2-Phenylbenzothiazole conjugated with cyclopentadienyl tricarbonyl [CpM(CO)3] (M = Re, (99m)Tc) complexes as potential imaging probes for β-amyloid plaques.

PubMed

Jia, Jianhua; Cui, Mengchao; Dai, Jiapei; Liu, Boli

2015-04-14

Technetium-99m-labeled cyclopentadienyl tricarbonyl complexes conjugated with the 2-phenylbenzothiazole binding motif were synthesized. The rhenium surrogates , , and were demonstrated to have moderate to high affinities for Aβ1-42 aggregates with Ki values of 142, 76, 64 and 24 nM, respectively. During the fluorescence staining of brain sections of transgenic mice and patients with Alzheimer's disease, these rhenium complexes demonstrated perfect and intense labeling of Aβ plaques. Moreover, in in vitro autoradiography, (99m)Tc-labeled complexes clearly detected β-amyloid plaques on sections of brain tissue from transgenic mice, which confirmed the sufficient affinity of these tracers for Aβ plaques. However, these compounds did not show desirable properties in vivo, especially showing poor brain uptake (below 0.5% ID g(-1)), which will hinder the further development of these tracers as brain imaging agents. Nonetheless, it is encouraging that these (99m)Tc-labeled complexes designed by a conjugate approach displayed sufficient affinities for Aβ plaques.

The Etiology of Cirrhosis is a Strong Determinant of Brain Reserve: A Multi-modal MR Imaging Study

PubMed Central

Ahluwalia, Vishwadeep; Wade, James B; Moeller, F Gerard; White, Melanie B; Unser, Ariel B; Gavis, Edith A; Sterling, Richard K; Stravitz, R Todd; Sanyal, Arun J; Siddiqui, Mohammad S; Puri, Puneet; Luketic, Velimir; Heuman, Douglas M; Fuchs, Michael; Matherly, Scott; Bajaj, Jasmohan S

2015-01-01

Background Poor brain reserve in alcoholic cirrhosis could worsen insight regarding disease severity and increase the patients’ vulnerability towards further deterioration. Aim To analyze brain reserve in abstinent alcoholic (Alc) compared to non-alcoholic (Nalc) cirrhosis patients in the context of hepatic encephalopathy (HE) and evaluate relative change in brain reserve between groups over time and before/after elective TIPS placement. Methods Cross-sectional study 46 Alc and 102 Nalc outpatients with or without HE. Cognitive tests followed by magnetic resonance (MR) imaging including 1-H MR Spectroscopy (MRS), Diffusion tensor (DTI) and T1-weighted imaging. Prospective study MRS on subset of 10 patients before/after TIPS placement. Another subset of 26 patients underwent MRS at least one year apart. Results Cross-sectional study Alc patients were worse on cognitive tests than Nalc. MR results suggest a greater effect of hyperammonemia, brain edema and significantly higher cortical damage in Alc as compared to Nalc patients. Effect of HE status on cognitive tests and brain reserve was more marked in Nalc than in Alc group. TIPS study Nalc patients showed a greater adverse relative change after TIPS compared to Alc group. 1-year follow-up Both groups remained stable between the two visits. However, Alc patients continued to show poor brain reserve than Nalc over time. Conclusions Patients with alcoholic cirrhosis, despite abstinence, have a poor brain reserve while, non-alcoholic cirrhosis patients have a greater potential for brain reserve deterioration after HE and TIPS. Information regarding the brain reserve in cirrhosis could assist medical teams to refine their communication and monitoring strategies for different etiologies. PMID:25939692

Use of a benzimidazole derivative BF-188 in fluorescence multispectral imaging for selective visualization of tau protein fibrils in the Alzheimer's disease brain.

PubMed

Harada, Ryuichi; Okamura, Nobuyuki; Furumoto, Shozo; Yoshikawa, Takeo; Arai, Hiroyuki; Yanai, Kazuhiko; Kudo, Yukitsuka

2014-02-01

Selective visualization of amyloid-β and tau protein deposits will help to understand the pathophysiology of Alzheimer's disease (AD). Here, we introduce a novel fluorescent probe that can distinguish between these two deposits by multispectral fluorescence imaging technique. Fluorescence spectral analysis was performed using AD brain sections stained with novel fluorescence compounds. Competitive binding assay using [(3)H]-PiB was performed to evaluate the binding affinity of BF-188 for synthetic amyloid-β (Aβ) and tau fibrils. In AD brain sections, BF-188 clearly stained Aβ and tau protein deposits with different fluorescence spectra. In vitro binding assays indicated that BF-188 bound to both amyloid-β and tau fibrils with high affinity (K i  < 10 nM). In addition, BF-188 showed an excellent blood-brain barrier permeability in mice. Multispectral imaging with BF-188 could potentially be used for selective in vivo imaging of tau deposits as well as amyloid-β in the brain.

Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds.

PubMed

Choe, Myong-Sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S; Benasich, April A; Grant, P Ellen

2013-09-01

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.

Regional Infant Brain Development: An MRI-Based Morphometric Analysis in 3 to 13 Month Olds

PubMed Central

Choe, Myong-sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S.; Benasich, April A.; Grant, P. Ellen

2013-01-01

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants’ whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders. PMID:22772652

Beneficial effects of n-acetylcysteine on ischaemic brain injury

PubMed Central

Cuzzocrea, Salvatore; Mazzon, Emanuela; Costantino, Giuseppina; Serraino, Ivana; Dugo, Laura; Calabrò, Giusy; Cucinotta, Giovanni; De Sarro, Angela; Caputi, A P

2000-01-01

Nitric oxide (NO), peroxynitrite, formed from NO and superoxide anion, poly (ADP-ribole) synthetase have been implicated as mediators of neuronal damage following focal ischaemia. Here we have investigated the effects of n-acetylcysteine (NAC) treatment in Mongolian gerbils subjected to cerebral ischaemia.Treatment of gerbils with NAC (20 mg kg−1 30 min before reperfusion and 1, 2 and 6 h after reperfusion) reduced the formation of post-ischaemic brain oedema, evaluated by water content.NAC also attenuated the increase in the brain levels of malondialdehyde (MDA) and the increase in the hippocampus of myeloperoxidase (MPO) caused by cerebral ischaemia.Positive staining for nitrotyrosine was found in the hippocampus in Mongolian gerbils subjected to cerebral ischaemia. Hippocampus tissue sections from Mongolian gerbils subjected to cerebral ischaemia also showed positive staining for poly (ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and for PARS were markedly reduced in tissue sections obtained from animals that received NAC.NAC treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischaemia and reperfusion.Histological observations of the pyramidal layer of CA1 showed a reduction of neuronal loss in animals that received NAC.These results show that NAC improves brain injury induced by transient cerebral ischaemia. PMID:10903958

Neural Plasticity and Neurorehabilitation Following Traumatic Brain Injury

DTIC Science & Technology

2010-10-01

for sectioning and staining . To date, the brains have been sectioned and one set stained for Nissl . Using the Nissl stained sections, Dorothy...all behavioral data. • Brains have been harvested and sent to Dr. Jones’ lab • Dr. Jones’ lab has sliced the brains and stained one set with Nissl ...remaining sets of brain sections are currently being stained with markers of plasticity using immunohistochemistry. We have completed immunohistochemical

Research on terahertz properties of rat brain tissue sections during dehydration

NASA Astrophysics Data System (ADS)

Cui, Gangqiang; Liang, Jianfeng; Zhao, Hongwei; Zhao, Xianghui; Chang, Chao

2018-01-01

Biological tissue sections are always kept in a system purged with dry nitrogen for the measurement of terahertz spectrum. However, the injected nitrogen will cause dehydration of tissue sections, which will affect the accuracy of spectrum measurement. In this paper, terahertz time-domain spectrometer is used to measure the terahertz spectra of rat brain tissue sections during dehydration. The changes of terahertz properties, including terahertz transmittance, refractive index and extinction coefficient during dehydration are also analyzed. The amplitudes of terahertz time-domain spectra increase gradually during the dehydration process. Besides, the terahertz properties show obvious changes during the dehydration process. All the results indicate that the injected dry nitrogen has a significant effect on the terahertz spectra and properties of tissue sections. This study contributes to further research and application of terahertz technology in biomedical field.

In vivo detection of amyloid plaques in the mouse brain using the near-infrared fluorescence probe THK-265.

PubMed

Okamura, Nobuyuki; Mori, Masanori; Furumoto, Shozo; Yoshikawa, Takeo; Harada, Ryuichi; Ito, Satoshi; Fujikawa, Yosuke; Arai, Hiroyuki; Yanai, Kazuhiko; Kudo, Yukitsuka

2011-01-01

Noninvasive detection of amyloid-β (Aβ) deposits in the brain would be beneficial for an early and presymptomatic diagnosis of Alzheimer's disease (AD). We developed THK-265 as a candidate near-infrared fluorescence (NIRF) probe for the in vivo detection of amyloid deposits in the brain. The maximal emission wavelength of THK-265 was greater than 650nm and it showed high quantum yield and molar absorption coefficients. A fluorescence binding assay showed its high binding affinity to Aβ fibrils (Kd = 97 nM). THK-265 clearly stained amyloid plaques in AD neocortical brain sections and showed a moderate log p value (1.8). After intravenous administration of THK-265 in amyloid-β protein precursor (AβPP) transgenic mice, amyloid deposits in the brain were clearly labeled with THK-265. Furthermore, in vivo NIRF imaging demonstrated significantly higher fluorescence intensity in the brains of AβPP transgenic mice than in those of wild-type mice. As THK-265 showed profound hyperchromic effect upon binding to Aβ fibrils, good discrimination between AβPP transgenic and wild-type mice was demonstrated even early after THK-265 administration. Furthermore, the fluorescence intensity of THK-265 correlated with amyloid plaque burden in the brains of AβPP transgenic mice. These findings strongly support the usefulness of THK-265 as an NIRF imaging probe for the noninvasive measurement of brain amyloid load.

Food-induced changes of lipids in rat neuronal tissue visualized by ToF-SIMS imaging.

PubMed

Dowlatshahi Pour, Masoumeh; Jennische, Eva; Lange, Stefan; Ewing, Andrew G; Malmberg, Per

2016-09-06

Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to image the lipid localization in brain tissue sections from rats fed specially processed cereals (SPC). An IonTof 5 instrument equipped with a Bi cluster ion gun was used to analyze the tissue sections. Data from 15 brain samples from control and cereal-fed rats were recorded and exported to principal components analysis (PCA). The data clearly show changes of certain lipids in the brain following cereal feeding. PCA score plots show a good separation in lipid distribution between the control and the SPC-fed group. The loadings plot reveal that the groups separated mainly due to changes in cholesterol, vitamin E and c18:2, c16:0 fatty acid distribution as well as some short chain monocarboxylic fatty acid compositions. These insights relate to the working mechanism of SPC as a dietary supplement. SPC is thought to activate antisecretory factor (AF), an endogenous protein with regulatory function for inflammation and fluid secretion. These data provide insights into lipid content in brain following SPC feeding and suggest a relation to activating AF.

Mice overexpressing corticotropin-releasing factor show brain atrophy and motor dysfunctions.

PubMed

Goebel, Miriam; Fleming, Sheila M; Million, Mulugeta; Stengel, Andreas; Taché, Yvette; Wang, Lixin

2010-03-31

Chronic stress and persistently high glucocorticoid levels can induce brain atrophy. Corticotropin-releasing factor (CRF)-overexpressing (OE) mice are a genetic model of chronic stress with elevated brain CRF and plasma corticosterone levels and Cushing's syndrome. The brain structural alterations in the CRF-OE mice, however, are not well known. We found that adult male and female CRF-OE mice had significantly lower whole brain and cerebellum weights than their wild type (WT) littermates (347.7+/-3.6mg vs. 460.1+/-4.3mg and 36.3+/-0.8mg vs. 50.0+/-1.3mg, respectively) without sex-related difference. The epididymal/parametrial fat mass was significantly higher in CRF-OE mice. The brain weight was inversely correlated to epididymal/parametrial fat weight, but not to body weight. Computerized image analysis system in Nissl-stained brain sections of female mice showed that the anterior cingulate and sensorimotor cortexes of CRF-OE mice were significantly thinner, and the volumes of the hippocampus, hypothalamic paraventricular nucleus and amygdala were significantly reduced compared to WT, while the locus coeruleus showed a non-significant increase. Motor functions determined by beam crossing and gait analysis showed that CRF-OE mice took longer time and more steps to traverse a beam with more errors, and displayed reduced stride length compared to their WT littermates. These data show that CRF-OE mice display brain size reduction associated with alterations of motor coordination and an increase in visceral fat mass providing a novel animal model to study mechanisms involved in brain atrophy under conditions of sustained elevation of brain CRF and circulating glucocorticoid levels. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Brain Ultrasonography Findings in Neonatal Seizure; a Cross-sectional Study.

PubMed

Nabavi, Seyed Saeed; Partovi, Parinaz

2017-01-01

Screening of newborns with seizure, who have curable pathologic brain findings, might be able to improve their final outcome by accelerating treatment intervention. The present study aimed to evaluate the brain ultrasonography findings of newborns hospitalized with complaint of seizure. The present cross-sectional study designed to evaluate brain ultrasonography findings of hospitalized newborns complaining seizure. Neonatal seizure was defined as presence of tonic, clonic, myoclonic, and subtle attacks in 1 - 28 day old newborns. 100 newborns with the mean age of 5.82 ± 6.29 days were evaluated (58% male). Most newborns were in the < 10 days age range (76%), term (83%) and with normal birth weight (81%). 22 (22%) of the ultrasonography examinations showed a pathologic finding. A correlation was only found between birth age and probability of the presence of a pathologic problem in the brain as the frequency of these problems was significantly higher in pre-term newborns (p = 0.023). Based on the findings of the present study, frequency of pathologic findings in neonatal brain ultrasonography was 22%. Hemorrhage (12%) and hydrocephaly (7%) were the most common findings. The only factor correlating with increased probability of positive findings was the newborns being pre-term.

Sex differences and structural brain maturation from childhood to early adulthood.

PubMed

Koolschijn, P Cédric M P; Crone, Eveline A

2013-07-01

Recent advances in structural brain imaging have demonstrated that brain development continues through childhood and adolescence. In the present cross-sectional study, structural MRI data from 442 typically developing individuals (range 8-30) were analyzed to examine and replicate the relationship between age, sex, brain volumes, cortical thickness and surface area. Our findings show differential patterns for subcortical and cortical areas. Analysis of subcortical volumes showed that putamen volume decreased with age and thalamus volume increased with age. Independent of age, males demonstrated larger amygdala and thalamus volumes compared to females. Cerebral white matter increased linearly with age, at a faster pace for females than males. Gray matter showed nonlinear decreases with age. Sex-by-age interactions were primarily found in lobar surface area measurements, with males demonstrating a larger cortical surface up to age 15, while cortical surface in females remained relatively stable with increasing age. The current findings replicate some, but not all prior reports on structural brain development, which calls for more studies with large samples, replications, and specific tests for brain structural changes. In addition, the results point toward an important role for sex differences in brain development, specifically during the heterogeneous developmental phase of puberty. Copyright © 2013 Elsevier Ltd. All rights reserved.

MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survival.

PubMed

Noorbakhsh, Farshid; Ramachandran, Rithwik; Barsby, Nicola; Ellestad, Kristofor K; LeBlanc, Andrea; Dickie, Peter; Baker, Glen; Hollenberg, Morley D; Cohen, Eric A; Power, Christopher

2010-06-01

MicroRNAs (miRNAs) are small noncoding RNA molecules, which are known to regulate gene expression in physiological and pathological conditions. miRNA profiling was performed using brain tissue from patients with HIV encephalitis (HIVE), a neuroinflammatory/degenerative disorder caused by HIV infection of the brain. Microarray analysis showed differential expression of multiple miRNAs in HIVE compared to control brains. Target prediction and gene ontology enrichment analysis disclosed targeting of several gene families/biological processes by differentially expressed miRNAs (DEMs), with cell death-related genes, including caspase-6, showing a bias toward down-regulated DEMs. Consistent with the miRNA data, HIVE brains exhibited higher levels of caspase-6 transcripts compared with control patients. Immunohistochemical analysis showed localization of the cleaved form of caspase-6 in astrocytes in HIVE brain sections. Exposure of cultured human primary astrocytes to HIV viral protein R (Vpr) induced p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury. Transgenic mice, expressing Vpr in microglial cells, demonstrated astrocyte apoptosis in brain, which was associated with caspase-6 activation and neurobehavioral abnormalities. Overall, these data point to previously unrecognized alterations in miRNA profile in the brain during HIV infection, which contribute to cell death through dysregulation of cell death machinery.

Enhanced Sensitivity for High Spatial Resolution Lipid Analysis by Negative Ion Mode MALDI Imaging Mass Spectrometry

PubMed Central

Angel, Peggi M.; Spraggins, Jeffrey M.; Baldwin, H. Scott; Caprioli, Richard

2012-01-01

We have achieved enhanced lipid imaging to a ~10 μm spatial resolution using negative ion mode matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry, sublimation of 2,5-dihydroxybenzoic acid as the MALDI matrix and a sample preparation protocol that uses aqueous washes. We report on the effect of treating tissue sections by washing with volatile buffers at different pHs prior to negative ion mode lipid imaging. The results show that washing with ammonium formate, pH 6.4, or ammonium acetate, pH 6.7, significantly increases signal intensity and number of analytes recorded from adult mouse brain tissue sections. Major lipid species measured were glycerophosphoinositols, glycerophosphates, glycerolphosphoglycerols, glycerophosphoethanolamines, glycerophospho-serines, sulfatides, and gangliosides. Ion images from adult mouse brain sections that compare washed and unwashed sections are presented and show up to fivefold increases in ion intensity for washed tissue. The sample preparation protocol has been found to be applicable across numerous organ types and significantly expands the number of lipid species detectable by imaging mass spectrometry at high spatial resolution. PMID:22243218

Brain Metal Distribution and Neuro-Inflammatory Profiles after Chronic Vanadium Administration and Withdrawal in Mice

PubMed Central

Folarin, Oluwabusayo R.; Snyder, Amanda M.; Peters, Douglas G.; Olopade, Funmilayo; Connor, James R.; Olopade, James O.

2017-01-01

Vanadium is a potentially toxic environmental pollutant and induces oxidative damage in biological systems including the central nervous system (CNS). Its deposition in brain tissue may be involved in the pathogenesis of certain neurological disorders which after prolonged exposure can culminate into more severe pathology. Most studies on vanadium neurotoxicity have been done after acute exposure but in reality some populations are exposed for a lifetime. This work was designed to ascertain neurodegenerative consequences of chronic vanadium administration and to investigate the progressive changes in the brain after withdrawal from vanadium treatment. A total of 85 male BALB/c mice were used for the experiment and divided into three major groups of vanadium treated (intraperitoneally (i.p.) injected with 3 mg/kg body weight of sodium metavanadate and sacrificed every 3 months till 18 months); matched controls; and animals that were exposed to vanadium for 3 months and thereafter the metal was withdrawn. Brain tissues were obtained after animal sacrifice. Sagittal cut sections of paraffin embedded tissue (5 μm) were analyzed by the Laser ablation-inductively coupled plasma-mass spectrometry (LA–ICP–MS) to show the absorption and distribution of vanadium metal. Also, Haematoxylin and Eosin (H&E) staining of brain sections, and immunohistochemistry for Microglia (Iba-1), Astrocytes (GFAP), Neurons (Neu-N) and Neu-N + 4′,6-diamidine-2′-pheynylindole dihydrochloride (Dapi) Immunofluorescent labeling were observed for morphological and morphometric parameters. The LA–ICP–MS results showed progressive increase in vanadium uptake with time in different brain regions with prediction for regions like the olfactory bulb, brain stem and cerebellum. The withdrawal brains still show presence of vanadium metal in the brain slightly more than the controls. There were morphological alterations (of the layering profile, nuclear shrinkage) in the prefrontal cortex, cellular degeneration (loss of dendritic arborization) and cell death in the Hippocampal CA1 pyramidal cells and Purkinje cells of the cerebellum, including astrocytic and microglial activation in vanadium exposed brains which were all attenuated in the withdrawal group. With exposure into old age, the evident neuropathology was microgliosis, while progressive astrogliosis became more attenuated. We have shown that chronic administration of vanadium over a lifetime in mice resulted in metal accumulation which showed regional variabilities with time. The metal profile and pathological effects were not completely eliminated from the brain even after a long time withdrawal from vanadium metal. PMID:28790895

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

PubMed

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

2014-01-01

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

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

PubMed Central

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

2017-01-01

Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2–12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future. PMID:28533392

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain.

PubMed

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

2017-06-06

Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2-12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future.

Unraveling ALS due to SOD1 mutation through the combination of brain and cervical cord MRI.

PubMed

Agosta, Federica; Spinelli, Edoardo Gioele; Marjanovic, Ivan V; Stevic, Zorica; Pagani, Elisabetta; Valsasina, Paola; Salak-Djokic, Biljana; Jankovic, Milena; Lavrnic, Dragana; Kostic, Vladimir S; Filippi, Massimo

2018-02-20

To explore structural and functional changes of the brain and cervical cord in patients with amyotrophic lateral sclerosis (ALS) due to mutation in the superoxide dismutase ( SOD1 ) gene compared with sporadic ALS. Twenty patients with SOD1 ALS, 11 with sporadic ALS, and 33 healthy controls underwent clinical evaluation and brain MRI. Cortical thickness analysis, diffusion tensor MRI of the corticospinal tracts (CST) and corpus callosum, and resting-state functional connectivity were performed. Patients with ALS also underwent cervical cord MRI to evaluate cord cross-sectional area and magnetization transfer ratio (MTR). Patients with SOD1 ALS showed longer disease duration and slower rate of functional decline relative to those with sporadic ALS. No cortical thickness abnormalities were found in patients with ALS compared with controls. Fractional anisotropy showed that sporadic ALS patients had significant CST damage relative to both healthy controls ( p = 0.001-0.02) and SOD1-related ALS ( p = 0.05), although the latter showed alterations that were intermediate between controls and sporadic ALS. Functional hyperconnectivity of the motor cortex in the sensorimotor network was observed in patients with sporadic ALS relative to controls. Conversely, patients with SOD1 ALS showed lower cord cross-sectional area along the whole cervical cord relative to those with sporadic ALS ( p < 0.001). No cord MTR differences were found between patient groups. Patients with SOD1 ALS showed cervical cord atrophy relative to those with sporadic ALS and a relative preservation of brain motor structural and functional networks. Neurodegeneration in SOD1 ALS is likely to occur primarily in the spinal cord. An objective and accurate estimate of spinal cord damage has potential in the future assessment of preventive SOD1 ALS therapies. © 2018 American Academy of Neurology.

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats

PubMed Central

Pong, Alice C.; Jugé, Lauriane; Bilston, Lynne E.; Cheng, Shaokoon

2017-01-01

Introduction Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Methods Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Results Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. Conclusions This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus. PMID:28837671

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

PubMed

Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

2017-01-01

Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

A Cross-Sectional Voxel-Based Morphometric Study of Age- and Sex-Related Changes in Gray Matter Volume in the Normal Aging Brain.

PubMed

Peng, Fei; Wang, Lixin; Geng, Zuojun; Zhu, Qingfeng; Song, Zhenhu

2016-01-01

The aim of the study was to carry out a cross-sectional study of 124 cognitively normal Chinese adults using the voxel-based morphometry approach to delineate age-related changes in the gray matter volume of regions of interest (ROI) in the brain and further analyze their correlation with age. One hundred twenty-four cognitively normal adults were divided into the young age group, the middle age group, and the old age group. Conventional magnetic resonance imaging was performed with the Achieva 3.0 T system. Structural images were processed using VBM8 and SPM8. Regions of interest were obtained by WFU PickAtlas and all realigned images were spatially normalized. Females showed significantly greater total gray matter volume than males (t = 4.81, P = 0.0000, false discovery rate corrected). Compared with young subjects, old-aged subjects showed extensive reduction in gray matter volumes in all ROIs examined except the occipital lobe. In young- and middle-aged subjects, female and male subjects showed significant difference in the right middle temporal gyrus, right superior temporal gyrus, left angular gyrus, right middle occipital lobe, left middle cingulate gyrus, and the pars triangularis of the right inferior frontal gyrus, suggesting an interaction between age and sex (P < 0.001, uncorrected). Logistic regression analysis revealed linear negative correlation between the total gray matter volume and age (R = 0.529, P < 0.001). Significant age-related differences are present in gray matter volume across multiple brain regions during aging. The VPM approach may provide an emerging paradigm in the normal aging brain that may help differentiate underlying normal neurobiological aging changes of specific brain regions from neurodegenerative impairments.

Effect of time period after boric acid injection on 10B absorption in different regions of adult male rat's brain.

PubMed

Khojasteh, Nasrin Baghban; Pazirandeh, Ali; Jameie, Behnam; Goodarzi, Samereh

2012-06-01

Distribution of (10)B in different regions of rat normal brain was studied. Two groups were chosen as control and trial. Trial group received 2 ml of neutral boron compound. 2, 4 and 6 h after the injection brain removed, coronal sections of forebrain, midbrain and hindbrain were sandwiched between two pieces of polycarbonate. Autoradiography plots of (10)B distribution showed significant differences in three regions with the highest (10)B concentration in the forebrain during 4 h after injection. Copyright © 2012 Elsevier Ltd. All rights reserved.

Label-free, multi-scale imaging of ex-vivo mouse brain using spatial light interference microscopy

NASA Astrophysics Data System (ADS)

Min, Eunjung; Kandel, Mikhail E.; Ko, Chemyong J.; Popescu, Gabriel; Jung, Woonggyu; Best-Popescu, Catherine

2016-12-01

Brain connectivity spans over broad spatial scales, from nanometers to centimeters. In order to understand the brain at multi-scale, the neural network in wide-field has been visualized in detail by taking advantage of light microscopy. However, the process of staining or addition of fluorescent tags is commonly required, and the image contrast is insufficient for delineation of cytoarchitecture. To overcome this barrier, we use spatial light interference microscopy to investigate brain structure with high-resolution, sub-nanometer pathlength sensitivity without the use of exogenous contrast agents. Combining wide-field imaging and a mosaic algorithm developed in-house, we show the detailed architecture of cells and myelin, within coronal olfactory bulb and cortical sections, and from sagittal sections of the hippocampus and cerebellum. Our technique is well suited to identify laminar characteristics of fiber tract orientation within white matter, e.g. the corpus callosum. To further improve the macro-scale contrast of anatomical structures, and to better differentiate axons and dendrites from cell bodies, we mapped the tissue in terms of its scattering property. Based on our results, we anticipate that spatial light interference microscopy can potentially provide multiscale and multicontrast perspectives of gross and microscopic brain anatomy.

Raman spectroscopic imaging as complementary tool for histopathologic assessment of brain tumors

NASA Astrophysics Data System (ADS)

Krafft, Christoph; Bergner, Norbert; Romeike, Bernd; Reichart, Rupert; Kalff, Rolf; Geiger, Kathrin; Kirsch, Matthias; Schackert, Gabriele; Popp, Jürgen

2012-02-01

Raman spectroscopy enables label-free assessment of brain tissues and tumors based on their biochemical composition. Combination of the Raman spectra with the lateral information allows grading of tumors, determining the primary tumor of brain metastases and delineating tumor margins - even during surgery after coupling with fiber optic probes. This contribution presents exemplary Raman spectra and images collected from low grade and high grade regions of astrocytic gliomas and brain metastases. A region of interest in dried tissue sections encompassed slightly increased cell density. Spectral unmixing by vertex component analysis (VCA) and N-FINDR resolved cell nuclei in score plots and revealed the spectral contributions of nucleic acids, cholesterol, cholesterol ester and proteins in endmember signatures. The results correlated with the histopathological analysis after staining the specimens by hematoxylin and eosin. For a region of interest in non-dried, buffer immersed tissue sections image processing was not affected by drying artifacts such as denaturation of biomolecules and crystallization of cholesterol. Consequently, the results correspond better to in vivo situations. Raman spectroscopic imaging of a brain metastases from renal cell carcinoma showed an endmember with spectral contributions of glycogen which can be considered as a marker for this primary tumor.

Chronic Ethanol Consumption Profoundly Alters Regional Brain Ceramide and Sphingomyelin Content in Rodents

PubMed Central

2015-01-01

Ceramides (CER) are involved in alcohol-induced neuroinflammation. In a mouse model of chronic alcohol exposure, 16 CER and 18 sphingomyelin (SM) concentrations from whole brain lipid extracts were measured using electrospray mass spectrometry. All 18 CER concentrations in alcohol exposed adults increased significantly (range: 25–607%); in juveniles, 6 CER decreased (range: −9 to −37%). In contrast, only three SM decreased in adult and one increased significantly in juvenile. Next, regional identification at 50 μm spatial resolution from coronal sections was obtained with matrix implanted laser desorption/ionization mass spectrometry imaging (MILDI-MSI) by implanting silver nanoparticulate matrices followed by focused laser desorption. Most of the CER and SM quantified in whole brain extracts were detected in MILDI images. Coronal sections from three brain levels show qualitative regional changes in CER-SM ion intensities, as a function of group and brain region, in cortex, striatum, accumbens, habenula, and hippocampus. Highly correlated changes in certain white matter CER-SM pairs occur in regions across all groups, including the hippocampus and the lateral (but not medial) cerebellar cortex of adult mice. Our data provide the first microscale MS evidence of regional lipid intensity variations induced by alcohol. PMID:25387107

Contribution of transcranial magnetic stimulation to assessment of brain connectivity and networks.

PubMed

Hallett, Mark; Di Iorio, Riccardo; Rossini, Paolo Maria; Park, Jung E; Chen, Robert; Celnik, Pablo; Strafella, Antonio P; Matsumoto, Hideyuki; Ugawa, Yoshikazu

2017-11-01

The goal of this review is to show how transcranial magnetic stimulation (TMS) techniques can make a contribution to the study of brain networks. Brain networks are fundamental in understanding how the brain operates. Effects on remote areas can be directly observed or identified after a period of stimulation, and each section of this review will discuss one method. EEG analyzed following TMS is called TMS-evoked potentials (TEPs). A conditioning TMS can influence the effect of a test TMS given over the motor cortex. A disynaptic connection can be tested also by assessing the effect of a pre-conditioning stimulus on the conditioning-test pair. Basal ganglia-cortical relationships can be assessed using electrodes placed in the process of deep brain stimulation therapy. Cerebellar-cortical relationships can be determined using TMS over the cerebellum. Remote effects of TMS on the brain can be found as well using neuroimaging, including both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The methods complement each other since they give different views of brain networks, and it is often valuable to use more than one technique to achieve converging evidence. The final product of this type of work is to show how information is processed and transmitted in the brain. Published by Elsevier B.V.

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

Lewis, M.E.; Khachaturian, H.; Watson, S.J.

Using adjacent section autoradiography-immunocytochemistry, the distribution of (TH)naloxone binding sites was studied in relation to neuronal systems containing (Leu)enkephalin, dynorphin A, or beta-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of (TH)naloxone, the pharmacological (mu-like) properties of which appear unaltered. In contrast, specific binding of the delta ligand (TH)D-Ala2,D-Leu5-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, the authors have noted associations between (TH)naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed.more » Within regions, the relationship was complex. The complexity of the association between (TH)naloxone binding sites and the multiple opioid systems, and previous reports of co-localization of mu and kappa receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission.« less

Atlas of neuroanatomy with radiologic correlation and pathologic illustration

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

Dublin, A.B.; Dublin, W.B.

1982-01-01

This atlas correlates gross neuroanatomic specimens with radiographs and computed tomographic scans. Pathologic specimens and radiographs are displayed in a similar manner. The first chapter, on embryology, shows the development of the telencephalon, diencephalon, mesencephalon, and metencephalon through a series of overlays. The anatomical section shows the surface of the brain, the ventricles and their adjacent structures, and the vascular system. CT anatomy is demonstrated by correlating CT scans with pathologic brain specimens cut in the axial plane. Pathologic changes associated with congenital malformations, injections, injuries, tumors, and other causes are demonstrated in the last six chapters.

