAE during each trimester of pregnancy in the exposed group. This demonstrates that measures of IQ and facial dysmorphology predict, to some degree, the structural brain development that occurs in subsequent years. These results are encouraging in that interventions aimed at altering "experience" over time may improve brain trajectories in individuals with heavy PAE and possibly other neurodevelopmental disorders. PMID:23115162

  2. The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

    PubMed Central

    Gaser, Christian; Franke, Katja

    2016-01-01

    In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) with their causes, diagnosis, treatment, and disease prediction. We applied the Brain Age Gap Estimation (BrainAGE) method to examine the impact of the Apolipoprotein E (APOE) genotype on structural brain aging, utilizing longitudinal magnetic resonance image (MRI) data of 405 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We tested for differences in neuroanatomical aging between carrier and non-carrier of APOE ε4 within the diagnostic groups and for longitudinal changes in individual brain aging during about three years follow-up. We further examined whether a combination of BrainAGE and APOE status could improve prediction accuracy of conversion to AD in MCI patients. The influence of the APOE status on conversion from MCI to AD was analyzed within all allelic subgroups as well as for ε4 carriers and non-carriers. The BrainAGE scores differed significantly between normal controls, stable MCI (sMCI) and progressive MCI (pMCI) as well as AD patients. Differences in BrainAGE changing rates over time were observed for APOE ε4 carrier status as well as in the pMCI and AD groups. At baseline and during follow-up, BrainAGE scores correlated significantly with neuropsychological test scores in APOE ε4 carriers and non-carriers, especially in pMCI and AD patients. Prediction of conversion was most accurate using the BrainAGE score as compared to neuropsychological test scores, even when the patient’s APOE status was unknown. For assessing the individual risk of coming down with AD as well as predicting conversion from MCI to AD, the BrainAGE method proves to be a useful and accurate tool even if the information of the patient’s APOE status is missing. PMID:27410431

  3. The effect of ingested sulfite on visual evoked potentials, lipid peroxidation, and antioxidant status of brain in normal and sulfite oxidase-deficient aged rats.

    PubMed

    Ozsoy, Ozlem; Aras, Sinem; Ozkan, Ayse; Parlak, Hande; Aslan, Mutay; Yargicoglu, Piraye; Agar, Aysel

    2016-07-01

    Sulfite, commonly used as a preservative in foods, beverages, and pharmaceuticals, is a very reactive and potentially toxic molecule which is detoxified by sulfite oxidase (SOX). Changes induced by aging may be exacerbated by exogenous chemicals like sulfite. The aim of this study was to investigate the effects of ingested sulfite on visual evoked potentials (VEPs) and brain antioxidant statuses by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Brain lipid oxidation status was also determined via thiobarbituric acid reactive substances (TBARS) in normal- and SOX-deficient aged rats. Rats do not mimic the sulfite responses seen in humans because of their relatively high SOX activity level. Therefore this study used SOX-deficient rats since they are more appropriate models for studying sulfite toxicity. Forty male Wistar rats aged 24 months were randomly assigned to four groups: control (C), sulfite (S), SOX-deficient (D) and SOX-deficient + sulfite (DS). SOX deficiency was established by feeding rats with low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg kg(-1) day(-1)) was given by gavage. Treatment continued for 6 weeks. At the end of the experimental period, flash VEPs were recorded. Hepatic SOX activity was measured to confirm SOX deficiency. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with the normal rats. The activity of SOX in deficient rats was thus in the range of humans. There was no significant difference between control and treated groups in either latence or amplitude of VEP components. Brain SOD, CAT, and GPx activities and brain TBARS levels were similar in all experimental groups compared with the control group. Our results indicate that exogenous administration of sulfite does not affect VEP components and the antioxidant/oxidant status of aged rat brains. PMID:25342669

  4. An In Vivo Microdialysis Study of FLZ Penetration through the Blood-Brain Barrier in Normal and 6-Hydroxydopamine Induced Parkinson's Disease Model Rats

    PubMed Central

    Hou, Jinfeng; Liu, Qian; Li, Yingfei; Sun, Hua; Zhang, Jinlan

    2014-01-01

    FLZ (N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) is a novel synthetic squamosamide derivative and a potential anti-Parkinson's disease (PD) agent. The objective of the present study was to investigate the penetration of free FLZ across the BBB and the effects of P-gp inhibition on FLZ transport in normal and 6-hydroxydopamine (6-OHDA) induced PD model rats. In vivo microdialysis was used to collect FLZ containing brain and blood dialysates following intravenous (i.v.) drug administration either with or without pretreatment with the specific P-gp inhibitor, zosuquidar trihydrochloride (zosuquidar·3HCl). A sensitive, rapid, and reliable ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed and validated to quantitate free FLZ levels in the dialysates. No significant differences were observed in the brain/blood FLZ area under the concentration-time curve (AUC) ratio between normal and PD model rats. However, pretreatment with zosuquidar·3HCl markedly increased the AUC ratio in both rat models. In addition, FLZ penetration was similar in zosuquidar·3HCl-pretreated normal and PD rats. These results suggest that P-gp inhibition increases BBB permeability to FLZ, thereby supporting the hypothesis that P-gp normally restricts FLZ transfer to the brain. These findings could provide reference data for future clinical trials and may aid investigation of the BBB permeability of other CNS-active substances. PMID:25045708

  5. A voxel-based morphometric study of age- and sex-related changes in white matter volume in the normal aging brain

    PubMed Central

    Liu, Haijing; Wang, Lixin; Geng, Zuojun; Zhu, Qingfeng; Song, Zhenhu; Chang, Ruiting; Lv, Huandi

    2016-01-01

    Objective To carry out a cross-sectional study of 187 cognitively normal Chinese adults using the voxel-based morphometry (VBM) approach to delineate age-related changes in the white matter volume of regions of interest in the brain and further analyze their correlation with age. Materials and methods A total of 187 cognitively normal adults were divided into the young, middle, and old age-groups. Conventional magnetic resonance imaging was performed with the Achieva 3.0 T system. Structural images were processed using VBM8 and statistical parametric mapping 8. Regions of interest were obtained by WFU PickAtlas, and all realigned images were spatially normalized. Results Females showed significantly greater total white matter volume than males (t=2.36, P=0.0096, false-discovery rate [FDR] corrected). VBM demonstrated statistically significant age-related differences in white matter volume between the young age-group and the middle age-group (P<0.05, FDR corrected) and between the middle age-group and the old age-group (P<0.05, FDR corrected). No interaction was found between age and sex on white matter volume (P<0.05, FDR corrected). Logistic regression analysis revealed nonlinear correlation between total white matter volume and age (R2=0.124, P<0.001). White matter volume gradually increased before 40 years of age, peaked around 50 years of age, and rapidly declined after 60 years of age. Conclusion Significant age-related differences are present in white matter volume across multiple brain regions during aging. The VBM approach may help differentiate underlying normal neurobiological aging changes of specific brain regions from neurodegenerative impairments. PMID:26966366

  6. "Where Brains Had a Chance": William Mayo and Rhetorical Instruction at East Texas Normal College, 1889-1917

    ERIC Educational Resources Information Center

    Gold, David

    2005-01-01

    The rhetorical training of students at East Texas Normal College is examined with reference to the rhetorical practices and educational ideologies of William Mayo, the experiences of his students and the features of his teaching. Examination of the history of schools like East Texas Normal College helps in dealing with concerns regarding…

  7. Tolerance to Dose Escalation in Minibeam Radiation Therapy Applied to Normal Rat Brain: Long-Term Clinical, Radiological and Histopathological Analysis.

    PubMed

    Prezado, Yolanda; Deman, Pierre; Varlet, Pascale; Jouvion, Gregory; Gil, Silvia; Le Clec'H, Céline; Bernard, Hélène; Le Duc, Géraldine; Sarun, Sukhena

    2015-09-01

    The major limitation to reaching a curative radiation dose in radioresistant tumors such as malignant gliomas is the high sensitivity to radiation and subsequent damage of the surrounding normal tissues. Novel dose delivery methods such as minibeam radiation therapy (MBRT) may help to overcome this limitation. MBRT utilizes a combination of spatial fractionation of the dose and submillimetric (600 μm) field sizes with an array ("comb") of parallel thin beams ("teeth"). The dose profiles in MBRT consist of peaks and valleys. In contrast, the seamless irradiations of the several squared centimeter field sizes employed in standard radiotherapy result in homogeneous dose distributions (and consequently, flat dose profiles). The innovative dose delivery methods employed in MBRT, unlike standard radiation therapy, have demonstrated remarkable normal tissue sparing. In this pilot work, we investigated the tolerance of the rat brain after whole-brain MBRT irradiation. A dose escalation was used to study the tissue response as a function of dose, so that a threshold could be established: doses as high as 100 Gy in one fraction were still well tolerated by the rat brain. This finding suggests that MBRT may be used to deliver higher and potentially curative radiation doses in clinical practice. PMID:26284420

  8. 7-Tesla Susceptibility-Weighted Imaging to Assess the Effects of Radiotherapy on Normal-Appearing Brain in Patients With Glioma

    SciTech Connect

    Lupo, Janine M.; Chuang, Cynthia F.; Chang, Susan M.; Barani, Igor J.; Jimenez, Bert; Hess, Christopher P.; Nelson, Sarah J.

    2012-03-01

    Purpose: To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI). Methods and Materials: SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data. Results: Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation. These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere. Conclusions: High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.

  9. Maternal omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalizes angiogenic markers in the pup brain at birth.

    PubMed

    Rathod, Richa S; Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

    2015-06-01

    Vitamin B12 and omega-3 fatty acids are critical for normal brain development and function and their deficiencies during pregnancy could have adverse effects on cognitive performance in children. Our earlier studies indicate that both maternal vitamin B12 and omega-3 fatty acids influence brain development by regulating the levels of neurotrophins. Literature suggests that there exists a cross talk between neurotrophins like nerve growth factor (NGF) and angiogenic factors like vascular endothelial growth factor (VEGF). It remains to be established whether maternal nutrients like vitamin B12 and omega-3 fatty acids influence the levels of angiogenic markers like VEGF and NGF in the brain of the offspring. Therefore the present study examines the effect of maternal vitamin B12 and omega-3 fatty acids on protein and mRNA levels of VEGF, HIF-1 alpha (hypoxia inducible factor alpha) and NGF in the pup brain at birth. Pregnant Wistar rats were divided into five dietary groups (n=8 each): control, vitamin B12 deficient, vitamin B12 deficient+omega-3 fatty acid, vitamin B12 supplemented, vitamin B12 supplemented+omega-3 fatty acid. At birth the pups were dissected to collect the brain tissue. Maternal vitamin B12 deficiency showed lower (p<0.05) pup brain mRNA and protein levels (p<0.01) of VEGF, higher (p<0.01) HIF-1 alpha protein levels, lower (p<0.05) NGF protein levels while NGF mRNA levels were not altered. Omega-3 fatty acid supplementation to a vitamin B12 deficient group normalized the VEGF mRNA levels, NGF protein levels and HIF-1 alpha protein levels. Vitamin B12 supplementation showed similar protein and mRNA levels of VEGF and NGF as well as HIF-1 alpha protein levels as compared to control. Omega-3 fatty acid supplementation to the vitamin B12 supplemented group showed higher (p<0.01) protein and mRNA levels of NGF but the protein and mRNA levels of VEGF were comparable to control. In conclusion maternal vitamin B12 and omega-3 fatty acids both influence the

  10. GRAPPA-based Susceptibility-Weighted Imaging of Normal Volunteers and Patients with Brain Tumor at 7T

    PubMed Central

    Lupo, Janine M.; Banerjee, Suchandrima; Hammond, Kathryn E.; Kelley, Douglas A.C.; Xu, Duan; Chang, Susan M.; Vigneron, Daniel B.; Majumdar, Sharmila; Nelson, Sarah J.

    2016-01-01

    Susceptibility-weighted imaging (SWI) is a valuable technique for high-resolution imaging of brain vasculature that greatly benefits from the emergence higher field strength MR scanners. Autocalibrating partially parallel imaging techniques can be employed to reduce lengthy acquisition times as long as the decrease in signal-to-noise ratio does not significantly affect the contrast between vessels and brain parenchyma. This study assessed the feasibility of a GRAPPA-based SWI technique at 7 Tesla in both healthy volunteers and brain tumor patients. GRAPPA-based SWI allowed a 2-fold or more reduction in scan time without compromising vessel contrast and small vessel detection. Post-processing parameters for the SWI needed to be modified for patients where the tumor causes high-frequency phase wrap artifacts but did not adversely affect vessel contrast. GRAPPA-based SWI at 7T revealed regions of microvascularity, hemorrhage, and calcification within heterogeneous brain tumors that may aid in characterizing active or necrotic tumor and monitoring treatment effects. PMID:18823730

  11. Changes in Ascorbate, Glutathione and α-tocopherol Concentrations in the Brain Regions during Normal Development and Moderate Hypoglycemia in Rats

    PubMed Central

    Rao, Anirudh R.; Quach, Hung; Smith, Ed; Rao, Raghavendra

    2014-01-01

    Ascorbate, glutathione and α-tocopherol are the major low molecular weight antioxidants in the brain. The simultaneous changes in these compounds during normal development, and under a pro-oxidant condition are poorly understood. Ascorbate, glutathione and α-tocopherol concentrations in the olfactory bulb, cerebral cortex, hippocampus, striatum, hypothalamus, midbrain, cerebellum, pons and medulla oblongata were determined in postnatal day (P) 7, P14 and P60 male rats. A separate group of P14 and P60 rats were subjected to acute hypoglycemia, a pro-oxidant condition, prior to tissue collection. The concentrations of all three antioxidants were 100-600% higher in the brain regions at P7 and P14, relative to P60. The neuron-rich anterior brain regions (cerebral cortex and hippocampus) had higher concentrations of all three antioxidants than the myelin-rich posterior regions (pons and medulla oblongata) at P14 and P60. Hypoglycemia had a differential effect on the antioxidants. Glutathione was decreased at both P14 and P60. However, the decrease was localized at P14 and global at P60. Hypoglycemia had no effect on ascorbate and α-tocopherol at either age. Higher antioxidant concentrations in the developing brain may reflect the risk of oxidant stress during the early postnatal period and explain the relative resistance to oxidant-mediated injury at this age. PMID:24686186

  12. In Silico Neuro-Oncology: Brownian Motion-Based Mathematical Treatment as a Potential Platform for Modeling the Infiltration of Glioma Cells into Normal Brain Tissue

    PubMed Central

    Antonopoulos, Markos; Stamatakos, Georgios

    2015-01-01

    Intensive glioma tumor infiltration into the surrounding normal brain tissues is one of the most critical causes of glioma treatment failure. To quantitatively understand and mathematically simulate this phenomenon, several diffusion-based mathematical models have appeared in the literature. The majority of them ignore the anisotropic character of diffusion of glioma cells since availability of pertinent truly exploitable tomographic imaging data is limited. Aiming at enriching the anisotropy-enhanced glioma model weaponry so as to increase the potential of exploiting available tomographic imaging data, we propose a Brownian motion-based mathematical analysis that could serve as the basis for a simulation model estimating the infiltration of glioblastoma cells into the surrounding brain tissue. The analysis is based on clinical observations and exploits diffusion tensor imaging (DTI) data. Numerical simulations and suggestions for further elaboration are provided. PMID:26309390

  13. Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers

    PubMed Central

    Zlatar, Zvinka Z.; Bischoff-Grethe, Amanda; Hays, Chelsea C.; Liu, Thomas T.; Meloy, M. J.; Rissman, Robert A.; Bondi, Mark W.; Wierenga, Christina E.

    2016-01-01

    Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk. PMID:27445794

  14. Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers.

    PubMed

    Zlatar, Zvinka Z; Bischoff-Grethe, Amanda; Hays, Chelsea C; Liu, Thomas T; Meloy, M J; Rissman, Robert A; Bondi, Mark W; Wierenga, Christina E

    2016-01-01

    Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk. PMID:27445794

  15. Immune responses at brain barriers and implications for brain development and neurological function in later life

    PubMed Central

    Stolp, Helen B.; Liddelow, Shane A.; Sá-Pereira, Inês; Dziegielewska, Katarzyna M.; Saunders, Norman R.

    2013-01-01

    For a long time the brain has been considered an immune-privileged site due to a muted inflammatory response and the presence of protective brain barriers. It is now recognized that neuroinflammation may play an important role in almost all neurological disorders and that the brain barriers may be contributing through either normal immune signaling or disruption of their basic physiological mechanisms. The distinction between normal function and dysfunction at the barriers is difficult to dissect, partly due to a lack of understanding of normal barrier function and partly because of physiological changes that occur as part of normal development and ageing. Brain barriers consist of a number of interacting structural and physiological elements including tight junctions between adjacent barrier cells and an array of influx and efflux transporters. Despite these protective mechanisms, the capacity for immune-surveillance of the brain is maintained, and there is evidence of inflammatory signaling at the brain barriers that may be an important part of the body's response to damage or infection. This signaling system appears to change both with normal ageing, and during disease. Changes may affect diapedesis of immune cells and active molecular transfer, or cause rearrangement of the tight junctions and an increase in passive permeability across barrier interfaces. Here we review the many elements that contribute to brain barrier functions and how they respond to inflammation, particularly during development and aging. The implications of inflammation–induced barrier dysfunction for brain development and subsequent neurological function are also discussed. PMID:23986663

  16. Demonstration of Normal and Abnormal Fetal Brains Using 3D Printing from In Utero MR Imaging Data.

    PubMed

    Jarvis, D; Griffiths, P D; Majewski, C

    2016-09-01

    3D printing is a new manufacturing technology that produces high-fidelity models of complex structures from 3D computer-aided design data. Radiology has been particularly quick to embrace the new technology because of the wide access to 3D datasets. Models have been used extensively to assist orthopedic, neurosurgical, and maxillofacial surgical planning. In this report, we describe methods used for 3D printing of the fetal brain by using data from in utero MR imaging. PMID:27079366

  17. In vitro determination of normal and neoplastic human brain tissue optical properties using inverse adding-doubling.

    PubMed

    Gebhart, S C; Lin, W C; Mahadevan-Jansen, A

    2006-04-21

    To complement a project towards the development of real-time optical biopsy for brain tissue discrimination and surgical resection guidance, the optical properties of various brain tissues were measured in vitro and correlated to features within clinical diffuse reflectance tissue spectra measured in vivo. Reflectance and transmission spectra of in vitro brain tissue samples were measured with a single-integrating-sphere spectrometer for wavelengths 400-1300 nm and converted to absorption and reduced scattering spectra using an inverse adding-doubling technique. Optical property spectra were classified as deriving from white matter, grey matter or glioma tissue according to histopathologic diagnosis, and mean absorption and reduced scattering spectra were calculated for the three tissue categories. Absolute reduced scattering and absorption values and their relative differences between histopathological groups agreed with previously reported results with the exception that absorption coefficients were often overestimated, most likely due to biologic variability or unaccounted light loss during reflectance/transmission measurement. Absorption spectra for the three tissue classes were dominated by haemoglobin absorption below 600 nm and water absorption above 900 nm and generally determined the shape of corresponding clinical diffuse reflectance spectra. Reduced scattering spectral shapes followed the power curve predicted by the Rayleigh limit of Mie scattering theory. While tissue absorption governed the shape of clinical diffuse reflectance spectra, reduced scattering determined their relative emission intensities between the three tissue categories. PMID:16585842

  18. L-Phenylalanine preloading reduces the (10)B(n, α)(7)Li dose to the normal brain by inhibiting the uptake of boronophenylalanine in boron neutron capture therapy for brain tumours.

    PubMed

    Watanabe, Tsubasa; Tanaka, Hiroki; Fukutani, Satoshi; Suzuki, Minoru; Hiraoka, Masahiro; Ono, Koji

    2016-01-01

    Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. Previously, high doses of one of the boron compounds used for BNCT, L-BPA, were found to reduce the boron-derived irradiation dose to the central nervous system. However, injection with a high dose of L-BPA is not feasible in clinical settings. We aimed to find an alternative method to improve the therapeutic efficacy of this therapy. We examined the effects of oral preloading with various analogues of L-BPA in a xenograft tumour model and found that high-dose L-phenylalanine reduced the accumulation of L-BPA in the normal brain relative to tumour tissue. As a result, the maximum irradiation dose in the normal brain was 19.2% lower in the L-phenylalanine group relative to the control group. This study provides a simple strategy to improve the therapeutic efficacy of conventional boron compounds for BNCT for brain tumours and the possibility to widen the indication of BNCT to various kinds of other tumours. PMID:26455769

  19. Intrinsic Brain Activity of Cognitively Normal Older Persons Resembles More That of Patients Both with and at Risk for Alzheimer's Disease Than That of Healthy Younger Persons

    PubMed Central

    Pasquini, Lorenzo; Tonch, Annika; Plant, Claudia; Zherdin, Andrew; Ortner, Marion; Kurz, Alexander; Förstl, Hans; Zimmer, Claus; Grimmer, Timo; Wohlschäger, Afra; Riedl, Valentin

    2014-01-01

    Abstract In Alzheimer's disease (AD), recent findings suggest that amyloid-β (Aβ)-pathology might start 20–30 years before first cognitive symptoms arise. To account for age as most relevant risk factor for sporadic AD, it has been hypothesized that lifespan intrinsic (i.e., ongoing) activity of hetero-modal brain areas with highest levels of functional connectivity triggers Aβ-pathology. This model induces the simple question whether in older persons without any cognitive symptoms intrinsic activity of hetero-modal areas is more similar to that of symptomatic patients with AD or to that of younger healthy persons. We hypothesize that due to advanced age and therefore potential impact of pre-clinical AD, intrinsic activity of older persons resembles more that of patients than that of younger controls. We tested this hypothesis in younger (ca. 25 years) and older healthy persons (ca. 70 years) and patients with mild cognitive impairment and AD-dementia (ca. 70 years) by the use of resting-state functional magnetic resonance imaging, distinct measures of intrinsic brain activity, and different hierarchical clustering approaches. Independently of applied methods and involved areas, healthy older persons' intrinsic brain activity was consistently more alike that of patients than that of younger controls. Our result provides evidence for larger similarity in intrinsic brain activity between healthy older persons and patients with or at-risk for AD than between older and younger ones, suggesting a significant proportion of pre-clinical AD cases in the group of cognitively normal older people. The observed link of aging and AD with intrinsic brain activity supports the view that lifespan intrinsic activity may contribute critically to the pathogenesis of AD. PMID:24689864

  20. Global Developmental Gene Expression and Pathway Analysis of Normal Brain Development and Mouse Models of Human Neuronal Migration Defects

    PubMed Central

    Pramparo, Tiziano; Libiger, Ondrej; Jain, Sonia; Li, Hong; Youn, Yong Ha; Hirotsune, Shinji; Schork, Nicholas J.; Wynshaw-Boris, Anthony

    2011-01-01

    Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3ε that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3ε), and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define

  1. Cellular resilience: 5-HT neurons in Tph2(-/-) mice retain normal firing behavior despite the lack of brain 5-HT.

    PubMed

    Montalbano, Alberto; Waider, Jonas; Barbieri, Mario; Baytas, Ozan; Lesch, Klaus-Peter; Corradetti, Renato; Mlinar, Boris

    2015-11-01

    Considerable evidence links dysfunction of serotonin (5-hydroxytryptamine, 5-HT) transmission to neurodevelopmental and psychiatric disorders characterized by compromised "social" cognition and emotion regulation. It is well established that the brain 5-HT system is under autoregulatory control by its principal transmitter 5-HT via its effects on activity and expression of 5-HT system-related proteins. To examine whether 5-HT itself also has a crucial role in the acquisition and maintenance of characteristic rhythmic firing of 5-HT neurons, we compared their intrinsic electrophysiological properties in mice lacking brain 5-HT, i.e. tryptophan hydroxylase-2 null mice (Tph2(-/-)) and their littermates, Tph2(+/-) and Tph2(+/+), by using whole-cell patch-clamp recordings in a brainstem slice preparation and single unit recording in anesthetized animals. We report that the active properties of dorsal raphe nucleus (DRN) 5-HT neurons in vivo (firing rate magnitude and variability; the presence of spike doublets) and in vitro (firing in response to depolarizing current pulses; action potential shape) as well as the resting membrane potential remained essentially unchanged across Tph2 genotypes. However, there were subtle differences in subthreshold properties, most notably, an approximately 25% higher input conductance in Tph2(-/-) mice compared with Tph2(+/-) and Tph2(+/+) littermates (p<0.0001). This difference may at least in part be a consequence of slightly bigger size of the DRN 5-HT neurons in Tph2(-/-) mice (approximately 10%, p<0.0001). Taken together, these findings show that 5-HT neurons acquire and maintain their signature firing properties independently of the presence of their principal neurotransmitter 5-HT, displaying an unexpected functional resilience to complete brain 5-HT deficiency. PMID:26409296

  2. Does Silent Reading Speed in Normal Adult Readers Depend on Early Visual Processes? Evidence from Event-Related Brain Potentials

    ERIC Educational Resources Information Center

    Korinth, Sebastian Peter; Sommer, Werner; Breznitz, Zvia

    2012-01-01

    Little is known about the relationship of reading speed and early visual processes in normal readers. Here we examined the association of the early P1, N170 and late N1 component in visual event-related potentials (ERPs) with silent reading speed and a number of additional cognitive skills in a sample of 52 adult German readers utilizing a Lexical…

  3. Quantification of metabolites from single-voxel in vivo 1H NMR data of normal human brain by means of time-domain data analysis.

    PubMed

    Ala-Korpela, M; Usenius, J P; Keisala, J; van den Boogaart, A; Vainio, P; Jokisaari, J; Soimakallio, S; Kauppinen, R

    1995-01-01

    We present here a combination of time-domain signal analysis procedures for quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for the N-acetylaspartate, creatine, and choline-containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1 wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties. PMID:8749730

  4. Cystic fibrosis transmembrane conductance regulator protein (CFTR) expression in the developing human brain: comparative immunohistochemical study between patients with normal and mutated CFTR.