Mutations of the Thyroid Hormone Transporter MCT8 Cause Prenatal Brain Damage and Persistent Hypomyelination

PubMed Central

López-Espíndola, Daniela; Morales-Bastos, Carmen; Grijota-Martínez, Carmen; Liao, Xiao-Hui; Lev, Dorit; Sugo, Ella; Verge, Charles F.; Refetoff, Samuel

2014-01-01

Context: Mutations in the MCT8 (SLC16A2) gene, encoding a specific thyroid hormone transporter, cause an X-linked disease with profound psychomotor retardation, neurological impairment, and abnormal serum thyroid hormone levels. The nature of the central nervous system damage is unknown. Objective: The objective of the study was to define the neuropathology of the syndrome by analyzing brain tissue sections from MCT8-deficient subjects. Design: We analyzed brain sections from a 30th gestational week male fetus and an 11-year-old boy and as controls, brain tissue from a 30th and 28th gestational week male and female fetuses, respectively, and a 10-year-old girl and a 12-year-old boy. Methods: Staining with hematoxylin-eosin and immunostaining for myelin basic protein, 70-kDa neurofilament, parvalbumin, calbindin-D28k, and synaptophysin were performed. Thyroid hormone determinations and quantitative PCR for deiodinases were also performed. Results: The MCT8-deficient fetus showed a delay in cortical and cerebellar development and myelination, loss of parvalbumin expression, abnormal calbindin-D28k content, impaired axonal maturation, and diminished biochemical differentiation of Purkinje cells. The 11-year-old boy showed altered cerebellar structure, deficient myelination, deficient synaptophysin and parvalbumin expression, and abnormal calbindin-D28k expression. The MCT8-deficient fetal cerebral cortex showed 50% reduction of thyroid hormones and increased type 2 deiodinase and decreased type 3 deiodinase mRNAs. Conclusions: The following conclusions were reached: 1) brain damage in MCT8 deficiency is diffuse, without evidence of focal lesions, and present from fetal stages despite apparent normality at birth; 2) deficient hypomyelination persists up to 11 years of age; and 3) the findings are compatible with the deficient action of thyroid hormones in the developing brain caused by impaired transport to the target neural cells. PMID:25222753

Life history of roach, Rutilus rutilus (Cyprinidae, Teleostei). A qualitative and quantitative study on the development of sensory brain areas.

PubMed

Brandstätter, R; Kotrschal, K

1989-01-01

The present study deals with aspects of the brain development in the roach, Rutilus rutilus, a common mid-European cyprinid fish. The morphogenesis of selected brain areas from hatching to early juveniles was examined on serial paraffin cross-sections. From early juveniles to large adults, brain growth was quantitatively analyzed by computer-aided planimetry. The hatchlings of roach show a cytologically distinct optic tectum, but a poorly differentiated brainstem, reflecting the predominance of the optic sense during the larval planktivorous period. The differentiation and outgrowth of chemosensory brainstem centers is related to the onset and development of benthivorous feeding in juveniles. The optic tectum decreases in size relative to the total brain volume from juveniles through adults. The corpus cerebelli increases in relative size, whereas chemosensory and acousticolateral centers grow isometrically with the brain as a whole.

High-Throughput Method of Whole-Brain Sectioning, Using the Tape-Transfer Technique.

PubMed

Pinskiy, Vadim; Jones, Jamie; Tolpygo, Alexander S; Franciotti, Neil; Weber, Kevin; Mitra, Partha P

2015-01-01

Cryostat sectioning is a popular but labor-intensive method for preparing histological brain sections. We have developed a modification of the commercially available CryoJane tape collection method that significantly improves the ease of collection and the final quality of the tissue sections. The key modification involves an array of UVLEDs to achieve uniform polymerization of the glass slide and robust adhesion between the section and slide. This report presents system components and detailed procedural steps, and provides examples of end results; that is, 20 μm mouse brain sections that have been successfully processed for routine Nissl, myelin staining, DAB histochemistry, and fluorescence. The method is also suitable for larger brains, such as rat and monkey.

High-Throughput Method of Whole-Brain Sectioning, Using the Tape-Transfer Technique

PubMed Central

Pinskiy, Vadim; Jones, Jamie; Tolpygo, Alexander S.; Franciotti, Neil; Weber, Kevin; Mitra, Partha P.

2015-01-01

Cryostat sectioning is a popular but labor-intensive method for preparing histological brain sections. We have developed a modification of the commercially available CryoJane tape collection method that significantly improves the ease of collection and the final quality of the tissue sections. The key modification involves an array of UVLEDs to achieve uniform polymerization of the glass slide and robust adhesion between the section and slide. This report presents system components and detailed procedural steps, and provides examples of end results; that is, 20μm mouse brain sections that have been successfully processed for routine Nissl, myelin staining, DAB histochemistry, and fluorescence. The method is also suitable for larger brains, such as rat and monkey. PMID:26181725

In vivo metabolic labeling of sialoglycans in the mouse brain by using a liposome-assisted bioorthogonal reporter strategy

PubMed Central

Xie, Ran; Dong, Lu; Du, Yifei; Zhu, Yuntao; Hua, Rui; Zhang, Chen; Chen, Xing

2016-01-01

Mammalian brains are highly enriched with sialoglycans, which have been implicated in brain development and disease progression. However, in vivo labeling and visualization of sialoglycans in the mouse brain remain a challenge because of the blood−brain barrier. Here we introduce a liposome-assisted bioorthogonal reporter (LABOR) strategy for shuttling 9-azido sialic acid (9AzSia), a sialic acid reporter, into the brain to metabolically label sialoglycoconjugates, including sialylated glycoproteins and glycolipids. Subsequent bioorthogonal conjugation of the incorporated 9AzSia with fluorescent probes via click chemistry enabled fluorescence imaging of brain sialoglycans in living animals and in brain sections. Newly synthesized sialoglycans were found to widely distribute on neuronal cell surfaces, in particular at synaptic sites. Furthermore, large-scale proteomic profiling identified 140 brain sialylated glycoproteins, including a wealth of synapse-associated proteins. Finally, by performing a pulse−chase experiment, we showed that dynamic sialylation is spatially regulated, and that turnover of sialoglycans in the hippocampus is significantly slower than that in other brain regions. The LABOR strategy provides a means to directly visualize and monitor the sialoglycan biosynthesis in the mouse brain and will facilitate elucidating the functional role of brain sialylation. PMID:27125855

[Distribution of human enterovirus 71 in brainstem of infants with brain stem encephalitis and infection mechanism].

PubMed

Hao, Bo; Gao, Di; Tang, Da-Wei; Wang, Xiao-Guang; Liu, Shui-Ping; Kong, Xiao-Ping; Liu, Chao; Huang, Jing-Lu; Bi, Qi-Ming; Quan, Li; Luo, Bin

2012-04-01

To explore the mechanism that how human enterovirus 71 (EV71) invades the brainstem and how intercellular adhesion molecules-1 (ICAM-1) participates by analyzing the expression and distribution of human EV71, and ICAM-1 in brainstem of infants with brain stem encephalitis. Twenty-two brainstem of infants with brain stem encephalitis were collected as the experimental group and 10 brainstems of fatal congenital heart disease were selected as the control group. The sections with perivascular cuffings were selected to observe EV71-VP1 expression by immunohistochemistry method and ICAM-1 expression was detected for the sections with EV71-VP1 positive expression. The staining image analysis and statistics analysis were performed. The experiment and control groups were compared. (1) EV71-VP1 positive cells in the experimental group were mainly astrocytes in brainstem with nigger-brown particles, and the control group was negative. (2) ICAM-1 positive cells showed nigger-brown. The expression in inflammatory cells (around blood vessels of brain stem and in glial nodules) and gliocytes increased. The results showed statistical difference comparing with control group (P < 0.05). The brainstem encephalitis can be used to diagnose fatal EV71 infection in infants. EV71 can invade the brainstem via hematogenous route. ICAM-1 may play an important role in the pathogenic process.

Imaging of Cerebral Amyloid Angiopathy with Bivalent 99mTc-Hydroxamamide Complexes

NASA Astrophysics Data System (ADS)

Iikuni, Shimpei; Ono, Masahiro; Watanabe, Hiroyuki; Matsumura, Kenji; Yoshimura, Masashi; Kimura, Hiroyuki; Ishibashi-Ueda, Hatsue; Okamoto, Yoko; Ihara, Masafumi; Saji, Hideo

2016-05-01

Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid aggregates in the walls of cerebral vasculature, is a major factor in intracerebral hemorrhage and vascular cognitive impairment and is also associated closely with Alzheimer’s disease (AD). We previously reported 99mTc-hydroxamamide (99mTc-Ham) complexes with a bivalent amyloid ligand showing high binding affinity for β-amyloid peptide (Aβ(1-42)) aggregates present frequently in the form in AD. In this article, we applied them to CAA-specific imaging probes, and evaluated their utility for CAA-specific imaging. In vitro inhibition assay using Aβ(1-40) aggregates deposited mainly in CAA and a brain uptake study were performed for 99mTc-Ham complexes, and all 99mTc-Ham complexes with an amyloid ligand showed binding affinity for Aβ(1-40) aggregates and very low brain uptake. In vitro autoradiography of human CAA brain sections and ex vivo autoradiography of Tg2576 mice were carried out for bivalent 99mTc-Ham complexes ([99mTc]SB2A and [99mTc]BT2B), and they displayed excellent labeling of Aβ depositions in human CAA brain sections and high affinity and selectivity to CAA in transgenic mice. These results may offer new possibilities for the development of clinically useful CAA-specific imaging probes based on the 99mTc-Ham complex.

Imaging of Cerebral Amyloid Angiopathy with Bivalent (99m)Tc-Hydroxamamide Complexes.

PubMed

Iikuni, Shimpei; Ono, Masahiro; Watanabe, Hiroyuki; Matsumura, Kenji; Yoshimura, Masashi; Kimura, Hiroyuki; Ishibashi-Ueda, Hatsue; Okamoto, Yoko; Ihara, Masafumi; Saji, Hideo

2016-05-16

Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid aggregates in the walls of cerebral vasculature, is a major factor in intracerebral hemorrhage and vascular cognitive impairment and is also associated closely with Alzheimer's disease (AD). We previously reported (99m)Tc-hydroxamamide ((99m)Tc-Ham) complexes with a bivalent amyloid ligand showing high binding affinity for β-amyloid peptide (Aβ(1-42)) aggregates present frequently in the form in AD. In this article, we applied them to CAA-specific imaging probes, and evaluated their utility for CAA-specific imaging. In vitro inhibition assay using Aβ(1-40) aggregates deposited mainly in CAA and a brain uptake study were performed for (99m)Tc-Ham complexes, and all (99m)Tc-Ham complexes with an amyloid ligand showed binding affinity for Aβ(1-40) aggregates and very low brain uptake. In vitro autoradiography of human CAA brain sections and ex vivo autoradiography of Tg2576 mice were carried out for bivalent (99m)Tc-Ham complexes ([(99m)Tc]SB2A and [(99m)Tc]BT2B), and they displayed excellent labeling of Aβ depositions in human CAA brain sections and high affinity and selectivity to CAA in transgenic mice. These results may offer new possibilities for the development of clinically useful CAA-specific imaging probes based on the (99m)Tc-Ham complex.

Iodine-122-labeled amphetamine derivative with potential for PET brain blood-flow studies

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

Mathis, C.A.; Sargent, T. 3d.; Shulgin, A.T.

1985-11-01

The positron emitter SSI (t1/2 3.6 min) was collected from a xenon- SS/iodine- SS ( SSXe/ SSI) generator and incorporated into an amphetamine analog, 2,4-dimethoxy-N,N-dimethyl-5-( SSI)iodophenylisopropylamine (5-( SSI)-2,4-DNNA). The remote synthesis was achieved in 3 min with a 50% radioincorporation yield and a product radiopurity of greater than 98%. 5-( SSI)-2,4-DNNA was injected into a beagle dog and a brain section imaged with positron emission tomography (PET). The uptake and retention of 5-( SSI)-2,4-DNNA was compared to that of YSRb in the same animal. Dynamic PET activity data were obtained 0-20 min postinjection of 5-( SSI)-2,4-DNNA and showed rapid uptakemore » by brain and good cerebral/extracerebral tissue distinction. A whole-body scan of a dog was also obtained with 5-123I-2,4-DNNA showing uptake in brain, lung, and other body organs. The feasibility of incorporating SSI into an extracted brain perfusion agent for use with PET is demonstrated.« less

Demeclocycline as a contrast agent for detecting brain neoplasms using confocal microscopy

NASA Astrophysics Data System (ADS)

Wirth, Dennis; Smith, Thomas W.; Moser, Richard; Yaroslavsky, Anna N.

2015-04-01

Complete resection of brain tumors improves life expectancy and quality. Thus, there is a strong need for high-resolution detection and microscopically controlled removal of brain neoplasms. The goal of this study was to test demeclocycline as a contrast enhancer for the intraoperative detection of brain tumors. We have imaged benign and cancerous brain tumors using multimodal confocal microscopy. The tumors investigated included pituitary adenoma, meningiomas, glioblastomas, and metastatic brain cancers. Freshly excised brain tissues were stained in 0.75 mg ml-1 aqueous solution of demeclocyline. Reflectance images were acquired at 402 nm. Fluorescence signals were excited at 402 nm and registered between 500 and 540 nm. After imaging, histological sections were processed from the imaged specimens and compared to the optical images. Fluorescence images highlighted normal and cancerous brain cells, while reflectance images emphasized the morphology of connective tissue. The optical and histological images were in accordance with each other for all types of tumors investigated. Demeclocyline shows promise as a contrast agent for intraoperative detection of brain tumors.

Expression of the ADHD candidate gene Diras2 in the brain.

PubMed

Grünewald, Lena; Becker, Nils; Camphausen, Annika; O'Leary, Aet; Lesch, Klaus-Peter; Freudenberg, Florian; Reif, Andreas

2018-06-01

The distinct subgroup of the Ras family member 2 (DIRAS2) gene has been found to be associated with attention-deficit/hyperactivity disorder (ADHD) in one of our previous studies. This gene is coding for a small Ras GTPase with unknown function. DIRAS2 is highly expressed in the brain. However, the exact neural expression pattern of this gene was unknown so far. Therefore, we investigated the expressional profile of DIRAS2 in the human and murine brain. In the present study, qPCR analyses in the human and in the developing mouse brain, immunocytological double staining on murine hippocampal primary cells and RNA in situ hybridization (ISH) on brain sections of C57BL/6J wild-type mice, have been used to reveal the expression pattern of DIRAS2 in the brain. We could show that DIRAS2 expression in the human brain is the highest in the hippocampus and the cerebral cortex, which is in line with the ISH results in the mouse brain. During mouse brain development, Diras2 levels strongly increase from prenatal to late postnatal stages. Co-expression studies indicate Diras2 expression in glutamatergic and catecholaminergic neurons. Our findings support the idea of DIRAS2 as a candidate gene for ADHD as the timeline of its expression as well as the brain regions and cell types that show Diras2 expression correspond to those assumed to underlie the pathomechanisms of the disease.

Registration of in vivo MR to histology of rodent brains using blockface imaging

NASA Astrophysics Data System (ADS)

Uberti, Mariano; Liu, Yutong; Dou, Huanyu; Mosley, R. Lee; Gendelman, Howard E.; Boska, Michael

2009-02-01

Registration of MRI to histopathological sections can enhance bioimaging validation for use in pathobiologic, diagnostic, and therapeutic evaluations. However, commonly used registration methods fall short of this goal due to tissue shrinkage and tearing after brain extraction and preparation. In attempts to overcome these limitations we developed a software toolbox using 3D blockface imaging as the common space of reference. This toolbox includes a semi-automatic brain extraction technique using constraint level sets (CLS), 3D reconstruction methods for the blockface and MR volume, and a 2D warping technique using thin-plate splines with landmark optimization. Using this toolbox, the rodent brain volume is first extracted from the whole head MRI using CLS. The blockface volume is reconstructed followed by 3D brain MRI registration to the blockface volume to correct the global deformations due to brain extraction and fixation. Finally, registered MRI and histological slices are warped to corresponding blockface images to correct slice specific deformations. The CLS brain extraction technique was validated by comparing manual results showing 94% overlap. The image warping technique was validated by calculating target registration error (TRE). Results showed a registration accuracy of a TRE < 1 pixel. Lastly, the registration method and the software tools developed were used to validate cell migration in murine human immunodeficiency virus type one encephalitis.

Comparison of effectiveness between cork-screw and peg-screw electrodes for transcranial motor evoked potential monitoring using the finite element method.

PubMed

Tomio, Ryosuke; Akiyama, Takenori; Ohira, Takayuki; Yoshida, Kazunari

2016-01-01

Intraoperative monitoring of motor evoked potentials by transcranial electric stimulation is popular in neurosurgery for monitoring motor function preservation. Some authors have reported that the peg-screw electrodes screwed into the skull can more effectively conduct current to the brain compared to subdermal cork-screw electrodes screwed into the skin. The aim of this study was to investigate the influence of electrode design on transcranial motor evoked potential monitoring. We estimated differences in effectiveness between the cork-screw electrode, peg-screw electrode, and cortical electrode to produce electric fields in the brain. We used the finite element method to visualize electric fields in the brain generated by transcranial electric stimulation using realistic three-dimensional head models developed from T1-weighted images. Surfaces from five layers of the head were separated as accurately as possible. We created the "cork-screws model," "1 peg-screw model," "peg-screws model," and "cortical electrode model". Electric fields in the brain radially diffused from the brain surface at a maximum just below the electrodes in coronal sections. The coronal sections and surface views of the brain showed higher electric field distributions under the peg-screw compared to the cork-screw. An extremely high electric field was observed under cortical electrodes. Our main finding was that the intensity of electric fields in the brain are higher in the peg-screw model than the cork-screw model.

Interactive 3D visualization of structural changes in the brain of a person with corticobasal syndrome

PubMed Central

Hänel, Claudia; Pieperhoff, Peter; Hentschel, Bernd; Amunts, Katrin; Kuhlen, Torsten

2014-01-01

The visualization of the progression of brain tissue loss in neurodegenerative diseases like corticobasal syndrome (CBS) can provide not only information about the localization and distribution of the volume loss, but also helps to understand the course and the causes of this neurodegenerative disorder. The visualization of such medical imaging data is often based on 2D sections, because they show both internal and external structures in one image. Spatial information, however, is lost. 3D visualization of imaging data is capable to solve this problem, but it faces the difficulty that more internally located structures may be occluded by structures near the surface. Here, we present an application with two designs for the 3D visualization of the human brain to address these challenges. In the first design, brain anatomy is displayed semi-transparently; it is supplemented by an anatomical section and cortical areas for spatial orientation, and the volumetric data of volume loss. The second design is guided by the principle of importance-driven volume rendering: A direct line-of-sight to the relevant structures in the deeper parts of the brain is provided by cutting out a frustum-like piece of brain tissue. The application was developed to run in both, standard desktop environments and in immersive virtual reality environments with stereoscopic viewing for improving the depth perception. We conclude, that the presented application facilitates the perception of the extent of brain degeneration with respect to its localization and affected regions. PMID:24847243

The potential role of Morus alba leaves extract on the brain of mice infected with Schistosoma mansoni.

PubMed

Bauomy, Amira A

2014-01-01

Schistosomiasis is a neglected tropical disease which is associated with neuropsychiatric and neuropathological disorders. Herein, the main goal of the presented work is to investigate the effect of Morus alba leaves extract in mice brain infected with Schistosoma mansoni. Since, the resistance of Schistosomes to antischistosomal drug (praziquantel) has been examined, schistosomiasis induced brain oxidative stress as evidenced by the decrease of glutathione level, total antioxidant capacity and the activity of catalase significantly, while a significant elevation in the levels of nitrite/nitrate and malondialdhyde. In addition, the infection resulted in neurochemical disturbances, the main inhibitory amino acid, γ- aminobutyric acid level was decreased. In contrast, the level of chloride ions and acetylcholine esterase activity were significantly increased. Moreover, the histopathological section showed some impairments in the brain. The treatment with Morus alba leaves extract ameliorated the induced disturbances in schistosome-infected mice where the levels of non-enzymatic and enzymatic antioxidants were elevated. On the other hand, the levels of nitrite/nitrate and malondialdhyde were significantly reduced. Likewise, treatment of mice with Morus alba leaves extract improved the altered levels of γ- aminobutyric acid level and chloride ion. Also, it improved the recorded impairments of the histopathological section in the brain of schistosome infected mice.

O-GlcNAc modification of radial glial vimentin filaments in the developing chick brain.

PubMed

Farach, Andrew M; Galileo, Deni S

2008-12-01

We examined the post-translational modification of intracellular proteins by beta-O-linked N-acetylglucosamine (O-GlcNAc) with regard to neurofilament phosphorylation in the developing chick optic tectum. A regulated developmental pattern of O-GlcNAcylation was discovered in the developing brain. Most notably, discernible staining occurs along radial glial filaments but not along neuronal filaments in vivo. Immunohistochemical analyses in sections of progressive stages of development suggest upregulation of O-GlcNAc in the ependyma, tectofugal neuron bodies, and radial glial processes, but not in axons. In contrast, double-label immunostaining of monolayer cultures made from dissociated embryonic day (E) 7 optic tecta revealed O-GlcNAcylation of most axons. Labeling of brain sections together with Western blot analyses showed O-GlcNAc modification of a few discrete proteins throughout development, and suggested vimentin as the protein in radial glia. Immunoprecipitation of vimentin from E9 whole brain lysates confirmed O-GlcNAcylation of vimentin in development. These results indicate a regulated pattern of O-GlcNAc modification of vimentin filaments, which in turn suggests a role for O-GlcNAc-modified intermediate filaments in radial glia, but not in neurons during brain development. The control mechanisms that regulate this pattern in vivo, however, are disrupted when cells are placed in vitro.

3D culture of murine neural stem cells on decellularized mouse brain sections.

PubMed

De Waele, Jorrit; Reekmans, Kristien; Daans, Jasmijn; Goossens, Herman; Berneman, Zwi; Ponsaerts, Peter

2015-02-01

Transplantation of neural stem cells (NSC) in diseased or injured brain tissue is widely studied as a potential treatment for various neurological pathologies. However, effective cell replacement therapy relies on the intrinsic capacity of cellular grafts to overcome hypoxic and/or immunological barriers after transplantation. In this context, it is hypothesized that structural support for grafted NSC will be of utmost importance. With this study, we present a novel decellularization protocol for 1.5 mm thick mouse brain sections, resulting in the generation of acellular three-dimensional (3D) brain sections. Next, the obtained 3D brain sections were seeded with murine NSC expressing both the eGFP and luciferase reporter proteins (NSC-eGFP/Luc). Using real-time bioluminescence imaging, the survival and growth of seeded NSC-eGFP/Luc cells was longitudinally monitored for 1-7 weeks in culture, indicating the ability of the acellular brain sections to support sustained ex vivo growth of NSC. Next, the organization of a 3D maze-like cellular structure was examined using confocal microscopy. Moreover, under mitogenic stimuli (EGF and hFGF-2), most cells in this 3D culture retained their NSC phenotype. Concluding, we here present a novel protocol for decellularization of mouse brain sections, which subsequently support long-term 3D culture of undifferentiated NSC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain activation patterns in women with acquired hypoactive sexual desire disorder and women with normal sexual function: a cross-sectional pilot study.

PubMed

Woodard, Terri L; Nowak, Nicole T; Balon, Richard; Tancer, Manuel; Diamond, Michael P

2013-10-01

To examine and compare brain activation patterns of premenopausal women with normal sexual function and those with hypoactive sexual desire disorder (HSDD) during viewing of validated sexually explicit film clips. Cross-sectional pilot study. University-based clinical research center. Premenopausal women. None. Areas of brain activation during viewing of sexually explicit film clips. Women with normal sexual function showed significantly greater activation of the right thalamus, left insula, left precentral gyrus, and left parahippocampal gyrus in comparison with women with HSDD, who exhibited greater activation of the right medial frontal gyrus and left precuneus regions. Women with HSDD may have alterations in activation of limbic and cortical structures responsible for acquiring, encoding, and retrieving memory, the processing and memory of emotional reactions, and areas responsible for heightened attention to one's own physical state. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Brain activation patterns in women with acquired hypoactive sexual desire disorder and women with normal sexual function: a cross-sectional pilot study

PubMed Central

Woodard, Terri L.; Nowak, Nicole T.; Balon, Richard; Tancer, Manuel; Diamond, Michael P.

2013-01-01

Objective To examine and compare brain activation patterns of premenopausal women with normal sexual function and those with hypoactive sexual desire disorder (HSDD) during viewing of validated sexually explicit film clips. Design Cross-sectional pilot study. Setting University-based clinical research center. Patient(s) Premenopausal women. Intervention(s) None. Main Outcome Measure(s) Areas of brain activation during viewing of sexually explicit film clips. Result(s) Women with normal sexual function showed significantly greater activation of the right thalamus, left insula, left precentral gyrus, and left parahippocampal gyrus in comparison with women with HSDD, who exhibited greater activation of the right medial frontal gyrus and left precuneus regions. Conclusion(s) Women with HSDD may have alterations in activation of limbic and cortical structures responsible for acquiring, encoding, and retrieving memory, the processing and memory of emotional reactions, and areas responsible for heightened attention to one’s own physical state. PMID:23830149

III. The importance of physical activity and aerobic fitness for cognitive control and memory in children.

PubMed

Chaddock-Heyman, Laura; Hillman, Charles H; Cohen, Neal J; Kramer, Arthur F

2014-12-01

In this chapter, we review literature that examines the association among physical activity, aerobic fitness, cognition, and the brain in elementary school children (ages 7-10 years). Specifically, physical activity and higher levels of aerobic fitness in children have been found to benefit brain structure, brain function, cognition, and school achievement. For example, higher fit children have larger brain volumes in the basal ganglia and hippocampus, which relate to superior performance on tasks of cognitive control and memory, respectively, when compared to their lower fit peers. Higher fit children also show superior brain function during tasks of cognitive control, better scores on tests of academic achievement, and higher performance on a real-world street crossing task, compared to lower fit and less active children. The cross-sectional findings are strengthened by a few randomized, controlled trials, which demonstrate that children randomly assigned to a physical activity intervention group show greater brain and cognitive benefits compared to a control group. Because these findings suggest that the developing brain is plastic and sensitive to lifestyle factors, we also discuss typical structural and functional brain maturation in children to provide context in which to interpret the effects of physical activity and aerobic fitness on the developing brain. This research is important because children are becoming increasingly sedentary, physically inactive, and unfit. An important goal of this review is to emphasize the importance of physical activity and aerobic fitness for the cognitive and brain health of today's youth. © 2014 The Society for Research in Child Development, Inc.

A new approach of light microscopic immunohistochemical triple-staining: combination of Fos labeling with diaminobenzidine-nickel and neuropeptides labeled with Alexa488 and Alexa555 fluorescent dyes.

PubMed

Majercikova, Z; Weering, H van; Scsukova, S; Mikkelsen, J D; Kiss, A

2012-10-01

The aim of the present study was to introduce a new approach of the light microscopic immunohistochemical triple-staining enabling to study the differences in the activity of at least two different phenotypes of neurons on the same histological section. For this purpose combination of Fos (a product of the immediate early gene) labeling with nickel intensified diaminobenzidine (DAB-Ni) and two neuropeptides labeled with Alexa488 and Alexa555 fluorescent dyes on cryo-processed 35-40 µm thick free-floating brain sections was selected. The parallel occurrence of three antibodies studied, i.e. Fos, hypocretin (HCRT), and melanin-concentrating hormone (MCH), was studied by a new methodic approach utilizing combination of Fos immunolabeled with DAB-Ni and HCRT and MCH labeled with Alexa488 and Alexa555 fluorescent dyes, respectively. Fos stimulation was induced by a single immobilization (IM0) for 120 min. Then, the rats were sacrificed, the brains removed, soaked with 30% sucrose in 0.1 M phosphate buffer (PB), cryo-sectioned throughout the hypothalamus into 35-40 μm thick coronal sections, collected, and washed in the same buffer for 10-15 min. Fos was revealed by avidin-biotin-peroxidase (ABC) complex and visualized by diaminobenzidine chromogen containing nickel chloride salt. HCRT and MCH neurons were visualized by the above mentioned fluorescent dyes. Evaluation of the Fos and fluorescent staining was performed in the computerized Axo Imager Carl Zeiss microscope using light and fluorescent illuminations. All the antibodies used showed clear immunoreactive staining. Fos staining occurred in the form of black color located in the cell nuclei. HCRH and MCH neuropeptides showed clear green and red fluorescence in the cell perikarya, respectively. The final merged picture showed Fos protein in the activated green HCRT or red MCH neurons in the form of white nuclei. The present study clearly demonstrate that the combination of Fos labeling with DAB-Ni and neuropeptides labeled with Alexa488 and Alexa555 on cryo-processed 35-40 µm thick free-floating brain sections is an excellent approach providing further advantages for quick and reproducible triple immuno-staining enabling to compare the activity of at least two phenotypes of neurons on the same section. Alexa488 and Alexa555 fluorescent dyes, Fos, hypocretin, melanin-concentrating hormone, cryostat sections, triple labeling immunohistochemistry, rat.

Batch Immunostaining for Large-Scale Protein Detection in the Whole Monkey Brain

PubMed Central

Zangenehpour, Shahin; Burke, Mark W.; Chaudhuri, Avi; Ptito, Maurice

2009-01-01

Immunohistochemistry (IHC) is one of the most widely used laboratory techniques for the detection of target proteins in situ. Questions concerning the expression pattern of a target protein across the entire brain are relatively easy to answer when using IHC in small brains, such as those of rodents. However, answering the same questions in large and convoluted brains, such as those of primates presents a number of challenges. Here we present a systematic approach for immunodetection of target proteins in an adult monkey brain. This approach relies on the tissue embedding and sectioning methodology of NeuroScience Associates (NSA) as well as tools developed specifically for batch-staining of free-floating sections. It results in uniform staining of a set of sections which, at a particular interval, represents the entire brain. The resulting stained sections can be subjected to a wide variety of analytical procedures in order to measure protein levels, the population of neurons expressing a certain protein. PMID:19636291

A Proposal of New Reference System for the Standard Axial, Sagittal, Coronal Planes of Brain Based on the Serially-Sectioned Images

PubMed Central

Park, Jin Seo; Park, Hyo Seok; Shin, Dong Sun; Har, Dong-Hwan; Cho, Zang-Hee; Kim, Young-Bo; Han, Jae-Yong; Chi, Je-Geun

2010-01-01

Sectional anatomy of human brain is useful to examine the diseased brain as well as normal brain. However, intracerebral reference points for the axial, sagittal, and coronal planes of brain have not been standardized in anatomical sections or radiological images. We made 2,343 serially-sectioned images of a cadaver head with 0.1 mm intervals, 0.1 mm pixel size, and 48 bit color and obtained axial, sagittal, and coronal images based on the proposed reference system. This reference system consists of one principal reference point and two ancillary reference points. The two ancillary reference points are the anterior commissure and the posterior commissure. And the principal reference point is the midpoint of two ancillary reference points. It resides in the center of whole brain. From the principal reference point, Cartesian coordinate of x, y, z could be made to be the standard axial, sagittal, and coronal planes. PMID:20052359

Aging reduces the stimulating effect of blue light on cognitive brain functions.

PubMed

Daneault, Véronique; Hébert, Marc; Albouy, Geneviève; Doyon, Julien; Dumont, Marie; Carrier, Julie; Vandewalle, Gilles

2014-01-01

Light exposure, particularly blue light, is being recognized as a potent mean to stimulate alertness and cognition in young individuals. Aging is associated with changes in alertness regulation and cognition. Whether the effect of light on cognitive brain function changes with aging is unknown, however. Cross-sectional study. Functional Neuroimaging Unit, University of Montreal Geriatric Institute. Sixteen younger (23 ± 4.1 y) and 14 older (61 ± 4.5 y) healthy participants were recruited in the current study. Blue light administration. We used functional magnetic resonance imaging to record brain responses to an auditory working memory task in young and older healthy individuals, alternatively maintained in darkness or exposed to blue light. Results show that the older brain remains capable of showing sustained responses to light in several brain areas. However, compared to young individuals, the effect of blue light is decreased in the pulvinar, amygdala, and tegmentum as well as in the insular, prefrontal, and occipital cortices in elderly individuals. The effect of blue light on brain responses diminishes with aging in areas typically involved in visual functions and in key regions for alertness regulation and higher executive processes. Our findings provide the first indications that the effect of light on cognition may be reduced in healthy aging.

Large-Scale Mass Spectrometry Imaging Investigation of Consequences of Cortical Spreading Depression in a Transgenic Mouse Model of Migraine

NASA Astrophysics Data System (ADS)

Carreira, Ricardo J.; Shyti, Reinald; Balluff, Benjamin; Abdelmoula, Walid M.; van Heiningen, Sandra H.; van Zeijl, Rene J.; Dijkstra, Jouke; Ferrari, Michel D.; Tolner, Else A.; McDonnell, Liam A.; van den Maagdenberg, Arn M. J. M.