    PubMed

    Marcorelles, Pascale; Friocourt, Gaëlle; Uguen, Arnaud; Ledé, Françoise; Férec, Claude; Laquerrière, Annie

    2014-11-01

    Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein has recently been shown to be expressed in the human adult central nervous system (CNS). As CFTR expression has also been documented during embryonic development in several organs, such as the respiratory tract, the intestine and the male reproductive system, suggesting a possible role during development we decided to investigate the expression of CFTR in the human developing CNS. In addition, as some, although rare, neurological symptoms have been reported in patients with CF, we compared the expression of normal and mutated CFTR at several fetal stages. Immunohistochemistry was performed on brain and spinal cord samples of foetuses between 13 and 40 weeks of gestation and compared with five patients with cystic fibrosis (CF) of similar ages. We showed in this study that CFTR is only expressed in neurons and has an early and widespread distribution during development. Although we did not observe any cerebral abnormality in patients with CF, we observed a slight delay in the maturation of several brain structures. We also observed different expression and localization of CFTR depending on the brain structure or the cell maturation stage. Our findings, along with a literature review on the neurological phenotypes of patients with CF, suggest that this gene may play previously unsuspected roles in neuronal maturation or function. PMID:25062999

  5. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice.

    PubMed

    Dixit, Shilpy; Bernardo, Alexandra; Walker, Jennifer Michelle; Kennard, John Andrew; Kim, Grace Youngeun; Kessler, Eric Sean; Harrison, Fiona Edith

    2015-04-15

    Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1(+) bigenic mice with SVCT2(+/-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2(+/-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2(+/-) and APP/PSEN1(+) mice and the combination genotype SVCT2(+/-)APP/PSEN1(+) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2(+/-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2(+/-) mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2(+/-)APP/PSEN1(+) mice compared to APP/PSEN1(+) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways. PMID:25642732

  6. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally-aging mice

    PubMed Central

    Dixit, Shilpy; Bernardo, Alexandra; Walker, Michelle Jennifer; Kennard, John Andrew; Kim, Grace Youngeun; Kessler, Eric Sean; Harrison, Fiona Edith

    2015-01-01

    Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer’s disease and normal aging is understudied. In the present study we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer’s disease, by crossing APP/PSEN1+ bigenic mice with SVCT2+/− heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2+/− mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2+/− and APP/PSEN1+, mice, and the combination genotype SVCT2+/−APP/PSEN1+, were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2+/−) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2+/− mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2+/−APP/PSEN1+ mice compared to APP/PSEN1+ mice with normal brain vitamin C. The data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways. PMID:25642732

  7. Altered Expression Patterns of Inflammation-Associated and Trophic Molecules in Substantia Nigra and Striatum Brain Samples from Parkinson's Disease, Incidental Lewy Body Disease and Normal Control Cases

    PubMed Central

    Walker, Douglas G.; Lue, Lih-Fen; Serrano, Geidy; Adler, Charles H.; Caviness, John N.; Sue, Lucia I.; Beach, Thomas G.

    2016-01-01

    Evidence of inflammation has been consistently associated with pathology in Parkinson's disease (PD)-affected brains, and has been suggested as a causative factor. Dopaminergic neurons in the substantia nigra (SN) pars compacta, whose loss results in the clinical symptoms associated with PD, are particularly susceptible to inflammatory damage and oxidative stress. Inflammation in the striatum, where SN dopaminergic neurons project, is also a feature of PD brains. It is not known whether inflammatory changes occur first in striatum or SN. Many animal models of PD have implicated certain inflammatory molecules with dopaminergic cell neuronal loss; however, there have been few studies to validate these findings by measuring the levels of these and other inflammatory factors in human PD brain samples. This study also included samples from incidental Lewy body disease (ILBD) cases, since ILBD is considered a non-symptomatic precursor to PD, with subjects having significant loss of tyrosine hydroxylase-producing neurons. We hypothesized that there may be a progressive change in key inflammatory factors in ILBD samples intermediate between neurologically normal and PD. To address this, we used a quantitative antibody-array platform (Raybiotech-Quantibody arrays) to measure the levels of 160 different inflammation-associated cytokines, chemokines, growth factors, and related molecules in extracts of SN and striatum from clinically and neuropathologically characterized PD, ILBD, and normal control cases. Patterns of changes in inflammation and related molecules were distinctly different between SN and striatum. Our results showed significantly different levels of interleukin (IL)-5, IL-15, monokine induced by gamma interferon, and IL-6 soluble receptor in SN between disease groups. A different panel of 13 proteins with significant changes in striatum, with IL-15 as the common feature, was identified. Although the ability to detect some proteins was limited by sensitivity

  8. Auditory evoked potentials to spectro-temporal modulation of complex tones in normal subjects and patients with severe brain injury.

    PubMed

    Jones, S J; Vaz Pato, M; Sprague, L; Stokes, M; Munday, R; Haque, N

    2000-05-01

    In order to assess higher auditory processing capabilities, long-latency auditory evoked potentials (AEPs) were recorded to synthesized musical instrument tones in 22 post-comatose patients with severe brain injury causing variably attenuated behavioural responsiveness. On the basis of normative studies, three different types of spectro-temporal modulation were employed. When a continuous 'clarinet' tone changes pitch once every few seconds, N1/P2 potentials are evoked at latencies of approximately 90 and 180 ms, respectively. Their distribution in the fronto-central region is consistent with generators in the supratemporal cortex of both hemispheres. When the pitch is modulated at a much faster rate ( approximately 16 changes/s), responses to each change are virtually abolished but potentials with similar distribution are still elicited by changing the timbre (e.g. 'clarinet' to 'oboe') every few seconds. These responses appear to represent the cortical processes concerned with spectral pattern analysis and the grouping of frequency components to form sound 'objects'. Following a period of 16/s oscillation between two pitches, a more anteriorly distributed negativity is evoked on resumption of a steady pitch. Various lines of evidence suggest that this is probably equivalent to the 'mismatch negativity' (MMN), reflecting a pre-perceptual, memory-based process for detection of change in spectro-temporal sound patterns. This method requires no off-line subtraction of AEPs evoked by the onset of a tone, and the MMN is produced rapidly and robustly with considerably larger amplitude (usually >5 microV) than that to discontinuous pure tones. In the brain-injured patients, the presence of AEPs to two or more complex tone stimuli (in the combined assessment of two authors who were 'blind' to the clinical and behavioural data) was significantly associated with the demonstrable possession of discriminative hearing (the ability to respond differentially to verbal commands

  9. Cognitive Deficits, Changes in Synaptic Function, and Brain Pathology in a Mouse Model of Normal Aging1,2,3

    PubMed Central

    Wu, Tiffany; Hanson, Jesse E.; Alam, Nazia M.; Ngu, Hai; Lauffer, Benjamin E.; Lin, Han H.; Dominguez, Sara L.; Reeder, Jens; Tom, Jennifer; Steiner, Pascal; Foreman, Oded; Prusky, Glen T.

    2015-01-01

    Abstract Age is the main risk factor for sporadic Alzheimer’s disease. Yet, cognitive decline in aged rodents has been less well studied, possibly due to concomitant changes in sensory or locomotor function that can complicate cognitive tests. We tested mice that were 3, 11, and 23 months old in cognitive, sensory, and motor measures, and postmortem measures of gliosis and neural activity (c-Fos). Hippocampal synaptic function was also examined. While age-related impairments were detectable in tests of spatial memory, greater age-dependent effects were observed in tests of associative learning [active avoidance (AA)]. Gross visual function was largely normal, but startle responses to acoustic stimuli decreased with increased age, possibly due to hearing impairments. Therefore, a novel AA variant in which light alone served as the conditioning stimuli was used. Age-related deficits were again observed. Mild changes in vision, as measured by optokinetic responses, were detected in 19- versus 4-month-old mice, but these were not correlated to AA performance. Thus, deficits in hearing or vision are unlikely to account for the observed deficits in cognitive measures. Increased gliosis was observed in the hippocampal formation at older ages. Age-related changes in neural function and plasticity were observed with decreased c-Fos in the dentate gyrus, and decreased synaptic strength and paired-pulse facilitation in CA1 slices. This work, which carefully outlines age-dependent impairments in cognitive and synaptic function, c-Fos activity, and gliosis during normal aging in the mouse, suggests robust translational measures that will facilitate further study of the biology of aging. PMID:26473169

  10. Global and regional brain volumes normalization in weight-recovered adolescents with anorexia nervosa: preliminary findings of a longitudinal voxel-based morphometry study

    PubMed Central

    Bomba, Monica; Riva, Anna; Morzenti, Sabrina; Grimaldi, Marco; Neri, Francesca; Nacinovich, Renata

    2015-01-01

    The recent literature on anorexia nervosa (AN) suggests that functional and structural abnormalities of cortico-limbic areas might play a role in the evolution of the disease. We explored global and regional brain volumes in a cross-sectional and follow-up study on adolescents affected by AN. Eleven adolescents with AN underwent a voxel-based morphometry study at time of diagnosis and immediately after weight recovery. Data were compared to volumes carried out in eight healthy, age and sex matched controls. Subjects with AN showed increased cerebrospinal fluid volumes and decreased white and gray matter volumes, when compared to controls. Moreover, significant regional gray matter decrease in insular cortex and cerebellum was found at time of diagnosis. No regional white matter decrease was found between samples and controls. Correlations between psychological evaluation and insular volumes were explored. After weight recovery gray matter volumes normalized while reduced global white matter volumes persisted. PMID:25834442

  11. Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice.

    PubMed

    Detrait, Eric R; Carr, Greg V; Weinberger, Daniel R; Lamberty, Yves

    2016-08-01

    The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brain-penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders. PMID:26919286

  12. Nutrient intake and brain biomarkers of Alzheimer's disease in at-risk cognitively normal individuals: a cross-sectional neuroimaging pilot study

    PubMed Central

    Mosconi, Lisa; Murray, John; Davies, Michelle; Williams, Schantel; Pirraglia, Elizabeth; Spector, Nicole; Tsui, Wai H; Li, Yi; Butler, Tracy; Osorio, Ricardo S; Glodzik, Lidia; Vallabhajosula, Shankar; McHugh, Pauline; Marmar, Charles R; de Leon, Mony J

    2014-01-01

    Objective There is increasing evidence to suggest that diet, one of the most important modifiable environmental factors, may play a role in preventing or delaying cognitive decline and Alzheimer's disease (AD). This study examines the relationship between dietary nutrients and brain biomarkers of AD in cognitively normal individuals (NL) with and without AD risk factors. Design As part of an ongoing brain imaging study, participants received clinical and laboratory examinations, a neurocognitive test battery, positron emission tomography (PET) with 11C-Pittsburgh Compound-B (PiB; a measure of amyloid-β (Aβ) load) and 18F-fluorodeoxyglucose (FDG; a proxy of neuronal activity), and completed semiquantitative food frequency questionnaires. Setting Research centre affiliated with the Alzheimer's disease Core Center at New York University School of Medicine. Participants 49 NL individuals (age 25–72 years, 69% women) with dietary information, 11C-PiB and 18F-FDG PET scans were examined. Results Controlling for age and total caloric intake, higher intake of vitamin B12, vitamin D and ω-3 polyunsaturated fatty acid (PUFA) was associated with lower Aβ load in AD regions on PiB-PET, while higher intake of β-carotene and folate was associated with higher glucose metabolism on FDG-PET. β-carotene and folate were associated with reduced glucose metabolism for women, apolipoprotein E epsilon 4 (APOE4) carriers and participants with positive AD family history, but not for their risk-free counterparts. The associations of vitamin B12, vitamin D and ω-3 PUFA with PiB retention were independent of gender, APOE and family history. The identified nutrient combination was associated with higher intake of vegetables, fruit, whole grains, fish and legumes, and lower intake of high-fat dairies, meat and sweets. Conclusions Our data provide a potential pathophysiological mechanism for epidemiological findings showing that dietary interventions may play a role in the prevention

  13. The Association of Cytokine Levels With Cognitive Function in Children With Sickle Cell Disease and Normal MRI Studies of the Brain.

    PubMed

    Andreotti, Charissa; King, Allison A; Macy, Elizabeth; Compas, Bruce E; DeBaun, Michael R

    2015-09-01

    Children with sickle cell disease, including those without evidence for cerebral infarcts, are at increased risk for cognitive deficits that can contribute to difficulties in academic and social functioning. Chronic inflammatory processes are endemic to sickle cell disease and are apparent in common comorbidities including asthma. Cytokines mediating inflammatory processes can influence cognition. The authors examined the relationship between plasma levels of cytokines commonly associated with asthma and cognitive functioning using standardized neuropsychological measures in 25 children with sickle cell disease with normal magnetic resonance imaging studies of the brain. Children with sickle cell disease performed significantly below the normative mean on tests of cognitive function. Pearson correlations indicated significant negative relations between cytokines (IL-4, IL-5, IL-8, and IL-13) and standardized tests of executive function (r = -.54 to -.74). Preliminary evidence suggests an association between cytokine levels and executive function in children with sickle cell disease, indicating a potential role for inflammatory processes in cognitive outcomes in these children. PMID:25512362

  14. Neural-network-based classification of cognitively normal, demented, Alzheimer disease and vascular dementia from single photon emission with computed tomography image data from brain.

    PubMed Central

    deFigueiredo, R J; Shankle, W R; Maccato, A; Dick, M B; Mundkur, P; Mena, I; Cotman, C W

    1995-01-01

    Single photon emission with computed tomography (SPECT) hexamethylphenylethyleneamineoxime technetium-99 images were analyzed by an optimal interpolative neural network (OINN) algorithm to determine whether the network could discriminate among clinically diagnosed groups of elderly normal, Alzheimer disease (AD), and vascular dementia (VD) subjects. After initial image preprocessing and registration, image features were obtained that were representative of the mean regional tissue uptake. These features were extracted from a given image by averaging the intensities over various regions defined by suitable masks. After training, the network classified independent trials of patients whose clinical diagnoses conformed to published criteria for probable AD or probable/possible VD. For the SPECT data used in the current tests, the OINN agreement was 80 and 86% for probable AD and probable/possible VD, respectively. These results suggest that artificial neural network methods offer potential in diagnoses from brain images and possibly in other areas of scientific research where complex patterns of data may have scientifically meaningful groupings that are not easily identifiable by the researcher. Images Fig. 1 PMID:7777543

  15. The Brain as a Mixer, II. A Pilot Study of Central Auditory Integration Abilities of Normal and Retarded Children. Studies in Language and Language Behavior, Progress Report Number VII.

    ERIC Educational Resources Information Center

    Semmel, Melvyn I.; And Others

    To explore the binaural integration abilities of six educable mentally retarded boys (ages 8 to 13) and six normal boys (ages 7 to 12) to detect possible brain inju"y, an adaptation of Matzker's (1958) technique involving separating words into high and low frequencies was used. One frequency filter system presented frequencies from 425 to 1275…

  16. The International Research Training Group on "Brain-Behavior Relationship of Normal and Disturbed Emotions in Schizophrenia and Autism" as an Example of German-American Cooperation in Doctoral Training

    ERIC Educational Resources Information Center

    Schneider, Frank; Gur, Ruben C.

    2008-01-01

    The International Research Training Group "Brain-Behavior Relationship of Normal and Disturbed Emotions in Schizophrenia and Autism" (IRTG 1328), funded by the German Research Council (DFG), is a German-American cooperation. Its major aims are interdisciplinary and international scientific cooperation and the support of young scientists with…

  17. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  18. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  19. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  20. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  1. Brain-derived neurotrophic factor induces post-lesion transcommissural growth of olivary axons that develop normal climbing fibers on mature Purkinje cells.

    PubMed

    Dixon, Kirsty J; Sherrard, Rachel M

    2006-11-01

    In the adult mammalian central nervous system, reinnervation and recovery from trauma is limited. During development, however, post-lesion plasticity may generate alternate paths providing models to investigate factors that promote reinnervation to appropriate targets. Following unilateral transection of the neonatal rat olivocerebellar pathway, axons from the remaining inferior olive reinnervate the denervated hemicerebellum and develop climbing fiber arbors on Purkinje cells. However, the capacity to recreate this accurate target reinnervation in a mature system remains unknown. In rats lesioned on day 15 (P15) or 30 and treated with intracerebellar injection of brain-derived neurotrophic factor (BDNF) or vehicle 24 h later, the morphology and organisation of transcommissural olivocerebellar reinnervation was examined using neuronal tracing and immunohistochemistry. In all animals BDNF, but not vehicle, induced transcommissural olivocerebellar axonal growth into the denervated hemicerebellum. The distribution of reinnervating climbing fibers was not confined to the injection sites but extended throughout the denervated hemivermis and, less densely, up to 3.5 mm into the hemisphere. Transcommissural olivocerebellar axons were organised into parasagittal microzones that were almost symmetrical to those in the right hemicerebellum. Reinnervating climbing fiber arbors were predominantly normal, but in the P30-lesioned group 10% were either branched within the molecular layer forming a smaller secondary arbor or were less branched, and in the P15 lesion group the reinnervating arbors extended their terminals almost to the pial surface and were larger than control arbors (P < 0.02). These results show that BDNF can induce transcommissural olivocerebellar reinnervation, which resembles developmental neuroplasticity to promote appropriate target reinnervation in a mature environment. PMID:16790241

  2. Segmentation editing improves efficiency while reducing inter-expert variation and maintaining accuracy for normal brain tissues in the presence of space-occupying lesions

    NASA Astrophysics Data System (ADS)

    Deeley, M. A.; Chen, A.; Datteri, R. D.; Noble, J.; Cmelak, A.; Donnelly, E.; Malcolm, A.; Moretti, L.; Jaboin, J.; Niermann, K.; Yang, Eddy S.; Yu, David S.; Dawant, B. M.

    2013-06-01

    Image segmentation has become a vital and often rate-limiting step in modern radiotherapy treatment planning. In recent years, the pace and scope of algorithm development, and even introduction into the clinic, have far exceeded evaluative studies. In this work we build upon our previous evaluation of a registration driven segmentation algorithm in the context of 8 expert raters and 20 patients who underwent radiotherapy for large space-occupying tumours in the brain. In this work we tested four hypotheses concerning the impact of manual segmentation editing in a randomized single-blinded study. We tested these hypotheses on the normal structures of the brainstem, optic chiasm, eyes and optic nerves using the Dice similarity coefficient, volume, and signed Euclidean distance error to evaluate the impact of editing on inter-rater variance and accuracy. Accuracy analyses relied on two simulated ground truth estimation methods: simultaneous truth and performance level estimation and a novel implementation of probability maps. The experts were presented with automatic, their own, and their peers’ segmentations from our previous study to edit. We found, independent of source, editing reduced inter-rater variance while maintaining or improving accuracy and improving efficiency with at least 60% reduction in contouring time. In areas where raters performed poorly contouring from scratch, editing of the automatic segmentations reduced the prevalence of total anatomical miss from approximately 16% to 8% of the total slices contained within the ground truth estimations. These findings suggest that contour editing could be useful for consensus building such as in developing delineation standards, and that both automated methods and even perhaps less sophisticated atlases could improve efficiency, inter-rater variance, and accuracy.

  3. Poster — Thur Eve — 64: Preliminary investigation of arc configurations for optimal sparing of normal tissue in hypofractionated stereotactic radiotherapy (HF-SRT) of multiple brain metastases using a 5mm interdigitating micro-multileaf collimator

    SciTech Connect

    Leavens, C; Wronski, M; Lee, YK; Ruschin, M; Soliman, H; Sahgal, A

    2014-08-15

    Purpose: To evaluate normal tissue sparing in intra-cranial HF-SRT, comparing various arc configurations with the Synergy Beam Modulator (SynBM) and Agility linacs, the latter incorporating leaf interdigitation and backup jaws. Methods: Five patients with multiple brain metastases (BMs), (5 BMs (n=2), 3 BMs (n=3)) treated with HF-SRT using 25 Gy (n=2) or 30 Gy (n=3) in 5 fractions, were investigated. Clinical treatment plans used the SynBM. Each patient was retrospectively re-planned on Agility, employing three planning strategies: (A) one isocenter and dedicated arc for each BM; (B) a single isocenter, centrally placed with respect to BMs; (C) the isocenter and arc configuration used in the SynBM plan, where closely spaced (<5cm) BMs used a dedicated isocenter and arcs. Agility plans were normalized for PTV coverage and heterogeneity. Results and Conclusion: Strategy A obtained the greatest improvements over the SynBM plan, where the maximum OAR dose, and mean dose to normal brain (averaged for all patients) were reduced by 55cGy and 25cGy, respectively. Strategy B was limited by having a single isocenter, hence less jaw shielding and increased MLC leakage. The maximum OAR dose was reduced by 13cGy, however mean dose to normal brain increased by 84cGy. Strategy C reduced the maximum OAR dose and mean dose to normal brain by 32cGy and 9cGy, respectively. The results from this study indicate that, for intra-cranial HF-SRT of multiple BMs, Agility plans are equal or better than SynBM plans. Further planning is needed to investigate dose sparing using Strategy A and the SynBM.

  4. Normal faults, normal friction?

    NASA Astrophysics Data System (ADS)

    Collettini, Cristiano; Sibson, Richard H.

    2001-10-01

    Debate continues as to whether normal faults may be seismically active at very low dips (δ < 30°) in the upper continental crust. An updated compilation of dip estimates (n = 25) has been prepared from focal mechanisms of shallow, intracontinental, normal-slip earthquakes (M > 5.5; slip vector raking 90° ± 30° in the fault plane) where the rupture plane is unambiguously discriminated. The dip distribution for these moderate-to-large normal fault ruptures extends from 65° > δ > 30°, corresponding to a range, 25° < θr < 60°, for the reactivation angle between the fault and inferred vertical σ1. In a comparable data set previously obtained for reverse fault ruptures (n = 33), the active dip distribution is 10° < δ = θr < 60°. For vertical and horizontal σ1 trajectories within extensional and compressional tectonic regimes, respectively, dip-slip reactivation is thus restricted to faults oriented at θr ≤ 60° to inferred σ1. Apparent lockup at θr ≈ 60° in each dip distribution and a dominant 30° ± 5° peak in the reverse fault dip distribution, are both consistent with a friction coefficient μs ≈ 0.6, toward the bottom of Byerlee's experimental range, though localized fluid overpressuring may be needed for reactivation of less favorably oriented faults.

  5. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  6. 43 CFR 420.3 - Adjacent lands.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Adjacent lands. 420.3 Section 420.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR...-managing agencies on adjacent lands (both public and private)....

  7. 43 CFR 420.3 - Adjacent lands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Adjacent lands. 420.3 Section 420.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR...-managing agencies on adjacent lands (both public and private)....

  8. 43 CFR 420.3 - Adjacent lands.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Adjacent lands. 420.3 Section 420.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR OFF-ROAD VEHICLE USE § 420.3 Adjacent lands. When administratively feasible, the regulation of off-road vehicle use on Reclamation lands will...

  9. 43 CFR 420.3 - Adjacent lands.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Adjacent lands. 420.3 Section 420.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR...-managing agencies on adjacent lands (both public and private)....

  10. 43 CFR 420.3 - Adjacent lands.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Adjacent lands. 420.3 Section 420.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR OFF-ROAD VEHICLE USE § 420.3 Adjacent lands. When administratively feasible, the regulation of...

  11. Xenon contrast CT-CBF scanning of the brain differentiates normal age-related changes from multi-infarct dementia and senile dementia of Alzheimer type

    SciTech Connect

    Tachibana, H.; Meyer, J.S.; Okayasu, H.; Shaw, T.G.; Kandula, P.; Rogers, R.L.

    1984-07-01

    Local cerebral blood flow (LCBF) and partition coefficients (L lambda) were measured during inhalation of stable xenon gas with serial CT scanning among normal volunteers (N . 15), individuals with multi-infarct dementia (MID, N . 10), and persons with senile dementia of Alzheimer type (SDAT, N . 8). Mean gray matter flow values were reduced in both MID and SDAT. Age-related declines in LCBF values in normals were marked in frontal cortex and basal ganglia. LCBF values were decreased beyond normals in frontal and temporal cortices and thalamus in MID and SDAT, in basal ganglia only in MID. Unlike SDAT and age-matched normals, L lambda values were reduced in fronto-temporal cortex and thalamus in MID. Multifocal nature of lesions in MID was apparent. Coefficients of variation for LCBFs were greater in MID compared with SDAT and/or age-matched normals.

  12. Optimal technique of linear accelerator-based stereotactic radiosurgery for tumors adjacent to brainstem.

    PubMed

    Chang, Chiou-Shiung; Hwang, Jing-Min; Tai, Po-An; Chang, You-Kang; Wang, Yu-Nong; Shih, Rompin; Chuang, Keh-Shih

    2016-01-01

    Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC)-based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single-fraction radiosurgery. In all, 5 different lesion catalogs were collected, and the patients were divided into 2 distance groups-1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5cm, and the other of 10 patients with a target-to-brainstem distance of ≥ 0.5 and < 1cm. Comparison was then made among the following 3 types of LINAC-based radiosurgery: dynamic conformal arcs (DCA), intensity-modulated radiosurgery (IMRS), and volumetric modulated arc radiotherapy (VMAT). All techniques included multiple noncoplanar beams or arcs with or without intensity-modulated delivery. The volume of gross tumor volume (GTV) ranged from 0.2cm(3) to 21.9cm(3). Regarding the dose homogeneity index (HIICRU) and conformity index (CIICRU) were without significant difference between techniques statistically. However, the average CIICRU = 1.09 ± 0.56 achieved by VMAT was the best of the 3 techniques. Moreover, notable improvement in gradient index (GI) was observed when VMAT was used (0.74 ± 0.13), and this result was significantly better than those achieved by the 2 other techniques (p < 0.05). For V4Gy of brainstem, both VMAT (2.5%) and IMRS (2.7%) were significantly lower than DCA (4.9%), both at the p < 0.05 level. Regarding V2Gy of normal brain, VMAT plans had attained 6.4 ± 5%; this was significantly better (p < 0.05) than

  13. Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice.

    PubMed

    de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2015-03-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation. PMID:25445491

  14. Learning abilities, NGF and BDNF brain levels in two lines of TNF-alpha transgenic mice, one characterized by neurological disorders, the other phenotypically normal.

    PubMed

    Aloe, L; Properzi, F; Probert, L; Akassoglou, K; Kassiotis, G; Micera, A; Fiore, M

    1999-09-01

    In this study we used two lines of transgenic mice overexpressing tumor necrosis factor alpha (TNF-alpha) in the central nervous system (CNS), one characterized by reactive gliosis, inflammatory demyelination and neurological deficits (Tg6074) the other showing no neurological or phenotypical alterations (TgK3) to investigate the effect of TNF-alpha on brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels and learning abilities. The results showed that the amount of NGF in the brain of Tg6074 and TgK3 transgenic mice is low in the hippocampus and in the spinal cord, increases in the hypothalamus of Tg6074 and showed no significant changes in the cortex. BDNF levels were low in the hippocampus and spinal cord of TgK3. BDNF increased in the hypothalamus of TgK3 and Tg6074 while in the cortex, BDNF increased only in Tg6074 mice. Transgenic mice also had memory impairments as revealed by the Morris Water Maze test. These findings indicate that TNF-alpha significantly influences BDNF and NGF synthesis, most probably in a dose-dependent manner. Learning abilities were also differently affected by overexpression of TNF-alpha, but were not associated with inflammatory activity. The possible functional implications of our findings are discussed. PMID:10517960

  15. Brain imaging and brain function

    SciTech Connect

    Sokoloff, L.

    1985-01-01

    This book is a survey of the applications of imaging studies of regional cerebral blood flow and metabolism to the investigation of neurological and psychiatric disorders. Contributors review imaging techniques and strategies for measuring regional cerebral blood flow and metabolism, for mapping functional neural systems, and for imaging normal brain functions. They then examine the applications of brain imaging techniques to the study of such neurological and psychiatric disorders as: cerebral ischemia; convulsive disorders; cerebral tumors; Huntington's disease; Alzheimer's disease; depression and other mood disorders. A state-of-the-art report on magnetic resonance imaging of the brain and central nervous system rounds out the book's coverage.

  16. An aqueous normal-phase chromatography coupled with tandem mass spectrometry method for determining unbound brain-to-plasma concentration ratio of AZD1775, a Wee1 kinase inhibitor, in patients with glioblastoma.

    PubMed

    Wu, Jianmei; Sanai, Nader; Bao, Xun; LoRusso, Patricia; Li, Jing

    2016-08-15

    A rapid, sensitive, and robust aqueous normal-phase chromatography method coupled with tandem mass spectrometry was developed and validated for the quantitation of AZD1775, a Wee-1 inhibitor, in human plasma and brain tumor tissue. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on ethylene bridged hybrid stationary phases (i.e., Waters XBridge Amide column) under an isocratic elution with the mobile phase consisting of acetonitrile/ammonium formate in water (10mM, pH 3.0) (85:15,v/v) at a flow rate of 0.8mL/min for 5min. The lower limit of quantitation (LLOQ) was 0.2ng/mL of AZD1775 in plasma and tissue homogenate. The calibration curve was linear over AZD1775 concentration range of 0.2-1000ng/mL in plasma and tissue homogenate. The intra- and inter-day precision and accuracy were within the generally accepted criteria for bioanalytical method (<15%). The method was successfully applied to assess the penetration of AZD1775 across the blood-brain tumor barrier, as assessed by the unbound brain-to-plasma ratio, in patients with glioblastoma. PMID:27318641

  17. Distribution of hematoporphyrin derivative in the rat 9l gliosarcoma brain tumor analyzed by digital video fluorescence microscopy.

    PubMed

    Boggan, J E; Walter, R; Edwards, M S; Borcich, J K; Davis, R L; Koonce, M; Berns, M W

    1984-12-01

    A digital video fluorescence microscopy technique was used to evaluate the distribution of hematoporphyrin derivative (HPD) in the rat intracerebral 9L gliosarcoma brain-tumor model at 4, 24, 48, and 72 hours after intravenous administration of 10 mg/kg of the drug. Compared to surrounding normal brain, there was significant preferential uptake of HPD into the tumor. In sections surveyed, fluorescence reached a maximum value by 24 hours; however, only 33% to 44% of the tumor was fluorescent. In contrast, fluorescence within the surrounding normal brain was maximum at 4 hours, but was present in less than 1% of the brain tissue evaluated. The effect of HPD sensitization to a laser light dose (633 nm) of 30 joules/sq cm delivered through the intact skull was evaluated histologically in 10 rats. A patchy coagulation necrosis, possibly corresponding to the distribution of HPD fluorescence seen within the tumor, was observed. There was evidence that photoradiation therapy (PRT) affects defective tumor vasculature and that a direct tumor cell toxicity spared normal brain tissue. Despite these findings, limited uptake of HPD in tumor and the brain adjacent to tumor may decrease the effectiveness of PRT in the 9L gliosarcoma brain-tumor model. Because of the similarity between the capillary system of the 9L tumor and human brain tumors, PRT may have a limited therapeutic effect in patients with malignant brain tumors. PMID:6239014

  18. Long-term normal-appearing brain tissue monitoring after irradiation using proton magnetic resonance spectroscopy in vivo: Statistical analysis of a large group of patients

    SciTech Connect

    Matulewicz, Lukasz . E-mail: lukasz.matulewicz@io.gliwice.pl; Sokol, Maria; Michnik, Anna; Wydmanski, Jerzy

    2006-11-01

    Purpose: The aim of this study was to detect the non-neoplastic white-matter changes vs. time after irradiation using {sup 1}H nuclear magnetic resonance (NMR) spectroscopy in vivo. Methods and Materials: A total of 394 {sup 1}H MR spectra were acquired from 100 patients (age 19-74 years; mean and median age, 43 years) before and during 2 years after radiation therapy (the mean absorbed doses calculated for the averaged spectroscopy voxels are similar and close to 20 Gy). Results: Ocilations were observed in choline-containing compounds (Cho)/creatine and phosphocreatine (Cr), Cho/N-acetylaspartate (NAA), and center of gravity (CG) of the lipid band in the range of 0.7-1.5 ppm changes over time reveal oscillations. The parameters have the same 8-month cycle period; however the CG changes precede the other by 2 months. Conclusions: The results indicate the oscillative nature of the brain response to irradiation, which may be caused by the blood-brain barrier disruption and repair processes. These oscillations may influence the NMR results, depending on the cycle phase in which the NMR measurements are performed in. The earliest manifestation of radiation injury detected by magnetic resonance spectroscopy is the CG shift.

  19. On the time-course of adjacent and non-adjacent transposed-letter priming

    PubMed Central

    Ktori, Maria; Kingma, Brechtsje; Hannagan, Thomas; Holcomb, Phillip J.; Grainger, Jonathan

    2014-01-01

    We compared effects of adjacent (e.g., atricle-ARTICLE) and non-adjacent (e.g., actirle-ARTICLE) transposed-letter (TL) primes in an ERP study using the sandwich priming technique. TL priming was measured relative to the standard double-substitution condition. We found significantly stronger priming effects for adjacent transpositions than non-adjacent transpositions (with 2 intervening letters) in behavioral responses (lexical decision latencies), and the adjacent priming effects emerged earlier in the ERP signal, at around 200 ms post-target onset. Non-adjacent priming effects emerged about 50 ms later and were short-lived, being significant only in the 250-300 ms time-window. Adjacent transpositions on the other hand continued to produce priming in the N400 time-window (300-500 ms post-target onset). This qualitatively different pattern of priming effects for adjacent and non-adjacent transpositions is discussed in the light of different accounts of letter transposition effects, and the utility of drawing a distinction between positional flexibility and positional noise. PMID:25364497

  20. Letm1, the mitochondrial Ca2+/H+ antiporter, is essential for normal glucose metabolism and alters brain function in Wolf-Hirschhorn syndrome.

    PubMed

    Jiang, Dawei; Zhao, Linlin; Clish, Clary B; Clapham, David E

    2013-06-11

    Mitochondrial metabolism, respiration, and ATP production necessitate ion transport across the inner mitochondrial membrane. Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1), one of the genes deleted in Wolf-Hirschhorn syndrome, encodes a putative mitochondrial Ca(2+)/H(+) antiporter. Cellular Letm1 knockdown reduced Ca(2+)mito uptake, H(+)mito extrusion and impaired mitochondrial ATP generation capacity. Homozygous deletion of Letm1 in mice resulted in embryonic lethality before day 6.5 of embryogenesis and ~50% of the heterozygotes died before day 13.5 of embryogenesis. The surviving heterozygous mice exhibited altered glucose metabolism, impaired control of brain ATP levels, and increased seizure activity. We conclude that loss of Letm1 contributes to the pathology of Wolf-Hirschhorn syndrome in humans and may contribute to seizure phenotypes by reducing glucose oxidation and other specific metabolic alterations. PMID:23716663

  1. Blockade of Astrocytic Calcineurin/NFAT Signaling Helps to Normalize Hippocampal Synaptic Function and Plasticity in a Rat Model of Traumatic Brain Injury

    PubMed Central

    Furman, Jennifer L.; Sompol, Pradoldej; Kraner, Susan D.; Pleiss, Melanie M.; Putman, Esther J.; Dunkerson, Jacob; Mohmmad Abdul, Hafiz; Roberts, Kelly N.; Scheff, Stephen W.

    2016-01-01

    Increasing evidence suggests that the calcineurin (CN)-dependent transcription factor NFAT (Nuclear Factor of Activated T cells) mediates deleterious effects of astrocytes in progressive neurodegenerative conditions. However, the impact of astrocytic CN/NFAT signaling on neural function/recovery after acute injury has not been investigated extensively. Using a controlled cortical impact (CCI) procedure in rats, we show that traumatic brain injury is associated with an increase in the activities of NFATs 1 and 4 in the hippocampus at 7 d after injury. NFAT4, but not NFAT1, exhibited extensive labeling in astrocytes and was found throughout the axon/dendrite layers of CA1 and the dentate gyrus. Blockade of the astrocytic CN/NFAT pathway in rats using adeno-associated virus (AAV) vectors expressing the astrocyte-specific promoter Gfa2 and the NFAT-inhibitory peptide VIVIT prevented the injury-related loss of basal CA1 synaptic strength and key synaptic proteins and reduced the susceptibility to induction of long-term depression. In conjunction with these seemingly beneficial effects, VIVIT treatment elicited a marked increase in the expression of the prosynaptogenic factor SPARCL1 (hevin), especially in hippocampal tissue ipsilateral to the CCI injury. However, in contrast to previous work on Alzheimer's mouse models, AAV-Gfa2-VIVIT had no effects on the levels of GFAP and Iba1, suggesting that synaptic benefits of VIVIT were not attributable to a reduction in glial activation per se. Together, the results implicate the astrocytic CN/NFAT4 pathway as a key mechanism for disrupting synaptic remodeling and homeostasis in the hippocampus after acute injury. SIGNIFICANCE STATEMENT Similar to microglia, astrocytes become strongly “activated” with neural damage and exhibit numerous morphologic/biochemical changes, including an increase in the expression/activity of the protein phosphatase calcineurin. Using adeno-associated virus (AAV) to inhibit the calcineurin

  2. Matrix metalloproteinase-1 expression in breast cancer and cancer-adjacent tissues by immunohistochemical staining

    PubMed Central

    XUAN, JIAJIA; ZHANG, YUNFENG; ZHANG, XIUJUN; HU, FEN

    2015-01-01

    Although matrix metalloproteinase-1 (MMP-1) has been considered a factor of crucial importance for breast cancer cells invasion and metastasis, the expression of MMP-1 in different breast cancer and cancer-adjacent tissues have not been fully examined. In the present study, immunohistochemical staining was used to detect the MMP-1 expression in non-specific invasive ductal carcinoma of the breast, cancer-adjacent normal breast tissue, lymph node metastatic non-specific invasive ductal carcinoma of the breast and normal lymph node tissue. The results showed that MMP-1 expression is different in the above tissues. MMP-1 had a positive expression in normal lymph node tissue and lymph node metastatic non-specific invasive ductal carcinoma. The MMP-1 negative expression rate was only 6.1% in non-specific invasive ductal carcinoma of the breast and 2.9% in cancer-adjacent normal breast tissue respectively. MMP-1 expression is higher in non-specific invasive ductal carcinoma and lymph node metastatic non-specific invasive ductal carcinoma compared to cancer-adjacent normal breast tissue and normal lymph node tissue. In conclusion, higher expression of MMP-1 in breast cancer may play a crucial role in promoting breast cancer metastasis. PMID:26137243

  3. SOLIDS TRANSPORT BETWEEN ADJACENT CAFB FLUIDIZED BEDS

    EPA Science Inventory

    The report gives results of an experimental investigation of a pulsed, dense-phase pneumatic transport system for controlled circulation between adjacent fluidized beds. A model was developed to predict performance. The program provides technical support for EPA's program to demo...

  4. Border separation for adjacent orthogonal fields

    SciTech Connect

    Werner, B.L.; Khan, F.M.; Sharma, S.C.; Lee, C.K.; Kim, T.H. )

    1991-06-01

    Field border separations for adjacent orthogonal fields can be calculated geometrically, given the validity of some important assumptions such as beam alignment and field uniformity. Thermoluminescent dosimetry (TLD) measurements were used to investigate dose uniformity across field junctions as a function of field separation and, in particular, to review the CCSG recommendation for the treatment of medulloblastoma with separate head and spine fields.

  5. Spontaneous chronic subdural hematomas in human immunodeficiency virus-infected patients with normal platelet count and no appreciable brain atrophy: Two case reports and review of literature

    PubMed Central

    Jokonya, Luxwell; Musara, Aaron; Cakana, Andrew; Kalangu, Kazadi K. N.

    2016-01-01

    Background: Chronic subdural hematomas (CSDHs) usually occur in elderly patients following minor head trauma. Their occurrence is usually linked to cerebral atrophy secondary to alcohol, old age, or human immunodeficiency virus (HIV) infection. Spontaneous CSDHs have also been documented but are rare. They are usually caused by coagulopathies and various pathologies resulting in intracranial hypotension. Cases: We have observed a number of spontaneous CSDHs in HIV patients with normal platelet counts and no appreciable cerebral atrophy possibly caused by platelet dysfunction, hence we report about two such cases. To the best of our knowledge, no such cases have been reported in literature before. Conclusion: It is important to include CSDHs in the differential diagnosis of HIV patients presenting with neurological deficits even without a history of trauma. PMID:27308093

  6. Loss of spatial memory, learning and motor coordination during normal aging is accompanied by changes in brain presenilin 1 and 2 expression levels

    PubMed Central

    Kaja, Simon; Sumien, Natalie; Shah, Vidhi V.; Puthawala, Imran; Maynard, Alexandra N.; Khullar, Nitasha; Payne, Andrew J.; Forster, Michael J.; Koulen, Peter

    2014-01-01

    Mutations in presenilin (PS) proteins cause familial Alzheimer’s disease. We herein tested the hypothesis that the expression levels of PS proteins are differentially affected during healthy aging, in the absence of pathological mutations. We used a preclinical model for aging to identify associations between PS expression and quantitative behavioral parameters for spatial memory and learning and motor coordination. We identified significant changes of PS protein expression in both cerebellum and forebrain that correlated with the performance in behavioral paradigms for motor coordination and memory and learning. Overall, PS1 levels were decreased, while PS2 levels were increased in aged mice compared with young controls. Our study presents novel evidence for the differential expression of PS proteins in a non-genetic model for aging, resulting in an overall increase of the PS2 to PS1 ratio. Our findings provide a novel mechanistic basis for molecular and functional changes during normal aging. PMID:25204494

  7. Event-related brain potentials, bilateral electrodermal activity and Mangina-Test performance in learning disabled/ADHD pre-adolescents with severe behavioral disorders as compared to age-matched normal controls.

    PubMed

    Mangina, C A; Beuzeron-Mangina, J H; Grizenko, N

    2000-07-01

    The most frequently encountered developmental problems of learning disabilities/ADHD often co-exist with severe behavioral disorders. As a direct consequence, this condition opens the way to delinquency, school drop-out, depression, suicide, substance abuse, work absenteeism, and other psycho-social complications. In this paper, we are presenting a selective overview of our previous research and its clinical applications in this field as it relates to our present research data pertaining to the effects of our original Memory Workload Paradigm on the event-related brain potentials in differentiating normal and pathological pre-adolescents (learning disabled/ADHD with concomitant severe behavioral disorders such as oppositional and conduct). In addition, it provides data on the bilateral electrodermal activity during cognitive workload and Mangina-Test performance of pathological and normal pre-adolescents conducted in separate sessions. The results of our present research indicate that a significant memory load effect for the P450 latency (F(3,27)=4.98, P<0.01) and the P450 amplitude (F(3,27)=3.57, P<0.05) was present for normal pre-adolescents which was absent in pathological pre-adolescents. Moreover, enhanced N450 ERP amplitudes to our Memory Workload Paradigm in pre-frontal and frontal regions clearly differentiated normal from pathological pre-adolescents (F(1, 18)=12.21, P<0.004). Furthermore, significant differences between normal and pathological groups were found in bilateral electrodermal activity (F(1,18)=23.86, P<0.001) and on the Mangina-Test performance (F(1,18)=75.35, P<0.001). Our present research findings provide an original and valuable demonstration of an integrative and effective clinical psychophysiological application of central (ERPs), autonomic (bilateral electrodermal activity) and neuro-psychometric aspects (Mangina-Test) which characterize normal and pathological pre-adolescents and underpin the neurophysiological basis of learning

  8. The Thermomagnetic Instability in Superconducting Films with Adjacent Metal Layer

    NASA Astrophysics Data System (ADS)

    Vestgården, J. I.; Galperin, Y. M.; Johansen, T. H.

    2013-12-01

    Dendritic flux avalanches is a frequently encountered consequence of the thermomagnetic instability in type-II superconducting films. The avalanches, which are potentially harmful for superconductor-based devices, can be suppressed by an adjacent normal metal layer, even when the two layers are not in thermal contact. The suppression of the avalanches in this case is due to so-called magnetic braking, caused by eddy currents generated in the metal layer by propagating magnetic flux. We develop a theory of magnetic braking by analyzing coupled electrodynamics and heat flow in a superconductor-normal metal bilayer. The equations are solved by linearization and by numerical simulation of the avalanche dynamics. We find that in an uncoated superconductor, even a uniform thermomagnetic instability can develop into a dendritic flux avalanche. The mechanism is that a small non-uniformity caused by the electromagnetic non-locality induces a flux-flow hot spot at a random position. The hot spot quickly develops into a finger, which at high speeds penetrates into the superconductor, forming a branching structure. Magnetic braking slows the avalanches, and if the normal metal conductivity is sufficiently high, it can suppress the formation of the dendritic structure. During avalanches, the braking by the normal metal layer prevents the temperature from exceeding the transition temperature of the superconductor. Analytical criteria for the instability threshold are developed using the linear stability analysis. The criteria are found to match quantitatively the instability onsets obtained in simulations.

  9. Increased apoptosis in gastric mucosa adjacent to intestinal metaplasia

    PubMed Central

    van Grieken, N C T; Meijer, G A; zur Hausen, A; Meuwissen, S G M; Baak, J P A; Kuipers, E J

    2003-01-01

    Background: The biological processes involved in the development of gastric mucosal atrophy and intestinal metaplasia are still incompletely understood. Reports testing the hypothesis that apoptosis leads to atrophy have yielded conflicting results. The availability of new antibodies for the detection of apoptotic cells in tissue sections has facilitated the analysis of the role of apoptosis in the gastritis–atrophy–intestinal metaplasia sequence. Methods: Archival material from 40 gastric resection specimens with normal mucosa (n = 5), chronic active gastritis (n = 17), or intestinal metaplasia (n = 18) was studied. Immunohistochemistry was performed using antibodies directed against cleaved cytokeratin 18 and active caspase 3. Slides were scored on a 0–3 scale for the presence of apoptotic cells. Results: Normal gastric mucosa contained low numbers of apoptotic cells at the surface epithelium (mean score, 0.20). This number was significantly increased in cases with chronic gastritis (mean score, 1.06) and in those with intestinal metaplasia (mean score, 2.56). Within the intestinal metaplasia cases, 44 different foci of intestinal metaplasia were identified. In 39 of these 44 areas, concentrations of apoptotic cells were seen immediately adjacent to the foci of intestinal metaplasia, but not in the metaplastic epithelium itself. Conclusions: Apoptosis is uncommon in normal gastric mucosa. Chronic inflammation and intestinal metaplasia are associated with increased apoptosis, but occur mainly at the mucosal surface and not in the deeper layers. These findings do not support the concept that apoptosis underlies the loss of gastric glands and leads to atrophy, but the observed concentration of apoptotic epithelial cells adjacent to foci of intestinal metaplasia could be related to heterogeneity of epithelial damage, causing apoptosis, to which intestinal metaplasia is a response. PMID:12719456

  10. Adjacent Segment Pathology after Lumbar Spinal Fusion.

    PubMed

    Lee, Jae Chul; Choi, Sung-Woo

    2015-10-01

    One of the major clinical issues encountered after lumbar spinal fusion is the development of adjacent segment pathology (ASP) caused by increased mechanical stress at adjacent segments, and resulting in various radiographic changes and clinical symptoms. This condition may require surgical intervention. The incidence of ASP varies with both the definition and methodology adopted in individual studies; various risk factors for this condition have been identified, although a significant controversy still exists regarding their significance. Motion-preserving devices have been developed, and some studies have shown their efficacy of preventing ASP. Surgeons should be aware of the risk factors of ASP when planning a surgery, and accordingly counsel their patients preoperatively. PMID:26435804

  11. Adjacent Segment Pathology after Anterior Cervical Fusion

    PubMed Central

    Chung, Jae Yoon; Park, Jong-Beom; Seo, Hyoung-Yeon

    2016-01-01

    Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion. PMID:27340541

  12. Adjacent Segment Pathology after Anterior Cervical Fusion.

    PubMed

    Chung, Jae Yoon; Park, Jong-Beom; Seo, Hyoung-Yeon; Kim, Sung Kyu

    2016-06-01

    Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion. PMID:27340541

  13. Density abnormalities in normal-appearing gray matter in the middle-aged brain with white matter hyperintense lesions: a DARTEL-enhanced voxel-based morphometry study

    PubMed Central

    Peng, Yan; Li, Shenhong; Zhuang, Ying; Liu, Xiaojia; Wu, Lin; Gong, Honghan; Liu, Dewu; Zhou, Fuqing

    2016-01-01

    Background and purpose Little is known about the structural alterations within gray matter (GM) in middle-aged subjects with white matter hyperintense (WMH) lesions. Here, we aimed to examine the anatomical changes within the GM and their relationship to WMH lesion loads in middle-aged subjects. Participants and methods Twenty-three middle-aged subjects with WMH lesions (WMH group) and 23 demographically matched healthy control subjects participated in the study. A Diffeomorphic Anatomical Registration Through Exponentiated Liealgebra-enhanced voxel-based morphometry was used to measure the GM density, and the correlations between WMH lesion volume and extracted GM values in abnormal regions were identified by voxel-based morphometry analysis. Results Compared with the healthy control subjects, the WMH group had a significantly decreased GM density in the left middle frontal gyrus, bilateral anterior cingulate cortex, left and right premotor cortex, and left and right middle cingulate cortex and an increased GM density in the bilateral cerebellum anterior lobe, left middle temporal gyrus, right temporoparietal junction, left and right prefrontal cortex (PFC), and left inferior parietal lobule. A relationship was observed between the normalized WMH lesion volume and the decreased GM density, including the left middle frontal gyrus (ρ=−0.629, P=0.002), bilateral anterior cingulate cortex (ρ=−0.507, P=0.019), right middle cingulate cortex (ρ=−0.484, P=0.026), and right premotor cortex (ρ=−0.438, P=0.047). The WMH lesion loads also negatively correlated with increased GM density in the right temporoparietal junction (ρ=−0.484, P=0.026), left PFC (ρ=−0.469, P=0.032), and right PFC (ρ=−0.438, P=0.047). Conclusion We observed that lesion load-associated structural plasticity corresponds to bidirectional changes in regional GM density in the WMH group. PMID:27274211

  14. GAP junctional communication in brain secondary organizers.

    PubMed

    Bosone, Camilla; Andreu, Abraham; Echevarria, Diego

    2016-06-01

    Gap junctions (GJs) are integral membrane proteins that enable the direct cytoplasmic exchange of ions and low molecular weight metabolites between adjacent cells. They are formed by the apposition of two connexons belonging to adjacent cells. Each connexon is formed by six proteins, named connexins (Cxs). Current evidence suggests that gap junctions play an important part in ensuring normal embryo development. Mutations in connexin genes have been linked to a variety of human diseases, although the precise role and the cell biological mechanisms of their action remain almost unknown. Among the big family of Cxs, several are expressed in nervous tissue but just a few are expressed in the anterior neural tube of vertebrates. Many efforts have been made to elucidate the molecular bases of Cxs cell biology and how they influence the morphogenetic signal activity produced by brain signaling centers. These centers, orchestrated by transcription factors and morphogenes determine the axial patterning of the mammalian brain during its specification and regionalization. The present review revisits the findings of GJ composed by Cx43 and Cx36 in neural tube patterning and discuss Cx43 putative enrollment in the control of Fgf8 signal activity coming from the well known secondary organizer, the isthmic organizer. PMID:27273333

  15. Early Alzheimer's Linked to Brain 'Leakage'

    MedlinePlus

    ... news/fullstory_159116.html Early Alzheimer's Linked to Brain 'Leakage' Normally, blood-brain barrier prevents this from happening To use the ... more "leaks" in the barrier that separates the brain from the bloodstream, a small study suggests. Known ...