2015-06-01

Cortical spreading depression (CSD) is the electrophysiological correlate of migraine aura. Transgenic mice carrying the R192Q missense mutation in the Cacna1a gene, which in patients causes familial hemiplegic migraine type 1 (FHM1), exhibit increased propensity to CSD. Herein, mass spectrometry imaging (MSI) was applied for the first time to an animal cohort of transgenic and wild type mice to study the biomolecular changes following CSD in the brain. Ninety-six coronal brain sections from 32 mice were analyzed by MALDI-MSI. All MSI datasets were registered to the Allen Brain Atlas reference atlas of the mouse brain so that the molecular signatures of distinct brain regions could be compared. A number of metabolites and peptides showed substantial changes in the brain associated with CSD. Among those, different mass spectral features showed significant ( t-test, P < 0.05) changes in the cortex, 146 and 377 Da, and in the thalamus, 1820 and 1834 Da, of the CSD-affected hemisphere of FHM1 R192Q mice. Our findings reveal CSD- and genotype-specific molecular changes in the brain of FHM1 transgenic mice that may further our understanding about the role of CSD in migraine pathophysiology. The results also demonstrate the utility of aligning MSI datasets to a common reference atlas for large-scale MSI investigations.

Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents

PubMed Central

Dobrivojević, Marina; Bohaček, Ivan; Erjavec, Igor; Gorup, Dunja; Gajović, Srećko

2013-01-01

Aim To explore the possibility of brain imaging by microcomputed tomography (microCT) using x-ray contrasting methods to visualize mouse brain ischemic lesions after middle cerebral artery occlusion (MCAO). Methods Isolated brains were immersed in ionic or nonionic radio contrast agent (RCA) for 5 days and subsequently scanned using microCT scanner. To verify whether ex-vivo microCT brain images can be used to characterize ischemic lesions, they were compared to Nissl stained serial histological sections of the same brains. To verify if brains immersed in RCA may be used afterwards for other methods, subsequent immunofluorescent labeling with anti-NeuN was performed. Results Nonionic RCA showed better gray to white matter contrast in the brain, and therefore was selected for further studies. MicroCT measurement of ischemic lesion size and cerebral edema significantly correlated with the values determined by Nissl staining (ischemic lesion size: P=0.0005; cerebral edema: P=0.0002). Brain immersion in nonionic RCA did not affect subsequent immunofluorescent analysis and NeuN immunoreactivity. Conclusion MicroCT method was proven to be suitable for delineation of the ischemic lesion from the non-infarcted tissue, and quantification of lesion volume and cerebral edema. PMID:23444240

Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents.

PubMed

Dobrivojević, Marina; Bohaček, Ivan; Erjavec, Igor; Gorup, Dunja; Gajović, Srećko

2013-02-01

To explore the possibility of brain imaging by microcomputed tomography (microCT) using x-ray contrasting methods to visualize mouse brain ischemic lesions after middle cerebral artery occlusion (MCAO). Isolated brains were immersed in ionic or nonionic radio contrast agent (RCA) for 5 days and subsequently scanned using microCT scanner. To verify whether ex-vivo microCT brain images can be used to characterize ischemic lesions, they were compared to Nissl stained serial histological sections of the same brains. To verify if brains immersed in RCA may be used afterwards for other methods, subsequent immunofluorescent labeling with anti-NeuN was performed. Nonionic RCA showed better gray to white matter contrast in the brain, and therefore was selected for further studies. MicroCT measurement of ischemic lesion size and cerebral edema significantly correlated with the values determined by Nissl staining (ischemic lesion size: P=0.0005; cerebral edema: P=0.0002). Brain immersion in nonionic RCA did not affect subsequent immunofluorescent analysis and NeuN immunoreactivity. MicroCT method was proven to be suitable for delineation of the ischemic lesion from the non-infarcted tissue, and quantification of lesion volume and cerebral edema.

Abdominal fat distribution and its relationship to brain changes: the differential effects of age on cerebellar structure and function: a cross-sectional, exploratory study

PubMed Central

Raschpichler, Matthias; Straatman, Kees; Schroeter, Matthias Leopold; Arelin, Katrin; Schlögl, Haiko; Fritzsch, Dominik; Mende, Meinhard; Pampel, André; Böttcher, Yvonne; Stumvoll, Michael; Villringer, Arno; Mueller, Karsten

2013-01-01

Objectives To investigate whether the metabolically important visceral adipose tissue (VAT) relates differently to structural and functional brain changes in comparison with body weight measured as body mass index (BMI). Moreover, we aimed to investigate whether these effects change with age. Design Cross-sectional, exploratory. Setting University Clinic, Integrative Research and Treatment Centre. Participants We included 100 (mean BMI=26.0 kg/m², 42 women) out of 202 volunteers randomly invited by the city's registration office, subdivided into two age groups: young-to-mid-age (n=51, 20–45 years of age, mean BMI=24.9, 24 women) versus old (n=49, 65–70 years of age, mean BMI=27.0, 18 women). Main outcome measures VAT, BMI, subcutaneous abdominal adipose tissue, brain structure (grey matter density), functional brain architecture (eigenvector centrality, EC). Results We discovered a loss of cerebellar structure with increasing VAT in the younger participants, most significantly in regions involved in motor processing. This negative correlation disappeared in the elderly. Investigating functional brain architecture showed again inverse VAT–cerebellum correlations, whereas now regions involved in cognitive and emotional processing were significant. Although we detected similar results for EC using BMI, significant age interaction for both brain structure and functional architecture was only found using VAT. Conclusions Visceral adiposity is associated with cerebellar changes of both structure and function, whereas the regions involved contribute to motor, cognitive and emotional processes. Furthermore, these associations seem to be age dependent, with younger adults’ brains being adversely affected. PMID:23355665

MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat.

PubMed

Casas, Rafael; Muthusamy, Siva; Wakim, Paul G; Sinharay, Sanhita; Lentz, Margaret R; Reid, William C; Hammoud, Dima A

2018-01-01

HIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients. Cross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits. Cross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats. The disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain damage becomes irreversible.

Structural and molecular interrogation of intact biological systems

PubMed Central

Chung, Kwanghun; Wallace, Jenelle; Kim, Sung-Yon; Kalyanasundaram, Sandhiya; Andalman, Aaron S.; Davidson, Thomas J.; Mirzabekov, Julie J.; Zalocusky, Kelly A.; Mattis, Joanna; Denisin, Aleksandra K.; Pak, Sally; Bernstein, Hannah; Ramakrishnan, Charu; Grosenick, Logan; Gradinaru, Viviana; Deisseroth, Karl

2014-01-01

Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease. PMID:23575631

High-throughput 3D whole-brain quantitative histopathology in rodents

PubMed Central

Vandenberghe, Michel E.; Hérard, Anne-Sophie; Souedet, Nicolas; Sadouni, Elmahdi; Santin, Mathieu D.; Briet, Dominique; Carré, Denis; Schulz, Jocelyne; Hantraye, Philippe; Chabrier, Pierre-Etienne; Rooney, Thomas; Debeir, Thomas; Blanchard, Véronique; Pradier, Laurent; Dhenain, Marc; Delzescaux, Thierry

2016-01-01

Histology is the gold standard to unveil microscopic brain structures and pathological alterations in humans and animal models of disease. However, due to tedious manual interventions, quantification of histopathological markers is classically performed on a few tissue sections, thus restricting measurements to limited portions of the brain. Recently developed 3D microscopic imaging techniques have allowed in-depth study of neuroanatomy. However, quantitative methods are still lacking for whole-brain analysis of cellular and pathological markers. Here, we propose a ready-to-use, automated, and scalable method to thoroughly quantify histopathological markers in 3D in rodent whole brains. It relies on block-face photography, serial histology and 3D-HAPi (Three Dimensional Histology Analysis Pipeline), an open source image analysis software. We illustrate our method in studies involving mouse models of Alzheimer’s disease and show that it can be broadly applied to characterize animal models of brain diseases, to evaluate therapeutic interventions, to anatomically correlate cellular and pathological markers throughout the entire brain and to validate in vivo imaging techniques. PMID:26876372

Preclinical Evaluation of 18F-JNJ64349311, a Novel PET Tracer for Tau Imaging.

PubMed

Declercq, Lieven; Rombouts, Frederik; Koole, Michel; Fierens, Katleen; Mariën, Jonas; Langlois, Xavier; Andrés, José Ignacio; Schmidt, Mark; Macdonald, Gregor; Moechars, Diederik; Vanduffel, Wim; Tousseyn, Thomas; Vandenberghe, Rik; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy

2017-06-01

In this study, we have synthesized and evaluated 18 F-JNJ64349311, a tracer with high affinity for aggregated tau (inhibition constant value, 8 nM) and high (≥500×) in vitro selectivity for tau over β-amyloid, in comparison with the benchmark compound 18 F-AV1451 ( 18 F-T807) in mice, rats, and a rhesus monkey. Methods: In vitro binding characteristics were determined for Alzheimer's disease, progressive supranuclear palsy, and corticobasal degeneration patient brain tissue slices using autoradiography studies. Ex vivo biodistribution studies were performed in mice. Radiometabolites were quantified in the brain and plasma of mice and in the plasma of a rhesus monkey using high-performance liquid chromatography. Dynamic small-animal PET studies were performed in rats and a rhesus monkey to evaluate tracer pharmacokinetics in the brain. Results: Mouse biodistribution studies showed moderate initial brain uptake and rapid brain washout. Radiometabolite analyses after injection of 18 F-JNJ64349311 in mice showed the presence of a polar radiometabolite in plasma, but not in the brain. Semiquantitative autoradiography studies on postmortem tissue sections of human Alzheimer's disease brains showed highly displaceable binding to tau-rich regions. No specific binding was, however, found on human progressive supranuclear palsy and corticobasal degeneration brain slices. Small-animal PET scans of Wistar rats revealed moderate initial brain uptake (SUV, ∼1.5 at 1 min after injection) and rapid brain washout. Gradual bone uptake was, however, also observed. Blocking and displacement did not affect brain time-activity curves, suggesting no off-target specific binding of the tracer in the healthy rat brain. A small-animal PET scan of a rhesus monkey revealed moderate initial brain uptake (SUV, 1.9 at 1 min after injection) with a rapid washout. In the monkey, no bone uptake was detected during the 120-min scan. Conclusion: This biologic evaluation suggests that 18 F-JNJ64349311 is a promising tau PET tracer candidate, with a favorable pharmacokinetic profile, as compared with 18 F-AV1451. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Altered spontaneous brain activity in Cushing's disease: a resting-state functional MRI study.

PubMed

Jiang, Hong; He, Na-Ying; Sun, Yu-Hao; Jian, Fang-Fang; Bian, Liu-Guan; Shen, Jian-Kang; Yan, Fu-Hua; Pan, Si-Jian; Sun, Qing-Fang

2017-03-01

Cushing's disease (CD) provides a unique and naturalist model for studying the influence of hypercortisolism on the human brain and the reversibility of these effects after resolution of the condition. This cross-sectional study used resting-state fMRI (rs-fMRI) to investigate the altered spontaneous brain activity in CD patients and the trends for potential reversibility after the resolution of the hypercortisolism. We also aim to determine the relationship of these changes with clinical characteristics and cortisol levels. Active CD patients (n = 18), remitted CD patients (n = 14) and healthy control subjects (n = 22) were included in this study. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. Our study resulted in three major findings: (i) active CD patients showed significantly altered spontaneous brain activity in the posterior cingulate cortex (PCC)/precuneus (PCu), occipital lobe (OC)/cerebellum, thalamus, right postcentral gyrus (PoCG) and left prefrontal cortex (PFC); (ii) trends for partial restoration of altered spontaneous brain activity after the resolution hypercortisolism were found in several brain regions; and (iii) active CD patients showed a significant correlation between cortisol levels and ALFF/ReHo values in the PCC/PCu, a small cluster in the OC and the right IPL. This study provides a new approach to investigating brain function abnormalities in patients with CD and enhances our understanding of the effect of hypercortisolism on the human brain. Furthermore, our explorative potential reversibility study of patients with CD may facilitate the development of future longitudinal studies. © 2016 John Wiley & Sons Ltd.

Technical Note: Immunohistochemical evaluation of mouse brain irradiation targeting accuracy with 3D-printed immobilization device.

PubMed

Zarghami, Niloufar; Jensen, Michael D; Talluri, Srikanth; Foster, Paula J; Chambers, Ann F; Dick, Frederick A; Wong, Eugene

2015-11-01

Small animal immobilization devices facilitate positioning of animals for reproducible imaging and accurate focal radiation therapy. In this study, the authors demonstrate the use of three-dimensional (3D) printing technology to fabricate a custom-designed mouse head restraint. The authors evaluate the accuracy of this device for the purpose of mouse brain irradiation. A mouse head holder was designed for a microCT couch using cad software and printed in an acrylic based material. Ten mice received half-brain radiation while positioned in the 3D-printed head holder. Animal placement was achieved using on-board image guidance and computerized asymmetric collimators. To evaluate the precision of beam localization for half-brain irradiation, mice were sacrificed approximately 30 min after treatment and brain sections were stained for γ-H2AX, a marker for DNA breaks. The distance and angle of the γ-H2AX radiation beam border to longitudinal fissure were measured on histological samples. Animals were monitored for any possible trauma from the device. Visualization of the radiation beam on ex vivo brain sections with γ-H2AX immunohistochemical staining showed a sharp radiation field within the tissue. Measurements showed a mean irradiation targeting error of 0.14±0.09 mm (standard deviation). Rotation between the beam axis and mouse head was 1.2°±1.0° (standard deviation). The immobilization device was easily adjusted to accommodate different sizes of mice. No signs of trauma to the mice were observed from the use of tooth block and ear bars. The authors designed and built a novel 3D-printed mouse head holder with many desired features for accurate and reproducible radiation targeting. The 3D printing technology was found to be practical and economical for producing a small animal imaging and radiation restraint device and allows for customization for study specific needs.

Technical Note: Immunohistochemical evaluation of mouse brain irradiation targeting accuracy with 3D-printed immobilization device

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

Zarghami, Niloufar, E-mail: nzargham@uwo.ca; Jensen, Michael D.; Talluri, Srikanth

Purpose: Small animal immobilization devices facilitate positioning of animals for reproducible imaging and accurate focal radiation therapy. In this study, the authors demonstrate the use of three-dimensional (3D) printing technology to fabricate a custom-designed mouse head restraint. The authors evaluate the accuracy of this device for the purpose of mouse brain irradiation. Methods: A mouse head holder was designed for a microCT couch using CAD software and printed in an acrylic based material. Ten mice received half-brain radiation while positioned in the 3D-printed head holder. Animal placement was achieved using on-board image guidance and computerized asymmetric collimators. To evaluate themore » precision of beam localization for half-brain irradiation, mice were sacrificed approximately 30 min after treatment and brain sections were stained for γ-H2AX, a marker for DNA breaks. The distance and angle of the γ-H2AX radiation beam border to longitudinal fissure were measured on histological samples. Animals were monitored for any possible trauma from the device. Results: Visualization of the radiation beam on ex vivo brain sections with γ-H2AX immunohistochemical staining showed a sharp radiation field within the tissue. Measurements showed a mean irradiation targeting error of 0.14 ± 0.09 mm (standard deviation). Rotation between the beam axis and mouse head was 1.2° ± 1.0° (standard deviation). The immobilization device was easily adjusted to accommodate different sizes of mice. No signs of trauma to the mice were observed from the use of tooth block and ear bars. Conclusions: The authors designed and built a novel 3D-printed mouse head holder with many desired features for accurate and reproducible radiation targeting. The 3D printing technology was found to be practical and economical for producing a small animal imaging and radiation restraint device and allows for customization for study specific needs.« less

Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after rat transient cerebral ischemia

PubMed Central

2010-01-01

Background Although agmatine therapy in a mouse model of transient focal cerebral ischemia is highly protective against neurological injury, the mechanisms underlying the protective effects of agmatine are not fully elucidated. This study aimed to investigate the effects of agmatine on brain apoptosis, astrogliosis and edema in the rats with transient cerebral ischemia. Methods Following surgical induction of middle cerebral artery occlusion (MCAO) for 90 min, agmatine (100 mg/kg, i.p.) was injected 5 min after beginning of reperfusion and again once daily for the next 3 post-operative days. Four days after reperfusion, both motor and proprioception functions were assessed and then all rats were sacrificed for determination of brain infarct volume (2, 3, 5-triphenyltetrazolium chloride staining), apoptosis (TUNEL staining), edema (both cerebral water content and amounts of aquaporin-4 positive cells), gliosis (glial fibrillary acidic protein [GFAP]-positive cells), and neurotoxicity (inducible nitric oxide synthase [iNOS] expression). Results The results showed that agmatine treatment was found to accelerate recovery of motor (from 55 degrees to 62 degrees) and proprioception (from 54% maximal possible effect to 10% maximal possible effect) deficits and to prevent brain infarction (from 370 mm3 to 50 mm3), gliosis (from 80 GFAP-positive cells to 30 GFAP-positive cells), edema (cerebral water contents decreased from 82.5% to 79.4%; AQP4 positive cells decreased from 140 to 84 per section), apoptosis (neuronal apoptotic cells decreased from 100 to 20 per section), and neurotoxicity (iNOS expression cells decreased from 64 to 7 per section) during MCAO ischemic injury in rats. Conclusions The data suggest that agmatine may improve outcomes of transient cerebral ischemia in rats by reducing brain apoptosis, astrogliosis and edema. PMID:20815926

Functional imaging studies of emotion regulation: A synthetic review and evolving model of the cognitive control of emotion

PubMed Central

Ochsner, Kevin N.; Silvers, Jennifer A.; Buhle, Jason T.

2014-01-01

This paper reviews and synthesizes functional imaging research that over the past decade has begun to offer new insights into the brain mechanisms underlying emotion regulation. Towards that end, the first section of the paper outlines a model of the processes and neural systems involved in emotion generation and regulation. The second section surveys recent research supporting and elaborating the model, focusing primarily on studies of the most commonly investigated strategy, which is known as reappraisal. At its core, the model specifies how prefrontal and cingulate control systems modulate activity in perceptual, semantic and affect systems as a function of one's regulatory goals, tactics, and the nature of the stimuli and emotions being regulated. This section also shows how the model can be generalized to understand the brain mechanisms underlying other emotion regulation strategies as well as a range of other allied phenomena. The third and last section considers directions for future research, including how basic models of emotion regulation can be translated to understand changes in emotion across the lifespan and in clinical disorders. PMID:23025352

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus

PubMed Central

Hagan, Cindy C.; Graham, Julia M.E.; Tait, Roger; Widmer, Barry; van Nieuwenhuizen, Adrienne O.; Ooi, Cinly; Whitaker, Kirstie J.; Simas, Tiago; Bullmore, Edward T.; Lennox, Belinda R.; Sahakian, Barbara J.; Goodyer, Ian M.; Suckling, John

2015-01-01

Objective There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity. Method Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects. Results Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms. Conclusions The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain. PMID:25685707

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus.

PubMed

Hagan, Cindy C; Graham, Julia M E; Tait, Roger; Widmer, Barry; van Nieuwenhuizen, Adrienne O; Ooi, Cinly; Whitaker, Kirstie J; Simas, Tiago; Bullmore, Edward T; Lennox, Belinda R; Sahakian, Barbara J; Goodyer, Ian M; Suckling, John

2015-01-01

There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity. Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects. Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms. The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain.

Determining Optimal Microwave Antigen Retrieval Conditions for Microtubule-Associated Protein 2 Immunohistochemistry in the Guinea Pig Brain

DTIC Science & Technology

2002-12-01

sections of formalin-fixed guinea pig brains using different MAP-2 monoclonal antibodies. Brain sections were boiled in sodium citrate, citric acid...citric acid solution at pH 6.0 is the optimal microwave-assisted AR method for immunolabeling MAP-2 in formalin-fixed, paraffin-processed guinea pig brain...studies on archival guinea pig brain paraffin blocks, ultimately relaxing the use of additional animals to evaluate changes in MAP-2 expression between chemical warfare nerve agent-treated and control samples.

In Vivo Fiber-Optic Raman Mapping Of Metastases In Mouse Brains

NASA Astrophysics Data System (ADS)

Stelling, A.; Kirsch, M.; Steiner, G.; Krafft, C.; Schackert, G.; Salzer, R.

2010-08-01

Vibrational spectroscopy, in particular Raman spectroscopy, has potential applications in the field of in vivo diagnostics. Raman and FT-IR spectroscopy analyze the complete biochemical information at any given pixel within the visual field. Here we demonstrate the feasibility of performing Raman spectroscopic measurements on living mice brains using a fiber-optic probe with a nominal spatial resolution of 60 μm. The objectives of this study were to 1) evaluate preclinical models, namely murine brain slices containing experimental tumors, 2) optimize the preparation of pristine brain tissue to obtain reference information, to 3) optimize the conditions for introducing a fiber-optic probe to acquire Raman maps in vivo, and 4) to transfer results obtained from human brain tumors to an animal model. Disseminated brain metastases of malignant melanomas were induced by injecting tumor cells into the carotid artery of mice. The procedure mimicked hematogenous tumor spread in one brain hemisphere while the other hemisphere remained tumor free. Three series of sections were prepared consecutively from whole mouse brains: pristine, 2-mm thick sections for Raman mapping and dried, thin sections for FT-IR imaging, hematoxylin and eosin-stained thin sections for histopathological assessment. Raman maps were collected serially using a spectrometer coupled to a fiber-optic probe. FT-IR images were recorded using a spectrometer with a multi-channel detector. The FT-IR images and the Raman maps were evaluated by multivariate data analysis. The results obtained from the thin section studies were employed to guide measurements of murine brains in vivo. Raman maps with an acquisition time of over an hour could be performed on the living animals. No damage to the tissue was observed.

Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis.

PubMed

Kronbichler, Lisa; Tschernegg, Melanie; Martin, Anna Isabel; Schurz, Matthias; Kronbichler, Martin

2017-10-21

Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

PubMed

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer’s disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing. PMID:24271328

Microbleeds in postmortem brains of patients with Alzheimer disease: a T2*-weighted gradient-echo 7.0 T magnetic resonance imaging study.

PubMed

De Reuck, Jacques L; Cordonnier, Charlotte; Deramecourt, Vincent; Auger, Florent; Durieux, Nicolas; Bordet, Regis; Maurage, Claude-Alain; Leys, Didier; Pasquier, Florence

2013-01-01

This study aims to determine the distribution and to quantify microbleeds (MBs) in postmortem brains of patients with Alzheimer disease (AD) on T2*-weighted gradient-echo 7.0 T magnetic resonance imaging. Twenty-eight AD brains were compared with 5 controls. The AD brains were subdivided further: 18 without and 10 with additional severe cerebral amyloid angiopathy (AD-CAA). The distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central, and the occipital level of a cerebral hemisphere. MBs prevailed in the central sections (P=0.005) of AD brains without CAA, whereas in AD-CAA brains, they were more frequent in all coronal sections (P≤0.002). They prevailed in the deep cortical layers of the AD brains and of the controls (P≤0.03). They were significantly increased in all cortical layers of the AD-CAA brains (P≤0.04), compared with the controls. MBs prevalence in brains of AD patients had a different topographic distribution according to the absence or presence of severe CAA.

Synthesis of IL-2 mRNA in cells of rat hypothalamic structures after injection of short peptides.

PubMed

Kazakova, T B; Barabanova, S V; Novikova, N S; Glushikhina, M S; Khavinson, V Kh; Malinin, V V; Korneva, E A

2005-06-01

In situ hybridization on paraffin sections of the rat brain showed that synthetic peptides Vilon, Epithalon, and Cortagen modulated the expression of IL-2 gene in vivo in cells of some hypothalamic structures depending on the terms and routes of administration.

A Novel Liposomal Nanoparticle for the Imaging of Amyloid Plaque by Magnetic Resonance Imaging.

PubMed

Tanifum, Eric A; Ghaghada, Ketan; Vollert, Craig; Head, Elizabeth; Eriksen, Jason L; Annapragada, Ananth

2016-01-01

Amyloid binding molecules with greater hydrophilicity than existing ligands were synthesized. The lead candidate ET6-21 bound amyloid fibrils, and amyloid deposits in dog brain and human brain tissue ex vivo. The ligand was used to prepare novel amyloid-targeted liposomal nanoparticles. The preparation was tested in the Tg2576 and TetO/APP mouse models of amyloid deposition. Gd chelates and Indocyanine green were included in the particles for visualization by MRI and near-infrared microscopy. Upon intravenous injection, the particles successfully traversed the blood-brain barrier in these mice, and bound to the plaques. Magnetic resonance imaging (T1-MRI) conducted 4 days after injection demonstrated elevated signal in the brains of mice with amyloid plaques present. No signal was observed in amyloid-negative mice, or in amyloid-positive mice injected with an untargeted version of the same agent. The MRI results were confirmed by immunohistochemical and fluorescent microscopic examination of mouse brain sections, showing colocalization of the fluorescent tags and amyloid deposits.

Abnormal functional activation and maturation of ventromedial prefrontal cortex and cerebellum during temporal discounting in autism spectrum disorder.

PubMed

Murphy, Clodagh M; Christakou, Anastasia; Giampietro, Vincent; Brammer, Michael; Daly, Eileen M; Ecker, Christine; Johnston, Patrick; Spain, Debbie; Robertson, Dene M; Murphy, Declan G; Rubia, Katya

2017-11-01

People with autism spectrum disorder (ASD) have poor decision-making and temporal foresight. This may adversely impact on their everyday life, mental health, and productivity. However, the neural substrates underlying poor choice behavior in people with ASD, or its' neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking. This cross-sectional developmental fMRI study investigated the neural substrates underlying performance on a temporal discounting (TD) task in 38 healthy (11-35 years old) male adolescents and adults with ASD and 40 age, sex, and IQ-matched typically developing healthy controls. Most importantly, we assessed group differences in the neurofunctional maturation of TD across childhood and adulthood. Males with ASD had significantly poorer task performance and significantly lower brain activation in typical regions that mediate TD for delayed choices, in predominantly right hemispheric regions of ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex, striatolimbic regions, and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Findings provide first cross-sectional evidence that reduced activation of TD mediating brain regions in people with ASD during TD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of ASD. Hum Brain Mapp 38:5343-5355, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Only Time Will Tell: Cross-Sectional Studies Offer No Solution to the Age-Brain-Cognition Triangle--Comment on Salthouse (2011)

ERIC Educational Resources Information Center

Raz, Naftali; Lindenberger, Ulman

2011-01-01

Salthouse (2011) critically reviewed cross-sectional and longitudinal relations among adult age, brain structure, and cognition (ABC) and identified problems in interpretation of the extant literature. His review, however, missed several important points. First, there is enough disparity among the measures of brain structure and cognitive…

Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain Stimulation Treatments for Cocaine-Dependent Individuals.

PubMed

Hanlon, C A; Dowdle, L T; Jones, J L

2016-01-01

Cocaine dependence is one of the most difficult substance use disorders to treat. While the powerful effects of cocaine use on behavior were documented in the 19th century, it was not until the late 20th century that we realized cocaine use was affecting brain tissue and function. Following a brief introduction (Section 1), this chapter will summarize our current knowledge regarding alterations in neural circuit function typically observed in chronic cocaine users (Section 2) and highlight an emerging body of literature which suggests that pretreatment limbic circuit activity may be a reliable predictor of clinical outcomes among individuals seeking treatment for cocaine (Section 3). Finally, as the field of addiction research strives to translate this neuroimaging data into something clinically meaningful, we will highlight several new brain stimulation approaches which utilize functional brain imaging data to design noninvasive brain stimulation interventions for individuals seeking treatment for substance dependence disorders (Section 4). © 2016 Elsevier Inc. All rights reserved.

Short Nissl staining for incubated cryostat sections of the brain.

PubMed

Lindroos, O F

1991-01-01

Nissl stain often binds poorly to cryostat sections which have been incubated in solutions of radiolabeled ligands. Such incubation is used in receptor autoradiography of the brain when using the in vitro method. We have developed a rapid (16 min) modification of Nissl staining for sections that bind stain poorly, e.g., incubated sections. The method stains well sections which cannot be stained with other rapid Nissl staining methods.

The association between seizures and deposition of collagen in the brain in porcine Taenia solium neurocysticercosis.

PubMed

Christensen, Nina M; Trevisan, Chiara; Leifsson, Páll S; Johansen, Maria V

2016-09-15

Neurocysticercosis caused by infection with Taenia solium is a significant cause of epilepsy and seizures in humans. The aim of this study was to assess the association between seizures and the deposition of collagen in brain tissue in pigs with T. solium neurocysticercosis. In total 78 brain tissue sections from seven pigs were examined histopathologically i.e. two pigs with epileptic seizures and T. solium cysts, four pigs without seizures but with cysts, and one non-infected control pig. Pigs with epileptic seizures had a larger amount of collagen in their brain tissue, showing as large fibrotic scars and moderate amount of collagen deposited around cysts, compared to pigs without seizures and the negative control pig. Our results indicate that collagen is likely to play a considerable part in the pathogenesis of seizures in T. solium neurocysticercosis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer’s Post-Mortem Brain

PubMed Central

Emery, David C.; Shoemark, Deborah K.; Batstone, Tom E.; Waterfall, Christy M.; Coghill, Jane A.; Cerajewska, Tanya L.; Davies, Maria; West, Nicola X.; Allen, Shelley J.

2017-01-01

The neurological deterioration associated with Alzheimer’s disease (AD), involving accumulation of amyloid-beta peptides and neurofibrillary tangles, is associated with evident neuroinflammation. This is now seen to be a significant contributor to pathology. Recently the tenet of the privileged status of the brain, regarding microbial compromise, has been questioned, particularly in terms of neurodegenerative diseases. It is now being considered that microbiological incursion into the central nervous system could be either an initiator or significant contributor to these. This is a novel study using 16S ribosomal gene-specific Next generation sequencing (NGS) of extracted brain tissue. A comparison was made of the bacterial species content of both frozen and formaldehyde fixed sections of a small cohort of Alzheimer-affected cases with those of cognitively unimpaired (normal). Our findings suggest an increase in bacterial populations in Alzheimer brain tissue compared with normal. PMID:28676754

Optimization of immunolabeling and clearing techniques for indelibly-labeled memory traces.

PubMed

Pavlova, Ina P; Shipley, Shannon C; Lanio, Marcos; Hen, René; Denny, Christine A

2018-04-16

Recent genetic tools have allowed researchers to visualize and manipulate memory traces (i.e. engrams) in small brain regions. However, the ultimate goal is to visualize memory traces across the entire brain in order to better understand how memories are stored in neural networks and how multiple memories may coexist. Intact tissue clearing and imaging is a new and rapidly growing area of focus that could accomplish this task. Here, we utilized the leading protocols for whole-brain clearing and applied them to the ArcCreER T2 mice, a murine line that allows for the indelible labeling of memory traces. We found that CLARITY and PACT greatly distorted the tissue, and iDISCO quenched enhanced yellow fluorescent protein (EYFP) fluorescence and hindered immunolabeling. Alternative clearing solutions, such as tert-Butanol, circumvented these harmful effects, but still did not permit whole-brain immunolabeling. CUBIC and CUBIC with Reagent 1A produced improved antibody penetration and preserved EYFP fluorescence, but also did not allow for whole-brain memory trace visualization. Modification of CUBIC with Reagent-1A resulted in EYFP fluorescence preservation and immunolabeling of the immediate early gene (IEG) Arc in deep brain areas; however, optimized memory trace labeling still required tissue slicing into mm-thick tissue sections. In summary, our data show that CUBIC with Reagent-1A* is the ideal method for reproducible clearing and immunolabeling for the visualization of memory traces in mm-thick tissue sections from ArcCreER T2 mice. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

MRI evaluation and functional assessment of brain injury after hypoxic ischemia in neonatal mice.

PubMed

Adén, Ulrika; Dahlberg, Viktoria; Fredholm, Bertil B; Lai, Li-Ju; Chen, Zhengguan; Bjelke, Börje

2002-05-01

Severe perinatal asphyxia is an important cause of brain injury in the newborn infant. We examined early events after hypoxic ischemia (HI) in the 7-day-old mouse brain by MRI and related them to long-term functional effects and histopathology in the same animals at 4 to 5 weeks of age. HI was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated in vivo by MRI (T2 maps and apparent diffusion coefficient maps) at 3, 6, and 24 hours and 5 days after hypoxia. Locomotion and sensorimotor function were analyzed after 3 weeks. Four weeks after HI, the mice were killed, and cresyl violet-stained brain sections were examined morphologically. A decrease in apparent diffusion coefficient values in cortex on the affected side was found at 3 hours after HI. T2 values were significantly increased after 6 hours and remained so for 5 days. Maximal size of the lesion was attained at 3 to 6 hours after HI and declined thereafter. Animals with MRI-detected lesions had decreased forward locomotion, performed worse than controls in the beam-walking test, and showed a unilateral hypotrophy in the cresyl violet-stained brain sections 4 weeks later. The temporal progression of the damage after HI in 7-day-old mice differs from that of the adult brain as judged by MRI. The early lesions detected by MRI were related to functional impairments for these mice in near-adult life.

Comparison of a modified mid-coronal sectioning technique and Wilson's technique when conducting eye and brain examinations in rabbit teratology studies.

PubMed

Ziejewski, Mary K; Solomon, Howard M; Rendemonti, Joyce; Stanislaus, Dinesh

2015-02-01

There are two methods used when examining fetal rabbit eyes and brain in teratology studies. One method employs prior fixation before serial sectioning (Wilson's technique) and the other uses fresh tissue (mid-coronal sectioning). We modified the mid-coronal sectioning technique to include removal of eyes and brain for closer examination and to increase the number of structures that can be evaluated and compared it to the Wilson's technique. We found that external examination of the head, in conjunction with either sectioning method, is equally sensitive in identifying developmental defects. We evaluated 40,401 New Zealand White (NZW) and Dutch-Belted (DB) rabbit fetuses for external head alterations, of which 28,538 fetuses were further examined for eye and brain alterations using the modified mid-coronal sectioning method (16,675 fetuses) or Wilson's technique (11,863 fetuses). The fetuses were from vehicle control or drug-treated pregnant rabbits in embryo-fetal development studies conducted to meet international regulatory requirements for the development of new drugs. Both methods detected the more common alterations (microphthalmia and dilated lateral cerebral ventricles) and other less common findings (changes in size and/or shape of eye and brain structures). While both methods are equally sensitive at detecting common and rare developmental defects, the modified mid-coronal sectioning technique eliminates the use of chemicals and concomitant fixation artifacts that occur with the Wilson's technique and allows for examination of 100% intact fetuses thereby increasing potential for detecting eye and brain alterations as these findings occur infrequently in rabbits. © 2015 Wiley Periodicals, Inc.

Neuroimmune Axes of the Blood–Brain Barriers and Blood–Brain Interfaces: Bases for Physiological Regulation, Disease States, and Pharmacological Interventions

PubMed Central

Erickson, Michelle A.

2018-01-01

Central nervous system (CNS) barriers predominantly mediate the immune-privileged status of the brain, and are also important regulators of neuroimmune communication. It is increasingly appreciated that communication between the brain and immune system contributes to physiologic processes, adaptive responses, and disease states. In this review, we discuss the highly specialized features of brain barriers that regulate neuroimmune communication in health and disease. In section I, we discuss the concept of immune privilege, provide working definitions of brain barriers, and outline the historical work that contributed to the understanding of CNS barrier functions. In section II, we discuss the unique anatomic, cellular, and molecular characteristics of the vascular blood–brain barrier (BBB), blood–cerebrospinal fluid barrier, and tanycytic barriers that confer their functions as neuroimmune interfaces. In section III, we consider BBB-mediated neuroimmune functions and interactions categorized as five neuroimmune axes: disruption, responses to immune stimuli, uptake and transport of immunoactive substances, immune cell trafficking, and secretions of immunoactive substances. In section IV, we discuss neuroimmune functions of CNS barriers in physiologic and disease states, as well as pharmacological interventions for CNS diseases. Throughout this review, we highlight many recent advances that have contributed to the modern understanding of CNS barriers and their interface functions. PMID:29496890

Towards Ultra-High Resolution Fibre Tract Mapping of the Human Brain – Registration of Polarised Light Images and Reorientation of Fibre Vectors

PubMed Central

Palm, Christoph; Axer, Markus; Gräßel, David; Dammers, Jürgen; Lindemeyer, Johannes; Zilles, Karl; Pietrzyk, Uwe; Amunts, Katrin

2009-01-01

Polarised light imaging (PLI) utilises the birefringence of the myelin sheaths in order to visualise the orientation of nerve fibres in microtome sections of adult human post-mortem brains at ultra-high spatial resolution. The preparation of post-mortem brains for PLI involves fixation, freezing and cutting into 100-μm-thick sections. Hence, geometrical distortions of histological sections are inevitable and have to be removed for 3D reconstruction and subsequent fibre tracking. We here present a processing pipeline for 3D reconstruction of these sections using PLI derived multimodal images of post-mortem brains. Blockface images of the brains were obtained during cutting; they serve as reference data for alignment and elimination of distortion artefacts. In addition to the spatial image transformation, fibre orientation vectors were reoriented using the transformation fields, which consider both affine and subsequent non-linear registration. The application of this registration and reorientation approach results in a smooth fibre vector field, which reflects brain morphology. PLI combined with 3D reconstruction and fibre tracking is a powerful tool for human brain mapping. It can also serve as an independent method for evaluating in vivo fibre tractography. PMID:20461231

The Brain of the Archerfish Toxotes chatareus: A Nissl-Based Neuroanatomical Atlas and Catecholaminergic/Cholinergic Systems

PubMed Central

Karoubi, Naomi; Segev, Ronen; Wullimann, Mario F.

2016-01-01

Over recent years, the seven-spot archerfish (Toxotes chatareus) has emerged as a new model for studies in visual and behavioral neuroscience thanks to its unique hunting strategy. Its natural ability to spit at insects outside of water can be used in the laboratory for well controlled behavioral experiments where the fish is trained to aim at targets on a screen. The need for a documentation of the neuroanatomy of this animal became critical as more research groups use it as a model. Here we present an atlas of adult T. chatareus specimens caught in the wild in South East Asia. The atlas shows representative sections of the brain and specific structures revealed by a classic Nissl staining as well as corresponding schematic drawings. Additional immunostainings for catecholaminergic and cholinergic systems were conducted to corroborate the identification of certain nuclei and the data of a whole brain scanner is available online. We describe the general features of the archerfish brain as well as its specificities, especially for the visual system and compare the neuroanatomy of the archerfish with other teleosts. This atlas of the archerfish brain shows all levels of the neuraxis and intends to provide a solid basis for further neuroscientific research on T. chatareus, in particular electrophysiological studies. PMID:27891081

Brain imaging research in autism spectrum disorders: in search of neuropathology and health across the lifespan.

PubMed

Lainhart, Janet E

2015-03-01

Advances in brain imaging research in autism spectrum disorders (ASD) are rapidly occurring, and the amount of neuroimaging research has dramatically increased over the past 5 years. In this review, advances during the past 12 months and longitudinal studies are highlighted. Cross-sectional neuroimaging research provides evidence that the neural underpinnings of the behavioral signs of ASD involve not only dysfunctional integration of information across distributed brain networks but also basic dysfunction in primary cortices.Longitudinal studies of ASD show abnormally enlarged brain volumes and increased rates of brain growth during early childhood in only a small minority of ASD children. There is evidence of disordered development of white matter microstructure and amygdala growth, and at 2 years of age, network inefficiencies in posterior cerebral regions.From older childhood into adulthood, atypical age-variant and age-invariant changes in the trajectories of total and regional brain volumes and cortical thickness are apparent at the group level. There is evidence of abnormalities in posterior lobes and posterior brain networks during the first 2 years of life in ASD and, even in older children and adults, dysfunction in primary cortical areas.

Quantifying Mesoscale Neuroanatomy Using X-Ray Microtomography

PubMed Central

Gray Roncal, William; Prasad, Judy A.; Fernandes, Hugo L.; Gürsoy, Doga; De Andrade, Vincent; Fezzaa, Kamel; Xiao, Xianghui; Vogelstein, Joshua T.; Jacobsen, Chris; Körding, Konrad P.

2017-01-01

Methods for resolving the three-dimensional (3D) microstructure of the brain typically start by thinly slicing and staining the brain, followed by imaging numerous individual sections with visible light photons or electrons. In contrast, X-rays can be used to image thick samples, providing a rapid approach for producing large 3D brain maps without sectioning. Here we demonstrate the use of synchrotron X-ray microtomography (µCT) for producing mesoscale (∼1 µm 3 resolution) brain maps from millimeter-scale volumes of mouse brain. We introduce a pipeline for µCT-based brain mapping that develops and integrates methods for sample preparation, imaging, and automated segmentation of cells, blood vessels, and myelinated axons, in addition to statistical analyses of these brain structures. Our results demonstrate that X-ray tomography achieves rapid quantification of large brain volumes, complementing other brain mapping and connectomics efforts. PMID:29085899

Combination of metallic impregnation and autoradiography of brain sections. A method for differentiation of proliferating glial cells in the brain of adult rats and mice.

PubMed

Korr, H

1978-12-29

After labeling with 14C-thymidine, frozen sections or paraffin sections of the brain of adult mice or rats were first stained by metallic impregnation and then coated with chrome alum gelatine and with an emulsion layer of about 10 micron. On the autoradiographs 14C-tracks are readily recognized above labelled astrocytes or oligodendrocytes, and these can be well discriminated, if the sections are processed by the silver carbonate method of Rio-Hortega. In contrast, no labelling is obtained, if the gold chloride sublimate method of Cajal is applied.

A method for acetylcholinesterase staining of brain sections previously processed for receptor autoradiography.

PubMed

Lim, M M; Hammock, E A D; Young, L J

2004-02-01

Receptor autoradiography using selective radiolabeled ligands allows visualization of brain receptor distribution and density on film. The resolution of specific brain regions on the film often can be difficult to discern owing to the general spread of the radioactive label and the lack of neuroanatomical landmarks on film. Receptor binding is a chemically harsh protocol that can render the tissue virtually unstainable by Nissl and other conventional stains used to delineate neuroanatomical boundaries of brain regions. We describe a method for acetylcholinesterase (AChE) staining of slides previously processed for receptor binding. AChE staining is a useful tool for delineating major brain nuclei and tracts. AChE staining on sections that have been processed for receptor autoradiography provides a direct comparison of brain regions for more precise neuroanatomical description. We report a detailed thiocholine protocol that is a modification of the Koelle-Friedenwald method to amplify the AChE signal in brain sections previously processed for autoradiography. We also describe several temporal and experimental factors that can affect the density and clarity of the AChE signal when using this protocol.

Mild traumatic brain injury is associated with reduced cortical thickness in those at risk for Alzheimer's disease.

PubMed

Hayes, Jasmeet P; Logue, Mark W; Sadeh, Naomi; Spielberg, Jeffrey M; Verfaellie, Mieke; Hayes, Scott M; Reagan, Andrew; Salat, David H; Wolf, Erika J; McGlinchey, Regina E; Milberg, William P; Stone, Annjanette; Schichman, Steven A; Miller, Mark W

2017-03-01

Moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for the development of neurodegenerative diseases such as late-onset Alzheimer's disease, although it is unclear whether mild traumatic brain injury, or concussion, also confers risk. This study examined mild traumatic brain injury and genetic risk as predictors of reduced cortical thickness in brain regions previously associated with early Alzheimer's disease, and their relationship with episodic memory. Participants were 160 Iraq and Afghanistan War veterans between the ages of 19 and 58, many of whom carried mild traumatic brain injury and post-traumatic stress disorder diagnoses. Whole-genome polygenic risk scores for the development of Alzheimer's disease were calculated using summary statistics from the largest Alzheimer's disease genome-wide association study to date. Results showed that mild traumatic brain injury moderated the relationship between genetic risk for Alzheimer's disease and cortical thickness, such that individuals with mild traumatic brain injury and high genetic risk showed reduced cortical thickness in Alzheimer's disease-vulnerable regions. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness, suggesting that cortical thinning in Alzheimer's disease-vulnerable brain regions is a mechanism for reduced memory performance. Finally, analyses that examined the apolipoprotein E4 allele, post-traumatic stress disorder, and genetic risk for schizophrenia and depression confirmed the specificity of the Alzheimer's disease polygenic risk finding. These results provide evidence that mild traumatic brain injury is associated with greater neurodegeneration and reduced memory performance in individuals at genetic risk for Alzheimer's disease, with the caveat that the order of causal effects cannot be inferred from cross-sectional studies. These results underscore the importance of documenting head injuries even within the mild range as they may interact with genetic risk to produce negative long-term health consequences such as neurodegenerative disease. Published by Oxford University Press on behalf of the Guarantors of Brain 2017. This work is written by US Government employees and is in the public domain in the United States.

Creating normograms of dural sinuses in healthy persons using computer-assisted detection for analysis and comparison of cross-section dural sinuses in the brain.

PubMed

Anconina, Reut; Zur, Dinah; Kesler, Anat; Lublinsky, Svetlana; Toledano, Ronen; Novack, Victor; Benkobich, Elya; Novoa, Rosa; Novic, Evelyne Farkash; Shelef, Ilan

2017-06-01

Dural sinuses vary in size and shape in many pathological conditions with abnormal intracranial pressure. Size and shape normograms of dural brain sinuses are not available. The creation of such normograms may enable computer-assisted comparison to pathologic exams and facilitate diagnoses. The purpose of this study was to quantitatively evaluate normal magnetic resonance venography (MRV) studies in order to create normograms of dural sinuses using a computerized algorithm for vessel cross-sectional analysis. This was a retrospective analysis of MRV studies of 30 healthy persons. Data were analyzed using a specially developed Matlab algorithm for vessel cross-sectional analysis. The cross-sectional area and shape measurements were evaluated to create normograms. Mean cross-sectional size was 53.27±13.31 for the right transverse sinus (TS), 46.87+12.57 for the left TS (p=0.089) and 36.65+12.38 for the superior sagittal sinus. Normograms were created. The distribution of cross-sectional areas along the vessels showed distinct patterns and a parallel course for the median, 25th, 50th and 75th percentiles. In conclusion, using a novel computerized method for vessel cross-sectional analysis we were able to quantitatively characterize dural sinuses of healthy persons and create normograms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia

PubMed Central

Newson, Penny; Lynch-Frame, Ann; Roach, Rebecca; Bennett, Sarah; Carr, Vaughan; Chahl, Loris A

2005-01-01

Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin-sensitive primary afferent neurons might be abnormal in schizophrenia. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg−1 subcutaneously, or vehicle (control) at 24–36 h of life. At 5–7 weeks behavioural observations were made, and brains removed, fixed and sectioned. The mean body weight of capsaicin-treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. Capsaicin-treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. Coronal brain sections of capsaicin-treated rats had smaller cross-sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia. PMID:16041396

Non-imaged based method for matching brains in a common anatomical space for cellular imagery.

PubMed

Midroit, Maëllie; Thevenet, Marc; Fournel, Arnaud; Sacquet, Joelle; Bensafi, Moustafa; Breton, Marine; Chalençon, Laura; Cavelius, Matthias; Didier, Anne; Mandairon, Nathalie

2018-04-22

Cellular imagery using histology sections is one of the most common techniques used in Neuroscience. However, this inescapable technique has severe limitations due to the need to delineate regions of interest on each brain, which is time consuming and variable across experimenters. We developed algorithms based on a vectors field elastic registration allowing fast, automatic realignment of experimental brain sections and associated labeling in a brain atlas with high accuracy and in a streamlined way. Thereby, brain areas of interest can be finely identified without outlining them and different experimental groups can be easily analyzed using conventional tools. This method directly readjusts labeling in the brain atlas without any intermediate manipulation of images. We mapped the expression of cFos, in the mouse brain (C57Bl/6J) after olfactory stimulation or a non-stimulated control condition and found an increased density of cFos-positive cells in the primary olfactory cortex but not in non-olfactory areas of the odor-stimulated animals compared to the controls. Existing methods of matching are based on image registration which often requires expensive material (two-photon tomography mapping or imaging with iDISCO) or are less accurate since they are based on mutual information contained in the images. Our new method is non-imaged based and relies only on the positions of detected labeling and the external contours of sections. We thus provide a new method that permits automated matching of histology sections of experimental brains with a brain reference atlas. Copyright © 2018 Elsevier B.V. All rights reserved.

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science)

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

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of (F18)fluorinated benzamides (dopamine D-2 receptor tracers), (F18)fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of (F18)-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

The iconographic brain. A critical philosophical inquiry into (the resistance of) the image

PubMed Central

De Vos, Jan

2014-01-01

The brain image plays a central role in contemporary image culture and, in turn, (co)constructs contemporary forms of subjectivity. The central aim of this paper is to probe the unmistakably potent interpellative power of brain images by delving into the power of imaging and the power of the image itself. This is not without relevance for the neurosciences, inasmuch as these do not take place in a vacuum; hence the importance of inquiring into the status of the image within scientific culture and science itself. I will mount a critical philosophical investigation of the brain qua image, focusing on the issue of mapping the mental onto the brain and how, in turn, the brain image plays a pivotal role in processes of subjectivation. Hereto, I draw upon Science & Technology Studies, juxtaposed with culture and ideology critique and theories of image culture. The first section sets out from Althusser's concept of interpellation, linking ideology to subjectivity. Doing so allows to spell out the central question of the paper: what could serve as the basis for a critical approach, or, where can a locus of resistance be found? In the second section, drawing predominantly on Baudrillard, I delve into the dimension of virtuality as this is opened up by brain image culture. This leads to the question of whether the digital brain must be opposed to old analog psychology: is it the psyche which resists? This issue is taken up in the third section which, ultimately, concludes that the psychological is not the requisite locus of resistance. The fourth section proceeds to delineate how the brain image is constructed from what I call the data-gaze (the claim that brain data are always already visual). In the final section, I discuss how an engagement with theories of iconology affords a critical understanding of the interpellative force of the brain image, which culminates in the somewhat unexpected claim that the sought after resistance lies in the very status of the image itself. PMID:24860480

A special form of cerebral lacunae: expanding lacunae.

PubMed Central

Homeyer, P; Cornu, P; Lacomblez, L; Chiras, J; Derouesné, C

1996-01-01

The case of a 42 year old man with headache, blurred vision, and diplopia allowed the description of a particular form of cerebral lacunae-that is, expanding lacunae. Brain MRI showed hydrocephalus and multiple lesions in the thalamomesencephalic region. The radiological features of these lesions were similar to the histological brain coronal section of a case reported in 1983 in which expanding lacunae were related to a dilatation of the perivascular spaces and a focal segmental necrotising angiitis. The role of the lymphatic drainage of the brain is discussed to explain the dilatation of the perivascular spaces. The hypothesis of a hydrodynamic factor being responsible for the expanding character of the lacunae was suggested by the location of the lesions and the influence of various clinical events on the symptomatology. Images PMID:8708692

A comparison of neural network and fuzzy clustering techniques in segmenting magnetic resonance images of the brain

NASA Technical Reports Server (NTRS)

Hall, Lawrence O.; Bensaid, Amine M.; Clarke, Laurence P.; Velthuizen, Robert P.; Silbiger, Martin S.; Bezdek, James C.

1992-01-01

Magnetic resonance (MR) brain section images are segmented and then synthetically colored to give visual representations of the original data with three approaches: the literal and approximate fuzzy c-means unsupervised clustering algorithms and a supervised computational neural network, a dynamic multilayered perception trained with the cascade correlation learning algorithm. Initial clinical results are presented on both normal volunteers and selected patients with brain tumors surrounded by edema. Supervised and unsupervised segmentation techniques provide broadly similar results. Unsupervised fuzzy algorithms were visually observed to show better segmentation when compared with raw image data for volunteer studies. However, for a more complex segmentation problem with tumor/edema or cerebrospinal fluid boundary, where the tissues have similar MR relaxation behavior, inconsistency in rating among experts was observed.

Three-dimensional atlas of iron, copper, and zinc in the mouse cerebrum and brainstem.

PubMed

Hare, Dominic J; Lee, Jason K; Beavis, Alison D; van Gramberg, Amanda; George, Jessica; Adlard, Paul A; Finkelstein, David I; Doble, Philip A

2012-05-01

Atlases depicting molecular and functional features of the brain are becoming an integral part of modern neuroscience. In this study we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS) to quantitatively measure iron (Fe), copper (Cu), and zinc (Zn) levels in a serially sectioned C57BL/6 mouse brain (cerebrum and brainstem). Forty-six sections were analyzed in a single experiment of approximately 158 h in duration. We constructed a 46-plate reference atlas by aligning quantified images of metal distribution with corresponding coronal sections from the Allen Mouse Brain Reference Atlas. The 46 plates were also used to construct three-dimensional models of Fe, Cu, and Zn distribution. This atlas represents the first reconstruction of quantitative trace metal distribution through the brain by LA-ICPMS and will facilitate the study of trace metals in the brain and help to elucidate their role in neurobiology.

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. © 2011 Blackwell Verlag GmbH.

Brain BLAQ: Post-hoc thick-section histochemistry for localizing optogenetic constructs in neurons and their distal terminals

PubMed Central

Kupferschmidt, David A.; Cody, Patrick A.; Lovinger, David M.; Davis, Margaret I.

2015-01-01

Optogenetic constructs have revolutionized modern neuroscience, but the ability to accurately and efficiently assess their expression in the brain and associate it with prior functional measures remains a challenge. High-resolution imaging of thick, fixed brain sections would make such post-hoc assessment and association possible; however, thick sections often display autofluorescence that limits their compatibility with fluorescence microscopy. We describe and evaluate a method we call “Brain BLAQ” (Block Lipids and Aldehyde Quench) to rapidly reduce autofluorescence in thick brain sections, enabling efficient axon-level imaging of neurons and their processes in conventional tissue preparations using standard epifluorescence microscopy. Following viral-mediated transduction of optogenetic constructs and fluorescent proteins in mouse cortical pyramidal and dopaminergic neurons, we used BLAQ to assess innervation patterns in the striatum, a region in which autofluorescence often obscures the imaging of fine neural processes. After BLAQ treatment of 250–350 μm-thick brain sections, axons and puncta of labeled afferents were visible throughout the striatum using a standard epifluorescence stereomicroscope. BLAQ histochemistry confirmed that motor cortex (M1) projections preferentially innervated the matrix component of lateral striatum, whereas medial prefrontal cortex projections terminated largely in dorsal striosomes and distinct nucleus accumbens subregions. Ventral tegmental area dopaminergic projections terminated in a similarly heterogeneous pattern within nucleus accumbens and ventral striatum. Using a minimal number of easily manipulated and visualized sections, and microscopes available in most neuroscience laboratories, BLAQ enables simple, high-resolution assessment of virally transduced optogenetic construct expression, and post-hoc association of this expression with molecular markers, physiology and behavior. PMID:25698938

Maternal Oxytocin Administration Before Birth Influences the Effects of Birth Anoxia on the Neonatal Rat Brain.

PubMed

Boksa, Patricia; Zhang, Ying; Nouel, Dominique

2015-08-01

Ineffective contractions and prolonged labor are common birth complications in primiparous women, and oxytocin is the most common agent given for induction or augmentation of labor. Clinical studies in humans suggest oxytocin might adversely affect the CNS response to hypoxia at birth. In this study, we used a rat model of global anoxia during Cesarean section birth to test if administering oxytocin to pregnant dams prior to birth affects the acute neonatal CNS response to birth anoxia. Anoxic pups born from dams pre-treated with intravenous injections or infusions of oxytocin before birth showed significantly increased brain lactate, a metabolic indicator of CNS hypoxia, compared to anoxic pups from dams pre-treated with saline. Anoxic pups born from dams given oxytocin before birth also showed decreased brain ATP compared to anoxic pups from saline dams. Direct injection of oxytocin to postnatal day 2 rat pups followed by exposure to anoxia also resulted in increased brain lactate and decreased brain ATP, compared to anoxia exposure alone. Oxytocin pre-treatment of the dam decreased brain malondialdehyde, a marker of lipid peroxidation, as well as protein kinase C activity, both in anoxic pups and controls, suggesting oxytocin may reduce aspects of oxidative stress. Finally, when dams were pretreated with indomethacin, a cyclooxygenase (COX) inhibitor, maternal oxytocin no longer potentiated effects of anoxia on neonatal brain lactate, suggesting this effect of oxytocin may be mediated via prostaglandin production or other COX-derived products. The results indicate that maternal oxytocin administration may have multiple acute effects on CNS metabolic responses to anoxia at birth.

Cell-cell interactions of isolated and cultured oligodendrocytes: formation of linear occluding junctions and expression of peculiar intramembrane particles.

PubMed

Massa, P T; Szuchet, S; Mugnaini, E

1984-12-01

Oligodendrocytes were isolated from lamb brain. Freshly isolated cells and cultured cells, either 1- to 4-day-old unattached or 1- to 5-week-old attached, were examined by thin section and freeze-fracture electron microscopy. Freeze-fracture of freshly isolated oligodendrocytes showed globular and elongated intramembrane particles similar to those previously described in oligodendrocytes in situ. Enrichment of these particles was seen at sites of inter-oligodendrocyte contact. Numerous gap junctions and scattered linear tight junctional arrays were apparent. Gap junctions were connected to blebs of astrocytic plasma membrane sheared off during isolation, whereas tight junctions were facing extracellular space or blebs of oligodendrocytic plasma membrane. Thin sections of cultured, unattached oligodendrocytes showed rounded cell bodies touching one another at points without forming specialized cell junctions. Cells plated on polylysine-coated aclar dishes attached, emanated numerous, pleomorphic processes, and expressed galactocerebroside and myelin basic protein, characteristic markers for oligodendrocytes. Thin sections showed typical oligodendrocyte ultrastructure but also intermediate filaments not present in unattached cultures. Freeze-fracture showed intramembrane particles similar to but more numerous, and with a different fracture face repartition, than those seen in oligodendrocytes, freshly isolated or in situ. Gap junctions were small and rare. Apposed oligodendrocyte plasma membrane formed linear tight junctions which became more numerous with time in culture. Thus, cultured oligodendrocytes isolated from ovine brains develop and maintain features characteristic of mature oligodendrocytes in situ and can be used to explore formation and maintenance of tight junctions and possibly other classes of cell-cell interactions important in the process of myelination.

Brain morphology in school-aged children with prenatal opioid exposure: A structural MRI study.

PubMed

Sirnes, Eivind; Oltedal, Leif; Bartsch, Hauke; Eide, Geir Egil; Elgen, Irene B; Aukland, Stein Magnus

Both animal and human studies have suggested that prenatal opioid exposure may be detrimental to the developing fetal brain. However, results are somewhat conflicting. Structural brain changes in children with prenatal opioid exposure have been reported in a few studies, and such changes may contribute to neuropsychological impairments observed in exposed children. To investigate the association between prenatal opioid exposure and brain morphology in school-aged children. A cross-sectional magnetic resonance imaging (MRI) study of prenatally opioid-exposed children and matched controls. A hospital-based sample (n=16) of children aged 10-14years with prenatal exposure to opioids and 1:1 sex- and age-matched unexposed controls. Automated brain volume measures obtained from T1-weighted MRI scans using FreeSurfer. Volumes of the basal ganglia, thalamus, and cerebellar white matter were reduced in the opioid-exposed group, whereas there were no statistically significant differences in global brain measures (total brain, cerebral cortex, and cerebral white matter volumes). In line with the limited findings reported in the literature to date, our study showed an association between prenatal opioid exposure and reduced regional brain volumes. Adverse effects of opioids on the developing fetal brain may explain this association. However, further research is needed to explore the causal nature and functional consequences of these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Against Strong Ethical Parity: Situated Cognition Theses and Transcranial Brain Stimulation

PubMed Central

Heinrichs, Jan-Hendrik

2017-01-01

According to a prominent suggestion in the ethics of transcranial neurostimulation the effects of such devices can be treated as ethically on par with established, pre-neurotechnological alterations of the mind. This parity allegedly is supported by situated cognition theories showing how external devices can be part of a cognitive system. This article will evaluate this suggestion. It will reject the claim, that situated cognition theories support ethical parity. It will however point out another reason, why external carriers or modifications of the mental might come to be considered ethically on par with internal carriers. Section “Why Could There Be Ethical Parity between Neural Tissue and External Tools?” presents the ethical parity theses between external and internal carriers of the mind as well as neurotechnological alterations and established alterations. Section “Extended, Embodied, Embedded: Situated Cognition as a Relational Thesis” will elaborate the different situated cognition approaches and their relevance for ethics. It will evaluate, whether transcranial stimulation technologies are plausible candidates for situated cognition theses. Section “On the Ethical Relevance of Situated Cognition Theses” will discuss criteria for evaluating whether a cognitive tool is deeply embedded with a cognitive system and apply these criteria to transcranial brain stimulation technologies. Finally it will discuss the role diverse versions of situated cognition theory can play in the ethics of altering mental states, especially the ethics of transcranial brain stimulation technologies. PMID:28443008

Against Strong Ethical Parity: Situated Cognition Theses and Transcranial Brain Stimulation.

PubMed

Heinrichs, Jan-Hendrik

2017-01-01

According to a prominent suggestion in the ethics of transcranial neurostimulation the effects of such devices can be treated as ethically on par with established, pre-neurotechnological alterations of the mind. This parity allegedly is supported by situated cognition theories showing how external devices can be part of a cognitive system. This article will evaluate this suggestion. It will reject the claim, that situated cognition theories support ethical parity. It will however point out another reason, why external carriers or modifications of the mental might come to be considered ethically on par with internal carriers. Section "Why Could There Be Ethical Parity between Neural Tissue and External Tools?" presents the ethical parity theses between external and internal carriers of the mind as well as neurotechnological alterations and established alterations. Section "Extended, Embodied, Embedded: Situated Cognition as a Relational Thesis" will elaborate the different situated cognition approaches and their relevance for ethics. It will evaluate, whether transcranial stimulation technologies are plausible candidates for situated cognition theses. Section "On the Ethical Relevance of Situated Cognition Theses" will discuss criteria for evaluating whether a cognitive tool is deeply embedded with a cognitive system and apply these criteria to transcranial brain stimulation technologies. Finally it will discuss the role diverse versions of situated cognition theory can play in the ethics of altering mental states, especially the ethics of transcranial brain stimulation technologies.

Functionality predictors in acquired brain damage.

PubMed

Huertas Hoyas, E; Pedrero Pérez, E J; Águila Maturana, A M; García López-Alberca, S; González Alted, C

2015-01-01

Most individuals who have survived an acquired brain injury present consequences affecting the sensorimotor, cognitive, affective or behavioural components. These deficits affect the proper performance of daily living activities. The aim of this study is to identify functional differences between individuals with unilateral acquired brain injury using functional independence, capacity, and performance of daily activities. Descriptive cross-sectional design with a sample of 58 people, with right-sided injury (n=14 TBI; n=15 stroke) or left-sided injury (n = 14 TBI, n = 15 stroke), right handed, and with a mean age of 47 years and time since onset of 4 ± 3.65 years. The functional assessment/functional independence measure (FIM/FAM) and the International Classification of Functioning (ICF) were used for the study. The data showed significant differences (P<.000), and a large size effect (dr=0.78) in the cross-sectional estimates, and point to fewer restrictions for patients with a lesion on their right side. The major differences were in the variables 'speaking' and 'receiving spoken messages' (ICF variables), and 'Expression', 'Writing' and 'intelligible speech' (FIM/FAM variables). In the linear regression analysis, the results showed that only 4 FIM/FAM variables, taken together, predict 44% of the ICF variance, which measures the ability of the individual, and up to 52% of the ICF, which measures the individual's performance. Gait alone predicts a 28% of the variance. It seems that individuals with acquired brain injury in the left hemisphere display important differences regarding functional and communication variables. The motor aspects are an important prognostic factor in functional rehabilitation. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Continuous delivery of naltrexone and nalmefene leads to tolerance in reducing alcohol drinking and to supersensitivity of brain opioid receptors.