  16. Laser ablation of human atherosclerotic plaque without adjacent tissue injury

    NASA Technical Reports Server (NTRS)

    Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

    1985-01-01

    Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

  17. Reconstructing genome mixtures from partial adjacencies.

    PubMed

    Mahmoody, Ahmad; Kahn, Crystal L; Raphael, Benjamin J

    2012-01-01

    Many cancer genome sequencing efforts are underway with the goal of identifying the somatic mutations that drive cancer progression. A major difficulty in these studies is that tumors are typically heterogeneous, with individual cells in a tumor having different complements of somatic mutations. However, nearly all DNA sequencing technologies sequence DNA from multiple cells, thus resulting in measurement of mutations from a mixture of genomes. Genome rearrangements are a major class of somatic mutations in many tumors, and the novel adjacencies (i.e. breakpoints) resulting from these rearrangements are readily detected from DNA sequencing reads. However, the assignment of each rearrangement, or adjacency, to an individual cancer genome in the mixture is not known. Moreover, the quantity of DNA sequence reads may be insufficient to measure all rearrangements in all genomes in the tumor. Motivated by this application, we formulate the k-minimum completion problem (k-MCP). In this problem, we aim to reconstruct k genomes derived from a single reference genome, given partial information about the adjacencies present in the mixture of these genomes. We show that the 1-MCP is solvable in linear time in the cases where: (i) the measured, incomplete genome has a single circular or linear chromosome; (ii) there are no restrictions on the chromosomal content of the measured, incomplete genome. We also show that the k-MCP problem, for k ≥ 3 in general, and the 2-MCP problem with the double-cut-and-join (DCJ) distance are NP-complete, when there are no restriction on the chromosomal structure of the measured, incomplete genome. These results lay the foundation for future algorithmic studies of the k-MCP and the application of these algorithms to real cancer sequencing data. PMID:23282028

  18. Spatiotemporal morphometry of adjacent tissue layers with application to the study of sulcal formation.

    PubMed

    Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A; Kim, Kio; Rousseau, François; Glenn, Orit A; Barkovich, A James; Studholme, Colin

    2011-01-01

    The process of brain growth involves the expansion of tissue at different rates at different points within the brain. As the layers within the developing brain evolve they can thicken or increase in area as the brain surface begins to fold. In this work we propose a new spatiotemporal formulation of tensor based volume morphometry that is derived in relation to tissue boundaries. This allows the study of the directional properties of tissue growth by separately characterizing the changes in area and thickness of the adjacent layers. The approach uses temporally weighted, local regression across a population of anatomies with different ages to model changes in components of the growth radial and tangential to the boundary between tissue layers. The formulation is applied to the study of sulcal formation from in-utero MR imaging of human fetal brain anatomy. Results show that the method detects differential growth of tissue layers adjacent to the cortical surface, particularly at sulcal locations, as early as 22 gestational weeks. PMID:21995063

  19. Multivariate normality

    NASA Technical Reports Server (NTRS)

    Crutcher, H. L.; Falls, L. W.

    1976-01-01

    Sets of experimentally determined or routinely observed data provide information about the past, present and, hopefully, future sets of similarly produced data. An infinite set of statistical models exists which may be used to describe the data sets. The normal distribution is one model. If it serves at all, it serves well. If a data set, or a transformation of the set, representative of a larger population can be described by the normal distribution, then valid statistical inferences can be drawn. There are several tests which may be applied to a data set to determine whether the univariate normal model adequately describes the set. The chi-square test based on Pearson's work in the late nineteenth and early twentieth centuries is often used. Like all tests, it has some weaknesses which are discussed in elementary texts. Extension of the chi-square test to the multivariate normal model is provided. Tables and graphs permit easier application of the test in the higher dimensions. Several examples, using recorded data, illustrate the procedures. Tests of maximum absolute differences, mean sum of squares of residuals, runs and changes of sign are included in these tests. Dimensions one through five with selected sample sizes 11 to 101 are used to illustrate the statistical tests developed.

  20. Radiation treatment of brain tumors: Concepts and strategies

    SciTech Connect

    Marks, J.E. )

    1989-01-01

    Ionizing radiation has demonstrated clinical value for a multitude of CNS tumors. Application of the different physical modalities available has made it possible for the radiotherapist to concentrate the radiation in the region of the tumor with relative sparing of the surrounding normal tissues. Correlation of radiation dose with effect on cranial soft tissues, normal brain, and tumor has shown increasing effect with increasing dose. By using different physical modalities to alter the distribution of radiation dose, it is possible to increase the dose to the tumor and reduce the dose to the normal tissues. Alteration of the volume irradiated and the dose delivered to cranial soft tissues, normal brain, and tumor are strategies that have been effective in improving survival and decreasing complications. The quest for therapeutic gain using hyperbaric oxygen, neutrons, radiation sensitizers, chemotherapeutic agents, and BNCT has met with limited success. Both neoplastic and normal cells are affected simultaneously by all modalities of treatment, including ionizing radiation. Consequently, one is unable to totally depopulate a tumor without irreversibly damaging the normal tissues. In the case of radiation, it is the brain that limits delivery of curative doses, and in the case of chemical additives, it is other organ systems, such as bone marrow, liver, lung, kidneys, and peripheral nerves. Thus, the major obstacle in the treatment of malignant gliomas is our inability to preferentially affect the tumor with the modalities available. Until it is possible to directly target the neoplastic cell without affecting so many of the adjacent normal cells, the quest for therapeutic gain will go unrealized.72 references.

  1. Exchange coupling between laterally adjacent nanomagnets.

    PubMed

    Dey, H; Csaba, G; Bernstein, G H; Porod, W

    2016-09-30

    We experimentally demonstrate exchange-coupling between laterally adjacent nanomagnets. Our results show that two neighboring nanomagnets that are each antiferromagnetically exchange-coupled to a common ferromagnetic bottom layer can be brought into strong ferromagnetic interaction. Simulations show that interlayer exchange coupling effectively promotes ferromagnetic alignment between the two nanomagnets, as opposed to antiferromagnetic alignment due to dipole-coupling. In order to experimentally demonstrate the proposed scheme, we fabricated arrays of pairs of elongated, single-domain nanomagnets. Magnetic force microscopy measurements show that most of the pairs are ferromagnetically ordered. The results are in agreement with micromagnetic simulations. The presented scheme can achieve coupling strengths that are significantly stronger than dipole coupling, potentially enabling far-reaching applications in Nanomagnet Logic, spin-wave devices and three-dimensional storage and computing. PMID:27535227

  2. Seismicity in Azerbaijan and Adjacent Caspian Sea

    SciTech Connect

    Panahi, Behrouz M.

    2006-03-23

    So far no general view on the geodynamic evolution of the Black Sea to the Caspian Sea region is elaborated. This is associated with the geological and structural complexities of the region revealed by geophysical, geochemical, petrologic, structural, and other studies. A clash of opinions on geodynamic conditions of the Caucasus region, sometimes mutually exclusive, can be explained by a simplified interpretation of the seismic data. In this paper I analyze available data on earthquake occurrences in Azerbaijan and the adjacent Caspian Sea region. The results of the analysis of macroseismic and instrumental data, seismic regime, and earthquake reoccurrence indicate that a level of seismicity in the region is moderate, and seismic event are concentrated in the shallow part of the lithosphere. Seismicity is mostly intra-plate, and spatial distribution of earthquake epicenters does not correlate with the plate boundaries.

  3. Boundary Layers of Air Adjacent to Cylinders

    PubMed Central

    Nobel, Park S.

    1974-01-01

    Using existing heat transfer data, a relatively simple expression was developed for estimating the effective thickness of the boundary layer of air surrounding cylinders. For wind velocities from 10 to 1000 cm/second, the calculated boundary-layer thickness agreed with that determined for water vapor diffusion from a moistened cylindrical surface 2 cm in diameter. It correctly predicted the resistance for water vapor movement across the boundary layers adjacent to the (cylindrical) inflorescence stems of Xanthorrhoea australis R. Br. and Scirpus validus Vahl and the leaves of Allium cepa L. The boundary-layer thickness decreased as the turbulence intensity increased. For a turbulence intensity representative of field conditions (0.5) and for νwindd between 200 and 30,000 cm2/second (where νwind is the mean wind velocity and d is the cylinder diameter), the effective boundary-layer thickness in centimeters was equal to [Formula: see text]. PMID:16658855

  4. Developmental thyroid hormone insufficiency and brain development: A role for brain-derived neurotrophic factor (BDNF)?*

    EPA Science Inventory

    Thyroid hormones (TH) are essential for normal brain development. Even subclinical hypothyroidism experienced in utero can result in neuropsychological deficits in children despite normal thyroid status at birth. Neurotrophins have been implicated in a host of brain cellular func...

  5. 30 CFR 56.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance on adjacent tracks. 56.9103 Section..., Hauling, and Dumping Traffic Safety § 56.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  6. 30 CFR 57.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Clearance on adjacent tracks. 57.9103 Section..., Hauling, and Dumping Traffic Safety § 57.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  7. 30 CFR 56.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Clearance on adjacent tracks. 56.9103 Section..., Hauling, and Dumping Traffic Safety § 56.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  8. 30 CFR 57.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance on adjacent tracks. 57.9103 Section..., Hauling, and Dumping Traffic Safety § 57.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  9. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  10. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  11. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  12. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  13. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  14. Brain Science, Brain Fiction.

    ERIC Educational Resources Information Center

    Bruer, John T.

    1998-01-01

    Three big ideas from brain science have arisen during the past 20 to 30 years: neural connections form rapidly early in life; critical periods occur in development; and enriched environments profoundly affect brain development during the early years. Current brain research has little to offer educational practice or policy. (10 references) (MLH)

  15. Normalizing Rejection.

    PubMed

    Conn, Vicki S; Zerwic, Julie; Jefferson, Urmeka; Anderson, Cindy M; Killion, Cheryl M; Smith, Carol E; Cohen, Marlene Z; Fahrenwald, Nancy L; Herrick, Linda; Topp, Robert; Benefield, Lazelle E; Loya, Julio

    2016-02-01

    Getting turned down for grant funding or having a manuscript rejected is an uncomfortable but not unusual occurrence during the course of a nurse researcher's professional life. Rejection can evoke an emotional response akin to the grieving process that can slow or even undermine productivity. Only by "normalizing" rejection, that is, by accepting it as an integral part of the scientific process, can researchers more quickly overcome negative emotions and instead use rejection to refine and advance their scientific programs. This article provides practical advice for coming to emotional terms with rejection and delineates methods for working constructively to address reviewer comments. PMID:26041785

  16. Interaction between adjacent lightning discharges in clouds

    NASA Astrophysics Data System (ADS)

    Wang, Yanhui; Zhang, Guangshu; Zhang, Tong; Li, Yajun; Wu, Bin; Zhang, Tinglong

    2013-07-01

    Using a 3D lightning radiation source locating system (LLS), three pairs of associated lightning discharges (two or more adjacent lightning discharges following an arbitrary rule that their space-gap was less than 10 km and their time-gap was less than 800 ms) were observed, and the interaction between associated lightning discharges was analyzed. All these three pairs of associated lightning discharges were found to involve three or more charge regions (the ground was considered as a special charge region). Moreover, at least one charge region involved two lightning discharges per pair of associated lightning discharges. Identified from electric field changes, the subsequent lightning discharges were suppressed by the prior lightning discharges. However, it is possible that the prior lightning discharge provided a remaining discharge channel to facilitate the subsequent lightning discharge. The third case provided evidence of this possibility. Together, the results suggested that, if the charges in the main negative charge region can be consumed using artificial lightning above the main negative charge regions, lightning accidents on the ground could be greatly reduced, on the condition that the height of the main negative charge region and the charge intensity of the lower positive charge region are suitable.

  17. Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas

    PubMed Central

    Skvortsova, Yulia V.; Zinovyeva, Marina V.; Stukacheva, Elena A.; Klimov, Alexey; Tryakin, Alexey A.; Azhikina, Tatyana L.

    2016-01-01

    PIWI pathway proteins are expressed during spermatogenesis where they play a key role in germ cell development. Epigenetic loss of PIWI proteins expression was previously demonstrated in testicular germ cell tumors (TGCTs), implying their involvement in TGCT development. In this work, apart from studying only normal testis and TGCT samples, we also analyzed an intermediate stage, i.e. preneoplastic testis tissues adjacent to TGCTs. Importantly, in this study, we minimized the contribution of patient-to-patient heterogeneity by using matched preneoplastic/TGCT samples. Surprisingly, expression of germ cell marker DDX4 suggests that spermatogenesis is retained in premalignant testis tissues adjacent to nonseminoma, but not those adjacent to seminoma. Moreover, this pattern is followed by expression of PIWI pathway genes, which impacts one of their functions: DNA methylation level over LINE-1 promoters is higher in preneoplastic testis tissues adjacent to nonseminomas than those adjacent to seminomas. This finding might imply distinct routes for development of the two types of TGCTs and could be used as a novel diagnostic marker, possibly, noninvasively. Finally, we studied the role of CpG island methylation in expression of PIWI genes in patient samples and using in vitro experiments in cell line models: a more complex interrelation between DNA methylation and expression of the corresponding genes was revealed. PMID:26843623

  18. Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas.

    PubMed

    Gainetdinov, Ildar V; Kondratieva, Sofia A; Skvortsova, Yulia V; Zinovyeva, Marina V; Stukacheva, Elena A; Klimov, Alexey; Tryakin, Alexey A; Azhikina, Tatyana L

    2016-04-19

    PIWI pathway proteins are expressed during spermatogenesis where they play a key role in germ cell development. Epigenetic loss of PIWI proteins expression was previously demonstrated in testicular germ cell tumors (TGCTs), implying their involvement in TGCT development. In this work, apart from studying only normal testis and TGCT samples, we also analyzed an intermediate stage, i.e. preneoplastic testis tissues adjacent to TGCTs. Importantly, in this study, we minimized the contribution of patient-to-patient heterogeneity by using matched preneoplastic/TGCT samples. Surprisingly, expression of germ cell marker DDX4 suggests that spermatogenesis is retained in premalignant testis tissues adjacent to nonseminoma, but not those adjacent to seminoma. Moreover, this pattern is followed by expression of PIWI pathway genes, which impacts one of their functions: DNA methylation level over LINE-1 promoters is higher in preneoplastic testis tissues adjacent to nonseminomas than those adjacent to seminomas. This finding might imply distinct routes for development of the two types of TGCTs and could be used as a novel diagnostic marker, possibly, noninvasively. Finally, we studied the role of CpG island methylation in expression of PIWI genes in patient samples and using in vitro experiments in cell line models: a more complex interrelation between DNA methylation and expression of the corresponding genes was revealed. PMID:26843623

  19. Brain herniation

    MedlinePlus

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  20. Petroleum basins of Sakhalin and adjacent shelf

    SciTech Connect

    Mavrinski, Y.; Koblov, E. )

    1993-09-01

    Sixty-seven oil and gas fields have been discovered on Sakhalin and the adjacent shelf but the distribution of fields is uneven in north Sakhalin, south Sakhalin, and the Tatar basins. The sedimentary cover is composed of sandy, clayey, and siliceous rocks, with volcanogenic and coal-bearing deposits of Upper Cretaceous, Paleogene, and Neogene 8-12 km thick. Marine clayey and siliceous oil source rocks are regionally developed in the section at different stratigraphic levels; the organic matter is of mixed type and the content varies from 0.5 to 1.5%. The upper Oligocene and middle-upper Miocene source rocks in the north Sakhalin basin are typical, and the organic carbon content ranges from 1 to 5%. The level of organic matter catagenesis and conversion into hydrocarbons is high because of the high differential geothermal gradient in the basins, 30-50[degrees]C per km. Porous sandstones in the Miocene form the reservoirs in all fields with the exception of Okruzhnoye, where the pay zone is a siliceous claystone. Growth-fault rollovers and anticlines form the main traps ranging in area from 5 to 300 km[sup 2], with amplitudes between 100 and 600 m. both stratigraphic and structural traps have been identified. Considerable volumes of reserves are associated with the Miocene deposits of north Sakhalin, which are characterized by an optimum combination of oil source rocks, focused migration paths, and thick sequences of reservoirs and cap rocks. Six large fields have been discovered in the past 15 yr. Oil and condensate reserves stand at over 300 million MT, and gas reserves are about 900 billion m[sup 3].

  1. Intracavitary moderator balloon combined with 252Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations

    PubMed Central

    Brandão, S F

    2015-01-01

    Objective: This article proposes a combination of californium-252 (252Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Methods: Dosimetric evaluations were performed on three protocol set-ups: 252Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Results: Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0–5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Conclusion: Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the 252Cf source, sparing the normal brain tissue. Advances in knowledge: Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis. PMID:25927876

  2. Can Breast Tumors Affect the Oxidative Status of the Surrounding Environment? A Comparative Analysis among Cancerous Breast, Mammary Adjacent Tissue, and Plasma

    PubMed Central

    Panis, C.; Victorino, V. J.; Herrera, A. C. S. A.; Cecchini, A. L.; Simão, A. N. C.; Tomita, L. Y.; Cecchini, R.

    2016-01-01

    In this paper, we investigated the oxidative profile of breast tumors in comparison with their normal adjacent breast tissue. Our study indicates that breast tumors present enhanced oxidative/nitrosative stress, with concomitant augmented antioxidant capacity when compared to the adjacent normal breast. These data indicate that breast cancers may be responsible for the induction of a prooxidant environment in the mammary gland, in association with enhanced TNF-α and nitric oxide. PMID:26697139

  3. Brain Plasticity and Behaviour in the Developing Brain

    PubMed Central

    Kolb, Bryan; Gibb, Robbin

    2011-01-01

    Objective: To review general principles of brain development, identify basic principles of brain plasticity, and discuss factors that influence brain development and plasticity. Method: A literature review of relevant English-language manuscripts on brain development and plasticity was conducted. Results: Brain development progresses through a series of stages beginning with neurogenesis and progressing to neural migration, maturation, synaptogenesis, pruning, and myelin formation. Eight basic principles of brain plasticity are identified. Evidence that brain development and function is influenced by different environmental events such as sensory stimuli, psychoactive drugs, gonadal hormones, parental-child relationships, peer relationships, early stress, intestinal flora, and diet. Conclusions: The development of the brain reflects more than the simple unfolding of a genetic blueprint but rather reflects a complex dance of genetic and experiential factors that shape the emerging brain. Understanding the dance provides insight into both normal and abnormal development. PMID:22114608

  4. Real-time intraoperative full-range complex FD-OCT guided cerebral blood vessel identification and brain tumor resection in neurosurgery

    NASA Astrophysics Data System (ADS)

    Zhang, Kang; Huang, Yong; Pradilla, Gustavo; Tyler, Betty; Kang, Jin U.

    2011-03-01

    This work utilized an ultra-high-speed full-range complex-conjugate-free optical coherence tomography (FD-OCT) system to perform real-time intraoperative imaging to guide two common neurosurgical procedures: the cerebral blood vessel identification and the brain tumor resection. The cerebral blood vessel identification experiment is conducted ex vivo on human cadaver specimen. Specific cerebral arteries and veins in different positions of the specimen are visualized and the spatial relations between adjacent vessels are indentified through real-time 3D visualization. The brain tumor resection experiment is conducted in vivo on 9L gliomas established in rat brains. The normal brain-tumor margin can be clearly identified in depth of the tissue from sagittal, coronal and axial slices of the intraoperatively acquired 3D data set. The real-time full-range FD-OCT guided in vivo rat flank tumor resection is also conducted.

  5. Ius Chasma Tributary Valleys and Adjacent Plains

    NASA Technical Reports Server (NTRS)

    2006-01-01

    This image covers valley tributaries of Ius Chasma, as well as the plains adjacent to the valleys. Ius Chasma is one of several canyons that make up the Valles Marineris canyon system. Valles Marineris likely formed by extension associated with the growth of the large volcanoes and topographic high of Tharsis to the northwest. As the ground was pulled apart, large and deep gaps resulted in the valleys seen in the top and bottom of this HiRISE image. Ice that was once in the ground could have also melted to create additional removal of material in the formation of the valleys. HiRISE is able to see the rocks along the walls of both these valleys and also impact craters in the image. Rock layers that appear lower down in elevation appear rougher and are shedding boulders. Near the top of the walls and also seen in patches along the smooth plains are brighter layers. These brighter layers are not shedding boulders so they must represent a different kind of rock formed in a different kind of environment than those further down the walls. Because they are highest in elevation, the bright layers are youngest in age. HiRISE is able to see dozens of the bright layers, which are perhaps only a meter in thickness. Darker sand dunes and ripples cover most of the plains and fill the floors of impact craters.

    Image PSP_001351_1715 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on November 9, 2006. The complete image is centered at -8.3 degrees latitude, 275.4 degrees East longitude. The range to the target site was 254.3 km (158.9 miles). At this distance the image scale ranges from 25.4 cm/pixel (with 1 x 1 binning) to 101.8 cm/pixel (with 4 x 4 binning). The image shown here has been map-projected to 25 cm/pixel and north is up. The image was taken at a local Mars time of 3:32 PM and the scene is illuminated from the west with a solar incidence angle of 59 degrees, thus the sun was about

  6. Effect of Treatment with Interferon Beta-1a on Changes in Voxel-Wise Magnetization Transfer Ratio in Normal Appearing Brain Tissue and Lesions of Patients with Relapsing–Remitting Multiple Sclerosis: A 24-Week, Controlled Pilot Study

    PubMed Central

    Zivadinov, Robert; Dwyer, Michael G.; Markovic-Plese, Silva; Kennedy, Cheryl; Bergsland, Niels; Ramasamy, Deepa P.; Durfee, Jacqueline; Hojnacki, David; Hayward, Brooke; Dangond, Fernando; Weinstock-Guttman, Bianca

    2014-01-01

    Background This pilot study investigated changes in remyelinating and demyelinating activity in normal appearing brain tissue (NABT) and lesions, by using voxel-wise magnetization transfer ratio (VW-MTR), in patients with relapsing–remitting multiple sclerosis (RRMS) receiving interferon beta-1a 44 mcg subcutaneously (IFN β-1a SC) three times weekly versus healthy controls (HCs) (NCT01085318). Methods Increasing (suggestive of remyelination) and decreasing (suggestive of demyelination) VW-MTR changes in NABT and in T2, T1 and gadolinium (Gd)-enhancing lesion volume were measured over 24 weeks in 23 patients treated with IFN β-1a SC and in 15 HCs (where applicable). VW-MTR changes were tested using the Wilcoxon signed–rank or Wilcoxon rank–sum test. Results A trend for greater volume of NABT with increasing VW-MTR at 24 weeks was observed for patients versus HCs (median [range] 1206 [0–15278]; 342 [0–951] mm3; p = 0.061). NABT volume with increasing VW-MTR at 12 weeks was significantly greater in patients than in HCs (852 [6–11577]; 360 [0–1755] mm3; p = 0.028). Similar findings were detected for lesion volumes. Two patients with notably high numbers of Gd-enhancing lesions at baseline had a markedly greater volume of tissue with increasing VW-MTR compared with other patients. Volume of NABT tissue with decreasing VW-MTR was significantly greater in patients versus HCs at 24 weeks (942 [0–6141]; 297 [0–852] mm3; p<0.001). Conclusions The significant change in NABT volume with increasing VW-MTR at 12 weeks suggests that active remyelination in patients with RRMS may occur during treatment with IFN β-1a SC. Findings from two patients with the highest number of Gd-enhancing lesions at baseline suggest that extensive remyelination in NABT may occur in patients with high disease activity. Tissue volume with decreasing VW-MTR was greater in patients than in HCs, despite treatment, validating the sensitivity of this technique for detecting MS

  7. View of north side from exterior stairs of adjacent building, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of north side from exterior stairs of adjacent building, bottom cut off by fringed buildings, view facing south-southwest - U.S. Naval Base, Pearl Harbor, Industrial X-Ray Building, Off Sixth Street, adjacent to and south of Facility No. 11, Pearl City, Honolulu County, HI

  8. Learning Non-Adjacent Regularities at Age 0 ; 7

    ERIC Educational Resources Information Center

    Gervain, Judit; Werker, Janet F.

    2013-01-01

    One important mechanism suggested to underlie the acquisition of grammar is rule learning. Indeed, infants aged 0 ; 7 are able to learn rules based on simple identity relations (adjacent repetitions, ABB: "wo fe fe" and non-adjacent repetitions, ABA: "wo fe wo", respectively; Marcus et al., 1999). One unexplored issue is…

  9. Delayed Acquisition of Non-Adjacent Vocalic Distributional Regularities

    ERIC Educational Resources Information Center

    Gonzalez-Gomez, Nayeli; Nazzi, Thierry

    2016-01-01

    The ability to compute non-adjacent regularities is key in the acquisition of a new language. In the domain of phonology/phonotactics, sensitivity to non-adjacent regularities between consonants has been found to appear between 7 and 10 months. The present study focuses on the emergence of a posterior-anterior (PA) bias, a regularity involving two…

  10. In vivo evaluation of the uptake of [(123)I]FIAU, [(123)I]IVFRU and [(123)I]IVFAU by normal mouse brain: potential for noninvasive assessment of HSV-1 thymidine kinase gene expression in gliomas.

    PubMed

    Li, H-F; Winkeler, A; Moharram, S; Knaus, E E; Dittmar, K; Stöckle, M; Heiss, W D; Wiebe, L I; Jacobs, A H; Jacob, A J

    2008-01-01

    Radioiodinated 5-iodo-1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)uracil (F *IAU) is most commonly used for noninvasive assessment of herpes simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression. However, it does not permeate the intact blood-brain barrier (BBB) because of its moderate lipophilicity. In this work, three iodo-nucleosides, FIAU, IVFRU, and IVFAU, were radiolabeled with iodine-123 and tested for permeation of the BBB in mice and for potential measurement of HSV-1-tk gene expression in gliomas. The results demonstrate that brain uptake and retention of these nucleosides is not directly related to their lipophilicity. The low brain uptake of IVFAU, in conjunction with its higher and constant brain/blood ratio, may reflect greater stability against hydrolysis of the N-glycosidic bond. In vivo PET evaluations of [(124)I]IVFRU and [(124)I]IVFAU in tumor-bearing mice are warranted. PMID:18188770

  11. Human Auditory and Adjacent Nonauditory Cerebral Cortices Are Hypermetabolic in Tinnitus as Measured by Functional Near-Infrared Spectroscopy (fNIRS)

    PubMed Central

    Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul

    2016-01-01

    Tinnitus is the phantom perception of sound in the absence of an acoustic stimulus. To date, the purported neural correlates of tinnitus from animal models have not been adequately characterized with translational technology in the human brain. The aim of the present study was to measure changes in oxy-hemoglobin concentration from regions of interest (ROI; auditory cortex) and non-ROI (adjacent nonauditory cortices) during auditory stimulation and silence in participants with subjective tinnitus appreciated equally in both ears and in nontinnitus controls using functional near-infrared spectroscopy (fNIRS). Control and tinnitus participants with normal/near-normal hearing were tested during a passive auditory task. Hemodynamic activity was monitored over ROI and non-ROI under episodic periods of auditory stimulation with 750 or 8000 Hz tones, broadband noise, and silence. During periods of silence, tinnitus participants maintained increased hemodynamic responses in ROI, while a significant deactivation was seen in controls. Interestingly, non-ROI activity was also increased in the tinnitus group as compared to controls during silence. The present results demonstrate that both auditory and select nonauditory cortices have elevated hemodynamic activity in participants with tinnitus in the absence of an external auditory stimulus, a finding that may reflect basic science neural correlates of tinnitus that ultimately contribute to phantom sound perception. PMID:27042360

  12. Early Alzheimer's Linked to Brain 'Leakage'

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159116.html Early Alzheimer's Linked to Brain 'Leakage' Normally, blood-brain barrier ... HealthDay News) -- People in the early stages of Alzheimer's disease may have more "leaks" in the barrier ...

  13. Metastasis Infiltration: An Investigation of the Postoperative Brain-Tumor Interface

    SciTech Connect

    Raore, Bethwel; Schniederjan, Matthew; Prabhu, Roshan; Brat, Daniel J.; Shu, Hui-Kuo; Olson, Jeffrey J.

    2011-11-15

    Purpose: This study aims to evaluate brain infiltration of metastatic tumor cells past the main tumor resection margin to assess the biological basis for the use of stereotactic radiosurgery treatment of the tumor resection cavity and visualized resection edge or clinical target volume. Methods and Materials: Resection margin tissue was obtained after gross total resection of a small group of metastatic lesions from a variety of primary sources. The tissue at the border of the tumor and brain tissue was carefully oriented and processed to evaluate the presence of tumor cells within brain tissue and their distance from the resection margin. Results: Microscopic assessment of the radially oriented tissue samples showed no tumor cells infiltrating the surrounding brain tissue. Among the positive findings were reactive astrocytosis observed on the brain tissue immediately adjacent to the tumor resection bed margin. Conclusions: The lack of evidence of metastatic tumor cell infiltration into surrounding brain suggests the need to target only a narrow depth of the resection cavity margin to minimize normal tissue injury and prevent treatment size-dependent stereotactic radiosurgery complications.

  14. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  15. A novel method for three-dimensional observation of the vascular networks in the whole mouse brain.

    PubMed

    Hashimoto, Hisashi; Kusakabe, Moriaki; Ishikawa, Hiroshi

    2008-01-01

    A novel method for acquiring serial images suitable for three-dimensional reconstruction of vascular networks in the whole brain of mouse was developed. The brain infused with a White India ink-gelatin solution was fixed and embedded in paraffin containing Sudan Black B through xylene also containing Sudan Black B. Each sliced surface of the paraffin block was coated with liquid paraffin and its image was serially acquired. Coating with liquid paraffin extremely improved the quality of the image. The series of serial images was free of distortion and a three-dimensional image was reconstructed without the problem of the alignment and registration of adjacent images. The volume-rendered image indicated three-dimensional distribution of blood vessels in a whole brain. No ghost or shadow was observed on a volume-rendered image of the White India ink-gelatin infused brain. The z-axial resolution examined on the orthogonal sections reconstituted from serial images obtained at an interval of 5 mum showed no cross talk, indicating that the z-axial resolution was no larger than 5 mum. A proper understanding of the vascular system in a whole brain is indispensable to reveal the development of the vascular system in the brain of normal and genetically manipulated mouse and vascular alterations in pathological situation, such as stroke and neurodegenerative disease. Although simple and inexpensive, this method will provide fundamental information on the vascular system in a whole brain. PMID:17868133

  16. Thermoelastic response of thin metal films and their adjacent materials

    SciTech Connect

    Kang, S.; Yoon, Y.; Kim, J.; Kim, W.

    2013-01-14

    A pulsed laser beam applied to a thin metal film is capable of launching an acoustic wave due to thermal expansion. Heat transfer from the thin metal film to adjacent materials can also induce thermal expansion; thus, the properties of these adjacent materials (as well as the thin metal film) should be considered for a complete description of the thermoelastic response. Here, we show that adjacent materials with a small specific heat and large thermal expansion coefficient can generate an enhanced acoustic wave and we demonstrate a three-fold increase in the peak pressure of the generated acoustic wave on substitution of parylene for polydimethylsiloxane.

  17. Radioresistance of Brain Tumors

    PubMed Central

    Kelley, Kevin; Knisely, Jonathan; Symons, Marc; Ruggieri, Rosamaria

    2016-01-01

    Radiation therapy (RT) is frequently used as part of the standard of care treatment of the majority of brain tumors. The efficacy of RT is limited by radioresistance and by normal tissue radiation tolerance. This is highlighted in pediatric brain tumors where the use of radiation is limited by the excessive toxicity to the developing brain. For these reasons, radiosensitization of tumor cells would be beneficial. In this review, we focus on radioresistance mechanisms intrinsic to tumor cells. We also evaluate existing approaches to induce radiosensitization and explore future avenues of investigation. PMID:27043632

  18. Brain abscess

    MedlinePlus

    Brain abscesses commonly occur when bacteria or fungi infect part of the brain. As a result, swelling and irritation (inflammation) develop. Infected brain cells, white blood cells, live and dead bacteria, ...

  19. Brain components

    MedlinePlus Videos and Cool Tools

    The brain is composed of more than a thousand billion neurons. Specific groups of them, working in concert, provide ... of information. The 3 major components of the brain are the cerebrum, cerebellum, and brain stem. The ...

  20. Brain surgery

    MedlinePlus

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  1. 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, ...

  2. Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer

    PubMed Central

    2014-01-01

    Background A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient’s gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response. Methods A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software). Results Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue. Conclusions The systems-level approach provides new insights into the micro-ecology of colorectal tumorogenesis. Disrupting this intricate molecular network of cell-cell communication and pro-inflammatory microenvironment could be a therapeutic target in CRC patients. PMID:24597571

  3. Early Growth Response1and Fatty Acid Synthase Expression is Altered in Tumor Adjacent Prostate Tissue and Indicates Field Cancerization

    PubMed Central

    Jones, Anna C.; Trujillo, Kristina A.; Phillips, Genevieve K.; Fleet, Trisha M.; Murton, Jaclyn K.; Severns, Virginia; Shah, Satyan K.; Davis, Michael S.; Smith, Anthony Y.; Griffith, Jeffrey K.; Fischer, Edgar G.; Bisoffi, Marco

    2011-01-01

    BACKGROUND Field cancerization denotes the occurrence of molecular alterations in histologically normal tissues adjacent to tumors. In prostate cancer, identification of field cancerization has several potential clinical applications. However, prostate field cancerization remains ill defined. Our previous work has shown up-regulated mRNA of the transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS) in tissues adjacent to prostate cancer. METHODS Immunofluorescence data were analyzed quantitatively by spectral imaging and linear unmixing to determine the protein expression levels of EGR-1 and FAS in human cancerous, histologically normal adjacent, and disease-free prostate tissues. RESULTS EGR-1 expression was elevated in both structurally intact tumor adjacent (1.6× on average) and in tumor (3.0× on average) tissues compared to disease-free tissues. In addition, the ratio of cytoplasmic versus nuclear EGR-1 expression was elevated in both tumor adjacent and tumor tissues. Similarly, FAS expression was elevated in both tumor adjacent (2.7× on average) and in tumor (2.5× on average) compared to disease-free tissues. CONCLUSIONS EGR-1 and FAS expression is similarly deregulated in tumor and structurally intact adjacent prostate tissues and defines field cancerization. In cases with high suspicion of prostate cancer but negative biopsy, identification of field cancerization could help clinicians target areas for repeat biopsy. Field cancerization at surgical margins on prostatectomy specimen should also be looked at as a predictor of cancer recurrence. EGR-1 and FAS could also serve as molecular targets for chemoprevention. PMID:22127986

  4. 73. PASSAGE ADJACENT TO ROOM 232, EAST WING, SECOND FLOOR, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    73. PASSAGE ADJACENT TO ROOM 232, EAST WING, SECOND FLOOR, LOOKING WEST BY NORTHWEST, SHOWING EASTERNMOST ARCH OF FORMER GREAT HALL NORTH ARCADE - Smithsonian Institution Building, 1000 Jefferson Drive, between Ninth & Twelfth Streets, Southwest, Washington, District of Columbia, DC

  5. View of viaduct, looking SE from roof of adjacent parking ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of viaduct, looking SE from roof of adjacent parking garage. - Mulberry Street Viaduct, Spanning Paxton Creek & Cameron Street (State Route 230) at Mulberry Street (State Route 3012), Harrisburg, Dauphin County, PA

  6. Cement Leakage into Adjacent Vertebral Body Following Percutaneous Vertebroplasty

    PubMed Central

    Park, Jae Hoo; Kim, Hyeun Sung

    2016-01-01

    Percutaneous vertebroplasty (PV) is a minimally invasive procedure for osteoporotic vertebral compression fractures that fail to respond to conventional conservative treatment. It significantly improves intolerable back pain within hours, and has a low complication rate. Although rare, PV is not free of complications, most of which are directly related to cement leakage. Because of its association with new adjacent fracture, the importance of cement leakage into the adjacent disc space is paramount. Here, we report an interesting case of cement leakage into the adjacent upper vertebral body as well as disc space following PV. To the best of our knowledge, there has been no report of cement leakage into the adjacent vertebral body following PV. This rare case is presented along with a review of the literature. PMID:27437018

  7. 1. HEBRONVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR. HEBRONVILLE, BRISTOL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. HEBRONVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR. HEBRONVILLE, BRISTOL CO., MA. Sec. 4116, MP 193.75. - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  8. 3. DODGEVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR DODGEVILLE, BRISTOL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. DODGEVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR DODGEVILLE, BRISTOL CO., MA. Sec. 4116, MP 195.55. - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  9. 33. HISTORIC PLAQUE MARKING WHERE JOHNSTON DIED, ADJACENT TO PATHWAY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. HISTORIC PLAQUE MARKING WHERE JOHNSTON DIED, ADJACENT TO PATHWAY WITH CONCRETE CULVERT LEADING NORTH OUT OF RAVINE TOWARD JOHNSTON MEMORIAL SITE. VIEW NW. - Shiloh National Military Park Tour Roads, Shiloh, Hardin County, TN

  10. Lock 4 View east of lock wall and adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Lock 4 - View east of lock wall and adjacent roadway built atop tow path. The gate pocket can be seen at center. - Savannah & Ogeechee Barge Canal, Between Ogeechee & Savannah Rivers, Savannah, Chatham County, GA

  11. 1. Ninth Street (west) facade. Adjacent on the north is ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Ninth Street (west) facade. Adjacent on the north is the 9th Street facade of 816 E Street. Both buildings were originally one property. - Riley Building, Rendezvous Adult Magazines & Films, 437 Ninth Street, Northwest, Washington, District of Columbia, DC

  12. 2. THREEQUARTER VIEW FROM ADJACENT ACCESS ROAD SHOWING THREE SPANS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. THREE-QUARTER VIEW FROM ADJACENT ACCESS ROAD SHOWING THREE SPANS AND NORTHWEST APPROACH SPANS, LOOKING SOUTHEAST - Red River Bridge, Spanning Red River at U.S. Highway 82, Garland, Miller County, AR

  13. 1. VIEW FROM ROOFTOP OF BUILDING (MOTEL) ADJACENT TO TECHWOOD ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. VIEW FROM ROOFTOP OF BUILDING (MOTEL) ADJACENT TO TECHWOOD HOMES, LOOKING SOUTH. GARAGE TO EXTREME LEFT, BUILDING 1 TO EXTREME RIGHT. - Techwood Homes (Public Housing), Bounded by North Avenue, Parker Street, William Street & Lovejoy Street, Atlanta, Fulton County, GA

  14. 3. View of north side of house facing from adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. View of north side of house facing from adjacent vacant property. Original wood lap siding and trim is covered by aluminum siding. Recessed side porch is in middle. - 645 South Eighteenth Street (House), Louisville, Jefferson County, KY

  15. 1. A BRICK AND CONCRETE FAN HOUSING ADJACENT TO ONE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. A BRICK AND CONCRETE FAN HOUSING ADJACENT TO ONE OF THE ADIT OPENINGS (VIEW TO THE NORTH). - Foster Gulch Mine, Fan Housing, Bear Creek 1 mile Southwest of Town of Bear Creek, Red Lodge, Carbon County, MT

  16. 7. August, 1970 9 ORANGE STREET, ADJACENT TO UNITARIAN CHURCH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. August, 1970 9 ORANGE STREET, ADJACENT TO UNITARIAN CHURCH (NOT IN STUDY AREA) - Orange & Union Streets Neighborhood Study, 8-31 Orange Street, 9-21 Union Street & Stone Alley, Nantucket, Nantucket County, MA

  17. OBLIQUE OF SOUTHWEST END AND SOUTHEAST SIDE, WITH ADJACENT FACILITY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    OBLIQUE OF SOUTHWEST END AND SOUTHEAST SIDE, WITH ADJACENT FACILITY 391 IN THE FOREGROUND. - U.S. Naval Base, Pearl Harbor, Joint Intelligence Center, Makalapa Drive in Makalapa Administration Area, Pearl City, Honolulu County, HI

  18. Complications in exodontia--accidental dislodgment to adjacent anatomical areas.

    PubMed

    Grandini, S A; Barros, V M; Salata, L A; Rosa, A L; Soares, U N

    1993-01-01

    The authors report 4 cases of accidental dislodgement of teeth to adjacent anatomical areas during extraction. The causes and their prevention are discussed and solutions for the problem are suggested. PMID:8241759

  19. 6. Detail, vertical guides adjacent to east portal of Tunnel ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Detail, vertical guides adjacent to east portal of Tunnel 28, view to southwest, 135mm lens with electronic flash fill. - Central Pacific Transcontinental Railroad, Tunnel No. 28, Milepost 134.75, Applegate, Placer County, CA

  20. VIEW OF CONSTRUCTION CAMP ROCK FEATURE WITH OVER, ADJACENT TO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF CONSTRUCTION CAMP ROCK FEATURE WITH OVER, ADJACENT TO THE COLUMBIA SOUTHERN CANAL. LOOKING NORTHWEST - Tumalo Irrigation District, Tumalo Project, West of Deschutes River, Tumalo, Deschutes County, OR

  1. Pump house adjacent to the superintendent's house at the west ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Pump house adjacent to the superintendent's house at the west end of the complex near Highway 101. Detail of Holloshaft pump. View to the south. - Prairie Creek Fish Hatchery, Hwy. 101, Orick, Humboldt County, CA

  2. VIEW OF NORTHERN AND EASTERN SIDES FROM PARKING LOT ADJACENT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF NORTHERN AND EASTERN SIDES FROM PARKING LOT ADJACENT TO BUILDING 199 (POLICE STATION) - U.S. Naval Base, Pearl Harbor, Post Office, Avenue A near Eleventh Avenue, Pearl City, Honolulu County, HI

  3. 24. INTERIOR VIEW, WILLIAM GRAY AT SIZING GUAGE ADJACENT TO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. INTERIOR VIEW, WILLIAM GRAY AT SIZING GUAGE ADJACENT TO BRADLEY HAMMER; NOTE THIS IS THE SAME TOOL AS BEING FORGED ABOVE - Warwood Tool Company, Foot of Nineteenth Street, Wheeling, Ohio County, WV

  4. Detail exterior view looking north showing piping system adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail exterior view looking north showing piping system adjacent to engine house. Gas cooling system is on far right. - Burnsville Natural Gas Pumping Station, Saratoga Avenue between Little Kanawha River & C&O Railroad line, Burnsville, Braxton County, WV

  5. VIEW OF LAMP FIXTURE (EXTERIOR) ADJACENT TO ENTRANCE AT SOUTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF LAMP FIXTURE (EXTERIOR) ADJACENT TO ENTRANCE AT SOUTHWEST CORNER OF BUILDING 23, FACING NORTH - Roosevelt Base, Auditorium-Gymnasium, West Virginia Street between Richardson & Reeves Avenues, Long Beach, Los Angeles County, CA

  6. 14. Charles Acey Cobb standing adjacent to the fish screen ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Charles Acey Cobb standing adjacent to the fish screen he designed and installed in the Congdon Canal, facing southeast. Photo dates ca. late 1920's. - Congdon Canal, Fish Screen, Naches River, Yakima, Yakima County, WA

  7. 52. EASTSIDE PLANT: GENERAL VIEW OF GOVERNOR ADJACENT TO GENERATOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. EASTSIDE PLANT: GENERAL VIEW OF GOVERNOR ADJACENT TO GENERATOR - American Falls Water, Power & Light Company, Island Power Plant, Snake River, below American Falls Dam, American Falls, Power County, ID

  8. Interior building details of Building A, dungeon cell adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Interior building details of Building A, dungeon cell adjacent to northwest cell: granite and brick threshold, poured concrete floors, plastered finished walls, vaulted veiling; northwesterly view - San Quentin State Prison, Building 22, Point San Quentin, San Quentin, Marin County, CA

  9. VIEW OF CONCRETE CHANNEL ADJACENT TO TUMALO FEED CANAL INTAKE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF CONCRETE CHANNEL ADJACENT TO TUMALO FEED CANAL INTAKE STRUCTURE (DOWNSTREAM SIDE). LOOKING EAST/NORTHEAST - Tumalo Irrigation District, Tumalo Project, West of Deschutes River, Tumalo, Deschutes County, OR

  10. Adjacent Segment Disease Perspective and Review of the Literature

    PubMed Central

    Saavedra-Pozo, Fanor M.; Deusdara, Renato A. M.; Benzel, Edward C.

    2014-01-01

    Background Adjacent segment disease has become a common topic in spine surgery circles because of the significant increase in fusion surgery in recent years and the development of motion preservation technologies that theoretically should lead to a decrease in this pathology. The purpose of this review is to organize the evidence available in the current literature on this subject. Methods For this literature review, a search was conducted in PubMed with the following keywords: adjacent segment degeneration and disease. Selection, review, and analysis of the literature were completed according to level of evidence. Results The PubMed search identified 850 articles, from which 41 articles were selected and reviewed. The incidence of adjacent segment disease in the cervical spine is close to 3% without a significant statistical difference between surgical techniques (fusion vs arthroplasty). Authors report the incidence of adjacent segment disease in the lumbar spine to range from 2% to 14%. Damage to the posterior ligamentous complex and sagittal imbalances are important risk factors for both degeneration and disease. Conclusion Insufficient evidence exists at this point to support the idea that total disc arthroplasty is superior to fusion procedures in minimizing the incidence of adjacent segment disease. The etiology is most likely multifactorial but it is becoming abundantly clear that adjacent segment disease is not caused by motion segment fusion alone. Fusion plus the presence of abnormal end-fusion alignment appears to be a major factor in creating end-fusion stresses that result in adjacent segment degeneration and subsequent disease. The data presented cast further doubt on previously established rationales for total disc arthroplasty, at least with regard to the effect of total disc arthroplasty on adjacent segment degeneration pathology. PMID:24688337

  11. Approximating the largest eigenvalue of network adjacency matrices

    NASA Astrophysics Data System (ADS)

    Restrepo, Juan G.; Ott, Edward; Hunt, Brian R.

    2007-11-01

    The largest eigenvalue of the adjacency matrix of a network plays an important role in several network processes (e.g., synchronization of oscillators, percolation on directed networks, and linear stability of equilibria of network coupled systems). In this paper we develop approximations to the largest eigenvalue of adjacency matrices and discuss the relationships between these approximations. Numerical experiments on simulated networks are used to test our results.

  12. Fluorescence spectroscopy to discriminate neoplastic human brain lesions: a study using the spectral intensity ratio and multivariate linear discriminant analysis

    NASA Astrophysics Data System (ADS)

    Nazeer, Shaiju S.; Saraswathy, Ariya; Gupta, Arun Kumar; Jayasree, Ramapurath S.

    2014-02-01

    Fluorescence spectroscopy is an emerging tool used to differentiate normal and malignant tissue based on the emission spectral profile from endogenous fluorophores. The goal of this study is to estimate the concentration of fluorophores using autofluorescence spectroscopy and try to utilize its diagnostic potential on samples of clinical importance. Brain tumor tissues from patients who received craniotomy for the removal of astrocytoma, glioma, meningioma and schwannoma were utilized in this study. Fluorescence emissions of the formalin fixed samples were recorded at excitation wavelengths of 320 and 410 nm. The emission characteristics of fluorophores such as collagen, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), phospholipids and porphyrins of tumor tissue and adjacent normal tissue were elicited. Exact tissue classification was carried out using the spectral intensity ratio (SIR) and multivariate principal component analysis-linear discriminant analysis (PCA-LDA). The diagnostic algorithm based on PCA-LDA provided better classification efficiency than SIR. Moreover, the spectral data based on an excitation wavelength of 410 nm are found to be more efficient in the classification than 320 nm excitation, using PCA-LDA. Better efficacy of PCA-LDA in tissue classification was further confirmed by the receiver operator characteristic (ROC) curve method. The results of this study establish the feasibility of using fluorescence spectroscopy based real time tools for the discrimination of brain tumors from the adjacent normal tissue during craniotomies, which at present faces a huge challenge.

  13. Can brains generate random numbers?

    NASA Astrophysics Data System (ADS)

    Chvátal, V.; Goldsmith, M.

    2013-01-01

    Motivated by EEG recordings of normal brain activity, we construct arbitrarily large McCulloch-Pitts neural networks that, without any external input, make every subset of their neurons fire in some iteration (and therefore in infinitely many iterations).

  14. Normalization as a canonical neural computation

    PubMed Central

    Carandini, Matteo; Heeger, David J.

    2012-01-01

    There is increasing evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply similar operations to different problems. A promising candidate for such a computation is normalization, in which the responses of neurons are divided by a common factor that typically includes the summed activity of a pool of neurons. Normalization was developed to explain responses in the primary visual cortex and is now thought to operate throughout the visual system, and in many other sensory modalities and brain regions. Normalization may underlie operations such as the representation of odours, the modulatory effects of visual attention, the encoding of value and the integration of multisensory information. Its presence in such a diversity of neural systems in multiple species, from invertebrates to mammals, suggests that it serves as a canonical neural computation. PMID:22108672

  15. The α1, α2, α3, and γ2 subunits of GABAA receptors show characteristic spatial and temporal expression patterns in rhombencephalic structures during normal human brain development.

    PubMed

    Stojanovic, Tamara; Capo, Ivan; Aronica, Eleonora; Adle-Biassette, Homa; Höger, Harald; Sieghart, Werner; Kovacs, Gabor G; Milenkovic, Ivan

    2016-06-15

    γ-Aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in adult mammalian brain, mediating its actions chiefly via a pentameric chloride ion channel, the GABAA receptor. Nineteen different subunits (α1-6, β1-3, γ1-3, δ, ε, π, θ, ρ1-3) can give rise to multiple receptor subtypes that are the site of action of many clinically important drugs. In the developing brain, however, GABAA receptors mediate excitatory actions due to an increased chloride concentration within neurons and seem to control cell proliferation, migration, differentiation, synapse maturation, and cell death. Little is known about the distribution of single subunits in the human brain. Here we describe developmental changes in the immunohistochemical distribution of four subunits (α1, α2, α3, and γ2) in the human rhombencephalon. The γ2 was the most abundant subunit in all rhombencephalic structures during development and in adults, whereas α subunits showed a structure- and age-characteristic distribution. The α1 was expressed prenatally in the molecular and Purkinje cell layer, but only postnatally in the granule cell layer and the dentate nucleus. Expression was completely absent in the inferior olivary nucleus. The α2 gradually increased during development, showing some layer specificity in the cerebellar cortex. The α3-immunoreactivity in the cerebellar cortex was relatively weak, but it was abundantly observed in different cell populations in the subcortical cerebellar structures. Structure- and age-characteristic colocalization between subunits during development suggests differences in GABAA receptor composition. Interestingly, subunit expression in several instances differed between human and rodent brain, underlining the importance of immunohistochemical studies in humans. J. Comp. Neurol. 524:1805-1824, 2016. © 2015 Wiley Periodicals, Inc. PMID:26518133

  16. Blood-brain barrier and new approaches to brain drug delivery.

    PubMed Central

    Pardridge, W. M.; Boado, R. J.; Black, K. L.; Cancilla, P. A.