PubMed

Korpi, Esa R; Linden, Anni-Maija; Hytönen, Heidi R; Paasikoski, Nelli; Vashchinkina, Elena; Dudek, Mateusz; Herr, Deron R; Hyytiä, Petri

2017-07-01

Opioid antagonist treatments reduce alcohol drinking in rodent models and in alcohol-dependent patients, with variable efficacy across different studies. These treatments may suffer from the development of tolerance and opioid receptor supersensitivity, as suggested by preclinical models showing activation of these processes during and after subchronic high-dose administration of the short-acting opioid antagonist naloxone. In the present study, we compared equipotent low and moderate daily doses of naltrexone and nalmefene, two opioid antagonists in the clinical practice for treatment of alcoholism. The antagonists were given here subcutaneously for 7 days either as daily injections or continuous osmotic minipump-driven infusions to alcohol-preferring AA rats having trained to drink 10% alcohol in a limited access protocol. One day after stopping the antagonist treatment, [ 35 S]GTPγS autoradiography on brain cryostat sections was carried out to examine the coupling of receptors to G protein activation. The results prove the efficacy of repeated injections over infused opioid antagonists in reducing alcohol drinking. Tolerance to the reducing effect on alcohol drinking and to the enhancement of G protein coupling to μ-opioid receptors in various brain regions were consistently detected only after infused antagonists. Supersensitivity of κ-opioid receptors was seen in the ventral and dorsal striatal regions especially by infused nalmefene. Nalmefene showed no clear agonistic activity in rat brain sections or at human recombinant κ-opioid receptors. The findings support the as-needed dosing practice, rather than the standard continual dosing, in the treatment of alcoholism with opioid receptor antagonists. © 2016 Society for the Study of Addiction.

Interaction of D-LSD with binding sites in brain: a study in vivo and in vitro

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

Ebersole, B.L.J.

The localization of (/sup 3/H)-d-lysergic acid diethylamide ((/sup 3/H)LSD) binding sites in the mouse brain was compared in vivo and in vitro. Radioautography of brain sections incubated with (/sup 3/H)LSD in vitro revealed substantial specific (/sup 3/H)LSD binding in cortical layers III-IV and areas CA1 and dentate gyrus in hippocampus. In contrast, in brain sections from animals that received (/sup 3/H)LSD in vivo, binding in hippocampus was scant and diffuse, although the pattern of labeling in cortex was similar to that seen in vitro. The low specific binding in hippocampus relative to cortex was confirmed by homogenate filtration studies ofmore » brain areas from mice that received injections of (/sup 3/H)LSD. Time-course studies established that peak specific binding at ten minutes was the same in cortex and hippocampus. At all times, binding in hippocampus was about one-third of that in cortex; in contrast, the concentration of free (/sup 3/H)LSD did not vary between regions. This finding was unexpected, because binding studies in vitro in membrane preparations indicated that the density and affinity of (/sup 3/H)LSD binding sites were similar in both brain regions. Saturation binding studies in vivo showed that the lower amount of (/sup 3/H)LSD binding in hippocampus was attributable to a lower density of sites labeled by (/sup 3/H)LSD. The pharmacological identify of (/sub 3/H)LSD binding sites in vivo may be relevant to the hallucinogenic properties of LSD and of other related hallucinogens.« less

Cannabis use and memory brain function in adolescent boys: a cross-sectional multicenter functional magnetic resonance imaging study.

PubMed

Jager, Gerry; Block, Robert I; Luijten, Maartje; Ramsey, Nick F

2010-06-01

Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and executive control. Prefrontal and temporal regions are critically involved in these functions. Maturational processes leave these brain areas prone to the potentially harmful effects of cannabis use. We performed a two-site (United States and The Netherlands; pooled data) functional magnetic resonance imaging (MRI) study with a cross-sectional design, investigating the effects of adolescent cannabis use on working memory (WM) and associative memory (AM) brain function in 21 abstinent but frequent cannabis-using boys (13-19) years of age and compared them with 24 nonusing peers. Brain activity during WM was assessed before and after rule-based learning (automatization). AM was assessed using a pictorial hippocampal-dependent memory task. Cannabis users performed normally on both memory tasks. During WM assessment, cannabis users showed excessive activity in prefrontal regions when a task was novel, whereas automatization of the task reduced activity to the same level in users and controls. No effect of cannabis use on AM-related brain function was found. In adolescent cannabis users, the WM system was overactive during a novel task, suggesting functional compensation. Inefficient WM recruitment was not related to a failure in automatization but became evident when processing continuously changing information. The results seem to confirm the vulnerability of still developing frontal lobe functioning for early-onset cannabis use. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science). Progress report, January 1, 1992--December 31, 1992

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

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of [F18]fluorinated benzamides (dopamine D-2 receptor tracers), [F18]fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of [F18]-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

Effect of dexamethasone on gliosis, ischemia, and dopamine extraction during microdialysis sampling in brain tissue.

PubMed

Jaquins-Gerstl, Andrea; Shu, Zhan; Zhang, Jing; Liu, Yansheng; Weber, Stephen G; Michael, Adrian C

2011-10-15

Microdialysis sampling of the brain is an analytical technique with numerous applications in neuroscience and the neurointensive care of brain-injured human patients. Even so, implanting microdialysis probes into brain tissue causes a penetration injury that triggers gliosis (the activation and proliferation of glial cells) and ischemia (the interruption of blood flow). Thus, the probe samples injured tissue. Mitigating the effects of the penetration injury might refine the technique. The synthetic glucocorticoid dexamethasone is a potent anti-inflammatory and immunosuppressant substance. We performed microdialysis in the rat brain for 5 days, with and without dexamethasone in the perfusion fluid (10 μM for the first 24 h and 2 μM thereafter). On the first and fourth day of the perfusion, we performed dopamine no-net-flux measurements. On the fifth day, we sectioned and stained the brain tissue and examined it by fluorescence microscopy. Although dexamethasone profoundly inhibited gliosis and ischemia around the probe tracks it had only modest effects on dopamine no-net-flux results. These findings show that dexamethasone is highly effective at suppressing gliosis and ischemia but is limited in its neuroprotective activity. © 2011 American Chemical Society

Cerebral Arterial Occlusion Did Not Promote the Prevalence of Cerebral Amyloid Angiopathy.

PubMed

Honda, Kazuhiro

2016-08-01

An impairment of amyloid-β (Aβ) clearance has been suggested in Alzheimer's disease. Perivascular drainage along cerebrovascular vessels is considered an important amyloid clearance pathway. This study examined the effect of reduced arterial pulsation that could cause an impairment in cerebral amyloid drainage on the prevalence of cortical microbleeds (CMBs), a surrogate marker for cerebral amyloid angiopathy (CAA). Patients who lost depiction of either side of the carotid artery or the middle cerebral artery on magnetic resonance angiography were studied. Those who showed acute cerebral infarction or a previous cortical cerebral infarction were excluded. The number of CMBs was counted on the occluded and non-occluded sides of the brain in each subject. The number of subjects who showed more CMBs on the occluded side of the brain was compared with the number of subjects who showed more CMBs on the non-occluded side of the brain. Twenty-eight patients were studied. The extent of lacunar infarction and white matter lesions was not different, irrespective of the occluded vessels or the distribution of CMBs. The prevalence of CMBs was not different between the occluded and non-occluded sides of the brain. In this cross-sectional study, reduction of arterial pulsation was not associated with a higher prevalence of CAA. Therefore, reduced arterial pulsation alone may not be enough to promote CAA.

V. Multi-level analysis of cortical neuroanatomy in Williams syndrome.

PubMed

Galaburda, A M; Bellugi, U

2000-01-01

The purpose of a neuroanatomical analysis of Williams Syndrome (WMS) brains is to help bridge the knowledge of the genetics of this disorder with the knowledge on behavior. Here, we outline findings of cortical neuroanatomy at multiple levels. We describe the gross anatomy with respect to brain shape, cortical folding, and asymmetry. This, as with most neuroanatomical information available in the literature on anatomical-functional correlations, links up best to the behavioral profile. Then, we describe the cytoarchitectonic appearance of the cortex. Further, we report on some histometric results. Finally, we present findings of immunocytochemistry that attempt to link up to the genomic deletion. The gross anatomical findings consist mainly of a small brain that shows curtailment in the posterior-parietal and occipital regions. There is also subtle dysmorphism of cortical folding. A consistent finding is a short central sulcus that does not become opercularized in the interhemispheric fissure, bringing attention to a possible developmental anomaly affecting the dorsal half of the hemispheres. There is also lack of asymmetry in the planum temporale. The cortical cytoarchitecture is relatively normal, with all sampled areas showing features typical of the region from which they are taken. Measurements in area 17 show increased cell size and decreased cell-packing density, which address the issue of possible abnormal connectivity. Immunostaining shows absence of elastin but normal staining for Lim-1 kinase, both of which are products of genes that are part of the deletion. Finally, one serially sectioned brain shows a fair amount of acquired pathology of microvascular origin related most likely to underlying hypertension and heart disease.

Optical coherence tomography and optical coherence domain reflectometry for deep brain stimulation probe guidance

NASA Astrophysics Data System (ADS)

Jeon, Sung W.; Shure, Mark A.; Baker, Kenneth B.; Chahlavi, Ali; Hatoum, Nagi; Turbay, Massud; Rollins, Andrew M.; Rezai, Ali R.; Huang, David

2005-04-01

Deep Brain Stimulation (DBS) is FDA-approved for the treatment of Parkinson's disease and essential tremor. Currently, placement of DBS leads is guided through a combination of anatomical targeting and intraoperative microelectrode recordings. The physiological mapping process requires several hours, and each pass of the microelectrode into the brain increases the risk of hemorrhage. Optical Coherence Domain Reflectometry (OCDR) in combination with current methodologies could reduce surgical time and increase accuracy and safety by providing data on structures some distance ahead of the probe. For this preliminary study, we scanned a rat brain in vitro using polarization-insensitive Optical Coherence Tomography (OCT). For accurate measurement of intensity and attenuation, polarization effects arising from tissue birefringence are removed by polarization diversity detection. A fresh rat brain was sectioned along the coronal plane and immersed in a 5 mm cuvette with saline solution. OCT images from a 1294 nm light source showed depth profiles up to 2 mm. Light intensity and attenuation rate distinguished various tissue structures such as hippocampus, cortex, external capsule, internal capsule, and optic tract. Attenuation coefficient is determined by linear fitting of the single scattering regime in averaged A-scans where Beer"s law is applicable. Histology showed very good correlation with OCT images. From the preliminary study using OCT, we conclude that OCDR is a promising approach for guiding DBS probe placement.

Gray Matter Characteristics in Mid and Old Aged Adults with ASD

ERIC Educational Resources Information Center

Koolschijn, P. Cédric M. P.; Geurts, Hilde M.

2016-01-01

It is widely acknowledged that the brain anatomy of children and adolescents with autism spectrum disorder (ASD) shows a different developmental pattern then typical age-matched peers. There is however, a paucity of studies examining gray matter in mid and late adulthood in ASD. In this cross-sectional neuroimaging study, we, performed vertex-wise…

Natural and Artificial Intelligence, Language, Consciousness, Emotion, and Anticipation

NASA Astrophysics Data System (ADS)

Dubois, Daniel M.

2010-11-01

The classical paradigm of the neural brain as the seat of human natural intelligence is too restrictive. This paper defends the idea that the neural ectoderm is the actual brain, based on the development of the human embryo. Indeed, the neural ectoderm includes the neural crest, given by pigment cells in the skin and ganglia of the autonomic nervous system, and the neural tube, given by the brain, the spinal cord, and motor neurons. So the brain is completely integrated in the ectoderm, and cannot work alone. The paper presents fundamental properties of the brain as follows. Firstly, Paul D. MacLean proposed the triune human brain, which consists to three brains in one, following the species evolution, given by the reptilian complex, the limbic system, and the neo-cortex. Secondly, the consciousness and conscious awareness are analysed. Thirdly, the anticipatory unconscious free will and conscious free veto are described in agreement with the experiments of Benjamin Libet. Fourthly, the main section explains the development of the human embryo and shows that the neural ectoderm is the whole neural brain. Fifthly, a conjecture is proposed that the neural brain is completely programmed with scripts written in biological low-level and high-level languages, in a manner similar to the programmed cells by the genetic code. Finally, it is concluded that the proposition of the neural ectoderm as the whole neural brain is a breakthrough in the understanding of the natural intelligence, and also in the future design of robots with artificial intelligence.

Mother-infant interactions and regional brain volumes in infancy: an MRI study.

PubMed

Sethna, Vaheshta; Pote, Inês; Wang, Siying; Gudbrandsen, Maria; Blasi, Anna; McCusker, Caroline; Daly, Eileen; Perry, Emily; Adams, Kerrie P H; Kuklisova-Murgasova, Maria; Busuulwa, Paula; Lloyd-Fox, Sarah; Murray, Lynne; Johnson, Mark H; Williams, Steven C R; Murphy, Declan G M; Craig, Michael C; McAlonan, Grainne M

2017-07-01

It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3- to 6-month-old infants (N = 39). In addition, we examined whether this relationship differed in male and female infants. We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes.

A brain-specific gene cluster isolated from the region of the mouse obesity locus is expressed in the adult hypothalamus and during mouse development

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

Laig-Webster, M.; Lim, M.E.; Chehab, F.F.

1994-09-01

The molecular defect underlying an autosomal recessive form of genetic obesity in a classical mouse model C57 BL/6J-ob/ob has not yet been elucidated. Whereas metabolic and physiological disturbances such as diabetes and hypertension are associated with obesity, the site of expression and the nature of the primary lesion responsible for this cascade of events remains elusive. Our efforts aimed at the positional cloning of the ob gene by YAC contig mapping and gene identification have resulted in the cloning of a brain-specific gene cluster from the ob critical region. The expression of this gene cluster is remarkably complex owing tomore » the multitude of brain-specific mRNA transcripts detected on Northern blots. cDNA cloning of these transcripts suggests that they are expressed from different genes as well as by alternate splicing mechanisms. Furthermore, the genomic organization of the cluster appears to consist of at least two identical promoters displaying CpG islands characteristic of housekeeping genes, yet clearly involving tissue-specific expression. Sense and anti-sense synthetic RNA probes were derived from a common DNA sequence on 3 cDNA clones and hybridized to 8-16 days mouse embryonic stages and mouse adult brain sections. Expression in development was noticeable as of the 11th day of gestation and confined to the central nervous system mainly in the telencephalon and spinal cord. Coronal and sagittal sections of the adult mouse brain showed expression only in 3 different regions of the brain stem. In situ hybridization to mouse hypothalamus sections revealed the presence of a localized and specialized group of cells expressing high levels of mRNA, suggesting that this gene cluster may also be involved in the regulation of hypothalamic activities. The hypothalamus has long been hypothesized as a primary candidate tissue for the expression of the obesity gene mainly because of its well-established role in the regulation of energy metabolism and food intake.« less

Monitoring Dopamine ex Vivo during Electrical Stimulation Using Liquid-Microjunction Surface Sampling.

PubMed

Gill, Emily L; Marks, Megan; Yost, Richard A; Vedam-Mai, Vinata; Garrett, Timothy J

2017-12-19

Liquid-microjunction surface sampling (LMJ-SS) is an ambient ionization technique based on the continuous flow of solvent using an in situ microextraction device in which solvent moves through the probe, drawing in the analytes in preparation for ionization using an electrospray ionization source. However, unlike traditional mass spectrometry (MS) techniques, it operates under ambient pressure and requires no sample preparation, thereby making it ideal for rapid sampling of thicker tissue sections for electrophysiological and other neuroscientific research studies. Studies interrogating neural synapses, or a specific neural circuit, typically employ thick, ex vivo tissue sections maintained under near-physiological conditions to preserve tissue viability and maintain the neural networks. Deep brain stimulation (DBS) is a surgical procedure used to treat the neurological symptoms that are associated with certain neurodegenerative and neuropsychiatric diseases. Parkinson's disease (PD) is a neurological disorder which is commonly treated with DBS therapy. PD is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta portion of the brain. Here, we demonstrate that the LMJ-SS methodology can provide a platform for ex vivo analysis of the brain during electrical stimulation, such as DBS. We employ LMJ-SS in the ex vivo analysis of mouse brain tissue for monitoring dopamine during electrical stimulation of the striatum region. The mouse brain tissue was sectioned fresh post sacrifice and maintained in artificial cerebrospinal fluid to create near-physiological conditions before direct sampling using LMJ-SS. A selection of metabolites, including time-sensitive metabolites involved in energy regulation in the brain, were identified using standards, and the mass spectral database mzCloud was used to assess the feasibility of the methodology. Thereafter, the intensity of m/z 154 corresponding to protonated dopamine was monitored before and after electrical stimulation of the striatum region, showing an increase in signal directly following a stimulation event. Dopamine is the key neurotransmitter implicated in PD, and although electrochemical detectors have shown such increases in dopamine post-DBS, this is the first study to do so using MS methodologies.

Cationic albumin-conjugated pegylated nanoparticles as novel drug carrier for brain delivery.

PubMed

Lu, Wei; Zhang, Yan; Tan, Yu-Zhen; Hu, Kai-Li; Jiang, Xin-Guo; Fu, Shou-Kuan

2005-10-20

In this paper, a novel drug carrier for brain delivery, cationic bovine serum albumin (CBSA) conjugated with poly(ethyleneglycol)-poly(lactide) (PEG-PLA) nanoparticle (CBSA-NP), was developed and its effects were evaluated. The copolymers of methoxy-PEG-PLA and maleimide-PEG-PLA were synthesized by ring opening polymerization of D,L-lactide initiated by methoxy-PEG and maleimide-PEG, respectively, which were applied to prepare pegylated nanoparticles by means of double emulsion and solvent evaporation procedure. Native bovine serum albumin (BSA) was cationized and thiolated, followed by conjugation through the maleimide function located at the distal end of PEG surrounding the nanoparticle's surface. Transmission electron micrograph (TEM) and dynamic light scattering results showed that CBSA-NP had a round and regular shape with a mean diameter around 100 nm. Surface nitrogen was detected by X-ray photoelectron spectroscopy (XPS), and colloidal gold stained around the nanoparticle's surface was visualized in TEM, which proved that CBSA was covalently conjugated onto its surface. To evaluate the effects of brain delivery, BSA conjugated with pegylated nanoparticles (BSA-NP) was used as the control group and 6-coumarin was incorporated into the nanoparticles as the fluorescent probe. The qualitative and quantitative results of CBSA-NP uptake experiment compared with those of BSA-NP showed that rat brain capillary endothelial cells (BCECs) took in much more CBSA-NP than BSA-NP at 37 degrees C, at different concentrations and time incubations. After a dose of 60 mg/kg CBSA-NP or BSA-NP injection in mice caudal vein, fluorescent microscopy of brain coronal sections showed a higher accumulation of CBSA-NP in the lateral ventricle, third ventricle and periventricular region than that of BSA-NP. There was no difference on BCECs' viability between CBSA-conjugated and -unconjugated pegylated nanoparticles. The significant results in vitro and in vivo showed that CBSA-NP was a promising brain drug delivery carrier with low toxicity.

Educating the Other Half: Implications of Left/Right Brain Research.

ERIC Educational Resources Information Center

Rubenzer, Ronald L.

The document looks at left/right brain research as it relates to learning styles and teaching styles, particularly in special education. An initial section on brain basics covers the history of brain research, methods of investigation, cerebral dominance, divisions of labor of the bifunctional brain, language and related functions, bilingualism,…

A network analysis of ¹⁵O-H₂O PET reveals deep brain stimulation effects on brain network of Parkinson's disease.

PubMed

Park, Hae-Jeong; Park, Bumhee; Kim, Hae Yu; Oh, Maeng-Keun; Kim, Joong Il; Yoon, Misun; Lee, Jong Doo; Chang, Jin Woo

2015-05-01

As Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. We obtained [¹⁵O]H₂O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

Brain embolic phenomena associated with cardiopulmonary bypass.

PubMed

Challa, V R; Moody, D M; Troost, B T

1993-07-01

Various biologic and non-biologic materials may be embolized to the brain after the use of cardiopulmonary bypass (CPB) pumps during open heart surgery but their relative frequency and importance are uncertain. Among the nonbiologic materials, Antifoam A, which contains organosilicates and silicon, continues to be employed as an additive to prevent frothing. Recent improvements in filtration and oxygenation techniques have clearly reduced the incidence of large emboli and complications like stroke but other neurologic sequelae following open heart surgery are common and in many cases poorly explained. A recently developed histochemical technique for the demonstration of the endothelial alkaline phosphatase (AP) was employed in a post-mortem study of brains from 8 patients and 6 dogs dying within a few days after open heart surgery employing cardiopulmonary bypass perfusion. Brains from 38 patients and 6 dogs who were not subjected to heart surgery were studied as controls with the same technique. The AP-stained slides are suitable for both light microscopic examination of the thick celloidin sections as well as a subsequent processing for high-resolution microradiography. Small capillary and arteriolar dilatations (SCADs) were seen in the test subjects/animals but not controls. SCADs were seen in all parts of the brain. Approximately 50% of the SCADs showed birefringence when examined with polarized light. SCADs are putative embolic phenomena and the exact nature and source of the embolic material is under investigation. A glycolipid component is indicated by preliminary studies. SCADs are difficult to find in routine paraffin sections and most if not all of the offending material seems to be dissolved during processing.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that a synthetic amyloid-ß oligomer-binding peptide (ABP) targets amyloid-ß deposits in transgenic mouse brain and human Alzheimer's disease brain.

PubMed

Chakravarthy, Balu; Ito, Shingo; Atkinson, Trevor; Gaudet, Chantal; Ménard, Michel; Brown, Leslie; Whitfield, James

2014-03-14

The synthetic ~5 kDa ABP (amyloid-ß binding peptide) consists of a region of the 228 kDa human pericentrioloar material-1 (PCM-1) protein that selectively and avidly binds in vitro Aβ1-42 oligomers, believed to be key co-drivers of Alzheimer's disease (AD), but not monomers (Chakravarthy et al., (2013) [3]). ABP also prevents Aß1-42 from triggering the apoptotic death of cultured human SHSY5Y neuroblasts, likely by sequestering Aß oligomers, suggesting that it might be a potential AD therapeutic. Here we support this possibility by showing that ABP also recognizes and binds Aβ1-42 aggregates in sections of cortices and hippocampi from brains of AD transgenic mice and human AD patients. More importantly, ABP targets Aβ1-42 aggregates when microinjected into the hippocampi of the brains of live AD transgenic mice. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

A radiologic correlation with the basic functional neuroanatomy of the brain.

PubMed

Bilicka, Z; Liska, M; Bluska, P; Bilicky, J

2014-01-01

Primary cortical areas for motor, sensory and sensitive functions are localized in certain areas of the brain cortex. In clinical practice, cross sectional imaging (computer tomography and magnetic resonance) is wildy used for diagnostics purpose, treatment planning and follow up of the patients. Accurate orientation in brain structures is necessary for the evaluation of radiological images. There are numerable landmark signs, which can be used for precise identification of important brain structures. In this review article, the mostly used anatomical landmarks are described and shown on the cross sectional images (magnetic resonance imaging) (Fig. 14, Ref. 25).

Investigation of the usefulness of fluorescein sodium fluorescence in stereotactic brain biopsy.

PubMed

Thien, Ady; Han, Julian Xinguang; Kumar, Krishan; Ng, Yew Poh; Rao, Jai Prashanth; Ng, Wai Hoe; King, Nicolas Kon Kam

2018-02-01

Intraoperative frozen section assessment, to confirm acquisition of pathological tissues, is used in stereotactic brain biopsy to minimise sampling errors. Limitations include the dependence on dedicated neuro-oncology pathologists and an increase in operative duration. We investigated the use of intraoperative fluorescein sodium, and compared it to frozen section assessment, for confirming pathological tissue samples in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. This prospective observational study consisted of 18 consecutive patients (12 men; median age, 63 years) who underwent stereotactic biopsy of gadolinium-contrast-enhancing brain lesions with intravenous fluorescein sodium administration. Twenty-three specimens were obtained and examined for the presence of fluorescence using a microscope with fluorescence visualisation capability. Positive and negative predictive values were calculated based on the fluorescence status of the biopsy samples with its corresponding intraoperative frozen section and definitive histopathological diagnosis. Nineteen specimens (83%) were fluorescent and four (17%) were non-fluorescent. All 19 fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment and were suitable for histopathological diagnosis. Three of the non-fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment. One non-fluorescent specimen was non-diagnostic on frozen section and histological assessments. The positive predictive value was 100% and the negative predictive value was 25%. Fluorescein sodium fluorescence is as accurate as frozen section assessment in confirming sampling of pathological tissue in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. Fluorescein sodium fluorescence-guided stereotactic biopsy is a useful addition to the neurosurgical armamentarium.

Optimization of Glial Fibrillary Acidic Protein Immunoreactivity in Formalin-fixed, Paraffin-Embedded Guinea Pig Brain Sections

DTIC Science & Technology

2003-09-01

fixed, paraffin-embedded guinea pig brain sections using a variety of commercially available GFAP antibody clones. Of the 7 clones tested for cross...determining neuropathological consequences in the guinea pig following exposure to chemical warfare nerve agent.

You can't stop the music: reduced auditory alpha power and coupling between auditory and memory regions facilitate the illusory perception of music during noise.

PubMed

Müller, Nadia; Keil, Julian; Obleser, Jonas; Schulz, Hannah; Grunwald, Thomas; Bernays, René-Ludwig; Huppertz, Hans-Jürgen; Weisz, Nathan

2013-10-01

Our brain has the capacity of providing an experience of hearing even in the absence of auditory stimulation. This can be seen as illusory conscious perception. While increasing evidence postulates that conscious perception requires specific brain states that systematically relate to specific patterns of oscillatory activity, the relationship between auditory illusions and oscillatory activity remains mostly unexplained. To investigate this we recorded brain activity with magnetoencephalography and collected intracranial data from epilepsy patients while participants listened to familiar as well as unknown music that was partly replaced by sections of pink noise. We hypothesized that participants have a stronger experience of hearing music throughout noise when the noise sections are embedded in familiar compared to unfamiliar music. This was supported by the behavioral results showing that participants rated the perception of music during noise as stronger when noise was presented in a familiar context. Time-frequency data show that the illusory perception of music is associated with a decrease in auditory alpha power pointing to increased auditory cortex excitability. Furthermore, the right auditory cortex is concurrently synchronized with the medial temporal lobe, putatively mediating memory aspects associated with the music illusion. We thus assume that neuronal activity in the highly excitable auditory cortex is shaped through extensive communication between the auditory cortex and the medial temporal lobe, thereby generating the illusion of hearing music during noise. Copyright © 2013 Elsevier Inc. All rights reserved.

The Feasibility of Detecting Neuropsychologic and Neuroanatomic Effects of Type 1 Diabetes in Young Children

PubMed Central

Aye, Tandy; Reiss, Allan L.; Kesler, Shelli; Hoang, Sherry; Drobny, Jessica; Park, Yaena; Schleifer, Kristin; Baumgartner, Heidi; Wilson, Darrell M.; Buckingham, Bruce A.

2011-01-01

OBJECTIVE To determine if frequent exposures to hypoglycemia and hyperglycemia during early childhood lead to neurocognitive deficits and changes in brain anatomy. RESEARCH DESIGN AND METHODS In this feasibility, cross-sectional study, young children, aged 3 to 10 years, with type 1 diabetes and age- and sex-matched healthy control (HC) subjects completed neuropsychologic (NP) testing and magnetic resonance imaging (MRI) scans of the brain. RESULTS NP testing and MRI scanning was successfully completed in 98% of the type 1 diabetic and 93% of the HC children. A significant negative relationship between HbA1c and Wechsler Intelligence Scale for Children (WISC) verbal comprehension was observed. WISC index scores were significantly reduced in type 1 diabetic subjects who had experienced seizures. White matter volume did not show the expected increase with age in children with type 1 diabetes compared with HC children (diagnosis by age interaction, P = 0.005). A similar trend was detected for hippocampal volume. Children with type 1 diabetes who had experienced seizures showed significantly reduced gray matter and white matter volumes relative to children with type 1 diabetes who had not experienced seizures. CONCLUSIONS It is feasible to perform MRI and NP testing in young children with type 1 diabetes. Further, early signs of neuroanatomic variation may be present in this population. Larger cross-sectional and longitudinal studies of neurocognitive function and neuroanatomy are needed to define the effect of type 1 diabetes on the developing brain. PMID:21562318

Development of an experimental model of brain tissue heterotopia in the lung

PubMed Central

Quemelo, Paulo Roberto Veiga; Sbragia, Lourenço; Peres, Luiz Cesar

2007-01-01

Summary The presence of heterotopic brain tissue in the lung is a rare abnormality. The cases reported thus far are usually associated with neural tube defects (NTD). As there are no reports of experimental models of NTD that present this abnormality, the objective of the present study was to develop a surgical method of brain tissue heterotopia in the lung. We used 24 pregnant Swiss mice divided into two groups of 12 animals each, denoted 17GD and 18GD according to the gestational day (GD) when caesarean section was performed to collect the fetuses. Surgery was performed on the 15th GD, one fetus was removed by hysterectomy and its brain tissue was cut into small fragments and implanted in the lung of its litter mates. Thirty-four live fetuses were obtained from the 17GD group. Of these, eight (23.5%) were used as control (C), eight (23.5%) were sham operated (S) and 18 (52.9%) were used for pulmonary brain tissue implantation (PBI). Thirty live fetuses were obtained from the females of the 18GD group. Of these, eight (26.6%) were C, eight (26.6%) S and 14 (46.6%) were used for PBI. Histological examination of the fetal trunks showed implantation of GFAP-positive brain tissue in 85% of the fetuses of the 17GD group and in 100% of those of the 18GD group, with no significant difference between groups for any of the parameters analysed. The experimental model proved to be efficient and of relatively simple execution, showing complete integration of the brain tissue with pulmonary and pleural tissue and thus representing a model that will permit the study of different aspects of cell implantation and interaction. PMID:17877535

Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I.

PubMed

Kakkis, E; McEntee, M; Vogler, C; Le, S; Levy, B; Belichenko, P; Mobley, W; Dickson, P; Hanson, S; Passage, M

2004-01-01

Enzyme replacement therapy (ERT) has been developed for several lysosomal storage disorders, including mucopolysaccharidosis I (MPS I), and is effective at reducing lysosomal storage in many tissues and in ameliorating clinical disease. However, intravenous ERT does not adequately treat storage disease in the central nervous system (CNS), presumably due to effects of the blood-brain barrier on enzyme distribution. To circumvent this barrier, we studied whether intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) could penetrate and treat the brain and meninges. An initial dose-response study showed that doses of 0.46-4.14 mg of IT rhIDU successfully penetrated the brain of normal dogs and reached tissue levels 5.6 to 18.9-fold normal overall and 2.7 to 5.9-fold normal in deep brain sections lacking CSF contact. To assess the efficacy and safety in treating lysosomal storage disease, four weekly doses of approximately 1 mg of IT rhIDU were administered to MPS I-affected dogs resulting in a mean 23- and 300-fold normal levels of iduronidase in total brain and meninges, respectively. Quantitative glycosaminoglycan (GAG) analysis showed that the IT treatment reduced mean total brain GAG to normal levels and achieved a 57% reduction in meningeal GAG levels accompanied by histologic improvement in lysosomal storage in all cell types. The dogs did develop a dose-dependent immune response against the recombinant human protein and a meningeal lymphocytic/plasmacytic infiltrate. The IT route of ERT administration may be an effective way to treat the CNS disease in MPS I and could be applicable to other lysosomal storage disorders.

Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.

PubMed

Lu, Zhengqi; Zhang, Bingjun; Qiu, Wei; Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

Comparative Brain Stem Lesions on MRI of Acute Disseminated Encephalomyelitis, Neuromyelitis Optica, and Multiple Sclerosis

PubMed Central

Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Background Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). Objectives To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Methods Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Results Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Conclusions Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases. PMID:21853047

Traumatic Brain Injury: An Educator's Manual. [Revised Edition.

ERIC Educational Resources Information Center

Fiegenbaum, Ed, Ed.; And Others

This manual for the Portland (Oregon) Public Schools presents basic information on providing educational services to children with traumatic brain injury (TBI). Individual sections cover the following topics: the brain, central nervous system and behavior; physical, psychological and emotional implication; traumatic brain injury in children versus…

Human brain microvascular endothelial cells resist elongation due to shear stress.

PubMed

Reinitz, Adam; DeStefano, Jackson; Ye, Mao; Wong, Andrew D; Searson, Peter C

2015-05-01

Endothelial cells in straight sections of vessels are known to elongate and align in the direction of flow. This phenotype has been replicated in confluent monolayers of bovine aortic endothelial cells and human umbilical vein endothelial cells (HUVECs) in cell culture under physiological shear stress. Here we report on the morphological response of human brain microvascular endothelial cells (HBMECs) in confluent monolayers in response to shear stress. Using a microfluidic platform we image confluent monolayers of HBMECs and HUVECs under shear stresses up to 16 dyne cm(-2). From live-cell imaging we quantitatively analyze the cell morphology and cell speed as a function of time. We show that HBMECs do not undergo a classical transition from cobblestone to spindle-like morphology in response to shear stress. We further show that under shear stress, actin fibers are randomly oriented in the cells indicating that there is no cytoskeletal remodeling. These results suggest that HBMECs are programmed to resist elongation and alignment under shear stress, a phenotype that may be associated with the unique properties of the blood-brain barrier. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain size growth in wild and captive chimpanzees (Pan troglodytes).