    1992-01-01

    Morbidity caused by brain dysfunction affects more than 50 million persons in the United States. Although new neuropharmaceuticals have the potential for treating specific brain diseases, they may not effectively enter brain from blood. Safe strategies are needed for drug delivery through the brain capillary wall, which makes up the blood-brain barrier in vivo. Two of these strategies are reviewed, as are related new developments in the molecular and cell biology of the brain capillary endothelium. The production of chimeric peptides represents a physiologic-based strategy for drug delivery. It entails the covalent coupling of the neuropharmaceutical to a brain transport vector, allowing transportation through the blood-brain barrier. Another strategy is biochemical opening of the blood-brain barrier: intracarotid leukotriene infusion is a method for selectively increasing blood-brain barrier permeability in brain tumors without affecting barrier permeability in normal brain tissue. Images PMID:1595245

  17. Biomechanical modelling of normal pressure hydrocephalus.

    PubMed

    Dutta-Roy, Tonmoy; Wittek, Adam; Miller, Karol

    2008-07-19

    This study investigates the mechanics of normal pressure hydrocephalus (NPH) growth using a computational approach. We created a generic 3-D brain mesh of a healthy human brain and modelled the brain parenchyma as single phase and biphasic continuum. In our model, hyperelastic constitutive law and finite deformation theory described deformations within the brain parenchyma. We used a value of 155.77Pa for the shear modulus (mu) of the brain parenchyma. Additionally, in our model, contact boundary definitions constrained the brain outer surface inside the skull. We used transmantle pressure difference to load the model. Fully nonlinear, implicit finite element procedures in the time domain were used to obtain the deformations of the ventricles and the brain. To the best of our knowledge, this was the first 3-D, fully nonlinear model investigating NPH growth mechanics. Clinicians generally accept that at most 1mm of Hg transmantle pressure difference (133.416Pa) is associated with the condition of NPH. Our computations showed that transmantle pressure difference of 1mm of Hg (133.416Pa) did not produce NPH for either single phase or biphasic model of the brain parenchyma. A minimum transmantle pressure difference of 1.764mm of Hg (235.44Pa) was required to produce the clinical condition of NPH. This suggested that the hypothesis of a purely mechanical basis for NPH growth needs to be revised. We also showed that under equal transmantle pressure difference load, there were no significant differences between the computed ventricular volumes for biphasic and incompressible/nearly incompressible single phase model of the brain parenchyma. As a result, there was no major advantage gained by using a biphasic model for the brain parenchyma. We propose that for modelling NPH, nearly incompressible single phase model of the brain parenchyma was adequate. Single phase treatment of the brain parenchyma simplified the mathematical description of the NPH model and resulted in

  18. Intraoperative virtual brain counseling

    NASA Astrophysics Data System (ADS)

    Jiang, Zhaowei; Grosky, William I.; Zamorano, Lucia J.; Muzik, Otto; Diaz, Fernando

    1997-06-01

    Our objective is to offer online real-tim e intelligent guidance to the neurosurgeon. Different from traditional image-guidance technologies that offer intra-operative visualization of medical images or atlas images, virtual brain counseling goes one step further. It can distinguish related brain structures and provide information about them intra-operatively. Virtual brain counseling is the foundation for surgical planing optimization and on-line surgical reference. It can provide a warning system that alerts the neurosurgeon if the chosen trajectory will pass through eloquent brain areas. In order to fulfill this objective, tracking techniques are involved for intra- operativity. Most importantly, a 3D virtual brian environment, different from traditional 3D digitized atlases, is an object-oriented model of the brain that stores information about different brain structures together with their elated information. An object-oriented hierarchical hyper-voxel space (HHVS) is introduced to integrate anatomical and functional structures. Spatial queries based on position of interest, line segment of interest, and volume of interest are introduced in this paper. The virtual brain environment is integrated with existing surgical pre-planning and intra-operative tracking systems to provide information for planning optimization and on-line surgical guidance. The neurosurgeon is alerted automatically if the planned treatment affects any critical structures. Architectures such as HHVS and algorithms, such as spatial querying, normalizing, and warping are presented in the paper. A prototype has shown that the virtual brain is intuitive in its hierarchical 3D appearance. It also showed that HHVS, as the key structure for virtual brain counseling, efficiently integrates multi-scale brain structures based on their spatial relationships.This is a promising development for optimization of treatment plans and online surgical intelligent guidance.

  19. Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation.

    PubMed

    Liao, Zhenhua; Fogel, Guy R; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

    2015-01-01

    BACKGROUND The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. MATERIAL AND METHODS Eighteen human cadaveric spines (C2-T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3-4 ACDR+C4-6 ACDF+C6-7ACDR; hybrid C3-5ACDF+C5-6ACDR+C6-7ACDR; hybrid C3-4ACDR+C4-5ACDR+C5-7ACDF); and 4-level fusion. RESULTS Four-level fusion resulted in significant decrease in the C3-C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. CONCLUSIONS Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835

  20. Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation

    PubMed Central

    Liao, Zhenhua; Fogel, Guy R.; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

    2015-01-01

    Background The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. Material/Methods Eighteen human cadaveric spines (C2–T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3–4 ACDR+C4–6 ACDF+C6–7ACDR; hybrid C3–5ACDF+C5–6ACDR+C6–7ACDR; hybrid C3–4ACDR+C4–5ACDR+C5–7ACDF); and 4-level fusion. Results Four-level fusion resulted in significant decrease in the C3–C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. Conclusions Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835

  1. Laplacian versus adjacency matrix in quantum walk search

    NASA Astrophysics Data System (ADS)

    Wong, Thomas G.; Tarrataca, Luís; Nahimov, Nikolay

    2016-06-01

    A quantum particle evolving by Schrödinger's equation contains, from the kinetic energy of the particle, a term in its Hamiltonian proportional to Laplace's operator. In discrete space, this is replaced by the discrete or graph Laplacian, which gives rise to a continuous-time quantum walk. Besides this natural definition, some quantum walk algorithms instead use the adjacency matrix to effect the walk. While this is equivalent to the Laplacian for regular graphs, it is different for non-regular graphs and is thus an inequivalent quantum walk. We algorithmically explore this distinction by analyzing search on the complete bipartite graph with multiple marked vertices, using both the Laplacian and adjacency matrix. The two walks differ qualitatively and quantitatively in their required jumping rate, runtime, sampling of marked vertices, and in what constitutes a natural initial state. Thus the choice of the Laplacian or adjacency matrix to effect the walk has important algorithmic consequences.

  2. Best Merge Region Growing Segmentation with Integrated Non-Adjacent Region Object Aggregation

    NASA Technical Reports Server (NTRS)

    Tilton, James C.; Tarabalka, Yuliya; Montesano, Paul M.; Gofman, Emanuel

    2012-01-01

    Best merge region growing normally produces segmentations with closed connected region objects. Recognizing that spectrally similar objects often appear in spatially separate locations, we present an approach for tightly integrating best merge region growing with non-adjacent region object aggregation, which we call Hierarchical Segmentation or HSeg. However, the original implementation of non-adjacent region object aggregation in HSeg required excessive computing time even for moderately sized images because of the required intercomparison of each region with all other regions. This problem was previously addressed by a recursive approximation of HSeg, called RHSeg. In this paper we introduce a refined implementation of non-adjacent region object aggregation in HSeg that reduces the computational requirements of HSeg without resorting to the recursive approximation. In this refinement, HSeg s region inter-comparisons among non-adjacent regions are limited to regions of a dynamically determined minimum size. We show that this refined version of HSeg can process moderately sized images in about the same amount of time as RHSeg incorporating the original HSeg. Nonetheless, RHSeg is still required for processing very large images due to its lower computer memory requirements and amenability to parallel processing. We then note a limitation of RHSeg with the original HSeg for high spatial resolution images, and show how incorporating the refined HSeg into RHSeg overcomes this limitation. The quality of the image segmentations produced by the refined HSeg is then compared with other available best merge segmentation approaches. Finally, we comment on the unique nature of the hierarchical segmentations produced by HSeg.

  3. Aquaporins and Brain Tumors.

    PubMed

    Maugeri, Rosario; Schiera, Gabriella; Di Liegro, Carlo Maria; Fricano, Anna; Iacopino, Domenico Gerardo; Di Liegro, Italia

    2016-01-01

    Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood-brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs). PMID:27367682

  4. Aquaporins and Brain Tumors

    PubMed Central

    Maugeri, Rosario; Schiera, Gabriella; Di Liegro, Carlo Maria; Fricano, Anna; Iacopino, Domenico Gerardo; Di Liegro, Italia

    2016-01-01

    Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood–brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs). PMID:27367682

  5. On the Adjacent Eccentric Distance Sum Index of Graphs

    PubMed Central

    Qu, Hui; Cao, Shujuan

    2015-01-01

    For a given graph G, ε(v) and deg(v) denote the eccentricity and the degree of the vertex v in G, respectively. The adjacent eccentric distance sum index of a graph G is defined as ξsv(G)=∑v∈V(G)ε(v)D(v)deg(v), where D(v)=∑u∈V(G)d(u,v) is the sum of all distances from the vertex v. In this paper we derive some bounds for the adjacent eccentric distance sum index in terms of some graph parameters, such as independence number, covering number, vertex connectivity, chromatic number, diameter and some other graph topological indices. PMID:26091095

  6. Nonlinear spin wave coupling in adjacent magnonic crystals

    NASA Astrophysics Data System (ADS)

    Sadovnikov, A. V.; Beginin, E. N.; Morozova, M. A.; Sharaevskii, Yu. P.; Grishin, S. V.; Sheshukova, S. E.; Nikitov, S. A.

    2016-07-01

    We have experimentally studied the coupling of spin waves in the adjacent magnonic crystals. Space- and time-resolved Brillouin light-scattering spectroscopy is used to demonstrate the frequency and intensity dependent spin-wave energy exchange between the side-coupled magnonic crystals. The experiments and the numerical simulation of spin wave propagation in the coupled periodic structures show that the nonlinear phase shift of spin wave in the adjacent magnonic crystals leads to the nonlinear switching regime at the frequencies near the forbidden magnonic gap. The proposed side-coupled magnonic crystals represent a significant advance towards the all-magnonic signal processing in the integrated magnonic circuits.

  7. Evaluation of the stress distribution change at the adjacent facet joints after lumbar fusion surgery: a biomechanical study.

    PubMed

    Ma, Jianxiong; Jia, Haobo; Ma, Xinlong; Xu, Weiguo; Yu, Jingtao; Feng, Rui; Wang, Jie; Xing, Dan; Wang, Ying; Zhu, Shaowen; Yang, Yang; Chen, Yang; Ma, Baoyi

    2014-07-01

    Spinal fusion surgery has been widely applied in clinical treatment, and the spinal fusion rate has improved markedly. However, its postoperative complications, especially adjacent segment degeneration, have increasingly attracted the attention of spinal surgeons. The most common pathological condition at adjacent segments is hypertrophic degenerative arthritis of the facet joint. To study the stress distribution changes at the adjacent facet joint after lumbar fusion with pedicle screw fixation, human cadaver lumbar spines were used in the present study, and electrical resistance strain gauges were attached on L1-L4 articular processes parallel or perpendicular to the articular surface of facet joints. Subsequently, electrical resistance strain gauge data were measured using anYJ-33 static resistance strain indicator with three types of models: the intact model, the laminectomy model, and the fusion model with pedicle screw fixation. The strain changes in the measurement sites indirectly reflect the stress changes. Significant differences in strain were observed between the normal and laminectomy state at all facet joints. Significant differences in strain were observed between the normal and the pedicle screw fixation fusion state at the L1/2 and L3/4 facet joints. The increased stress on the facet joints after lumbar fusion with pedicle screw fixation may be the cause of adjacent segment degeneration. PMID:24963037

  8. Brain abscess

    MedlinePlus

    ... with certain heart disorders, may receive antibiotics before dental or other procedures to help reduce the risk of infection. Alternative Names Abscess - brain; Cerebral abscess; CNS abscess Images Amebic brain ...

  9. Brain Diseases

    MedlinePlus

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  10. Brain surgery

    MedlinePlus

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... Before surgery, the hair on part of the scalp is shaved and the area is cleaned. The doctor makes ...

  11. Brain Health

    MedlinePlus

    ... exercise, diet and nutrition, cognitive activity, and social engagement — can help keep your body and brain ... Stay Mentally Active > Mentally challenging activities and social engagement may support brain health. Learn More Plan ahead ...

  12. 7. VIEW OF WATER TREATMENT PLANT, ADJACENT TO THE COAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. VIEW OF WATER TREATMENT PLANT, ADJACENT TO THE COAL CONVEYOR; IN THE DISTANCE IS THE FREQUENCY CHANGER HOUSE, WHICH IS ATTACHED TO SWITCH HOUSE NO. 1; LOOKING WEST. - Commonwealth Electric Company, Fisk Street Electrical Generating Station, 1111 West Cermak Avenue, Chicago, Cook County, IL

  13. Colposcopy of vaginal and vulvar human papillomavirus and adjacent sites.

    PubMed

    Hatch, K

    1993-03-01

    Human papillomaviral infections can affect the entire lower female genital tract as multifocal or multicentric disease as well as the surrounding anatomic and adjacent sites. The traditional colposcopic methods are necessary to assist in the diagnosis and help differentiate these infections from other disease mimics. PMID:8392676

  14. Biogeochemistry of hydrothermally and adjacent non-altered soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As a field/lab project, students in the Soil Biogeochemistry class of the University of Nevada, Reno described and characterized seven pedons, developed in hydrothermally and adjacent non-hydrothermally altered andesitic parent material near Reno, NV. Hydrothermally altered soils had considerably lo...

  15. 22. Float located adjacent to entry stair in filtration bed. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Float located adjacent to entry stair in filtration bed. The float actuates a valve that maintains water level over the bed. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  16. 2. VIEW FROM ROOFTOP OF BUILDING (MOTEL) ADJACENT TO TECHWOOD ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. VIEW FROM ROOFTOP OF BUILDING (MOTEL) ADJACENT TO TECHWOOD HOMES, LOOKING WEST. GEORGIA TECH DORMITORY BUILDING, 581-587 TECHWOOD DRIVE, IN FOREGROUND. - Techwood Homes (Public Housing), Bounded by North Avenue, Parker Street, William Street & Lovejoy Street, Atlanta, Fulton County, GA

  17. 10. Detail and contextual view of bridge and adjacent farmstead ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Detail and contextual view of bridge and adjacent farmstead setting. Note laced vertical compression members, latticed portal strut, decorative strut bracing, and lightness of diagonal and lateral tension members. View to southeast through southeast portal from truss mid-span. - Red Bank Creek Bridge, Spanning Red Bank Creek at Rawson Road, Red Bluff, Tehama County, CA

  18. LEHR NO. 2 AND LEHR NO. 3 ADJACENT TO FURNACE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    LEHR NO. 2 AND LEHR NO. 3 ADJACENT TO FURNACE ROOM; THE PIPES AT THE BOTTOM ARE PART OF THE RADIANT HEATING SYSTEM USED FOR HEATING THE FACTORY DURING COLD WEATHER. - Westmoreland Glass Company, Seventh & Kier Streets, Grapeville, Westmoreland County, PA

  19. Effects on stink bugs of field edges adjacent to woodland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Producers face significant crop losses from stink bug species in the southeastern USA, but the high mobility and polyphagy of the bugs make predictions of their presence in crops difficult. While there is some evidence that they colonize crops from adjacent crops, there are no studies of their colo...

  20. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING INTERSECTION OF ACACIA ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING INTERSECTION OF ACACIA ROAD WITH BIRCH CIRCLE. VIEW FACING NORTHEAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  1. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA AND ENTRY TO NEIGHBORHOOD. VIEW FACING SOUTHEAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  2. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING WESTERN SIDE OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING WESTERN SIDE OF NEIGHBORHOOD. VIEW FACING NORTHWEST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  3. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA ON RIGHT, AND HOUSING AREA ON LEFT. VIEW FACING EAST/NORTHEAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  4. How subaerial salt extrusions influence water quality in adjacent aquifers

    NASA Astrophysics Data System (ADS)

    Mehdizadeh, Razieh; Zarei, Mehdi; Raeisi, Ezzat

    2015-12-01

    Brines supplied from salt extrusions cause significant groundwater salinization in arid and semi-arid regions where salt rock is exposed to dissolution by episodic rainfalls. Here we focus on 62 of the 122 diapirs of Hormuz salt emergent in the southern Iran. To consider managing the degradation effect that salt extrusions have on the quality of adjoining aquifers, it is first necessary to understand how they influence adjacent water resources. We evaluate here the impacts that these diapirs have on adjacent aquifers based on investigating their geomorphologies, geologies, hydrologies and hydrogeologies. The results indicate that 28/62 (45%) of our sample of salt diapirs have no significant impact on the quality of groundwater in adjoining aquifers (namely Type N), while the remaining 34/62 (55%) degrade nearby groundwater quality. We offer simple conceptual models that account for how brines flowing from each of these types of salt extrusions contaminate adjacent aquifers. We identify three main mechanisms that lead to contamination: surface impact (Type A), subsurface intrusion (Type B) and indirect infiltration (Type C). A combination of all these mechanisms degrades the water quality in nearby aquifers in 19/62 (31%) of the salt diapirs studied. Having characterized the mechanism(s) by which each diapir affects the adjacent aquifer, we suggest a few possible remediation strategies to be considered. For instance, engineering the surface runoff of diapirs Types A and C into nearby evaporation basins would improve groundwater quality.

  5. 45. 1915 CLOTH ROOM ADJACENT TO PICKER ROOM, SECOND FLOOR, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    45. 1915 CLOTH ROOM ADJACENT TO PICKER ROOM, SECOND FLOOR, NORTH END OF MILL NO. 2, WALL ON LEFT DIVIDING CLOTH ROOM ADDED LATER (PROBABLY C. 1970s). - Prattville Manufacturing Company, Number One, 242 South Court Street, Prattville, Autauga County, AL

  6. Detail of north intermediate abutment pylon showing proximity of adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of north intermediate abutment pylon showing proximity of adjacent 1001-1007 East First Street (James K. Hill and Sons Pickle Works Building), facing east - First Street Bridge, Spanning Los Angeles River at First Street, Los Angeles, Los Angeles County, CA

  7. 8. Exterior view, showing tank and associated piping adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Exterior view, showing tank and associated piping adjacent to Test Cell 6, Systems Integration Laboratory Building (T-28), looking south. - Air Force Plant PJKS, Systems Integration Laboratory, Systems Integration Laboratory Building, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  8. 4. REAR ELEVATION, DETAIL OF CONSTRUCTION, ADJACENT CORNER POSTS BETWEEN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. REAR ELEVATION, DETAIL OF CONSTRUCTION, ADJACENT CORNER POSTS BETWEEN BUILDING PERIODS 1 AND 3. NOTE REUSED WOOD STRIP NAILED TO BUILDING PERIOD 1 POST INSCRIBED 'ST. LEONARD'. THERE ARE NO NAIL HOLES IN THE PERIOD 3 POST, THE FARRING STRIPS ADJUST FOR CLADDING - Charles' Gift, State Routes 2 & 4, Lusby, Calvert County, MD

  9. 1. OVERVIEW SHOWING FIRING CONTROL BLOCKHOUSE 0502 AND ADJACENT OBSERVATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. OVERVIEW SHOWING FIRING CONTROL BLOCKHOUSE 0502 AND ADJACENT OBSERVATION TOWER. WATER BRAKE TROUGH SEGMENT AT LOWER RIGHT. Looking north northeast. - Edwards Air Force Base, South Base Sled Track, Firing & Control Blockhouse for 10,000-foot Track, South of Sled Track at midpoint of 20,000-foot track, Lancaster, Los Angeles County, CA

  10. 4. Elevation looking southwest from adjacent hills on northeast side ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Elevation looking southwest from adjacent hills on northeast side of bridge, taken from river level. Note entire east side and substructure. - Presumpscot Falls Bridge, Spanning Presumptscot River at Allen Avenue extension, 0.75 mile west of U.S. Interstate 95, Falmouth, Cumberland County, ME

  11. 49 CFR 236.404 - Signals at adjacent control points.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Signals at adjacent control points. 236.404 Section 236.404 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RULES, STANDARDS, AND INSTRUCTIONS GOVERNING THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR...

  12. 12. LOG FOUNDATION ELEMENTS OF THE SAWMILL ADJACENT TO THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. LOG FOUNDATION ELEMENTS OF THE SAWMILL ADJACENT TO THE CANAL, LOOKING EAST. BARREN AREA IN FOREGROUND IS DECOMPOSING SAWDUST. DIRT PILE IN BACKGROUND IS THE EDGE OF THE SUMMIT COUNTY LANDFILL. - Snake River Ditch, Headgate on north bank of Snake River, Dillon, Summit County, CO

  13. The Brain from Within.

    PubMed

    di Porzio, Umberto

    2016-01-01

    Functional magnetic resonance imaging (fMRI) provides a powerful way to visualize brain functions and observe brain activity in response to tasks or thoughts. It allows displaying brain damages that can be quantified and linked to neurobehavioral deficits. fMRI can potentially draw a new cartography of brain functional areas, allow us to understand aspects of brain function evolution or even breach the wall into cognition and consciousness. However, fMRI is not deprived of pitfalls, such as limitation in spatial resolution, poor reproducibility, different time scales of fMRI measurements and neuron action potentials, low statistical values. Thus, caution is needed in the assessment of fMRI results and conclusions. Additional diagnostic techniques based on MRI such as arterial spin labeling (ASL) and the measurement of diffusion tensor imaging (DTI) provide new tools to assess normal brain development or disruption of anatomical networks in diseases. A cutting edge of recent research uses fMRI techniques to establish a "map" of neural connections in the brain, or "connectome". It will help to develop a map of neural connections and thus understand the operation of the network. New applications combining fMRI and real time visualization of one's own brain activity (rtfMRI) could empower individuals to modify brain response and thus could enable researchers or institutions to intervene in the modification of an individual behavior. The latter in particular, as well as the concern about the confidentiality and storage of sensitive information or fMRI and lie detectors forensic use, raises new ethical questions. PMID:27375460

  14. The Brain from Within

    PubMed Central

    di Porzio, Umberto

    2016-01-01

    Functional magnetic resonance imaging (fMRI) provides a powerful way to visualize brain functions and observe brain activity in response to tasks or thoughts. It allows displaying brain damages that can be quantified and linked to neurobehavioral deficits. fMRI can potentially draw a new cartography of brain functional areas, allow us to understand aspects of brain function evolution or even breach the wall into cognition and consciousness. However, fMRI is not deprived of pitfalls, such as limitation in spatial resolution, poor reproducibility, different time scales of fMRI measurements and neuron action potentials, low statistical values. Thus, caution is needed in the assessment of fMRI results and conclusions. Additional diagnostic techniques based on MRI such as arterial spin labeling (ASL) and the measurement of diffusion tensor imaging (DTI) provide new tools to assess normal brain development or disruption of anatomical networks in diseases. A cutting edge of recent research uses fMRI techniques to establish a “map” of neural connections in the brain, or “connectome”. It will help to develop a map of neural connections and thus understand the operation of the network. New applications combining fMRI and real time visualization of one’s own brain activity (rtfMRI) could empower individuals to modify brain response and thus could enable researchers or institutions to intervene in the modification of an individual behavior. The latter in particular, as well as the concern about the confidentiality and storage of sensitive information or fMRI and lie detectors forensic use, raises new ethical questions. PMID:27375460

  15. A case of mistaken identity: CD11c-eYFP(+) cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells.

    PubMed

    Dando, Samantha J; Naranjo Golborne, Cecilia; Chinnery, Holly R; Ruitenberg, Marc J; McMenamin, Paul G

    2016-08-01

    Under steady-state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c-eYFP mice. We previously showed that these mice carry the Crb1(rd8) mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c-eYFP(+) cells within the CNS may be due to pathology associated with the Crb1(rd8) mutation. We generated CD11c-eYFP Crb1(wt/wt) mice and compared the distribution and immunophenotype of CD11c-eYFP(+) cells in CD11c-eYFP mice with and without the Crb1(rd8) mutation. The number and distribution of CD11c-eYFP(+) cells in the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice. CD11c-eYFP(+) cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood-brain barrier. CD11c-eYFP(+) cells within the retina and cerebral cortex of CD11c-eYFP Crb1(wt/wt) mice expressed CD11b, F4/80, CD115 and Iba-1, but not DC or antigen presentation markers, whereas CD11c-eYFP(+) cells within the choroid plexus and pia mater expressed CD11c, I-A/I-E, CD80, CD86, CD103, DEC205, CD8α and CD135. The immunophenotype of CD11c-eYFP(+) cells and microglia within the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice; however, CD11c and I-A/I-E expression was significantly increased in CD11c-eYFP Crb1(rd8/rd8) mice. This study demonstrates that the overwhelming majority of CNS CD11c-eYFP(+) cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016;64:1331-1349. PMID:27189804

  16. The Brain.

    ERIC Educational Resources Information Center

    Hubel, David H.

    1979-01-01

    This article on the brain is part of an entire issue about neurobiology and the question of how the human brain works. The brain as an intricate tissue composed of cells is discussed based on the current knowledge and understanding of its composition and structure. (SA)

  17. Brain Aneurysm

    MedlinePlus

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  18. [Brain imaging in early onset anorexia].

    PubMed

    Bargiacchi, A

    2014-05-01

    Structural and functional brain alterations in the structures involved in taste processing, emotions regulation and the reward system have been described in anorexia nervosa. The neurodevelopmental origin of this disorder has been recently discussed. In this article, brain-imaging data in early onset anorexia nervosa will be recalled and the relationship between clinical symptoms, normal brain maturation and brain imaging data in adolescents and adults will be discussed. PMID:24726667

  19. Left Brain. Right Brain. Whole Brain

    ERIC Educational Resources Information Center

    Farmer, Lesley S. J.

    2004-01-01

    As the United States student population is becoming more diverse, library media specialists need to find ways to address these distinctive needs. However, some of these differences transcend culture, touching on variations in the brain itself. Most people have a dominant side of the brain, which can affect their personality and learning style.…

  20. Bender Gestalt Performance of Normal Older Adults.

    ERIC Educational Resources Information Center

    Lacks, Patricia; Storandt, Martha

    1982-01-01

    Provides normative data on the Bender Gestalt Test (BGT) with a sample of 334 normal older adults. Showed that these older adults do not perform on the BGT in a manner that can be called brain damaged. Use of the cut-off score developed with younger persons appears appropriate. (Author)

  1. Brain Basics: Know Your Brain

    MedlinePlus

    ... fact sheet is a basic introduction to the human brain. It may help you understand how the healthy ... largest and most highly developed part of the human brain: it consists primarily of the cerebrum ( 2 ) and ...

  2. Raman molecular imaging of brain frozen tissue sections.

    PubMed

    Kast, Rachel E; Auner, Gregory W; Rosenblum, Mark L; Mikkelsen, Tom; Yurgelevic, Sally M; Raghunathan, Aditya; Poisson, Laila M; Kalkanis, Steven N

    2014-10-01

    Raman spectroscopy provides a molecular signature of the region being studied. It is ideal for neurosurgical applications because it is non-destructive, label-free, not impacted by water concentration, and can map an entire region of tissue. The objective of this paper is to demonstrate the meaningful spatial molecular information provided by Raman spectroscopy for identification of regions of normal brain, necrosis, diffusely infiltrating glioma and solid glioblastoma (GBM). Five frozen section tissues (1 normal, 1 necrotic, 1 GBM, and 2 infiltrating glioma) were mapped in their entirety using a 300-µm-square step size. Smaller regions of interest were also mapped using a 25-µm step size. The relative concentrations of relevant biomolecules were mapped across all tissues and compared with adjacent hematoxylin and eosin-stained sections, allowing identification of normal, GBM, and necrotic regions. Raman peaks and peak ratios mapped included 1003, 1313, 1431, 1585, and 1659 cm(-1). Tissue maps identified boundaries of grey and white matter, necrosis, GBM, and infiltrating tumor. Complementary information, including relative concentration of lipids, protein, nucleic acid, and hemoglobin, was presented in a manner which can be easily adapted for in vivo tissue mapping. Raman spectroscopy can successfully provide label-free imaging of tissue characteristics with high accuracy. It can be translated to a surgical or laboratory tool for rapid, non-destructive imaging of tumor margins. PMID:25038847

  3. Neurogenesis in the aging brain

    PubMed Central

    Galvan, Veronica; Jin, Kunlin

    2007-01-01

    Neurogenesis, or the birth of new neural cells, was thought to occur only in the developing nervous system and a fixed neuronal population in the adult brain was believed to be necessary to maintain the functional stability of adult brain circuitry. However, recent studies have demonstrated that neurogenesis does indeed continue into and throughout adult life in discrete regions of the central nervous systems (CNS) of all mammals, including humans. Although neurogenesis may contribute to the ability of the adult brain to function normally and be induced in response to cerebral diseases for self-repair, this nevertheless declines with advancing age. Understanding the basic biology of neural stem cells and the molecular and cellular regulation mechanisms of neurogenesis in young and aged brain will allow us to modulate cell replacement processes in the adult brain for the maintenance of healthy brain tissues and for repair of disease states in the elderly. PMID:18225461

  4. Normal Pressure Hydrocephalus

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Normal Pressure Hydrocephalus Information Page Synonym(s): Hydrocephalus - Normal Pressure Table ... Español Additional resources from MedlinePlus What is Normal Pressure Hydrocephalus? Normal pressure hydrocephalus (NPH) is an abnormal ...

  5. The Brains Behind the Brain.

    ERIC Educational Resources Information Center

    D'Arcangelo, Marcia

    1998-01-01

    Interviews with five neuroscientists--Martin Diamond, Pat Wolfe, Robert Sylwester, Geoffrey Caine, and Eric Jensen--disclose brain-research findings of practical interest to educators. Topics include brain physiology, environmental enrichment, memorization, windows of learning opportunity, brain learning capacity, attention span, student interest,…

  6. Examining the decomposed brain.

    PubMed

    MacKenzie, James Mackintosh

    2014-12-01

    Examination of the decomposed brain is a largely neglected area of forensic neuropathology. However, careful examination often yields valuable information that may assist in criminal proceedings. Decomposition encompasses the processes of autolysis, putrefaction, and decay. Most decomposed brains will be affected by both autolysis and putrefaction, resulting in a brain that may, at one end of the spectrum, be almost normal or, at the other end, pulpified, depending on the conditions in which the body remained after death and the postmortem interval. Naked eye examination may detect areas of hemorrhage and also guides appropriate sampling for histology. Histological appearances are often better than what would be predicted from the state of the brain. Histology often confirms macroscopic abnormalities and may also reveal other features such as ischemic injury. Silver staining demonstrates neuritic plaques, and immunocytochemistry for β-amyloid precursor protein and other molecules produces results comparable with those seen in well-preserved fixed brains. The usefulness of information derived from the examination of the decomposed brain in criminal proceedings is illustrated with 6 case reports drawn from the author's own practice. PMID:25384305

  7. Chernobyl Birds Have Smaller Brains

    PubMed Central

    Møller, Anders Pape; Bonisoli-Alquati, Andea; Rudolfsen, Geir; Mousseau, Timothy A.

    2011-01-01

    Background Animals living in areas contaminated by radioactive material from Chernobyl suffer from increased oxidative stress and low levels of antioxidants. Therefore, normal development of the nervous system is jeopardized as reflected by high frequencies of developmental errors, reduced brain size and impaired cognitive abilities in humans. Alternatively, associations between psychological effects and radiation have been attributed to post-traumatic stress in humans. Methodology/Principal Finding Here we used an extensive sample of 550 birds belonging to 48 species to test the prediction that even in the absence of post-traumatic stress, there is a negative association between relative brain size and level of background radiation. We found a negative association between brain size as reflected by external head volume and level of background radiation, independent of structural body size and body mass. The observed reduction in brain size in relation to background radiation amounted to 5% across the range of almost a factor 5,000 in radiation level. Species differed significantly in reduction in brain size with increasing background radiation, and brain size was the only morphological character that showed a negative relationship with radiation. Brain size was significantly smaller in yearlings than in older individuals. Conclusions/Significance Low dose radiation can have significant effects on normal brain development as reflected by brain size and therefore potentially cognitive ability. The fact that brain size was smaller in yearlings than in older individuals implies that there was significant directional selection on brain size with individuals with larger brains experiencing a viability advantage. PMID:21390202

  8. Medical Perspectives on Brain Damage and Development. Revised.

    ERIC Educational Resources Information Center

    McCrae, Marcia Q.

    The author describes damage and normal development of the brain, as well as assessment and intervention with brain-damaged children. After a brief introduction on the complex and delicate process of brain development and a review of incidence, aspects of etiology such as genetic and postnatal causes are discussed. Brain development is examined…

  9. PDT-induced apoptosis in brain tissue in vivo: a retrospective study

    NASA Astrophysics Data System (ADS)

    Lilge, Lothar D.; Portnoy, Michelle; Wilson, Brian C.

    1999-07-01

    The apoptotic response of normal brain and intracranial VX2 tumor following photodynamic therapy mediated by five different photodynamic drugs, Photofrin, ALA, AlClPc, SnET2 and mTHPC, was evaluated in a preliminary retrospective analysis. Rabbit brain, with or without tumor, was treated by PDT with interstitial light delivery. Histological sections at 24 h post PDT were assessed by the TUNEL assay. Confocal fluorescence microscopy was used to determine the total apoptotic cell count and the spatial distribution of apoptotic bodies within the tissue. The data were confirmed qualitatively by light microscopy on adjacent H&E-stained sections. Light-only and drug-only controls produced background levels. The highest apoptotic count was seen with Photofrin. The counts in AlClPc-treated animals were not above the background level, while the other 3 photosensitizers gave intermediate levels. With some, but not all, drugs the spatial distribution of apoptotic bodies correlated well with the light fluence distribution. Apoptosis was seen outside the zone of frank coagulative necrosis. There was not apparent drug-dose dependency at the relatively high doses used here. The retrospective nature of this study did not allow optimization of the treatment parameters. Nevertheless, the findings have potentially significant implications, both for understanding the mechanisms of apoptosis in brain tissue and for improving the clinical use of PDT for treatment of patients with malignant brain tumors.

  10. Impact of diabetes in blood-testis and blood-brain barriers: resemblances and differences.

    PubMed

    Alves, Marco G; Oliveira, Pedro F; Socorro, Silvia; Moreira, Paula I

    2012-11-01

    Blood-tissue barriers prevent an uncontrolled exchange of large molecules between adjacent but metabolically separated compartments. There are several known barriers and two of the most important and tightest blood-tissue barriers are the blood-testis barrier (BTB) and the blood-brain barrier (BBB). Under normal conditions these barriers, formed by tight junctions between adjacent cells, control the entry of substances and metabolites. However, hyperglycemia and other diabetes-related complications, such as hypertension, impair the function of these biological barriers with dramatic consequences. Although both, BBB and BTB, are responsible for the maintenance of different biological processes, they have some remarkable similarities not always explored when looking at metabolic-related diseases such as diabetes. These barriers possess their own glucose sensing machinery, suffer a tied hormonal control and have specific mechanisms to counteract hyper- and hypoglycemia. In BBB and BTB the insulin signaling is also distinct from other tissues and organs thus evidencing their importance in protecting against or exacerbating the effects of diabetes on glucose metabolism. The control of glucose and lactate levels in brain and testis highlights the role of these barriers in protecting against peripheral glucose and lactate fluctuations that occur in the diabetic individual. We review the role of BBB and BTB in the control of glucose and metabolic dysfunction caused by diabetes in the brain and seminiferous epithelium. Gaining a better understanding of the molecular mechanisms through which glucose metabolism disrupts BBB and BTB function may highlight new opportunities for the treatment of diabetic complications in brain and male reproductive function. PMID:22934551

  11. Dosimetric Comparison Between 3DCRT and IMRT Using Different Multileaf Collimators in the Treatment of Brain Tumors

    SciTech Connect

    Ding Meisong Newman, Francis M.S.; Chen Changhu; Stuhr, Kelly; Gaspar, Laurie E.

    2009-04-01

    We investigated the differences between 3-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT), and the impact of collimator leaf-width on IMRT plans for the treatment of nonspherical brain tumors. Eight patients treated by 3DCRT with Novalis were selected. We developed 3 IMRT plans with different multileaf collimators (Novalis m3, Varian MLC-120, and Varian MLC-80) with the same treatment margins, number of beams, and gantry positions as in the 3DCRT treatment plans. Treatment planning utilized the BrainLAB treatment planning system. For each patient, the dose constraints and optimization parameters remained identical for all plans. The heterogeneity index, the percentage target coverage, critical structures, and normal tissue volumes receiving 50% of the prescription dose were calculated to compare the dosimetric difference. Equivalent uniform dose (EUD) and tumor control probability (TCP) were also introduced to evaluate the radiobiological effect for different plans. We found that IMRT significantly improved the target dose homogeneity compared to the 3DCRT. However, IMRT showed the same radiobiological effect as 3DCRT. For the brain tumors adjacent to (or partially overlapping with) critical structures, IMRT dramatically spared the volume of the critical structures to be irradiated. In IMRT plans, the smaller collimator leaf width could reduce the volume of critical structures irradiated to the 50% level for those partially overlapping with the brain tumors. For relatively large and spherical brain tumors, the smaller collimator leaf widths give no significant benefit.

  12. 38. VIEW OF COTTRELL MAGNETIC IMPULSE GENERATOR ADJACENT TO SIX ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. VIEW OF COTTRELL MAGNETIC IMPULSE GENERATOR ADJACENT TO SIX GAP ROTARY RECTIFIER. THIS UNIT GENERATED A MAGNETIC PULSE WHICH WAS TRANSMITTED TO THE COLLECTION PLATES IN THE ELECTROSTATIC PRECIPITATOR CHAMBER. THESE PERIODIC PULSES VIBRATE THE PLATES AND CAUSE PRECIPITATED ARTICLES OF SMOKE AND FLY ASH TO FALL TO THE BOTTOM OF THE PRECIPITATOR CHAMBER. - New York, New Haven & Hartford Railroad, Cos Cob Power Plant, Sound Shore Drive, Greenwich, Fairfield County, CT

  13. Conference room 211, adjacent to commander's quarters, with vault door ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Conference room 211, adjacent to commander's quarters, with vault door at right. Projection area at center is equipped with automatic security drapes. Projection room uses a 45 degree mirror to reflect the image onto the frosted glass screen. Door on far left leads to display area senior battle staff viewing bridge, and the commander's quarters - March Air Force Base, Strategic Air Command, Combat Operations Center, 5220 Riverside Drive, Moreno Valley, Riverside County, CA

  14. Epithelial dysplasia immediately adjacent to oral squamous cell carcinomas.

    PubMed

    Wright, A; Shear, M

    1985-08-01

    A number of workers have attempted to identify dysplastic features which may be predictors of malignant change, by prospective studies of dysplastic lesions. In the present study we have looked at dysplastic changes immediately adjacent to established squamous carcinomas in an attempt to determine whether any predictors can be identified in this way. Eighty cases were included in the study for whom information on tobacco usage was known. Clinical details were recorded. Histological features in epithelium immediately adjacent to the carcinoma were studied in representative sections. Eighteen specific histological characteristics were noted as present or absent. Data were transferred by Conversational Monitoring System (CMS) terminal, processed and analyzed by the Statistical Analysis System (SAS) Computer package. Only 8 patients were non-smokers (10%). Dysplastic changes in adjacent epithelium were frequently multicentric. Changes appear to occur first in the basal layer in the form of disturbance of polarity or basal cell hyperplasia, while other dysplastic features are absent. The feature referred to as basal cell hyperplasia appears, in fact, to represent disturbed epithelial maturation. In 80% of cases increased nucleo-cytoplasmic ratio appears to result from a decrease in cytoplasmic volume rather than increased nuclear size. A defect in RNA synthesis may be a factor. A sharp decrease in inflammatory cells in the lamina propria of adjacent epithelium, compared with that of the carcinoma, was observed. Russell bodies were noted in 5 of the 8 lesions in non-smokers (63%) and in 16 of 72 lesions in smokers (22%) (p less than 0.001; Chi2 17.65). PMID:3928850

  15. 20. Interior view of fuel storage pit or vault adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Interior view of fuel storage pit or vault adjacent to Test Cell 9 in Component Test Laboratory (T-27), looking west. Photograph shows upgraded instrumentation, piping, tanks, and technological modifications installed in 1997-99 to accommodate component testing requirements for the Atlas V missile. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  16. FMRI evidence of acupoints specificity in two adjacent acupoints.

    PubMed

    Liu, Hua; Xu, Jian-Yang; Li, Lin; Shan, Bao-Ci; Nie, Bin-Bin; Xue, Jing-Quan

    2013-01-01

    Objectives. Acupoint specificity is the foundation of acupuncture treatment. The aim of this study is to investigate whether the acupoint specificity exists in two adjacent acupoints. Design and Setting. Two adjacent real acupoints, LR3 (Taichong) and ST44 (Neiting), and a nearby nonacupoint were selected. Thirty-three health volunteers were divided into three groups in random order, and each group only received acupuncture at one of the three points. While they received acupuncture, fMRI scan was performed. Results. The common cerebral activated areas responding to LR3 and ST44 included the contralateral primary somatosensory area (SI) and ipsilateral cerebellum. Acupuncture at LR3 specifically activated contralateral middle occipital gyrus, ipsilateral medial frontal gyrus, superior parietal lobe, middle temporal gyrus, rostral anterior cingulate cortex (rACC), lentiform nucleus, insula, and contralateral thalamus. Stimulation at ST44 selectively activated ipsilateral secondary somatosensory area (SII), contralateral middle frontal gyrus, inferior frontal gyrus, lingual gyrus, lentiform nucleus, and bilateral posterior cingulate cortex (PCC). Conclusions. Acupuncture at adjacent acupoints elicits distinct cerebral activation patterns, and those specific patterns might be involved in the mechanism of the specific therapeutic effects of different acupoints. PMID:23762172

  17. Osteochondroma of the hip with adjacent bursal chondromatosis.

    PubMed

    Gould, Elaine S; Baker, Kevin S; Huang, Mingqian; Khan, Fazel; Hoda, Syed

    2014-12-01

    It is well established that irregular bursae can form adjacent to an osteochondroma (bursa exostotica) as a result of mechanical irritation and that these bursae can be complicated by inflammation, hemorrhage, or infection. Bursal chondromatosis is a rare complication, with only seven published cases in the literature according to our searches. We present the case of a 53-year-old female who presented with slowly progressive left hip/thigh pain and was found to have an osteochondroma arising from the lesser trochanter with numerous ossified bodies in the adjacent soft tissues. MRI demonstrated osteochondral bodies in a fluid-filled bursa adjacent to the osteochondroma, with several of the bodies noted to be fairly displaced from the osteochondroma cartilaginous cap. At surgery, the osteochondroma was removed and numerous bodies of varying sizes were excised, some of which were noted to be adherent to the bursal lining and others that were separated/distant from the cartilage cap. The question arises as to whether this process represents bursal chondromatosis resulting from benign neoplasia of cells lining the abnormal bursa, "cartilage shedding" from the osteochondromatous cap, or both. The purpose in presenting this case is to introduce a rare complication of an osteochondroma, demonstrate that soft tissue calcification and osteochondral densities displaced from an underlying osteochondroma are not always the result of sarcomatous degeneration, and provide support for the theory that cells lining a bursa in a nonphysiologic location can undergo benign neoplasia with subsequent formation of osteochondral bodies. PMID:25001874

  18. Using BRDFs for accurate albedo calculations and adjacency effect corrections

    SciTech Connect

    Borel, C.C.; Gerstl, S.A.W.

    1996-09-01

    In this paper the authors discuss two uses of BRDFs in remote sensing: (1) in determining the clear sky top of the atmosphere (TOA) albedo, (2) in quantifying the effect of the BRDF on the adjacency point-spread function and on atmospheric corrections. The TOA spectral albedo is an important parameter retrieved by the Multi-angle Imaging Spectro-Radiometer (MISR). Its accuracy depends mainly on how well one can model the surface BRDF for many different situations. The authors present results from an algorithm which matches several semi-empirical functions to the nine MISR measured BRFs that are then numerically integrated to yield the clear sky TOA spectral albedo in four spectral channels. They show that absolute accuracies in the albedo of better than 1% are possible for the visible and better than 2% in the near infrared channels. Using a simplified extensive radiosity model, the authors show that the shape of the adjacency point-spread function (PSF) depends on the underlying surface BRDFs. The adjacency point-spread function at a given offset (x,y) from the center pixel is given by the integral of transmission-weighted products of BRDF and scattering phase function along the line of sight.

  19. Noninvasive magnetic resonance spectroscopic imaging biomarkers to predict the clinical grade of pediatric brain tumors.

    PubMed

    Astrakas, Loukas G; Zurakowski, David; Tzika, A Aria; Zarifi, Maria K; Anthony, Douglas C; De Girolami, Umberto; Tarbell, Nancy J; Black, Peter McLaren

    2004-12-15

    The diagnosis and therapy of childhood brain tumors, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures, which limits diagnostic biopsy. Also, although new prognostic biomarkers identified by molecular analysis or DNA microarray gene profiling are promising, they too depend on invasive biopsy. Here, we test the hypothesis that combining information from biologically important intracellular molecules (biomarkers), noninvasively obtained by proton magnetic resonance spectroscopic imaging, will increase the diagnostic accuracy in determining the clinical grade of pediatric brain tumors. We evaluate the proton magnetic resonance spectroscopic imaging exams for 66 children with brain tumors. The intracellular biomarkers for choline-containing compounds (Cho), N-acetylaspartate, total creatine, and lipids and/or lactate were measured at the highest Cho region and normalized to the surrounding healthy tissue total creatine. Neuropathological grading was done with WHO criteria. Normalized Cho and lipids and/or lactate were elevated in high-grade (n = 23) versus low-grade (n = 43) tumors, which multiple logistic regression confirmed are independent predictors of tumor grade (for Cho, odds ratio 24.8, P < 0.001; and for lipids and/or lactate, odds ratio 4.4, P < 0.001). A linear combination of normalized Cho and lipids and/or lactate that maximizes diagnostic accuracy was calculated by maximizing the area under the receiver operating characteristic curve. Proton magnetic resonance spectroscopic imaging, although not a proxy for histology, provides noninvasive, in vivo biomarkers for predicting clinical grades of pediatric brain tumors. PMID:15623597

  20. Technique for sparing previously irradiated critical normal structures in salvage proton craniospinal irradiation

    PubMed Central

    2013-01-01

    Background Cranial reirradiation is clinically appropriate in some cases but cumulative radiation dose to critical normal structures remains a practical concern. The authors developed a simple technique in 3D conformal proton craniospinal irradiation (CSI) to block organs at risk (OAR) while minimizing underdosing of adjacent target brain tissue. Methods Two clinical cases illustrate the use of proton therapy to provide salvage CSI when a previously irradiated OAR required sparing from additional radiation dose. The prior radiation plan was coregistered to the treatment planning CT to create a planning organ at risk volume (PRV) around the OAR. Right and left lateral cranial whole brain proton apertures were created with a small block over the PRV. Then right and left lateral “inverse apertures” were generated, creating an aperture opening in the shape of the area previously blocked and blocking the area previously open. The inverse aperture opening was made one millimeter smaller than the original block to minimize the risk of dose overlap. The inverse apertures were used to irradiate the target volume lateral to the PRV, selecting a proton beam range to abut the 50% isodose line against either lateral edge of the PRV. Together, the 4 cranial proton fields created a region of complete dose avoidance around the OAR. Comparative photon treatment plans were generated with opposed lateral X-ray fields with custom blocks and coplanar intensity modulated radiation therapy optimized to avoid the PRV. Cumulative dose volume histograms were evaluated. Results Treatment plans were developed and successfully implemented to provide sparing of previously irradiated critical normal structures while treating target brain lateral to these structures. The absence of dose overlapping during irradiation through the inverse apertures was confirmed by film. Compared to the lateral X-ray and IMRT treatment plans, the proton CSI technique improved coverage of target brain tissue

  1. Functional angiocoupling between follicles and adjacent corpus luteum in heifers.

    PubMed

    Ginther, O J; Siddiqui, M A R; Baldrighi, J M

    2016-07-15

    In single ovulating cattle, ipsilateral versus contralateral interovarian relationships refer to a dominant follicle (DF) and CL in the same versus opposite ovaries. The ipsilateral relationship consists of the DF-CL and the devoid (no DF or CL) intraovarian pattern, and the contralateral relationship consists of the DF pattern and the CL pattern. The DF-CL pattern involves positive effects on both the DF and CL when adjacent (≤3-mm apart) versus separated as follows: greater diameter of DF (e.g., 10.5 ± 0.4 vs. 9.0 ± 0.4 mm), greater percentage of the DF wall with color Doppler signals of blood flow (40.2% ± 2.0% vs. 24.5% ± 1.9%), greater cross-sectional area of the CL (2.2 ± 0.1 vs. 1.8 ± 0.2 cm(2)), and greater percentage of the entire CL with blood flow signals (51.8% ± 1.2% vs. 42.5% ± 3.1%). Additional examples of positive coupling are (1) future DF on Day 0 (day of ovulation) is closer to the CL than the future largest subordinate and (2) diameter of growing follicles on Day 0 and the growth rate on Days 0 to 2 are greater for follicles that are adjacent than separated from the CL. An example of a negative intraovarian effect is decreasing diameter and loss of future DF status of a largest follicle when adjacent to a regressing CL. The impact of the continuity of ovarian angioarchitecture during the periovulatory follicular wave was exemplified in 17 of 18 waves by conversion of an ovary with only the preovulatory follicle to the postovulatory DF-CL pattern. Functional angiocoupling from commonality in angioarchitecture of the DF and adjacent CL would account for both the positive two-way coupling between DF and CL during the luteal phase and the negative effect of a regressing CL on an adjacent follicle during luteolysis. PMID:27056414

  2. On (ab)normality: Einstein's fusiform gyrus.

    PubMed

    Weiner, Kevin S

    2015-03-01

    Recently, Hines (2014) wrote an evocative paper challenging findings from both histological and morphological studies of Einstein's brain. In this discussion paper, I extend Hines' theoretical point and further discuss how best to determine 'abnormal' morphology. To do so, I assess the sulcal patterning of Einstein's fusiform gyrus (FG) for the first time. The sulcal patterning of the FG was unconsidered in prior studies because the morphological features of the mid-fusiform sulcus have only been clarified recently. On the one hand, the sulcal patterning of Einstein's FG is abnormal relative to averages of 'normal' brains generated from two independent datasets (N = 39 and N = 15, respectively). On the other hand, within the 108 hemispheres used to make these average brains, it is not impossible to find FG sulcal patterns that resemble those of Einstein. Thus, concluding whether a morphological pattern is normal or abnormal heavily depends on the chosen analysis method (e.g. group average vs. individual). Such findings question the functional meaning of morphological 'abnormalities' when determined by comparing an individual to an average brain or average frequency characteristics. These observations are not only important for analyzing a rare brain such as that of Einstein, but also for comparing macroanatomical features between typical and atypical populations. PMID:25562419

  3. Is My Penis Normal?

    MedlinePlus

    ... I Help a Friend Who Cuts? Is My Penis Normal? KidsHealth > For Teens > Is My Penis Normal? Print A A A Text Size en ... any guy who's ever worried about whether his penis is a normal size. There's a fairly wide ...

  4. Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury.

    PubMed

    Welch, Robert D; Ayaz, Syed I; Lewis, Lawrence M; Unden, Johan; Chen, James Y; Mika, Valerie H; Saville, Ben; Tyndall, Joseph A; Nash, Marshall; Buki, Andras; Barzo, Pal; Hack, Dallas; Tortella, Frank C; Schmid, Kara; Hayes, Ronald L; Vossough, Arastoo; Sweriduk, Stephen T; Bazarian, Jeffrey J

    2016-01-15

    Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70-0.88) for GFAP, 0.80 (0.71-0.89) for UCH-L1, and 0.75 (0.65-0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice. PMID:26467555

  5. Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury

    PubMed Central

    Ayaz, Syed I.; Lewis, Lawrence M.; Unden, Johan; Chen, James Y.; Mika, Valerie H.; Saville, Ben; Tyndall, Joseph A.; Nash, Marshall; Buki, Andras; Barzo, Pal; Hack, Dallas; Tortella, Frank C.; Schmid, Kara; Hayes, Ronald L.; Vossough, Arastoo; Sweriduk, Stephen T.; Bazarian, Jeffrey J.

    2016-01-01

    Abstract Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70–0.88) for GFAP, 0.80 (0.71–0.89) for UCH-L1, and 0.75 (0.65–0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice. PMID:26467555

  6. Normal Pressure Hydrocephalus (NPH)

    MedlinePlus

    ... Is Dementia Types of Dementia Chronic Traumatic Encephalopathy (CTE) Creutzfeldt-Jakob Disease Dementia with Lewy Bodies Down ... Research Traumatic Brain Injury and Chronic Traumatic Encephalopathy (CTE) Awardees Year Researcher Study Name 2015 Jesse Mez ...

  7. Normal pressure hydrocephalus (NPH)

    MedlinePlus

    ... usually surgery to place a tube called a shunt that routes the excess CSF out of the brain ventricles. This is called a ventricoperitoneal shunt . Outlook (Prognosis) Without treatment, symptoms often get worse ...