PubMed

Cofran, Zachary

2018-05-24

Despite many studies of chimpanzee brain size growth, intraspecific variation is under-explored. Brain size data from chimpanzees of the Taï Forest and the Yerkes Primate Research Center enable a unique glimpse into brain growth variation as age at death is known for individuals, allowing cross-sectional growth curves to be estimated. Because Taï chimpanzees are from the wild but Yerkes apes are captive, potential environmental effects on neural development can also be explored. Previous research has revealed differences in growth and health between wild and captive primates, but such habitat effects have yet to be investigated for brain growth. Here, I use an iterative curve fitting procedure to estimate brain growth and regression parameters for each population, statistically comparing growth models using bootstrapped confidence intervals. Yerkes and Taï brain sizes overlap at all ages, although the sole Taï newborn is at the low end of captive neonatal variation. Growth rate and duration are statistically indistinguishable between the two populations. Resampling the Yerkes sample to match the Taï sample size and age group composition shows that ontogenetic variation in the two groups are remarkably similar despite the latter's limited size. Best fit growth curves for each sample indicate cessation of brain size growth at around 2 years, earlier than has previously been reported. The overall similarity between wild and captive chimpanzees points to the canalization of brain growth in this species. © 2018 Wiley Periodicals, Inc.

Cortical and subcortical atrophy in Alzheimer disease: parallel atrophy of thalamus and hippocampus.

PubMed

Štěpán-Buksakowska, Irena; Szabó, Nikoletta; Hořínek, Daniel; Tóth, Eszter; Hort, Jakub; Warner, Joshua; Charvát, František; Vécsei, László; Roček, Miloslav; Kincses, Zsigmond T

2014-01-01

Brain atrophy is a key imaging hallmark of Alzheimer disease (AD). In this study, we carried out an integrative evaluation of AD-related atrophy. Twelve patients with AD and 13 healthy controls were enrolled. We conducted a cross-sectional analysis of total brain tissue volumes with SIENAX. Localized gray matter atrophy was identified with optimized voxel-wise morphometry (FSL-VBM), and subcortical atrophy was evaluated by active shape model implemented in FMRIB's Integrated Registration Segmentation Toolkit. SIENAX analysis demonstrated total brain atrophy in AD patients; voxel-based morphometry analysis showed atrophy in the bilateral mediotemporal regions and in the posterior brain regions. In addition, regarding the diminished volumes of thalami and hippocampi in AD patients, subsequent vertex analysis of the segmented structures indicated shrinkage of the bilateral anterior thalami and the left medial hippocampus. Interestingly, the volume of the thalami and hippocampi were highly correlated with the volume of the thalami and amygdalae on both sides in AD patients, but not in healthy controls. This complex structural information proved useful in the detailed interpretation of AD-related neurodegenerative process, as the multilevel approach showed both global and local atrophy on cortical and subcortical levels. Most importantly, our results raise the possibility that subcortical structure atrophy is not independent in AD patients.

Role of intraoperative ultrasound in achieving complete resection of intra-axial solid brain tumours.

PubMed

Mari, Abdul Razaque; Shah, Irfanullah; Imran, Muhammed; Ashraf, Junaid

2014-12-01

To determine the frequency of completeness of resection for intra-axial solid brain tumours with the help of intra-operative ultrasound to detect residual brain tumour. The cross-sectional study was conducted at the Department of Neurosurgery, Dow University of Health Sciences and Civil Hospital Karachi, from September 2009 to June 2010 and comprised patients with intra-axial solid brain lesion. During operation following standard craniotomy, multi-plane sonographic examination was performed using intra-operative ultrasound for tumour localisation and calculation of dimension, followed by tumour resection in the standard fashion. At the end of tumour resection ultrasound was again used for the detection of any residual tumour. Results of intra-operative ultrasound were compared with post-operative contrast magnetic resonance imaging. Of the 39 cases in which intra-operative ultrasound was performed, 32(82.1%) were males and 7(17.9%) were females, with an overall mean age of 42.6±19.7 years. Intra-operative ultrasonography was able to localise and delineate the tumour in all 39 (100%) cases. It showed no residual tumour in 36 (92.3%) cases, but in 3(7.7%) cases residual tumour was detected. Post-operative contrast enhancing magnetic resonance imaging showed no residual tumour in 35(89.7%) cases and in 4(10.3%) cases residual tumour was detected. The frequency of completely resected intra-axial solid brain tumour was 35(89.7%), while in 4(10.3%) cases incomplete resection was observed. The study concluded that intra-operative ultrasonography has an important role in achieving increased frequency of completely resected intra-axial solid brain tumours.

Brain SPECT scans in students with specific learning disability: Preliminary results.

PubMed

Karande, S; Deshmukh, N; Rangarajan, V; Agrawal, A; Sholapurwala, R

2018-06-08

Brain single-photon emission computed tomography (SPECT) assesses brain function through measurement of regional cerebral blood flow. This study was conducted to assess whether students with newly diagnosed specific learning disability (SpLD) show any abnormalities in cerebral cortex perfusion. Cross-sectional single-arm pilot study in two tertiary care hospitals. Nine students with SpLD were enrolled. Brain SPECT scan was done twice in each student. For the first or "baseline" scan, the student was first made to sit with eyes open in a quiet, dimly lit room for a period of 30-40 min and then injected intravenously with 20 mCi of 99mTc-ECD. An hour later, "baseline scan" was conducted. After a minimum gap of 4 days, a second or "test scan" was conducted, wherein the student performed an age-appropriate curriculum-based test for a period of 30-40 min to activate the areas in central nervous system related to learning before being injected with 20 mCi of 99mTc-ECD. Cerebral cortex perfusion at rest and after activation in each student was compared qualitatively by visual analysis and quantitatively using NeuroGam TM software. Visual analysis showed reduction in regional blood flow in temporoparietal areas in both "baseline" and "test" scans. However, when normalization was attempted and comparison done by Talairach analysis using NeuroGam software, no statistically significant change in regional perfusion in temporoparietal areas was appreciated. Brain SPECT scan may serve as a robust tool to identify changes in regional brain perfusion in students with SpLD.

Cognitive Development in Children with Brain Damage.

ERIC Educational Resources Information Center

Bortner, Morton

Presented is a report on a cross-sectional and longitudinal study concerned with the course of intellectual development in 210 children (6-12 years old) educationally designated as brain damaged (learning disabled and/or behavior problems) and assigned to special school placement. The report is divided into four sections which focus on…

Consecutive light microscopy, scanning-transmission electron microscopy and transmission electron microscopy of traumatic human brain oedema and ischaemic brain damage.

PubMed

Castejon, O J; Castejon, H V; Diaz, M; Castellano, A

2001-10-01

Cortical biopsies of 11 patients with traumatic brain oedema were consecutively studied by light microscopy (LM) using thick plastic sections, scanning-transmission electron microscopy ((S)TEM) using semithin plastic sections and transmission electron microscopy (TEM) using ultrathin sections. Samples were glutaraldehyde-osmium fixed and embedded in Araldite or Epon. Thick sections were stained with toluidine-blue for light microscopy. Semithin sections were examined unstained and uncoated for (S)TEM. Ultrathin sections were stained with uranyl and lead. Perivascular haemorrhages and perivascular extravasation of proteinaceous oedema fluid were observed in both moderate and severe oedema. Ischaemic pyramidal and non-pyramidal nerve cells appeared shrunken, electron dense and with enlargement of intracytoplasmic membrane compartment. Notably swollen astrocytes were observed in all samples examined. Glycogen-rich and glycogen-depleted astrocytes were identified in anoxic-ischaemic regions. Dark and hydropic satellite, interfascicular and perivascular oligodendrocytes were also found. The status spongiosus of severely oedematous brain parenchyma observed by LM and (S)TEM was correlated with the enlarged extracellular space and disrupted neuropil observed by TEM. The (S)TEM is recommended as a suitable technique for studying pathological processes in the central nervous system and as an informative adjunct to LM and TEM.

Anatomic brain disease in hemodialysis patients: a cross-sectional study

USDA-ARS?s Scientific Manuscript database

Although dialysis patients are at high risk of stroke and have a high burden of cognitive impairment, there are few reports of anatomic brain findings in the hemodialysis population. Using magnetic resonance imaging of the brain, we compared the prevalence of brain abnormalities in hemodialysis pati...

Reduced miR-512 and the Elevated Expression of Its Targets cFLIP and MCL1 Localize to Neurons With Hyperphosphorylated Tau Protein in Alzheimer Disease.

PubMed

Mezache, Louisa; Mikhail, Madison; Garofalo, Michela; Nuovo, Gerard J

2015-10-01

The cause for the neurofibrillary tangles and plaques in Alzheimer disease likely relates to an abnormal accumulation of their key components, which include β-amyloid and hyperphosphorylated tau protein. We segregated Alzheimer brain sections from people with end-stage disease into those with abundant hyperphosphorylated tau protein and those without and compared each to normal brains for global microRNA patterns. A significant reduced expression of several microRNAs, including miR-512, was evident in the Alzheimer brain sections with abundant hyperphosphorylated tau. Immunohistochemistry documented that 2 known targets of microRNA-512, cFLIP and MCL1, were significantly over expressed and each colocalized to neurons with the abnormal tau protein. Analysis for apoptosis including activated caspase-3, increased caspase-4 and caspase-8, apoptosis initiating factor, APAF-1 activity, and the TUNEL assay was negative in the areas where neurons showed hyperphosphorylated tau. MCM2 expression, a marker of neuroprogenitor cells, was significantly reduced in the Alzheimer sections that contained the hyperphosphorylated tau. These results suggest that a basic defect in Alzheimer disease may be the reduced microRNA-driven increased expression of proteins that may alter the apoptotic/antiapoptotic balance of neurons. This, in turn, could lead to the accumulation of key Alzheimer proteins such as hyperphosphorylated tau that ultimately prevent normal neuronal function and lead to disease symptomatology.

Frontal parenchymal atrophy measures in multiple sclerosis.

PubMed

Locatelli, Laura; Zivadinov, Robert; Grop, Attilio; Zorzon, Marino

2004-10-01

The aim of this study was to establish whether, in a cross-sectional study, the normalized measures of whole and regional brain atrophy correlate better with tests assessing the cognitive function than the absolute brain atrophy measures. The neuropsychological performances and disability have been assessed in 39 patients with relapsing-remitting multiple sclerosis (MS). T1- and T2-lesion load (LL) of total brain and frontal lobes (FLs) were measured using a reproducible semiautomated technique. The whole brain volume and the regional brain parenchymal volume (RBPV) of FLs were obtained using a computerized interactive program, which incorporates semiautomated and automated segmentation processes. Normalized measures of brain atrophy, i.e., brain parenchymal fraction (BPF) and regional brain parenchymal fraction (RBPF) of FLs, were calculated. The scan-rescan, inter- and intrarater coefficient of variation (COV) and intraclass correlation coefficient (ICC) have been estimated. The RBPF of FLs showed an acceptable level of reproducibility which ranged from 1.7% for intrarater variability to 3.2% for scan-rescan variability. The mean ICC was 0.88 (CI 0.82-0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with neuropsychological functioning, disability and quantitative MRI lesion measures than RBPV. These differences were statistically significant: P<0.001 for Stroop Color Word Interference test, P<0.001 for Paced Auditory Serial Addition Test, P=0.04 for Standard Raven Progressive Matrices, P=0.049 for Expanded Disability Status Scale, P=0.01 for T2-LL of FLs and P<0.001 for T1-LL of FLs. BPF demonstrated significant correlations with tests assessing cognitive functions, whereas BPAV did not. The correlation analysis results were supported by the results of multiple regression analysis which showed that only the normalized brain atrophy measures were associated with tests exploring the cognitive functions. These data suggest that RBPF is a reproducible and sensitive method for measuring frontal parenchymal atrophy. The normalized measures of whole and regional brain parenchymal atrophy should be preferred to absolute measures in future studies that correlate neuropsychological performances and brain atrophy measures in patients with MS.

Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain.

PubMed

Petro, Marianne; Jaffer, Hayder; Yang, Jun; Kabu, Shushi; Morris, Viola B; Labhasetwar, Vinod

2016-03-01

Inherent neuronal and circulating progenitor cells play important roles in facilitating neuronal and functional recovery post stroke. However, this endogenous repair process is rather limited, primarily due to unfavorable conditions in the infarcted brain involving reactive oxygen species (ROS)-mediated oxidative stress and inflammation following ischemia/reperfusion injury. We hypothesized that during reperfusion, effective delivery of antioxidants to ischemic brain would create an environment without such oxidative stress and inflammation, thus promoting activation and mobilization of progenitor cells in the infarcted brain. We administered recombinant human tissue-type plasminogen activator (tPA) via carotid artery at 3 h post stroke in a thromboembolic rat model, followed by sequential administration of the antioxidants catalase (CAT) and superoxide dismutase (SOD), encapsulated in biodegradable nanoparticles (nano-CAT/SOD). Brains were harvested at 48 h post stroke for immunohistochemical analysis. Ipsilateral brain slices from animals that had received tPA + nano-CAT/SOD showed a widespread distribution of glial fibrillary acidic protein-positive cells (with morphology resembling radial glia-like neural precursor cells) and nestin-positive cells (indicating the presence of immature neurons); such cells were considerably fewer in untreated animals or those treated with tPA alone. Brain sections from animals receiving tPA + nano-CAT/SOD also showed much greater numbers of SOX2- and nestin-positive progenitor cells migrating from subventricular zone of the lateral ventricle and entering the rostral migratory stream than in t-PA alone treated group or untreated control. Further, animals treated with tPA + nano-CAT/SOD showed far fewer caspase-positive cells and fewer neutrophils than did other groups, as well as an inhibition of hippocampal swelling. These results suggest that the antioxidants mitigated the inflammatory response, protected neuronal cells from undergoing apoptosis, and inhibited edema formation by protecting the blood-brain barrier from ROS-mediated reperfusion injury. A longer-term study would enable us to determine if our approach would assist progenitor cells to undergo neurogenesis and to facilitate neurological and functional recovery following stroke and reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

Automated brain volumetrics in multiple sclerosis: a step closer to clinical application

PubMed Central

Beadnall, H N; Hatton, S N; Bader, G; Tomic, D; Silva, D G

2016-01-01

Background Whole brain volume (WBV) estimates in patients with multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. Numerous algorithms to measure WBV have been developed over the past two decades. We compare Structural Image Evaluation using Normalisation of Atrophy-Cross-sectional (SIENAX) to NeuroQuant and MSmetrix, for assessment of cross-sectional WBV in patients with MS. Methods MRIs from 61 patients with relapsing-remitting MS and 2 patients with clinically isolated syndrome were analysed. WBV measurements were calculated using SIENAX, NeuroQuant and MSmetrix. Statistical agreement between the methods was evaluated using linear regression and Bland-Altman plots. Precision and accuracy of WBV measurement was calculated for (1) NeuroQuant versus SIENAX and (2) MSmetrix versus SIENAX. Results Precision (Pearson's r) of WBV estimation for NeuroQuant and MSmetrix versus SIENAX was 0.983 and 0.992, respectively. Accuracy (Cb) was 0.871 and 0.994, respectively. NeuroQuant and MSmetrix showed a 5.5% and 1.0% volume difference compared with SIENAX, respectively, that was consistent across low and high values. Conclusions In the analysed population, NeuroQuant and MSmetrix both quantified cross-sectional WBV with comparable statistical agreement to SIENAX, a well-validated cross-sectional tool that has been used extensively in MS clinical studies. PMID:27071647

Slide shows vs graphic tablet live drawing for anatomy teaching.

PubMed

Alsaid, B

2016-12-01

Blackboard drawing is the traditional and still widely learned method for anatomy teachers. However, for practical reasons, more and more lessons are done using slide shows. New digital learning tools are developed to create a more attractive teaching method. The objective of this study was to compare the use of graphic tablet live drawing versus slide shows. Sixty-five second-year students of the Faculty of Medicine participated in this study during their first semester of 2013-2014 academic year. The selected lecture dealt about neuroanatomy; two brain sections were taught: median sagittal and transverse. The sagittal section was presented via a slide show. The transverse section was taught using a graphics tablet using drawing software. Students were evaluated three times: before the lecture, immediately after the lecture and 8 weeks later. Means were compared using a t-test. Scores were significantly higher immediately after the lecture and 8 weeks later tests in comparing the transverse section (using the graphics tablet) versus the sagittal section (using PowerPoint ® ). Student satisfaction regarding the use of the tablet was high. The graphics tablet is a usable and efficient drawing tool in anatomy teaching. This tool requires a specific teacher training and preparation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Caring for Patients with traumatic brain injury: a survey of nurses' perceptions.

PubMed

Oyesanya, Tolu O; Brown, Roger L; Turkstra, Lyn S

2017-06-01

The purpose of this study was to determine nurses' perceptions about caring for patients with traumatic brain injury. Annually, it is estimated that over 10 million people sustain a traumatic brain injury around the world. Patients with traumatic brain injury and their families are often concerned with expectations about recovery and seek information from nurses. Nurses' perceptions of care might influence information provided to patients and families, particularly if inaccurate knowledge and perceptions are held. Thus, nurses must be knowledgeable about care of these patients. A cross-sectional survey, the Perceptions of Brain Injury Survey (PBIS), was completed electronically by 513 nurses between October and December 2014. Data were analysed with structural equation modelling, factor analysis, and pairwise comparisons. Using latent class analysis, authors were able to divide nurses into three homogeneous sub-groups based on perceived knowledge: low, moderate and high. Findings showed that nurses who care for patients with traumatic brain injury the most have the highest perceived confidence but the lowest perceived knowledge. Nurses also had significant variations in training. As there is limited literature on nurses' perceptions of caring for patients with traumatic brain injury, these findings have implications for training and educating nurses, including direction for development of nursing educational interventions. As the incidence of traumatic brain injury is growing, it is imperative that nurses be knowledgeable about care of patients with these injuries. The traumatic brain injury PBIS can be used to determine inaccurate perceptions about caring for patients with traumatic brain injury before educating and training nurses. © 2016 John Wiley & Sons Ltd.

Specific binding of [(18)F]fluoroethyl-harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain.

PubMed

Maschauer, Simone; Haller, Adelina; Riss, Patrick J; Kuwert, Torsten; Prante, Olaf; Cumming, Paul

2015-12-01

We investigated [(18)F]fluoroethyl-harmol ([(18)F]FEH) as a reversible and selective ligand for positron emission tomography (PET) studies of monoamine oxidase A (MAO-A). Binding of [(18)F]FEH in rat brain cryostat sections indicated high affinity (KD = 3 nM), and density (Bmax; 600 pmol/g). The plasma free fraction was 45%, and untransformed parent constituted only 13% of plasma radioactivity at 10 min after injection. Compartmental analysis of PET recordings in pargyline-treated rats showed high permeability to brain (K1; 0.32 mL/g/min) and slow washout (k2; 0.024/min), resulting in a uniformly high equilibrium distribution volume (VD; 20 mL/g). Using this VD to estimate unbound ligand in brain of untreated rats, the binding potential ranged from 4.2 in cerebellum to 7.2 in thalamus. We also calculated maps of rats receiving [(18)F]FEH at a range of specific activities, and then estimated saturation binding parameters in the living brain. In thalamus, striatum and frontal cortex KD was globally close to 300 nM and Bmax was close to 1600 pmol/g; the 100-fold discrepancy in affinity suggests a very low free fraction for [(18)F]FEH in the living brain. Based on a synthesis of findings, we calculate the endogenous dopamine concentration to be 0.4 μM in the striatal compartment containing MAO-A, thus unlikely to exert competition against [(18)F]FEH binding in vivo. In summary, [(18)F]FEH has good properties for the detection of MAO-A in the rat brain by PET, and may present logistic advantages for clinical research at centers lacking a medical cyclotron. We made a compartmental analysis of [(18)F]fluoroethylharmol ([(18)F]FEH) binding to monoamine oxidase A (MAO-A) in living rat brain and estimated the saturation binding parameters from the binding potential (BPND). The Bmax was of comparable magnitude to that in vitro, but with apparent affinity (300 nM), it was 100-fold lower in vivo. PET imaging with [(18) F]FEH is well suited for quantitation of MAO-A in living brain. © 2015 International Society for Neurochemistry.

Verbal and non-verbal intelligence changes in the teenage brain.

PubMed

Ramsden, Sue; Richardson, Fiona M; Josse, Goulven; Thomas, Michael S C; Ellis, Caroline; Shakeshaft, Clare; Seghier, Mohamed L; Price, Cathy J

2011-10-19

Intelligence quotient (IQ) is a standardized measure of human intellectual capacity that takes into account a wide range of cognitive skills. IQ is generally considered to be stable across the lifespan, with scores at one time point used to predict educational achievement and employment prospects in later years. Neuroimaging allows us to test whether unexpected longitudinal fluctuations in measured IQ are related to brain development. Here we show that verbal and non-verbal IQ can rise or fall in the teenage years, with these changes in performance validated by their close correlation with changes in local brain structure. A combination of structural and functional imaging showed that verbal IQ changed with grey matter in a region that was activated by speech, whereas non-verbal IQ changed with grey matter in a region that was activated by finger movements. By using longitudinal assessments of the same individuals, we obviated the many sources of variation in brain structure that confound cross-sectional studies. This allowed us to dissociate neural markers for the two types of IQ and to show that general verbal and non-verbal abilities are closely linked to the sensorimotor skills involved in learning. More generally, our results emphasize the possibility that an individual's intellectual capacity relative to their peers can decrease or increase in the teenage years. This would be encouraging to those whose intellectual potential may improve, and would be a warning that early achievers may not maintain their potential.

A comparison of neural network and fuzzy clustering techniques in segmenting magnetic resonance images of the brain.

PubMed

Hall, L O; Bensaid, A M; Clarke, L P; Velthuizen, R P; Silbiger, M S; Bezdek, J C

1992-01-01

Magnetic resonance (MR) brain section images are segmented and then synthetically colored to give visual representations of the original data with three approaches: the literal and approximate fuzzy c-means unsupervised clustering algorithms, and a supervised computational neural network. Initial clinical results are presented on normal volunteers and selected patients with brain tumors surrounded by edema. Supervised and unsupervised segmentation techniques provide broadly similar results. Unsupervised fuzzy algorithms were visually observed to show better segmentation when compared with raw image data for volunteer studies. For a more complex segmentation problem with tumor/edema or cerebrospinal fluid boundary, where the tissues have similar MR relaxation behavior, inconsistency in rating among experts was observed, with fuzz-c-means approaches being slightly preferred over feedforward cascade correlation results. Various facets of both approaches, such as supervised versus unsupervised learning, time complexity, and utility for the diagnostic process, are compared.

Modal demultiplexing properties of tapered and nanostructured optical fibers for in vivo optogenetic control of neural activity.

PubMed

Pisanello, Marco; Della Patria, Andrea; Sileo, Leonardo; Sabatini, Bernardo L; De Vittorio, Massimo; Pisanello, Ferruccio

2015-10-01

Optogenetic approaches to manipulate neural activity have revolutionized the ability of neuroscientists to uncover the functional connectivity underlying brain function. At the same time, the increasing complexity of in vivo optogenetic experiments has increased the demand for new techniques to precisely deliver light into the brain, in particular to illuminate selected portions of the neural tissue. Tapered and nanopatterned gold-coated optical fibers were recently proposed as minimally invasive multipoint light delivery devices, allowing for site-selective optogenetic stimulation in the mammalian brain [Pisanello , Neuron82, 1245 (2014)]. Here we demonstrate that the working principle behind these devices is based on the mode-selective photonic properties of the fiber taper. Using analytical and ray tracing models we model the finite conductance of the metal coating, and show that single or multiple optical windows located at specific taper sections can outcouple only specific subsets of guided modes injected into the fiber.

Characterization of the Distance Relationship Between Localized Serotonin Receptors and Glia Cells on Fluorescence Microscopy Images of Brain Tissue.

PubMed

Jacak, Jaroslaw; Schaller, Susanne; Borgmann, Daniela; Winkler, Stephan M

2015-08-01

We here present two new methods for the characterization of fluorescent localization microscopy images obtained from immunostained brain tissue sections. Direct stochastic optical reconstruction microscopy images of 5-HT1A serotonin receptors and glial fibrillary acidic proteins in healthy cryopreserved brain tissues are analyzed. In detail, we here present two image processing methods for characterizing differences in receptor distribution on glial cells and their distribution on neural cells: One variant relies on skeleton extraction and adaptive thresholding, the other on k-means based discrete layer segmentation. Experimental results show that both methods can be applied for distinguishing classes of images with respect to serotonin receptor distribution. Quantification of nanoscopic changes in relative protein expression on particular cell types can be used to analyze degeneration in tissues caused by diseases or medical treatment.

Characterization of encephalitis in wild birds naturally infected by highly pathogenic avian influenza H5N1.

PubMed

Bröjer, Caroline; Agren, Erik O; Uhlhorn, Henrik; Bernodt, Karin; Jansson, Désirée S; Gavier-Widén, Dolores

2012-03-01

During the outbreak of highly pathogenic avian influenza (HPAI) H5N1 in Sweden in 2006, disease and mortality were observed in a number of wild bird species. Encephalitis was one of the most consistent and severe findings in birds submitted for postmortem examination. However, the distribution and severity of the inflammation varied among individuals. This study characterized the encephalitis and the phenotype of the cellular infiltrate in brains of 40 birds of various species naturally infected with HPAI H5N1. Brain sections stained with hematoxylin and eosin and immunostained for influenza A viral antigen were evaluated in parallel to brain sections immunostained with antibodies against T lymphocytes (CD3+), B lymphocytes (CD79a+), macrophages (Lectin RCA-1+), and astrocytes expressing glial fibrillary acidic protein. The virus showed marked neurotropism, and the neuropathology included multifocal to diffuse areas of gliosis and inflammation in the gray matter, neuronal degeneration, neuronophagia, vacuolation of the neuropil, focal necrosis, perivascular cuffing, and meningitis. Broad ranges in severity, neuroanatomical distribution, and type of cellular infiltrate were observed among the different bird species. Since neurotropism is a key feature of HPAI H5N1 infection in birds and other species and because the clinical presentation can vary, the characterization of the inflammation in the brain is important in understanding the pathogenesis of the disease and also has important diagnostic implications for sample selection.

Autoradiographic analysis of the in vivo distribution of 3H-imipramine and 3H-desipramine in brain: Comparison to in vitro binding patterns

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

Duncan, G.E.; Paul, I.A.; Fassberg, J.B.

1991-03-01

Using high resolution autoradiographic techniques, the distribution of radioactivity in forebrain and brainstem was assessed after 4 injection of 3H-impramine or 3H-desipramine. Results were compared with regional binding of the drugs to brain sections in vitro. Similar topographic binding of 3H-imipramine and 3H-desipramine was observed in vitro among brain regions, except in the paraventricular nucleus of the hypothalamus and locus coeruleus, where binding was greater for 3H-desipramine. For both 3H-desipramine and 3H-imipramine, some brain regions that exhibited high binding in vitro also showed high accumulation after in vivo injection. However, certain regions that contained high densities of binding sites formore » the antidepressant drugs as measured by in vitro binding showed very low accumulation of radioactivity after in vivo treatment. Such regions included the dentate gyrus of the hippocampus, layer 1 of piriform cortex, caudate-putamen, pontine and midbrain central gray, and cerebellar granular layer. Compared to in vitro binding of the drugs, the distribution of imipramine and desipramine in vivo appears more anatomically selective. For imipramine, primary sites of action in vivo, as indicated by the topographic distribution in brain, appear to be the locus coeruleus, hippocampus, lateral septal nucleus, and amygdala. For desipramine, the greatest accumulation in vivo was found in the locus coeruleus, paraventricular nucleus of the hypothalamus, and anterior thalamic nuclei.« less

Ownership of an artificial limb induced by electrical brain stimulation

PubMed Central

Collins, Kelly L.; Cronin, Jeneva; Olson, Jared D.; Ehrsson, H. Henrik; Ojemann, Jeffrey G.

2017-01-01

Replacing the function of a missing or paralyzed limb with a prosthetic device that acts and feels like one’s own limb is a major goal in applied neuroscience. Recent studies in nonhuman primates have shown that motor control and sensory feedback can be achieved by connecting sensors in a robotic arm to electrodes implanted in the brain. However, it remains unknown whether electrical brain stimulation can be used to create a sense of ownership of an artificial limb. In this study on two human subjects, we show that ownership of an artificial hand can be induced via the electrical stimulation of the hand section of the somatosensory (SI) cortex in synchrony with touches applied to a rubber hand. Importantly, the illusion was not elicited when the electrical stimulation was delivered asynchronously or to a portion of the SI cortex representing a body part other than the hand, suggesting that multisensory integration according to basic spatial and temporal congruence rules is the underlying mechanism of the illusion. These findings show that the brain is capable of integrating “natural” visual input and direct cortical-somatosensory stimulation to create the multisensory perception that an artificial limb belongs to one’s own body. Thus, they serve as a proof of concept that electrical brain stimulation can be used to “bypass” the peripheral nervous system to induce multisensory illusions and ownership of artificial body parts, which has important implications for patients who lack peripheral sensory input due to spinal cord or nerve lesions. PMID:27994147

Fast assembling of neuron fragments in serial 3D sections.

PubMed

Chen, Hanbo; Iascone, Daniel Maxim; da Costa, Nuno Maçarico; Lein, Ed S; Liu, Tianming; Peng, Hanchuan

2017-09-01

Reconstructing neurons from 3D image-stacks of serial sections of thick brain tissue is very time-consuming and often becomes a bottleneck in high-throughput brain mapping projects. We developed NeuronStitcher, a software suite for stitching non-overlapping neuron fragments reconstructed in serial 3D image sections. With its efficient algorithm and user-friendly interface, NeuronStitcher has been used successfully to reconstruct very large and complex human and mouse neurons.

Fluorophilia: Fluorophore-containing compounds adhere non-specifically to injured neurons

PubMed Central

Hawkins, Bridget E.; Frederickson, Christopher J.; DeWitt, Douglas S.; Prough, Donald S.

2012-01-01

Ionic (free) zinc (Zn2+) is implicated in apoptotic neuronal degeneration and death. In our attempt to examine the effects of Zn2+ in neurodegeneration following brain injury, we serendipitously discovered that injured neurons bind fluorescein moieties, either alone or as part of an indicator dye, in histologic sections. This phenomenon, that we have termed “fluorophilia”, is analogous to the ability of degenerating neuronal somata and axons to bind silver ions (argyrophilia — the basis of silver degeneration stains). To provide evidence that fluorophilia occurs in sections of brain tissue, we used a wide variety of indicators such as Fluoro-Jade (FJ), a slightly modified fluorescein sold as a marker for degenerating neurons; Newport Green, a fluorescein-containing Zn2+ probe; Rhod-5N, a rhodamine-containing Ca2+ probe; and plain fluorescein. All yielded remarkably similar staining of degenerating neurons in the traumatic brain-injured tissue with the absence of staining in our sham-injured brains. Staining of presumptive injured neurons by these agents was not modified when Zn2+ in the brain section was removed by prior chelation with EDTA or TPEN, whereas staining by a non-fluorescein containing Zn2+ probe, N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide (TSQ), was suppressed by prior chelation. Thus, certain fluorophore-containing compounds nonspecifically stain degenerating neuronal tissue in histologic sections and may not reflect the presence of Zn2+. This may be of concern to researchers using indicator dyes to detect metals in brain tissue sections. Further experiments may be advised to clarify whether Zn2+-binding dyes bind more specifically in intact neurons in culture or organotypic slices. PMID:22137653

A Primer on Brain Imaging in Developmental Psychopathology: What Is It Good For?

ERIC Educational Resources Information Center

Pine, Daniel S.

2006-01-01

This primer introduces a Special Section on brain imaging, which includes a commentary and 10 data papers presenting applications of brain imaging to questions on developmental psychopathology. This primer serves two purposes. First, the article summarizes the strength and weaknesses of various brain-imaging techniques typically employed in…

Best Practices for Young Children's Music Education: Guidance from Brain Research

ERIC Educational Resources Information Center

Flohr, John W.

2010-01-01

This article reviews best practices for young children's music experiences in light of developments in brain research. The first section reviews research music and brain topics including neuromyths, effect of music on structural brain changes and general intelligence, plasticity, critical and optimal periods, and at-risk student populations. The…

Brain lesion correlates of fatigue in individuals with traumatic brain injury.

PubMed

Schönberger, Michael; Reutens, David; Beare, Richard; O'Sullivan, Richard; Rajaratnam, Shantha M W; Ponsford, Jennie

2017-10-01

The purpose of this study was to investigate the neurological correlates of both subjective fatigue as well as objective fatigability in individuals with traumatic brain injury (TBI). The study has a cross-sectional design. Participants (N = 53) with TBI (77% male, mean age at injury 38 years, mean time since injury 1.8 years) underwent a structural magnetic resonance imaging (MRI) scan and completed the Fatigue Severity Scale (FSS), while a subsample (N = 36) was also tested with a vigilance task. While subjective fatigue (FSS) was not related to measures of brain lesions, multilevel analyses showed that a change in the participants' decision time was significantly predicted by grey matter (GM) lesions in the right frontal lobe. The time-dependent development of the participants' error rate was predicted by total brain white matter (WM) lesion volumes, as well as right temporal GM and WM lesion volumes. These findings could be explained by decreased functional connectivity of attentional networks, which results in accelerated exhaustion during cognitive task performance. The disparate nature of objectively measurable fatigability on the one hand and the subjective experience of fatigue on the other needs further investigation.

The effects of ethanol on insulin-like growth factor-I immunoreactive neurons in the central nervous system.

PubMed

Dalcik, Cannur; Yildirim, Guler K; Dalcik, Hakki

2009-08-01

To evaluate the effect of chronically ethanol treatment on insulin-like growth factor-I (IGF-I) synthesis in various adult brain regions using immunocytochemistry. We performed this study at the Faculty of Medicine, Kocaeli University, Kocaeli, Turkey from March 2006 to October 2007. The vascular perfusion was utilized to fix the adult rat brains (10 for each group). After applying the routine histological techniques, the tissues were embedded in the paraffin. The immunohistochemical protocol was applied to the 10 um thick sections and the expression of IGF-I positive cells were observed in the neuro-anatomic areas. The distribution of IGF-I immunoreactive cells differed between the layers of the normal cerebral cortex and in the thalamic areas. In the alcoholic brain, the amount of IGF-I immunoreactive cells were decreased compared to the similar neuro-anatomical areas examined in the normal brains. The presence of IGF-I immunoreactivity in the neurons of the various neuro-anatomic areas demonstrates clearly that, these particular neurons are active in IGF-I synthesis. The decrease in the immunoreactivity of IGF-I in the chronically ethanol treated adult rat brain areas, show clearly that, ethanol effects negatively on the IGF-I synthesis.

Extending the mind: a review of ethnographies of neuroscience practice.

PubMed

Mahfoud, Tara

2014-01-01

THIS PAPER REVIEWS ETHNOGRAPHIES OF NEUROSCIENCE LABORATORIES IN THE UNITED STATES AND EUROPE, ORGANIZING THEM INTO THREE MAIN SECTIONS: (1) descriptions of the capabilities and limitations of technologies used in neuroimaging laboratories to map "activity" or "function" onto structural models of the brain; (2) discussions of the "distributed" or "extended" mind in neuroscience practice; and (3) the implications of neuroscience research and the power of brain images outside the laboratory. I will try to show the importance of ethnographic work in such settings, and place this body of ethnographic work within its historical framework-such ethnographies largely emerged within the Decade of the Brain, as announced by former President of the United States George H. W. Bush in 1990. The main argument is that neuroscience research and the context within which it is taking place has changed since the 1990's-specifically with the launch of "big science" projects such as the Human Brain Project (HBP) in the European Union and the BRAIN initiative in the United States. There is an opportunity for more research into the institutional and politico-economic context within which neuroscience research is taking place, and for continued engagement between the social and biological sciences.

Cloning the Antibody Response in Humans with Chronic Inflammatory Disease: Immunopanning of Subacute Sclerosing Panencephalitis (SSPE) Brain Sections with Antibody Phage Libraries Prepared from SSPE Brain Enriches for Antibody Recognizing Measles Virus Antigens In Situ

PubMed Central

Owens, Gregory P.; Williamson, R. Anthony; Burgoon, Mark P.; Ghausi, Omar; Burton, Dennis R.; Gilden, Donald H.

2000-01-01

In central nervous system (CNS) infectious and inflammatory diseases of known cause, oligoclonal bands represent antibody directed against the causative agent. To determine whether disease-relevant antibodies can be cloned from diseased brain, we prepared an antibody phage display library from the brain of a human with subacute sclerosing panencephalitis (SSPE), a chronic encephalitis caused by measles virus, and selected the library against SSPE brain sections. Antibodies that were retrieved reacted strongly with measles virus cell extracts by enzyme-linked immunosorbent assay and were specific for the measles virus nucleocapsid protein. These antibodies immunostained cells in different SSPE brains but not in control brain. Our data provide the first demonstration that diseased brain can be used to select in situ for antibodies directed against the causative agent of disease and point to the potential usefulness of this approach in identifying relevant antibodies in chronic CNS or systemic inflammatory diseases of unknown cause. PMID:10627565

Teaching Both Sides of the Brain: Book II: Reading.

ERIC Educational Resources Information Center

Dombrower, Jule; And Others

Part of a program to increase the academic growth of preschool and primary grade students through the utilization of brain hemisphere research, this volume contains lessons designed to improve basic reading skills. Material is divided into two sections. Section 1 contains 17 activities to develop letter and word recognition. In activities 1-12,…

Slice-to-Volume Nonrigid Registration of Histological Sections to MR Images of the Human Brain

PubMed Central

Osechinskiy, Sergey; Kruggel, Frithjof

2011-01-01

Registration of histological images to three-dimensional imaging modalities is an important step in quantitative analysis of brain structure, in architectonic mapping of the brain, and in investigation of the pathology of a brain disease. Reconstruction of histology volume from serial sections is a well-established procedure, but it does not address registration of individual slices from sparse sections, which is the aim of the slice-to-volume approach. This study presents a flexible framework for intensity-based slice-to-volume nonrigid registration algorithms with a geometric transformation deformation field parametrized by various classes of spline functions: thin-plate splines (TPS), Gaussian elastic body splines (GEBS), or cubic B-splines. Algorithms are applied to cross-modality registration of histological and magnetic resonance images of the human brain. Registration performance is evaluated across a range of optimization algorithms and intensity-based cost functions. For a particular case of histological data, best results are obtained with a TPS three-dimensional (3D) warp, a new unconstrained optimization algorithm (NEWUOA), and a correlation-coefficient-based cost function. PMID:22567290

An atlas of the prenatal mouse brain: gestational day 14.

PubMed

Schambra, U B; Silver, J; Lauder, J M

1991-11-01

A prenatal atlas of the mouse brain is presently unavailable and is needed for studies of normal and abnormal development, using techniques including immunocytochemistry and in situ hybridization. This atlas will be especially useful for researchers studying transgenic and mutant mice. This collection of photomicrographs and corresponding drawings of Gestational Day (GD) 14 mouse brain sections is an excerpt from a larger atlas encompassing GD 12-18. In composing this atlas, available published studies on the developing rodent brain were consulted to aid in the detailed labeling of embryonic brain structures. C57Bl/6J mice were mated for 1 h, and the presence of a copulation plug was designated as GD 0. GD 14 embryos were perfused transcardially with 4% paraformaldehyde in 0.1 M phosphate buffer and embedded in paraffin. Serial sections (10 microns thickness) were cut through whole heads in sagittal and horizontal planes. They were stained with hematoxylin and eosin and photographed. Magnifications were 43X and 31X for the horizontal and sagittal sections, respectively. Photographs were traced and line drawings prepared using an Adobe Illustrator on a Macintosh computer.

Experimental methods for testing the effects of neurotrophic peptide, ADNF-9, against alcohol-induced apoptosis during pregnancy in c57bl/6 mice.

PubMed

Sari, Youssef

2013-04-24

Experimental designs for investigating the effects of prenatal alcohol exposure during early embryonic stages in fetal brain growth are challenging. This is mostly due to the difficulty of microdissection of fetal brains and their sectioning for determination of apoptotic cells caused by prenatal exposure to alcohol. The experiments described here provide visualized techniques from mice breeding to the identification of cell death in fetal brain tissue. This study used C57BL/6 mice as the animal model for studying fetal alcohol exposure and the role of trophic peptide against alcohol-induced apoptosis. The breeding consists of a 2-hr matting window to determine the exact stage of embryonic age. An established fetal alcohol exposure model has been used in this study to determine the effects of prenatal alcohol exposure in fetal brains. This involves free access to alcohol or pair-fed liquid diets as the sole source of nutrients for the pregnant mice. The techniques involving dissection of fetuses and microdissection of fetal brains are described carefully, since the latter can be challenging. Microdissection requires a stereomicroscope and ultra-fine forceps. Step-by-step procedures for dissecting the fetal brains are provided visually. The fetal brains are dissected from the base of the primordium olfactory bulb to the base of the metencephalon. For investigating apoptosis, fetal brains are first embedded in gelatin using a peel-away mold to facilitate their sectioning with a vibratome apparatus. Fetal brains embedded and fixed in paraformaldehyde are easily sectioned, and the free floating sections can be mounted in superfrost plus slides for determination of apoptosis or cell death. TUNEL (TdT-mediated dUTP Nick End Labeling; TdT: terminal deoxynucleotidyl transferase) assay has been used to identify cell death or apoptotic cells. It is noteworthy that apoptosis and cell-mediated cytotoxicity are characterized by DNA fragmentation. Thus, the visualized TUNEL-positive cells are indicative of cell death or apoptotic cells. The experimental designs here provide information about the use of an established liquid diet for studying the effects of alcohol and the role of neurotrophic peptides during pregnancy in fetal brains. This involves breeding and feeding pregnant mice, microdissecting fetal brains, and determining apoptosis. Together, these visual and textual techniques might be a source for investigating prenatal exposure of harmful agents in fetal brains.

Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission.

PubMed

Ragnarsson, Oskar; Stomby, Andreas; Dahlqvist, Per; Evang, Johan A; Ryberg, Mats; Olsson, Tommy; Bollerslev, Jens; Nyberg, Lars; Johannsson, Gudmundur

2017-08-01

Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 controls matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working-memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p<0.001) and in the right inferior occipital gyrus (p<0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p=0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p<0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p<0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Semi-automated quantification and neuroanatomical mapping of heterogeneous cell populations.

PubMed

Mendez, Oscar A; Potter, Colin J; Valdez, Michael; Bello, Thomas; Trouard, Theodore P; Koshy, Anita A

2018-07-15

Our group studies the interactions between cells of the brain and the neurotropic parasite Toxoplasma gondii. Using an in vivo system that allows us to permanently mark and identify brain cells injected with Toxoplasma protein, we have identified that Toxoplasma-injected neurons (TINs) are heterogeneously distributed throughout the brain. Unfortunately, standard methods to quantify and map heterogeneous cell populations onto a reference brain atlas are time consuming and prone to user bias. We developed a novel MATLAB-based semi-automated quantification and mapping program to allow the rapid and consistent mapping of heterogeneously distributed cells on to the Allen Institute Mouse Brain Atlas. The system uses two-threshold background subtraction to identify and quantify cells of interest. We demonstrate that we reliably quantify and neuroanatomically localize TINs with low intra- or inter-observer variability. In a follow up experiment, we show that specific regions of the mouse brain are enriched with TINs. The procedure we use takes advantage of simple immunohistochemistry labeling techniques, use of a standard microscope with a motorized stage, and low cost computing that can be readily obtained at a research institute. To our knowledge there is no other program that uses such readily available techniques and equipment for mapping heterogeneous populations of cells across the whole mouse brain. The quantification method described here allows reliable visualization, quantification, and mapping of heterogeneous cell populations in immunolabeled sections across whole mouse brains. Copyright © 2018 Elsevier B.V. All rights reserved.

Expression of the water channel protein, aquaporin-4, in mouse brains exposed to mobile telephone radiofrequency fields.

PubMed

Finnie, John W; Blumbergs, Peter C; Cai, Zhao; Manavis, Jim

2009-01-01

To determine whether exposure to mobile telephone radiofrequency (RF) fields, either acutely or long-term, produces up-regulation of the water channel protein, aquaporin-4 (AQP-4). Using a purpose-designed exposure system at 900 MHz, mice were given a single, far-field whole body exposure at a specific absorption rate of 4 W/kg for 60 minutes or a similar exposure on 5 successive days/week for 104 weeks. Control mice were sham-exposed or freely mobile in a cage to control for any stress caused by restraint in the exposure module. A positive control group was given a clostridial toxin known to cause microvascular endothelial injury, severe vasogenic oedema and upregulation of AQP-4. Brains were perfusion fixed with 4% paraformaldehyde, coronal sections cut from six levels, and immunostained for the principal water channel protein in brain, AQP-4. There was no increase in AQP-4 expression in brains exposed to mobile phone microwaves compared to control (sham exposed and freely moving caged mice) brains after short or protracted exposure, while AQP-4 was substantially upregulated in the brains of mice given the clostridial toxin. Brains exposed to mobile telephone RF fields for a short (60 minutes) or long (2 years) duration did not show any immunohistochemically detectable up-regulation of the water channel protein, AQP-4, suggesting that there was no significant increase in blood-brain barrier permeability

Evidence of Big-Five personality changes following acquired brain injury from a prospective longitudinal investigation.

PubMed

Leonhardt, Anne; Schmukle, Stefan C; Exner, Cornelia

2016-03-01

Many studies using different assessment methods have reported personality changes after acquired brain injury (ABI). However, to our knowledge, no prospective study has yet been conducted to examine whether previous cross-sectional and retrospective results can be replicated in a longitudinal prospective design. Further, because clinical control groups were only rarely used, it remains debatable if the personality changes found are unique to patients with ABI or if they also affect patients with other disabilities. This study examined personality change in 114 participants with different kinds of ABI, 1321 matched controls (general control, GC), and 746 matched participants with restrictive impairments other than brain injury (clinical control, CC) in a prospective longitudinal design using data from the panel survey Household, Income and Labour Dynamics in Australia (HILDA). Participants with ABI showed significantly larger declines in Extraversion and Conscientiousness compared with the GC group. When the ABI participants were compared with the CC group, only the difference in Conscientiousness remained significant. Our prospective data corroborate evidence from previous cross-sectional studies that patients with ABI experience larger declines in Extraversion and Conscientiousness than the general population. Whereas the effect on Conscientiousness was unique to patients with ABI, the decline in Extraversion was also observed in participants with other impairments. Copyright © 2016 Elsevier Inc. All rights reserved.

Gray Matter Atrophy in the Cerebellum-Evidence of Increased Vulnerability of the Crus and Vermis with Advancing Age.

PubMed

Yu, Teresa; Korgaonkar, Mayuresh S; Grieve, Stuart M

2017-04-01

This study examined patterns of cerebellar volumetric gray matter (GM) loss across the adult lifespan in a large cross-sectional sample. Four hundred and seventy-nine healthy participants (age range: 7-86 years) were drawn from the Brain Resource International Database who provided T1-weighted MRI scans. The spatially unbiased infratentorial template (SUIT) toolbox in SPM8 was used for normalisation of the cerebellum structures. Global volumetric and voxel-based morphometry analyses were performed to evaluate age-associated trends and gender-specific age-patterns. Global cerebellar GM shows a cross-sectional reduction with advancing age of 2.5 % per decade-approximately half the rate seen in the whole brain. The male cerebellum is larger with a lower percentage of GM, however, after controlling for total brain volume, no gender difference was detected. Analysis of age-related changes in GM volume revealed large bilateral clusters involving the vermis and cerebellar crus where regional loss occurred at nearly twice the average cerebellar rate. No gender-specific patterns were detected. These data confirm that regionally specific GM loss occurs in the cerebellum with age, and form a solid base for further investigation to find functional correlates for this global and focal loss.

Proflavine derivatives as fluorescent imaging agents of amyloid deposits.

PubMed

Garin, Dominique; Oukhatar, Fatima; Mahon, Andrew B; Try, Andrew C; Dubois-Dauphin, Michel; Laferla, Frank M; Demeunynck, Martine; Sallanon, Marcelle Moulin; Chierici, Sabine

2011-04-15

A series of proflavine derivatives for use to further image Aβ amyloid deposits were synthesized and characterized. Aged 3xTg-AD (23 months old) mice hippocampus sections incubated with these derivatives revealed preferential labeling of amyloid plaques. Furthermore an in vitro binding study showed an inhibitory effect, although moderate, of these compounds on Aβ(40) fibril formation. This study highlights the potential of proflavine as a molecular scaffold for designing new Aβ imaging agents, its native fluorescence allowing in vitro neuropathological staining in AD damaged brain sections. Copyright © 2011 Elsevier Ltd. All rights reserved.

Developmental trajectories of the fronto-temporal lobes from infancy to early adulthood in healthy individuals.

PubMed

Tanaka, Chiaki; Matsui, Mie; Uematsu, Akiko; Noguchi, Kyo; Miyawaki, Toshio

2012-01-01

Brain development during early life in healthy individuals is rapid and dynamic, indicating that this period plays a very important role in neural and functional development. The frontal and temporal lobes are known to play a particularly important role in cognition. The study of healthy frontal and temporal lobe development in children is therefore of considerable importance. A better understanding of how these brain regions develop could also aid in the diagnosis and treatment of neurodevelopmental disorders. Some developmental studies have used magnetic resonance imaging (MRI) to examine infant brains, but it remains the case that relatively little is known about cortical brain development in the first few years of life. In the present study we examined whole brain, temporal lobe and frontal lobe developmental trajectories from infancy to early adulthood in healthy individuals, considering gender and brain hemisphere differences. We performed a cross-sectional, longitudinal morphometric MRI study of 114 healthy individuals (54 females and 60 males) aged 1 month to 25 years old (mean age ± SD 8.8 ± 6.9). We measured whole brain, temporal and frontal lobe gray matter (GM)/white matter (WM) volumes, following previously used protocols. There were significant non-linear age-related volume changes in all regions. Peak ages of whole brain, temporal lobe and frontal lobe development occurred around pre-adolescence (9-12 years old). GM volumes for all regions increased significantly as a function of age. Peak age was nevertheless lobe specific, with a pattern of earlier peak ages for females in both temporal and frontal lobes. Growth change in whole brain GM volume was larger in males than in females. However, GM volume growth changes for the temporal and frontal lobes showed a somewhat different pattern. GM volume for both temporal and frontal lobes showed a greater increase in females until around 5-6 years old, at which point this tendency reversed (GM volume changes in males became greater), with male GM volume increasing for a longer time than that of females. WM volume growth changes were similar across regions, all increasing rapidly until early childhood but slowing down thereafter. All regions displayed significant rightward volumetric asymmetry regardless of sex. Furthermore, the right temporal and frontal lobes showed a greater volumetric increase than the left for the first several years, with this tendency reversing at around 6 years of age. In addition, the left frontal and temporal lobes increased in volume for a longer period of time. Taken together, these findings indicated that brain developmental trajectories differ depending on brain region, sex and brain hemisphere. Gender-related factors such as sex hormones and functional laterality may affect brain development. Copyright © 2012 S. Karger AG, Basel.

77 FR 50508 - Brain-Pad, Inc; Analysis of Proposed Consent Order To Aid Public Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-21

... FEDERAL TRADE COMMISSION [File No. 122 3073] Brain-Pad, Inc; Analysis of Proposed Consent Order To... instructions in the Request for Comment part of the SUPPLEMENTARY INFORMATION section below. Write ``Brain-Pad... September 17, 2012. Write ``Brain-Pad, File No. 122 3073'' on your comment. Your comment--including your...

Which brain networks related to art perception are we talking about?. Comment on "Move me, astonish me…" delight my eyes and brain: The Vienna Integrated Model of top-down and bottom-up processes in Art Perception (VIMAP) and corresponding affective, evaluative, and neurophysiological correlates; by Matthew Pelowski et al.

NASA Astrophysics Data System (ADS)

Ayala, Francisco J.; Cela-Conde, Camilo J.

2017-07-01

The proposal by the Vienna Integrated Model of Art Perception (Pelowski et al., [4]; VIMAP, hereafter) is a valuable and much needed attempt to summarize and understand the cognitive processes underlying art perception. Very important in their model is, as expected, to ascertain the psychological and brain processes correlated with the perception of beauty in art works. In this commentary we'll focus exclusively on the consideration of VIMAP's section 5, ;Model stages and corresponding areas of the brain.; We'll examine the evidence advanced by VIMAP in the section about brain networks related to the perception of art.

Nuclear microscopic investigations into the elemental changes in the substantia nigra of unilaterally MPTP-lesioned Parkinsonian monkeys

NASA Astrophysics Data System (ADS)

Thong, P. S. P.; He, Y.; Lee, T.; Watt, F.

1997-07-01

Various transition metals, particularly iron, have been implicated in the aetiology of the neurodegenerative disease, Parkinson's disease, in which there is a characteristic loss of cells in the substantia nigra (SN) region of the brain. In this study, monkeys were unilaterally lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) to obtain primate models of parkinsonism, with the non-lesioned side of the brain serving as controls. The monkeys were sacrificed at one day, one week, two weeks, one month and one year after lesioning to investigate the time dependent elemental changes in the parkinsonian SN. Sections of the brain encompassing both the lesioned and non-lesioned SNs were analysed using the National University of Singapore nuclear microscope. Adjacent sections were tyrosine hydroxylase (TH) immunohistochemically stained to provide complementary information on dopaminergic cell loss and to facilitate definition of the SN boundaries during data analysis. In one-day and one-week monkeys (representing early stages of the disease), there were no changes in elemental concentrations within experimental errors and the adjacent TH-stained sections did not show apparent cell loss in the SN. At two weeks, cell loss was seen in the lesioned SN compared to the control SN. Although there was no bulk increase in SN iron, localised accumulation of iron in granules containing up to 15% by weight iron was observed in the lesioned SN of one of the two-week monkeys. An average 15% increase in nigral iron, significant at the 90% confidence level ( p < 0.1), was seen in the one-month monkeys. TH-stained sections for the one-month monkeys showed cell loss in the lesioned SN. In one-year samples (representing the advanced stage of the disease) there was a significant ( p < 0.05) 56% increase in iron, 14% increase in phosphorous and a 20% decrease in copper. Here an almost complete loss of cells in the lesioned SN was apparent from the adjacent TH-stained sections. These preliminary results suggest that while bulk increase in iron may seem to follow cell death, localised accumulation of SN iron in the early stages of the disease may play an important role in initiating and/or accelerating nigral cell death.

Dual Sarcocystis neurona and Toxoplasma gondii infection in a northern sea otter from Washington state, USA

USGS Publications Warehouse

Lindsay, D.S.; Thomas, N.J.; Rosypal, A.C.; Dubey, J.P.

2001-01-01

Dual Sarcocystis neurona and Toxoplasma gondii infection was observed in a Northern sea otter from Washington, USA. The animal was found stranded, convulsed, and died shortly thereafter. Encephalitis caused by both S. neurona and T. gondii was demonstrated in histological sections of brain. Immunohistochemical examination of sections with S. neurona specific antisera demonstrated developmental stages that divided by endopolygeny and produced numerous merozoites. PCR of brain tissue from the sea otter using primer pairs JNB33/JNB54 resulted in amplification of a 1100 bp product. This PCR product was cut in to 884 and 216 bp products by Dra I but was not cut by Hinf I indicating that it was S. neurona [J. Parasitol. 85 (1999) 221]. No PCR product was detected in the brain of a sea otter which had no lesions of encephalitis. Examination of brain sections using T. gondii specific antisera demonstrated tachyzoites and tissue cysts of T. gondii. The lesions induced by T. gondii suggested that the sea otter was suffering from reactivated toxoplasmosis. T. gondii was isolated in mice inoculated with brain tissue. A cat that was fed infected mouse brain tissue excreted T. gondii oocysts which were infective for mice. This is apparently the first report of dual S. neurona and T. gondii in a marine mammal.

Hyperphosphorylated tau in the brains of mice and monkeys with long-term administration of ketamine.

PubMed

Yeung, L Y; Wai, Maria S M; Fan, Ming; Mak, Y T; Lam, W P; Li, Zhen; Lu, Gang; Yew, David T

2010-03-15

Ketamine, a non-competitive antagonist at the glutamatergic N-methyl-d-aspartate (NMDA) receptor, might impair memory function of the brain. Loss of memory is also a characteristic of aging and Alzheimer's disease. Hyperphosphorylation of tau is an early event in the aging process and Alzheimer's disease. Therefore, we aimed to find out whether long-term ketmaine administration is related to hyperphosphorylation of tau or not in the brains of mice and monkeys. Results showed that after 6 months' administration of ketamine, in the prefrontal and entorhinal cortical sections of mouse and monkey brains, there were significant increases of positive sites for the hyperphosphorylated tau protein as compared to the control animals receiving no ketamine administration. Furthermore, about 15% of hyperphosphorylated tau positive cells were also positively labeled by terminal dUTP nick end labeling (TUNEL) indicating there might be a relationship between hyperphosphorylation of tau and apoptosis. Therefore, the long-term ketamine toxicity might involve neurodegenerative process similar to that of aging and/or Alzheimer's disease. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Preclinical Evaluation of [(18)F]THK-5105 Enantiomers: Effects of Chirality on Its Effectiveness as a Tau Imaging Radiotracer.

PubMed

Tago, Tetsuro; Furumoto, Shozo; Okamura, Nobuyuki; Harada, Ryuichi; Adachi, Hajime; Ishikawa, Yoichi; Yanai, Kazuhiko; Iwata, Ren; Kudo, Yukitsuka

2016-04-01

Noninvasive imaging of tau and amyloid-β pathologies would facilitate diagnosis of Alzheimer's disease (AD). Recently, we have developed [(18)F]THK-5105 for selective detection of tau pathology by positron emission tomography (PET). The purpose of this study was to clarify biological properties of optically pure [(18)F]THK-5105 enantiomers. Binding for tau aggregates in AD brain section was evaluated by autoradiography (ARG). In vitro binding assays were performed to evaluate the binding properties of enantiomers for AD brain homogenates. The pharmacokinetics in the normal mouse brains was assessed by ex vivo biodistribution assay The ARG of enantiomers showed the high accumulation of radioactivity corresponding to the distribution of tau deposits. In vitro binding assays revealed that (S)-[(18)F]THK-5105 has slower dissociation from tau than (R)-[(18)F]THK-5105. Biodistribution assays indicated that (S)-[(18)F]THK-5105 eliminated faster from the mouse brains and blood compared with (R)-[(18)F]THK-5105. (S)-[(18)F]THK-5105 could be more suitable than (R)-enantiomer for a tau imaging agent.

Cross-Sectional and Longitudinal Abnormalities in Brain Structure in Children with Severe Mood Dysregulation or Bipolar Disorder

ERIC Educational Resources Information Center

Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

2012-01-01

Background: There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time.…

Extending unbiased stereology of brain ultrastructure to three-dimensional volumes

NASA Technical Reports Server (NTRS)

Fiala, J. C.; Harris, K. M.; Koslow, S. H. (Principal Investigator)

2001-01-01

OBJECTIVE: Analysis of brain ultrastructure is needed to reveal how neurons communicate with one another via synapses and how disease processes alter this communication. In the past, such analyses have usually been based on single or paired sections obtained by electron microscopy. Reconstruction from multiple serial sections provides a much needed, richer representation of the three-dimensional organization of the brain. This paper introduces a new reconstruction system and new methods for analyzing in three dimensions the location and ultrastructure of neuronal components, such as synapses, which are distributed non-randomly throughout the brain. DESIGN AND MEASUREMENTS: Volumes are reconstructed by defining transformations that align the entire area of adjacent sections. Whole-field alignment requires rotation, translation, skew, scaling, and second-order nonlinear deformations. Such transformations are implemented by a linear combination of bivariate polynomials. Computer software for generating transformations based on user input is described. Stereological techniques for assessing structural distributions in reconstructed volumes are the unbiased bricking, disector, unbiased ratio, and per-length counting techniques. A new general method, the fractional counter, is also described. This unbiased technique relies on the counting of fractions of objects contained in a test volume. A volume of brain tissue from stratum radiatum of hippocampal area CA1 is reconstructed and analyzed for synaptic density to demonstrate and compare the techniques. RESULTS AND CONCLUSIONS: Reconstruction makes practicable volume-oriented analysis of ultrastructure using such techniques as the unbiased bricking and fractional counter methods. These analysis methods are less sensitive to the section-to-section variations in counts and section thickness, factors that contribute to the inaccuracy of other stereological methods. In addition, volume reconstruction facilitates visualization and modeling of structures and analysis of three-dimensional relationships such as synaptic connectivity.

Atypical cross talk between mentalizing and mirror neuron networks in autism spectrum disorder.

PubMed

Fishman, Inna; Keown, Christopher L; Lincoln, Alan J; Pineda, Jaime A; Müller, Ralph-Axel

2014-07-01

Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition. To investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS). Cross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ. Statistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures. Relative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction. Adolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect immature or aberrant developmental processes in 2 brain networks involved in understanding of others, a domain of impairment in ASD. Further, robust links with sociocommunicative symptoms of ASD implicate atypically increased ToM-MNS connectivity in social deficits observed in ASD.

Cerebro, lenguaje y comunicacion (Brain, Language, and Communication).

ERIC Educational Resources Information Center

Strejilevich, Leonardo

1978-01-01

Discusses the relationship between the brain, language, and communication in the following sections: (1) combining words, (2) language as a system, (3) language as a function of the brain, (4) the science of communication, and (5) language as a social institution. (NCR)

Severe malaria - a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report

PubMed Central

2010-01-01

Background Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here. Case presentation A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a post-mortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent. Conclusions The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further study of knowlesi malaria will aid the interpretation of, often conflicting, information on malaria pathophysiology in humans. PMID:20064229

Propidium iodide staining: a new application in fluorescence microscopy for analysis of cytoarchitecture in adult and developing rodent brain.

PubMed

Hezel, Marcus; Ebrahimi, Fahim; Koch, Marco; Dehghani, Faramarz

2012-10-01

Immunohistochemical visualization of antigens in specimen has evolved to an indispensable technique in biomedical research for investigations of cell morphology and pathology both in bright field and fluorescence microscopy. While there are couple of staining methods that reveal entire cytoarchitecture in bright field microscopy such as Nissl or hemalaun-eosin, there are still limitations in visualizations of cytoarchitecture in fluorescence microscopy. The present study reports a simple staining method that provides the required illustration of cell allocations and cellular composition in fluorescence microscopy in adult and in developing rodent central nervous system using the fluorophore propidium iodide (PI, 5μg/mL). PI is a well-accepted marker for degenerating cells when applied prior to fixation (pre-fixation PI staining). Here, PI was added to the sections after the fixation (post-fixation PI staining). This revised labeling procedure led to similar cytoarchitectural staining patterns in fluorescence microscopy as observed with hemalaun in bright field microscopy. This finding was proven in organotypic hippocampal slice cultures (OHSC) and brain sections obtained from different postnatal developmental stages. Excitotoxically lesioned OHSC subjected to pre-fixation PI staining merely showed brightly labeled condensed nuclei of degenerating neurons. In contrast, post-fixation PI staining additionally revealed extensive labeling of neuronal cell bodies and glial cells within the OHSC, thus allowing visualization of stratification of neuronal layers and cell morphology. Furthermore, post-fixation PI staining was combined with NeuN, calbindin, calretinin, glial fibrillary acidic protein or Griffonia simplicifolia isolectin B4 (IB(4)) in post natal (p1 and p9) and adult rats. In early post-natal brain sections almost all mentioned cellular markers led to an incomplete staining of the native cell organization and resulted in an inaccurate estimation of cell morphology when compared to adult brains. In contrast, post-fixation PI staining allowed investigation of the whole cytoarchitecture independent of the developmental stage. Taken together, post-fixation PI staining provides a detailed insight in the morphology of both developing and adult brain tissues in fluorescence microscopy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury

PubMed Central

Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

2018-01-01

Abstract Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the follow-up period, as well as to changes in memory performance, prior to multiple comparison correction. In conclusion, traumatic brain injury results in progressive loss of brain tissue volume, which continues for many years post-injury. Atrophy is most prominent in the white matter, but is also more pronounced in cortical sulci compared to gyri. These findings suggest the Jacobian determinant provides a method of quantifying brain atrophy following a traumatic brain injury and is informative in determining the long-term neurodegenerative effects after injury. Power calculations indicate that Jacobian determinant images are an efficient surrogate marker in clinical trials of neuroprotective therapeutics. PMID:29309542

Human Behavior, Learning, and the Developing Brain: Typical Development

ERIC Educational Resources Information Center

Coch, Donna, Ed.; Fischer, Kurt W., Ed.; Dawson, Geraldine, Ed.