  8. Brain tumor stem cells.

    PubMed

    Palm, Thomas; Schwamborn, Jens C

    2010-06-01

    Since the end of the 'no-new-neuron' theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies. PMID:20370314

  9. Do normal hips dislocate?

    PubMed

    Alshameeri, Zeiad; Rehm, Andreas

    2014-11-01

    There have been a small number of case reports describing late normal-hip dislocations in children who were later diagnosed with developmental dysplasia of the hip. Here, we contest the assumption that normal hips can dislocate. We argue that (as in our case) the ultrasound scans in all published case reports on late dislocated normal hips did not show results that were entirely normal and therefore, so far, there has been no convincing evidence of a dislocation of a normal hip. We also want to highlight the importance of meticulous ultrasound and clinical assessments of high-risk children by an experienced orthopaedic surgeon. PMID:25144883

  10. Correlation between Focal Nodular Low Signal Changes in Hoffa's Fat Pad Adjacent to Anterior Femoral Cartilage and Focal Cartilage Defect Underlying This Region and Its Possible Implication

    PubMed Central

    Ng, Wuey Min

    2016-01-01

    Purpose. This study investigates the association between focal nodular mass with low signal in Hoffa's fat pad adjacent to anterior femoral cartilage of the knee (FNMHF) and focal cartilage abnormality in this region. Method. The magnetic resonance fast imaging employing steady-state acquisition sequence (MR FIESTA) sagittal and axial images of the B1 and C1 region (described later) of 148 patients were independently evaluated by two reviewers and categorized into four categories: normal, FNMHF with underlying focal cartilage abnormality, FNMHF with normal cartilage, and cartilage abnormality with no FNMHF. Results. There was a significant association (p = 0.00) between FNMHF and immediate adjacent focal cartilage abnormality with high interobserver agreement. The absence of focal nodular lesions next to the anterior femoral cartilage has a very high negative predictive value for chondral injury (97.8%). Synovial biopsy of focal nodular lesion done during arthroscopy revealed some fibrocollagenous tissue and no inflammatory cells. Conclusion. We postulate that the FNMHF adjacent to the cartilage defects is a form of normal healing response to the cartilage damage. One patient with FHMHF and underlying cartilage abnormality was rescanned six months later. In this patient, the FNMHF disappeared and normal cartilage was observed in the adjacent region which may support this theory. PMID:27213085

  11. Groundwater recharge to the Gulf Coast aquifer system in Montgomery and Adjacent Counties, Texas

    USGS Publications Warehouse

    Oden, Timothy D.; Delin, Geoffrey N.

    2013-01-01

    Simply stated, groundwater recharge is the addition of water to the groundwater system. Most of the water that is potentially available for recharging the groundwater system in Montgomery and adjacent counties in southeast Texas moves relatively rapidly from land surface to surface-water bodies and sustains streamflow, lake levels, and wetlands. Recharge in southeast Texas is generally balanced by evapotranspiration, discharge to surface waters, and the downward movement of water into deeper parts of the groundwater system; however, this balance can be altered locally by groundwater withdrawals, impervious surfaces, land use, precipitation variability, or climate, resulting in increased or decreased rates of recharge. Recharge rates were compared to the 1971–2000 normal annual precipitation measured Cooperative Weather Station 411956, Conroe, Tex.

  12. Reconnaissance of the Hot Springs Mountains and adjacent areas, Churchill County, Nevada

    SciTech Connect

    Voegtly, N.E.

    1981-01-01

    A geological reconnaissance of the Hot Springs Mountains and adjacent areas, which include parts of the Brady-Hazen and the Stillwater-Soda Lake Known Geothermal Resource Areas (KGRA's), resulted in a reinterpretation of the nature and location of some Basin and Range faults. This reconnaissance took place during June-December 1975. In addition, the late Cenozoic stratigraphy has been modified, chiefly on the basis of radiometric dates of volcanic rocks by US Geological Survey personnel and others. The Hot Springs Mountains are in the western part of the Basin and Range province, which is characterized by east-west crustal extension and associated normal faulting. In the surrounding Trinity, West Humboldt, Stillwater, and Desert Mountains, Cenozoic rocks overlie basement rocks of Paleozoic and Mesozoic age. A similar relation is inferred in the Hot Springs Mountains. Folding and faulting have taken place from the late Tertiary to the present.

  13. Bicervical Normal Uterus with Normal Vagina

    PubMed Central

    Okeke, CE; Anele, TI; Onyejelam, CC

    2014-01-01

    This is a report of the form of uterine anomaly involving a dual cervical canal in a side-by-side disposition with normal uterine cavity and normal vagina. It portrays a form of congenital uterine anomaly not explicable by the existing classical theory of mullerian anomalies. However, there has been a proposed reclassification of mullerian anomalies, which includes this type of anomaly under Type IIIc. The patient was a 31-year-old woman being managed for “secondary infertility.” To report a case of uterine anomaly that is not explicable by the existing classical theory of mullerian anomalies. To the best of our knowledge, only few cases of bicervical normal uterus with normal vagina exist in the literature; one of the cases had an anterior-posterior disposition. This form of uterine abnormality is not explicable by the existing classical theory of mullerian anomalies and suggests that a complex interplay of events beyond the classical postulate gives rise to the female genital tract. PMID:25364608

  14. Impact of adjacent land use on coastal wetland sediments.

    PubMed

    Karstens, Svenja; Buczko, Uwe; Jurasinski, Gerald; Peticzka, Robert; Glatzel, Stephan

    2016-04-15

    Coastal wetlands link terrestrial with marine ecosystems and are influenced from both land and sea. Therefore, they are ecotones with strong biogeochemical gradients. We analyzed sediment characteristics including macronutrients (C, N, P, K, Mg, Ca, S) and heavy metals (Mn, Fe, Cu, Zn, Al, Co, Cr, Ni) of two coastal wetlands dominated by Phragmites australis at the Darss-Zingst Bodden Chain, a lagoon system at the Southern Baltic Sea, to identify the impact of adjacent land use and to distinguish between influences from land or sea. In the wetland directly adjacent to cropland (study site Dabitz) heavy metal concentrations were significantly elevated. Fertilizer application led to heavy metal accumulation in the sediments of the adjacent wetland zones. In contrast, at the other study site (Michaelsdorf), where the hinterland has been used as pasture, heavy metal concentrations were low. While the amount of macronutrients was also influenced by vegetation characteristics (e.g. carbon) or water chemistry (e.g. sulfate), the accumulation of heavy metals is regarded as purely anthropogenic influence. A principal component analysis (PCA) based on the sediment data showed that the wetland fringes of the two study sites are not distinguishable, neither in their macronutrient status nor in their concentrations of heavy metals, whereas the interior zones exhibit large differences in terms of heavy metal concentrations. This suggests that seaside influences are minor compared to influences from land. Altogether, heavy metal concentrations were still below national precautionary and action values. However, if we regard the macronutrient and heavy metal concentrations in the wetland fringes as the natural background values, an accumulation of trace elements from agricultural production in the hinterland is apparent. Thus, coastal wetlands bordering croplands may function as effective pollutant buffers today, but the future development has to be monitored closely to avoid

  15. Brain Diseases

    MedlinePlus

    ... know what causes some brain diseases, such as Alzheimer's disease. The symptoms of brain diseases vary widely depending on the specific problem. In some cases, damage is permanent. In other cases, treatments such as surgery, medicines, or physical therapy can correct the source of the problem or ...

  16. Exophytic Atheroma Mimicking Papillary Fibroelastoma Adjacent to the Aortic Valve.

    PubMed

    Cho, Tomoki; Tokunaga, Shigehiko; Yasuda, Shota; Izubuchi, Ryo; Masuda, Munetaka

    2015-09-01

    Follow-up echocardiography in a 69-year-old man with alcoholic cardiomyopathy showed a mass above the aortic valve near the left coronary ostium. Transesophageal echocardiography and computed tomography suggested a papillary fibroelastoma with a high risk of embolism. At operation we found an exophytic atheroma adjacent to the left coronary artery orifice. The atheroma was removed, and the patient made an uneventful recovery. We describe this very rare case of an exophytic atheroma mimicking a papillary fibroelastoma situated at the left coronary orifice. PMID:26354633

  17. Compression of adjacent anatomical structures by pulmonary artery dilation.

    PubMed

    Dakkak, Wael; Tonelli, Adriano R

    2016-06-01

    Pulmonary hypertension is the commonest condition leading to dilated pulmonary artery. We describe three different types of compression of adjacent anatomical structures by dilated pulmonary arteries. We included involvement of the left main coronary artery, left recurrent laryngeal nerve and tracheobronchial tree. Compression of these structures can cause major complications such as myocardial ischemia, hoarseness and major airway stenosis. We present a case for each scenario and review the literature for each of these complications, focusing on patients' characteristics and contemporary management. PMID:26898826

  18. Synthesis of a Molecule with Four Different Adjacent Pnictogens.

    PubMed

    Hinz, Alexander; Schulz, Axel; Villinger, Alexander

    2016-08-22

    The synthesis of a molecule containing four adjacent different pnictogens was attempted by conversion of a Group 15 allyl analogue anion [Mes*NAsPMes*](-) (Mes*=2,4,6-tri-tert-butylphenyl) with antimony(III) chloride. A suitable precursor is Mes*N(H)AsPMes* (1) for which several syntheses were investigated. The anions afforded by deprotonation of Mes*N(H)AsPMes* were found to be labile and, therefore, salts could not be isolated. However, the in situ generated anions could be quenched with SbCl3 , yielding Mes*N(SbCl2 )AsPMes* (4). PMID:27377437

  19. Stereoselective Organocatalytic Synthesis of Oxindoles with Adjacent Tetrasubstituted Stereocenters.

    PubMed

    Engl, Oliver D; Fritz, Sven P; Wennemers, Helma

    2015-07-01

    Oxindoles with adjacent tetrasubstituted stereocenters were obtained in high yields and stereoselectivities by organocatalyzed conjugate addition reactions of monothiomalonates (MTMs) to isatin-derived N-Cbz ketimines. The method requires only a low catalyst loading (2 mol %) and proceeds under mild reaction conditions. Both enantiomers are accessible in good yields and excellent stereoselectivities by using either Takemoto's catalyst or a cinchona alkaloid derivative. The synthetic methodology allowed establishment of a straightforward route to derivatives of the gastrin/cholecystokinin-B receptor antagonist AG-041R. PMID:26033441

  20. Interaction of Cracks Between Two Adjacent Indents in Glass

    NASA Technical Reports Server (NTRS)

    Choi, S. R.; Salem, J. A.

    1993-01-01

    Experimental observations of the interaction behavior of cracks between two adjacent indents were made using an indentation technique in soda-lime glass. It was specifically demonstrated how one indent crack initiates and propagates in the vicinity of another indent crack. Several types of crack interactions were examined by changing the orientation and distance of one indent relative to the other. It was found that the residual stress field produced by elastic/plastic indentation has a significant influence on controlling the mode of crack interaction. The interaction of an indent crack with a free surface was also investigated for glass and ceramic specimens.

  1. CLOUD PEAK PRIMITIVE AREA AND ADJACENT AREAS, WYOMING.

    USGS Publications Warehouse

    Kiilsgaard, Thor H.; Patten, Lowell L.

    1984-01-01

    The results of a mineral survey of the Cloud Peak Primitive Area and adjacent areas in Wyoming indicated little promise for the occurrence of mineral resources. There are some prospect workings, particularly in the northern part of the area, but in none of them were there indications that ore had been mined. Samples from the workings, from nearby rocks and sediments from streams that drain the area did not yield any metal values of significance. The crystalline rocks that underlie the area do not contain oil and gas or coal, products that are extracted from the younger rocks that underlie basins on both sides of the study area.

  2. Genetics and molecular biology of brain calcification.

    PubMed

    Deng, Hao; Zheng, Wen; Jankovic, Joseph

    2015-07-01

    Brain calcification is a common neuroimaging finding in patients with neurological, metabolic, or developmental disorders, mitochondrial diseases, infectious diseases, traumatic or toxic history, as well as in otherwise normal older people. Patients with brain calcification may exhibit movement disorders, seizures, cognitive impairment, and a variety of other neurologic and psychiatric symptoms. Brain calcification may also present as a single, isolated neuroimaging finding. When no specific cause is evident, a genetic etiology should be considered. The aim of the review is to highlight clinical disorders associated with brain calcification and provide summary of current knowledge of diagnosis, genetics, and pathogenesis of brain calcification. PMID:25906927

  3. Comparative quantitative study of 'signature' pathological lesions in the hippocampus and adjacent gyri of 12 neurodegenerative disorders.

    PubMed

    Armstrong, Richard A; Cairns, Nigel J

    2015-10-01

    The hippocampus (HC) and adjacent gyri are implicated in dementia in several neurodegenerative disorders. To compare HC pathology among disorders, densities of 'signature' pathological lesions were measured at a standard location in eight brain regions of 12 disorders. Principal components analysis of the data suggested that the disorders could be divided into three groups: (1) Alzheimer's disease (AD), Down's syndrome (DS), sporadic Creutzfeldt-Jakob disease, and variant Creutzfeldt-Jakob disease in which either β-amyloid (Aβ) or prion protein deposits were distributed in all sectors of the HC and adjacent gyri, with high densities being recorded in the parahippocampal gyrus and subiculum; (2) Pick's disease, sporadic frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions, and neuronal intermediate filament inclusion disease in which relatively high densities of neuronal cytoplasmic inclusions were present in the dentate gyrus (DG) granule cells; and (3) Parkinson's disease dementia, dementia with Lewy bodies, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy in which densities of signature lesions were relatively low. Variation in density of signature lesions in DG granule cells and CA1 were the most important sources of neuropathological variation among disorders. Hence, HC and adjacent gyri are differentially affected in dementia reflecting either variation in vulnerability of hippocampal neurons to specific molecular pathologies or in the spread of pathological proteins to the HC. Information regarding the distribution of pathology could ultimately help to explain variations in different cognitive domains, such as memory, observed in various disorders. PMID:25929331

  4. Image registration using a weighted region adjacency graph

    NASA Astrophysics Data System (ADS)

    Al-Hasan, Muhannad; Fisher, Mark

    2005-04-01

    Image registration is an important problem for image processing and computer vision with many proposed applications in medical image analysis.1, 2 Image registration techniques attempt to map corresponding features between two images. The problem is particularly difficult as anatomy is subject to elastic deformations. This paper considers this problem in the context of graph matching. Firstly, weighted Region Adjacency Graphs (RAGs) are constructed from each image using an approach based on watershed saliency. 3 The vertices of the RAG represent salient regions in the image and the (weighted) edges represent the relationship (bonding) between each region. Correspondences between images are then determined using a weighted graph matching method. Graph matching is considered to be one of the most complex problems in computer vision, due to its combinatorial nature. Our approach uses a multi-spectral technique to graph matching first proposed by Umeyama4 to find an approximate solution to the weighted graph matching problem (WGMP) based on the singular value decomposition of the adjacency matrix. Results show the technique is successful in co-registering 2-D MRI images and the method could be useful in co-registering 3-D volumetric data (e.g. CT, MRI, SPECT, PET etc.).

  5. Stress Wave Interaction Between Two Adjacent Blast Holes

    NASA Astrophysics Data System (ADS)

    Yi, Changping; Johansson, Daniel; Nyberg, Ulf; Beyglou, Ali

    2016-05-01

    Rock fragmentation by blasting is determined by the level and state of stress in the rock mass subjected to blasting. With the application of electronic detonators, some researchers stated that it is possible to achieve improved fragmentation through stress wave superposition with very short delay times. This hypothesis was studied through theoretical analysis in the paper. First, the stress in rock mass induced by a single-hole shot was analyzed with the assumptions of infinite velocity of detonation and infinite charge length. Based on the stress analysis of a single-hole shot, the stress history and tensile stress distribution between two adjacent holes were presented for cases of simultaneous initiation and 1 ms delayed initiation via stress superposition. The results indicated that the stress wave interaction is local around the collision point. Then, the tensile stress distribution at the extended line of two adjacent blast holes was analyzed for a case of 2 ms delay. The analytical results showed that the tensile stress on the extended line increases due to the stress wave superposition under the assumption that the influence of neighboring blast hole on the stress wave propagation can be neglected. However, the numerical results indicated that this assumption is unreasonable and yields contrary results. The feasibility of improving fragmentation via stress wave interaction with precise initiation was also discussed. The analysis in this paper does not support that the interaction of stress waves improves the fragmentation.

  6. Adjacent flaps for lower lip reconstruction after mucocele resection.

    PubMed

    Ying, Binbin

    2012-03-01

    Mucocele forms because of salivary gland mucous extravasation or retention and is usually related to trauma in the area of the lower lip. It is a common benign lesion in the oral region. Although there are many conservative treatments such as the creation of a pouch (marsupialization), freezing (cryosurgery), micromarsupialization, and CO2 laser vaporization, surgical resection is the most commonly used means. Generally speaking, an elliptic incision was made to fully enucleate the lesion along with the overlying mucosa and the affected glands, then direct suturing is adequate. However, in some cases, direct suturing could cause lower lip deformity, and adjacent flaps for lower lip reconstruction after mucocele resection might be quite necessary. Based on our experience, adjacent mucosal flaps could be used when lesions were close to or even break through the vermilion border or their diameters were much more than 1 cm. A-T advancement flaps and transposition flaps were the mostly applied ones. Follow-up showed that all patients realized primary healing after 1 week postoperatively with satisfactory lower lip appearance, and there was no sign of increasing incidence of relapse. PMID:22421867

  7. Historical volcanoes of Armenia and adjacent areas: What is revisited?

    NASA Astrophysics Data System (ADS)

    Karakhanian, A.; Jrbashyan, R.; Trifonov, V.; Philip, H.; Arakelian, S.; Avagyan, A.; Baghdassaryan, H.; Davtian, V.

    2006-07-01

    The validity of some data in Karakhanian et al. [Karakhanian, A., Djrbashian, R., Trifonov V., Philip H., Arakelian S., Avagian, A., 2002. Holocene-historical volcanism and active faults as natural risk factor for Armenia and adjacent countries. Journal of Volcanology and Geothermal Research, 113, 1, 319-344; Karakhanian, A., Jrbashyan, R., Trifonov, V., Philip, H., Arakelian, S., Avagyan, A., Baghdassaryan, H., Davtian, V., Ghoukassyan, Yu., 2003. Volcanic hazards in the region of the Armenian nuclear power plant. Journal of Volcanology and Geothermal Research, 126/1-2, 31-62] that are revisited by R. Haroutiunian is considered. A conclusion is made that the revisions suggested by Haroutiunian concern unessential parts of the content of work by Karakhanian et al. [Karakhanian, A., Djrbashian, R., Trifonov V., Philip H., Arakelian S., Avagian, A., 2002. Holocene-historical volcanism and active faults as natural risk factor for Armenia and adjacent countries. Journal of Volcanology and Geothermal Research, 113, 1, 319-344; Karakhanian, A., Jrbashyan, R., Trifonov, V., Philip, H., Arakelian, S., Avagyan, A., Baghdassaryan, H., Davtian, V., Ghoukassyan, Yu., 2003. Volcanic hazards in the region of the Armenian nuclear power plant. Journal of Volcanology and Geothermal Research, 126/1-2, 31-62]. This article presents new evidence and re-proves the earlier conclusions that are disputed or revised by R. Haroutiunian.

  8. Brain investigation and brain conceptualization

    PubMed Central

    Redolfi, Alberto; Bosco, Paolo; Manset, David; Frisoni, Giovanni B.

    Summary The brain of a patient with Alzheimer’s disease (AD) undergoes changes starting many years before the development of the first clinical symptoms. The recent availability of large prospective datasets makes it possible to create sophisticated brain models of healthy subjects and patients with AD, showing pathophysiological changes occurring over time. However, these models are still inadequate; representations are mainly single-scale and they do not account for the complexity and interdependence of brain changes. Brain changes in AD patients occur at different levels and for different reasons: at the molecular level, changes are due to amyloid deposition; at cellular level, to loss of neuron synapses, and at tissue level, to connectivity disruption. All cause extensive atrophy of the whole brain organ. Initiatives aiming to model the whole human brain have been launched in Europe and the US with the goal of reducing the burden of brain diseases. In this work, we describe a new approach to earlier diagnosis based on a multimodal and multiscale brain concept, built upon existing and well-characterized single modalities. PMID:24139654

  9. Cubic-normal distribution

    NASA Astrophysics Data System (ADS)

    Peng, Gan Chew; Hin, Pooi Ah; Ho, C. K.

    2015-12-01

    The power-normal distribution given in Yeo and Johnson in year 2000 is a unimodal distribution with wide ranges of skewness and kurtosis. A shortcoming of the power-normal distribution is that the negative and positve parts of the underlying random variable have to be specified by two different expressions of the standard normal random variable. In this paper, we construct a new distribution, called the cubic-normal distribution, via a single polynomial expression in cubic root function. Apart from having the properties which are similar to those of the power-normal distribution, this cubic-normal distribution can be developed into a multivariate version which is more attractive from the theoretical and computational points of view.

  10. Beyond a bigger brain: Multivariable structural brain imaging and intelligence

    PubMed Central

    Ritchie, Stuart J.; Booth, Tom; Valdés Hernández, Maria del C.; Corley, Janie; Maniega, Susana Muñoz; Gow, Alan J.; Royle, Natalie A.; Pattie, Alison; Karama, Sherif; Starr, John M.; Bastin, Mark E.; Wardlaw, Joanna M.; Deary, Ian J.

    2015-01-01

    People with larger brains tend to score higher on tests of general intelligence (g). It is unclear, however, how much variance in intelligence other brain measurements would account for if included together with brain volume in a multivariable model. We examined a large sample of individuals in their seventies (n = 672) who were administered a comprehensive cognitive test battery. Using structural equation modelling, we related six common magnetic resonance imaging-derived brain variables that represent normal and abnormal features—brain volume, cortical thickness, white matter structure, white matter hyperintensity load, iron deposits, and microbleeds—to g and to fluid intelligence. As expected, brain volume accounted for the largest portion of variance (~ 12%, depending on modelling choices). Adding the additional variables, especially cortical thickness (+~ 5%) and white matter hyperintensity load (+~ 2%), increased the predictive value of the model. Depending on modelling choices, all neuroimaging variables together accounted for 18–21% of the variance in intelligence. These results reveal which structural brain imaging measures relate to g over and above the largest contributor, total brain volume. They raise questions regarding which other neuroimaging measures might account for even more of the variance in intelligence. PMID:26240470

  11. Perspectives on Normalization.

    ERIC Educational Resources Information Center

    Thurman, S. Kenneth; Fiorelli, Joseph S.

    1979-01-01

    The paper discusses the principle of normalization for developmentally disabled persons from five viewpoints: empirical approaches, social integration, specialization and congregation, cultural norms, and prevention. (Author/CL)

  12. Cortical sulci recognition and spatial normalization.

    PubMed

    Perrot, Matthieu; Rivière, Denis; Mangin, Jean-François

    2011-08-01

    Brain mapping techniques pair similar anatomical information across individuals. In this context, spatial normalization is mainly used to reduce inter-subject differences to improve comparisons. These techniques may benefit from anatomically identified landmarks useful to drive the registration. Automatic labeling, classification or segmentation techniques provide such labels. Most of these approaches depend strongly on normalization, as much as normalization depends on landmark accuracy. We propose in this paper a coherent Bayesian framework to automatically identify approximately 60 sulcal labels per hemisphere based on a probabilistic atlas (a mixture of spam models: Statistical Probabilistic Anatomy Map) estimating simultaneously normalization parameters. This way, the labelization method provides also with no extra computational costs a new automatically constrained registration of sulcal structures. We have limited our study to global affine and piecewise affine registration. The suggested global affine approach outperforms significantly standard affine intensity-based normalization techniques in term of sulci alignments. Further, by combining global and local joint labeling, a final mean recognition rate of 86% has been obtained with much more reliable labeling posterior probabilities. The different methods described in this paper have been integrated since the release version 3.2.1 of the BrainVISA software platform (Riviére et al., 2009). PMID:21441062

  13. Right Hemisphere Brain Damage

    MedlinePlus

    ... Language and Swallowing / Disorders and Diseases Right Hemisphere Brain Damage [ en Español ] What is right hemisphere brain ... right hemisphere brain damage ? What is right hemisphere brain damage? Right hemisphere brain damage (RHD) is damage ...

  14. Brain tumor - primary - adults

    MedlinePlus

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

  15. Brain radiation - discharge

    MedlinePlus

    Radiation - brain - discharge; Cancer-brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  16. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    MedlinePlus Videos and Cool Tools

    ... decisions. Inside a normal healthy brain, billions of cells called neurons constantly communicate with one another. They ... Plaques form when specific proteins in the neuron's cell membrane are processed differently. Normally, an enzyme called ...

  17. Brain Development

    MedlinePlus

    ... new neural connections every second. This growing brain development is influenced by many factors, including a child’s relationships, experiences and environment. Learn more about the crucial role you play ...

  18. Brain herniation

    MedlinePlus

    Ling GSF. Traumatic brain injury and spinal cord injury. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 406. Stippler M. Trauma of ...

  19. Quantitative analysis of brain pathology based on MRI and brain atlases--applications for cerebral palsy.

    PubMed

    Faria, Andreia V; Hoon, Alexander; Stashinko, Elaine; Li, Xin; Jiang, Hangyi; Mashayekh, Ameneh; Akhter, Kazi; Hsu, John; Oishi, Kenichi; Zhang, Jiangyang; Miller, Michael I; van Zijl, Peter C M; Mori, Susumu

    2011-02-01

    We have developed a new method to provide a comprehensive quantitative analysis of brain anatomy in cerebral palsy patients, which makes use of two techniques: diffusion tensor imaging and automated 3D whole brain segmentation based on our brain atlas and a nonlinear normalization technique (large-deformation diffeomorphic metric mapping). This method was applied to 13 patients and normal controls. The reliability of the automated segmentation revealed close agreement with the manual segmentation. We illustrate some potential applications for individual characterization and group comparison. This technique also provides a framework for determining the impact of various neuroanatomic features on brain functions. PMID:20920589

  20. Quantitative Analysis of Brain Pathology Based on MRI and Brain Atlases - Applications for Cerebral Palsy

    PubMed Central

    Faria, Andreia V.; Hoon, Alexander; Stachinko, Elaine; Li, Xin; Jiang, Hangyi; Mashayekh, Ameneh; Akhter, Kazi; Hsu, John; Oishi, Kenichi; Zhang, Jiangyang; Miller, Michael I.; van Zijl, Peter C.M.; Mori, Susumu

    2010-01-01

    We have developed a new method to provide a comprehensive quantitative analysis of brain anatomy in cerebral palsy patients, which makes use of two techniques: diffusion tensor imaging and automated 3D whole brain segmentation based on our brain atlas and a nonlinear normalization technique (large-deformation diffeomorphic metric mapping). This method was applied to 13 patients and normal controls. The reliability of the automated segmentation revealed close agreement with the manual segmentation. We illustrate some potential applications for individual characterization and group comparison. This technique also provides a framework for determining the impact of various neuroanatomic features on brain functions. PMID:20920589