2010-01-01

This volume brings together leading authorities from multiple disciplines to examine the relationship between brain development and behavior in typically developing children. Presented are innovative cross-sectional and longitudinal studies that shed light on brain-behavior connections in infancy and toddlerhood through adolescence. Chapters…

Matrix Sublimation/Recrystallization for Imaging Proteins by Mass Spectrometry at High Spatial Resolution

PubMed Central

Yang, Junhai; Caprioli, Richard M.

2011-01-01

We have employed matrix deposition by sublimation for protein image analysis on tissue sections using a hydration/recrystallization process that produces high quality MALDI mass spectra and high spatial resolution ion images. We systematically investigated different washing protocols, the effect of tissue section thickness, the amount of sublimated matrix per unit area and different recrystallization conditions. The results show that an organic solvent rinse followed by ethanol/water rinses substantially increased sensitivity for the detection of proteins. Both the thickness of tissue section and amount of sinapinic acid sublimated per unit area have optimal ranges for maximal protein signal intensity. Ion images of mouse and rat brain sections at 50, 20 and 10 µm spatial resolution are presented and are correlated with H&E stained optical images. For targeted analysis, histology directed imaging can be performed using this protocol where MS analysis and H&E staining are performed on the same section. PMID:21639088

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China

PubMed Central

Luo, Xu-Ying; Hu, Ying-Hong; Cao, Xiang-Yuan; Kang, Yan; Liu, Li-Ping; Wang, Shou-Hong; Yu, Rong-Guo; Yu, Xiang-You; Zhang, Xia; Li, Bao-Shan; Ma, Zeng-Xiang; Weng, Yi-Bing; Zhang, Heng; Chen, De-Chang; Chen, Wei; Chen, Wen-Jin; Chen, Xiu-Mei; Du, Bin; Duan, Mei-Li; Hu, Jin; Huang, Yun-Feng; Jia, Gui-Jun; Li, Li-Hong; Liang, Yu-Min; Qin, Bing-Yu; Wang, Xian-Dong; Xiong, Jian; Yan, Li-Mei; Yang, Zheng-Ping; Dong, Chen-Ming; Wang, Dong-Xin; Zhan, Qing-Yuan; Fu, Shuang-Lin; Zhao, Lin; Huang, Qi-Bing; Xie, Ying-Guang; Huang, Xiao-Bo; Zhang, Guo-Bin; Xu, Wang-Bin; Xu, Yuan; Liu, Ya-Ling; Zhao, He-Ling; Sun, Rong-Qing; Sun, Ming; Cheng, Qing-Hong; Qu, Xin; Yang, Xiao-Feng; Xu, Ming; Shi, Zhong-Hua; Chen, Han; He, Xuan; Yang, Yan-Lin; Chen, Guang-Qiang; Sun, Xiu-Mei; Zhou, Jian-Xin

2016-01-01

Background: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. Methods: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. Results: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0–8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5–6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. Conclusions: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. Trial Registration: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073. PMID:27411450

Environment and brain plasticity: towards an endogenous pharmacotherapy.

PubMed

Sale, Alessandro; Berardi, Nicoletta; Maffei, Lamberto

2014-01-01

Brain plasticity refers to the remarkable property of cerebral neurons to change their structure and function in response to experience, a fundamental theoretical theme in the field of basic research and a major focus for neural rehabilitation following brain disease. While much of the early work on this topic was based on deprivation approaches relying on sensory experience reduction procedures, major advances have been recently obtained using the conceptually opposite paradigm of environmental enrichment, whereby an enhanced stimulation is provided at multiple cognitive, sensory, social, and motor levels. In this survey, we aim to review past and recent work concerning the influence exerted by the environment on brain plasticity processes, with special emphasis on the underlying cellular and molecular mechanisms and starting from experimental work on animal models to move to highly relevant work performed in humans. We will initiate introducing the concept of brain plasticity and describing classic paradigmatic examples to illustrate how changes at the level of neuronal properties can ultimately affect and direct key perceptual and behavioral outputs. Then, we describe the remarkable effects elicited by early stressful conditions, maternal care, and preweaning enrichment on central nervous system development, with a separate section focusing on neurodevelopmental disorders. A specific section is dedicated to the striking ability of environmental enrichment and physical exercise to empower adult brain plasticity. Finally, we analyze in the last section the ever-increasing available knowledge on the effects elicited by enriched living conditions on physiological and pathological aging brain processes.

Researching the Practice, Practicing the Research, and Promoting Responsible Policy: Usable Knowledge in Mind, Brain, and Education

ERIC Educational Resources Information Center

Christodoulou, Joanna A.; Daley, Samantha G.; Katzir, Tami

2009-01-01

The theme of Usable Knowledge in Mind, Brain, and Education will be a special section that will appear regularly in the journal. The section will focus on the synergistic connections between biology, cognitive science, and human development on the one hand and educational thought, policy, and practice on the other. Efforts to create usable…

Zingiber zerumbet L. (Smith) extract alleviates the ethanol-induced brain damage via its antioxidant activity.

PubMed

Hamid, Asmah; Ibrahim, Farah Wahida; Ming, Teoh Hooi; Nasrom, Mohd Nazir; Eusoff, Norelina; Husain, Khairana; Abdul Latif, Mazlyzam

2018-03-20

Zingiber zerumbet (L.) Smith belongs to the Zingiberaceae family that is widely distributed throughout the tropics, particularly in Southeast Asia. It is locally known as 'Lempoyang' and traditionally used to treat fever, constipation and to relieve pain. It is also known to possess antioxidant and anti-inflammatory activities. Based on these antioxidant and anti-inflammatory activities, this study was conducted to investigate the effects of ethyl-acetate extract of Z. zerumbet rhizomes against ethanol-induced brain damage in male Wistar rats. Twenty-four male Wistar rats were divided into four groups which consist of normal, 1.8 g/kg ethanol (40% v/v), 200 mg/kg Z. zerumbet extract plus ethanol and 400 mg/kg Z. zerumbet plus ethanol. The extract of Z. zerumbet was given once daily by oral gavage, 30 min prior to ethanol exposure via intraperitoneal route for 14 consecutive days. The rats were then sacrificed. Blood and brain homogenate were subjected to biochemical tests and part of the brain tissue was sectioned for histological analysis. Treatment with ethyl-acetate Z. zerumbet extract at 200 mg/kg and 400 mg/kg significantly reduced the level of malondialdehyde (MDA) and protein carbonyl (p < 0.05) in the brain homogenate. Both doses of extracts also significantly increased the level of serum superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities as well as glutathione (GSH) level (p < 0.05). However, administration of ethyl-acetate Z. zerumbet extract at 400 mg/kg showed better protective effects on the ethanol-induced brain damage as shown with higher levels of SOD, CAT, GPx and GSH in the brain homogenate as compared to 200 mg/kg dose. Histological observation of the cerebellum and cerebral cortex showed that the extract prevented the loss of Purkinje cells and retained the number and the shape of the cells. Ethyl-acetate extract of Z. zerumbet has protective effects against ethanol-induced brain damage and this is mediated through its antioxidant properties. Z. zerumbet extract protects against ethanol-induced brain damage via its antioxidant properties.

Quantitative and Qualitative Analysis of Transient Fetal Compartments during Prenatal Human Brain Development

PubMed Central

Vasung, Lana; Lepage, Claude; Radoš, Milan; Pletikos, Mihovil; Goldman, Jennifer S.; Richiardi, Jonas; Raguž, Marina; Fischi-Gómez, Elda; Karama, Sherif; Huppi, Petra S.; Evans, Alan C.; Kostovic, Ivica

2016-01-01

The cerebral wall of the human fetal brain is composed of transient cellular compartments, which show characteristic spatiotemporal relationships with intensity of major neurogenic events (cell proliferation, migration, axonal growth, dendritic differentiation, synaptogenesis, cell death, and myelination). The aim of the present study was to obtain new quantitative data describing volume, surface area, and thickness of transient compartments in the human fetal cerebrum. Forty-four postmortem fetal brains aged 13–40 postconceptional weeks (PCW) were included in this study. High-resolution T1 weighted MR images were acquired on 19 fetal brain hemispheres. MR images were processed using in-house software (MNI-ACE toolbox). Delineation of fetal compartments was performed semi-automatically by co-registration of MRI with histological sections of the same brains, or with the age-matched brains from Zagreb Neuroembryological Collection. Growth trajectories of transient fetal compartments were reconstructed. The composition of telencephalic wall was quantitatively assessed. Between 13 and 25 PCW, when the intensity of neuronal proliferation decreases drastically, the relative volume of proliferative (ventricular and subventricular) compartments showed pronounced decline. In contrast, synapse- and extracellular matrix-rich subplate compartment continued to grow during the first two trimesters, occupying up to 45% of telencephalon and reaching its maximum volume and thickness around 30 PCW. This developmental maximum coincides with a period of intensive growth of long cortico-cortical fibers, which enter and wait in subplate before approaching the cortical plate. Although we did not find significant age related changes in mean thickness of the cortical plate, the volume, gyrification index, and surface area of the cortical plate continued to exponentially grow during the last phases of prenatal development. This cortical expansion coincides developmentally with the transformation of embryonic cortical columns, dendritic differentiation, and ingrowth of axons. These results provide a quantitative description of transient human fetal brain compartments observable with MRI. Moreover, they will improve understanding of structural-functional relationships during brain development, will enable correlation between in vitro/in vivo imaging and fine structural histological studies, and will serve as a reference for study of perinatal brain injuries. PMID:26941612

A minimalist approach to MALDI imaging of glycerophospholipids and sphingolipids in rat brain sections

NASA Astrophysics Data System (ADS)

Wang, Hay-Yan J.; Post, Shelley N. Jackson Jeremy; Woods, Amina S.

2008-12-01

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful tool that has allowed researchers to directly probe tissue molecular structure and drug content with minimal manipulations, while maintaining anatomical integrity. In the present work glycerophospholipids and sphingolipids images were acquired from 16-[mu]m thick coronal rat brain sections using MALDI-MS. Images of phosphatidylinositol 38:4 (PI 38:4), sulfatide 24:1 (ST 24:1), and hydroxyl sulfatide 24:1 (ST 24:1 (OH)) were acquired in negative ion mode, while the images of phosphatidylcholine 34:1 (PC 34:1), potassiated phosphatidylcholines 32:0 (PC 32:0 + K+) and 36:1 (PC 36:1 + K+) were acquired in positive ion mode. The images of PI 38:4 and PC 36:1 + K+ show the preferential distribution of these two lipids in gray matter; and the images of two sulfatides and PC 32:0 + K+ show their preferential distribution in white matter. In addition, the gray cortical band and its adjacent anatomical structures were also identified by contrasting their lipid makeup. The resulting images were compared to lipid images acquired by secondary ion mass spectrometry (SIMS). The suitability of TLC sprayers, Collison Nebulizer, and artistic airbrush were also evaluated as means for matrix deposition.

Altered neural processing of emotional faces in remitted Cushing's disease.

PubMed

Bas-Hoogendam, Janna Marie; Andela, Cornelie D; van der Werff, Steven J A; Pannekoek, J Nienke; van Steenbergen, Henk; Meijer, Onno C; van Buchem, Mark A; Rombouts, Serge A R B; van der Mast, Roos C; Biermasz, Nienke R; van der Wee, Nic J A; Pereira, Alberto M

2015-09-01

Patients with long-term remission of Cushing's disease (CD) demonstrate residual psychological complaints. At present, it is not known how previous exposure to hypercortisolism affects psychological functioning in the long-term. Earlier magnetic resonance imaging (MRI) studies demonstrated abnormalities of brain structure and resting-state connectivity in patients with long-term remission of CD, but no data are available on functional alterations in the brain during the performance of emotional or cognitive tasks in these patients. We performed a cross-sectional functional MRI study, investigating brain activation during emotion processing in patients with long-term remission of CD. Processing of emotional faces versus a non-emotional control condition was examined in 21 patients and 21 matched healthy controls. Analyses focused on activation and connectivity of two a priori determined regions of interest: the amygdala and the medial prefrontal-orbitofrontal cortex (mPFC-OFC). We also assessed psychological functioning, cognitive failure, and clinical disease severity. Patients showed less mPFC activation during processing of emotional faces compared to controls, whereas no differences were found in amygdala activation. An exploratory psychophysiological interaction analysis demonstrated decreased functional coupling between the ventromedial PFC and posterior cingulate cortex (a region structurally connected to the PFC) in CD-patients. The present study is the first to show alterations in brain function and task-related functional coupling in patients with long-term remission of CD relative to matched healthy controls. These alterations may, together with abnormalities in brain structure, be related to the persisting psychological morbidity in patients with CD after long-term remission. Copyright © 2015 Elsevier Ltd. All rights reserved.

Age-related effects in the neocortical organization of chimpanzees: gray and white matter volume, cortical thickness, and gyrification.

PubMed

Autrey, Michelle M; Reamer, Lisa A; Mareno, Mary Catherine; Sherwood, Chet C; Herndon, James G; Preuss, Todd; Schapiro, Steve J; Hopkins, William D

2014-11-01

Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray and white matter over the adult lifespan. However, these previous studies were limited with a small sample of chimpanzees of the most advanced ages. In the present study, we sought to further test for potential age-related decline in cortical organization in chimpanzees by expanding the sample size of aged chimpanzees. We used the BrainVisa software to measure total brain volume, gray and white matter volumes, gray matter thickness, and gyrification index in a cross-sectional sample of 219 captive chimpanzees (8-53 years old), with 38 subjects being 40 or more years of age. Mean depth and cortical fold opening of 11 major sulci of the chimpanzee brains were also measured. We found that chimpanzees showed increased gyrification with age and a cubic relationship between age and white matter volume. For the association between age and sulcus depth and width, the results were mostly non-significant with the exception of one negative correlation between age and the fronto-orbital sulcus. In short, results showed that chimpanzees exhibit few age-related changes in global cortical organization, sulcus folding and sulcus width. These findings support previous studies and the theory that the age-related changes in the human brain is due to an extended lifespan. Copyright © 2014 Elsevier Inc. All rights reserved.

A combined histological and MRI brain atlas of the common marmoset monkey, Callithrix jacchus.

PubMed

Newman, John D; Kenkel, William M; Aronoff, Emily C; Bock, Nicholas A; Zametkin, Molly R; Silva, Afonso C

2009-12-11

The common marmoset, Callithrix jacchus, is of growing importance for research in neuroscience and related fields. In the present work, we describe a combined histological and magnetic resonance imaging (MRI) atlas constructed from the brains of two adult female marmosets. Histological sections were processed from Nissl staining and digitized to produce an atlas in a large format that facilitates visualization of structures with significant detail. Naming of identifiable brain structures was performed utilizing current terminology. The histological sections and a simplified schematic atlas are available online at http://udn.nichd.nih.gov/brainatlas_home.html.

Socially induced brain development in a facultatively eusocial sweat bee Megalopta genalis (Halictidae)

PubMed Central

Smith, Adam R.; Seid, Marc A.; Jiménez, Lissette C.; Wcislo, William T.

2010-01-01

Changes in the relative size of brain regions are often dependent on experience and environmental stimulation, which includes an animal's social environment. Some studies suggest that social interactions are cognitively demanding, and have examined predictions that the evolution of sociality led to the evolution of larger brains. Previous studies have compared species with different social organizations or different groups within obligately social species. Here, we report the first intraspecific study to examine how social experience shapes brain volume using a species with facultatively eusocial or solitary behaviour, the sweat bee Megalopta genalis. Serial histological sections were used to reconstruct and measure the volume of brain areas of bees behaving as social reproductives, social workers, solitary reproductives or 1-day-old bees that are undifferentiated with respect to the social phenotype. Social reproductives showed increased development of the mushroom body (an area of the insect brain associated with sensory integration and learning) relative to social workers and solitary reproductives. The gross neuroanatomy of young bees is developmentally similar to the advanced eusocial species previously studied, despite vast differences in colony size and social organization. Our results suggest that the transition from solitary to social behaviour is associated with modified brain development, and that maintaining dominance, rather than sociality per se, leads to increased mushroom body development, even in the smallest social groups possible (i.e. groups with two bees). Such results suggest that capabilities to navigate the complexities of social life may be a factor shaping brain evolution in some social insects, as for some vertebrates. PMID:20335213

Socially induced brain development in a facultatively eusocial sweat bee Megalopta genalis (Halictidae).

PubMed

Smith, Adam R; Seid, Marc A; Jiménez, Lissette C; Wcislo, William T

2010-07-22

Changes in the relative size of brain regions are often dependent on experience and environmental stimulation, which includes an animal's social environment. Some studies suggest that social interactions are cognitively demanding, and have examined predictions that the evolution of sociality led to the evolution of larger brains. Previous studies have compared species with different social organizations or different groups within obligately social species. Here, we report the first intraspecific study to examine how social experience shapes brain volume using a species with facultatively eusocial or solitary behaviour, the sweat bee Megalopta genalis. Serial histological sections were used to reconstruct and measure the volume of brain areas of bees behaving as social reproductives, social workers, solitary reproductives or 1-day-old bees that are undifferentiated with respect to the social phenotype. Social reproductives showed increased development of the mushroom body (an area of the insect brain associated with sensory integration and learning) relative to social workers and solitary reproductives. The gross neuroanatomy of young bees is developmentally similar to the advanced eusocial species previously studied, despite vast differences in colony size and social organization. Our results suggest that the transition from solitary to social behaviour is associated with modified brain development, and that maintaining dominance, rather than sociality per se, leads to increased mushroom body development, even in the smallest social groups possible (i.e. groups with two bees). Such results suggest that capabilities to navigate the complexities of social life may be a factor shaping brain evolution in some social insects, as for some vertebrates.

Genetic associations with childhood brain growth, defined in two longitudinal cohorts.

PubMed

Szekely, Eszter; Schwantes-An, Tae-Hwi Linus; Justice, Cristina M; Sabourin, Jeremy A; Jansen, Philip R; Muetzel, Ryan L; Sharp, Wendy; Tiemeier, Henning; Sung, Heejong; White, Tonya J; Wilson, Alexander F; Shaw, Philip

2018-06-01

Genome-wide association studies (GWASs) are unraveling the genetics of adult brain neuroanatomy as measured by cross-sectional anatomic magnetic resonance imaging (aMRI). However, the genetic mechanisms that shape childhood brain development are, as yet, largely unexplored. In this study we identify common genetic variants associated with childhood brain development as defined by longitudinal aMRI. Genome-wide single nucleotide polymorphism (SNP) data were determined in two cohorts: one enriched for attention-deficit/hyperactivity disorder (ADHD) (LONG cohort: 458 participants; 119 with ADHD) and the other from a population-based cohort (Generation R: 257 participants). The growth of the brain's major regions (cerebral cortex, white matter, basal ganglia, and cerebellum) and one region of interest (the right lateral prefrontal cortex) were defined on all individuals from two aMRIs, and a GWAS and a pathway analysis were performed. In addition, association between polygenic risk for ADHD and brain growth was determined for the LONG cohort. For white matter growth, GWAS meta-analysis identified a genome-wide significant intergenic SNP (rs12386571, P = 9.09 × 10 -9 ), near AKR1B10. This gene is part of the aldo-keto reductase superfamily and shows neural expression. No enrichment of neural pathways was detected and polygenic risk for ADHD was not associated with the brain growth phenotypes in the LONG cohort that was enriched for the diagnosis of ADHD. The study illustrates the use of a novel brain growth phenotype defined in vivo for further study. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

The effect of alcohol consumption on the adolescent brain: A systematic review of MRI and fMRI studies of alcohol-using youth

PubMed Central

Feldstein Ewing, Sarah W.; Sakhardande, Ashok; Blakemore, Sarah-Jayne

2014-01-01

Background A large proportion of adolescents drink alcohol, with many engaging in high-risk patterns of consumption, including binge drinking. Here, we systematically review and synthesize the existing empirical literature on how consuming alcohol affects the developing human brain in alcohol-using (AU) youth. Methods For this systematic review, we began by conducting a literature search using the PubMED database to identify all available peer-reviewed magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) studies of AU adolescents (aged 19 and under). All studies were screened against a strict set of criteria designed to constrain the impact of confounding factors, such as co-occurring psychiatric conditions. Results Twenty-one studies (10 MRI and 11 fMRI) met the criteria for inclusion. A synthesis of the MRI studies suggested that overall, AU youth showed regional differences in brain structure as compared with non-AU youth, with smaller grey matter volumes and lower white matter integrity in relevant brain areas. In terms of fMRI outcomes, despite equivalent task performance between AU and non-AU youth, AU youth showed a broad pattern of lower task-relevant activation, and greater task-irrelevant activation. In addition, a pattern of gender differences was observed for brain structure and function, with particularly striking effects among AU females. Conclusions Alcohol consumption during adolescence was associated with significant differences in structure and function in the developing human brain. However, this is a nascent field, with several limiting factors (including small sample sizes, cross-sectional designs, presence of confounding factors) within many of the reviewed studies, meaning that results should be interpreted in light of the preliminary state of the field. Future longitudinal and large-scale studies are critical to replicate the existing findings, and to provide a more comprehensive and conclusive picture of the effect of alcohol consumption on the developing brain. PMID:26958467

The effect of alcohol consumption on the adolescent brain: A systematic review of MRI and fMRI studies of alcohol-using youth.

PubMed

Ewing, Sarah W Feldstein; Sakhardande, Ashok; Blakemore, Sarah-Jayne

2014-01-01

A large proportion of adolescents drink alcohol, with many engaging in high-risk patterns of consumption, including binge drinking. Here, we systematically review and synthesize the existing empirical literature on how consuming alcohol affects the developing human brain in alcohol-using (AU) youth. For this systematic review, we began by conducting a literature search using the PubMED database to identify all available peer-reviewed magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) studies of AU adolescents (aged 19 and under). All studies were screened against a strict set of criteria designed to constrain the impact of confounding factors, such as co-occurring psychiatric conditions. Twenty-one studies (10 MRI and 11 fMRI) met the criteria for inclusion. A synthesis of the MRI studies suggested that overall, AU youth showed regional differences in brain structure as compared with non-AU youth, with smaller grey matter volumes and lower white matter integrity in relevant brain areas. In terms of fMRI outcomes, despite equivalent task performance between AU and non-AU youth, AU youth showed a broad pattern of lower task-relevant activation, and greater task-irrelevant activation. In addition, a pattern of gender differences was observed for brain structure and function, with particularly striking effects among AU females. Alcohol consumption during adolescence was associated with significant differences in structure and function in the developing human brain. However, this is a nascent field, with several limiting factors (including small sample sizes, cross-sectional designs, presence of confounding factors) within many of the reviewed studies, meaning that results should be interpreted in light of the preliminary state of the field. Future longitudinal and large-scale studies are critical to replicate the existing findings, and to provide a more comprehensive and conclusive picture of the effect of alcohol consumption on the developing brain.

The Golden Section as Optical Limitation.

PubMed

Elliott, Mark A; Kelly, Joy; Friedel, Jonas; Brodsky, Jennifer; Mulcahy, Paul

2015-01-01

The golden section, ϕ = (1 + √5)/2 = 1.618... and its companion ϕ = 1/ϕ = ϕ -1 = 0.618..., are irrational numbers which for centuries were believed to confer aesthetic appeal. In line with the presence of golden sectioning in natural growth patterns, recent EEG recordings show an absence of coherence between brain frequencies related by the golden ratio, suggesting the potential relevance of the golden section to brain dynamics. Using Mondrian-type patterns comprising a number of paired sections in a range of five section-section areal ratios (including golden-sectioned pairs), participants were asked to indicate as rapidly and accurately as possible the polarity (light or dark) of the smallest section in the patterns. They were also asked to independently assess the aesthetic appeal of the patterns. No preference was found for golden-sectioned patterns, while reaction times (RTs) tended to decrease overall with increasing ratio independently of each pattern's fractal dimensionality. (Fractal dimensionality was unrelated to ratio and measured in terms of the Minkowski-Bouligand box-counting dimension). The ease of detecting the smallest section also decreased with increasing ratio, although RTs were found to be substantially slower for golden-sectioned patterns under 8-paired sectioned conditions. This was confirmed by a significant linear relationship between RT and ratio (p < .001) only when the golden-sectioned RTs were excluded [the relationship was non-significant for the full complement of ratios (p = .217)]. Image analysis revealed an absence of spatial frequencies between 4 and 8 cycles-per-degree that was exclusive to the 8-paired (golden)-sectioned patterns. The significance of this was demonstrated in a subsequent experiment by addition of uniformly distributed random noise to the patterns. This provided a uniform spatial-frequency profile for all patterns, which did not influence the decrease in RT with increasing ratio but abolished the elevated RTs to golden-sectioned patterns. This suggests that optical limitation in the form of reduced inter-neural synchronization during spatial-frequency coding may be the foundation for the perceptual effects of golden sectioning.

Aging, Brain Size, and IQ.

ERIC Educational Resources Information Center

Bigler, Erin D.; And Others

1995-01-01

Whether cross-sectional rates of decline for brain volume and the Performance Intellectual Quotient of the Wechsler Adult Intelligence Scale-Revised were equivalent over the years 16 to 65 was studied with 196 volunteers. Results indicate remarkably similar rates of decline in perceptual-motor functions and aging brain volume loss. (SLD)

Anti-brain autoantibodies in the serum of schizophrenic patients: a case-control study.

PubMed

Margari, Francesco; Petruzzelli, Maria Giuseppina; Mianulli, Rossana; Toto, Maddalena; Pastore, Adriana; Bizzaro, Nicola; Tampoia, Marilina

2013-12-30

Schizophrenia is considered a neurodevelopmental disorder with a multifactorial pathogenesis where autoimmune factors may play a significant role. The aim of this study was to verify the presence of anti-brain autoantibodies in the serum of schizophrenic patients compared to healthy controls. Autoantibodies against brain were detected by the immunofluorescence method, utilizing sections of rat hippocampus and hypothalamus and of monkey cerebellum. Three different fluorescence patterns were observed, staining the nucleus-cytoplasm of neurons, the neuroendothelial of blood vessel and the neurofilaments. Search for other organ-specific and non organ-specific autoantibodies was performed in all sera by indirect immunofluorescence method, enzyme linked immunosorbent assay and chemiluminescence immunoassay. Results showed a significant association between schizophrenia and anti-brain autoantibodies against the neuroendothelium of blood vessel in hypothalamus, hippocampus and cerebellum; a significant nuclear and cytoplasmic staining of neurons was assessed only for the hippocampus. No other significant association was found, except between schizophrenia and anti-nuclear autoantibodies on HEp-2 cells. In conclusion, these results support the hypothesis of a significant association between schizophrenia and circulating anti-brain autoantibodies, suggesting a diffuse reactivity against the neuroendothelium of blood vessel and highlighting a nuclear and cytoplasmic staining of the neurons of hippocampus. © 2013 Published by Elsevier Ireland Ltd.

The effect of competitive and non-competitive NMDA receptor antagonists, ACPC and MK-801 on NPY and CRF-like immunoreactivity in the rat brain amygdala.

PubMed

Wierońska, J M; Brański, P; Pałvcha, A; Smiałowska, M

2001-01-01

Amygdala is the brain structure responsible for integrating all behavior connected with fear, and in this structure two neuropeptides, neuropeptide Y (NPY), corticoliberin (CRF) and the most abundant excitatory neurotransmitter glutamate seem to take part in the regulation of anxiety behavior. Our previous studies showed the modulation of NPY and CRF expression by classical neurotransmitters in some brain structures, therefore in the present study we investigated the effect of NMDA receptor antagonists on the expression of NPY and CRF immunoreactivity in the rat brain amygdala. A non-competitive NMDA receptor antagonist, MK-801, or a functional NMDA antagonist, ACPC were used. Brains were taken out and processed by immunohistochemical method using specific NPY or CRF antibodies. The staining intensity and density of IR neurons were evaluated under a microscope in amygdala sections. It was found that both MK-801 and ACPC induced a significant decrease in NPY-immunoreactivity in amygdala nerve cell bodies and terminals, which may suggest an increased release of this peptide. CRF-IR was decreased after ACPC only. The obtained results indicate that in the amygdala, the NMDA receptors mediated glutamatergic transmission may regulate NPY neurons. Copyright 2001 Harcourt Publishers Ltd.

Gestational Age and Neonatal Brain Microstructure in Term Born Infants: A Birth Cohort Study

PubMed Central

Broekman, Birit F. P.; Wang, Changqing; Li, Yue; Rifkin-Graboi, Anne; Saw, Seang Mei; Chong, Yap-Seng; Kwek, Kenneth; Gluckman, Peter D.; Fortier, Marielle V.; Meaney, Michael J.; Qiu, Anqi

2014-01-01

Objective Understanding healthy brain development in utero is crucial in order to detect abnormal developmental trajectories due to developmental disorders. However, in most studies neuroimaging was done after a significant postnatal period, and in those studies that performed neuroimaging on fetuses, the quality of data has been affected due to complications of scanning during pregnancy. To understand healthy brain development between 37–41 weeks of gestational age, our study assessed the in utero growth of the brain in healthy term born babies with DTI scanning soon after birth. Methods A cohort of 93 infants recruited from maternity hospitals in Singapore underwent diffusion tensor imaging between 5 to 17 days after birth. We did a cross-sectional examination of white matter microstructure of the brain among healthy term infants as a function of gestational age via voxel-based analysis on fractional anisotropy. Results Greater gestational age at birth in term infants was associated with larger fractional anisotropy values in early developing brain regions, when corrected for age at scan. Specifically, it was associated with a cluster located at the corpus callosum (corrected p<0.001), as well as another cluster spanning areas of the anterior corona radiata, anterior limb of internal capsule, and external capsule (corrected p<0.001). Conclusions Our findings show variation in brain maturation associated with gestational age amongst ‘term’ infants, with increased brain maturation when born with a relatively higher gestational age in comparison to those infants born with a relatively younger gestational age. Future studies should explore if these differences in brain maturation between 37 and 41 weeks of gestational age will persist over time due to development outside the womb. PMID:25535959

Ischemic Brain Injury Leads to Brain Edema via Hyperthermia-Induced TRPV4 Activation.

PubMed

Hoshi, Yutaka; Okabe, Kohki; Shibasaki, Koji; Funatsu, Takashi; Matsuki, Norio; Ikegaya, Yuji; Koyama, Ryuta

2018-06-20

Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain largely unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which male mouse brain slices were treated with oxygen-glucose deprivation (OGD) to mimic ischemia. We continuously measured the cross-sectional area of the brain slice for 150 min under macroscopic microscopy, finding that OGD induces swelling of brain slices. OGD-induced swelling was prevented by pharmacologically blocking or genetically knocking out the transient receptor potential vanilloid 4 (TRPV4), a member of the thermosensitive TRP channel family. Because TRPV4 is activated at around body temperature and its activation is enhanced by heating, we next elevated the temperature of the perfusate in the recording chamber, finding that hyperthermia induces swelling via TRPV4 activation. Furthermore, using the temperature-dependent fluorescence lifetime of a fluorescent-thermosensitive probe, we confirmed that OGD treatment increases the temperature of brain slices through the activation of glutamate receptors. Finally, we found that brain edema following traumatic brain injury was suppressed in TRPV4-deficient male mice in vivo Thus, our study proposes a novel mechanism: hyperthermia activates TRPV4 and induces brain edema after ischemia. SIGNIFICANCE STATEMENT Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which mouse brain slices were treated with oxygen-glucose deprivation. Using this system, we showed that the increase in brain temperature and the following activation of the thermosensitive cation channel TRPV4 (transient receptor potential vanilloid 4) are involved in the pathology of edema. Finally, we confirmed that TRPV4 is involved in brain edema in vivo using TRPV4-deficient mice, concluding that hyperthermia activates TRPV4 and induces brain edema after ischemia. Copyright © 2018 the authors 0270-6474/18/385700-10$15.00/0.

[Pathogen identification of 10 suspected cases of sparganosis mansoni].

PubMed

Zeng, Qing-Ren; He, Mei; Wang, Fang; Zhang, Zu-Ping; Su, Zhan-San; Zhou, Jun; Liu, Bao-An; Lan, Zhi-Hua; Hu, Mian-Juan; Cai, Li-Ting

2012-06-30

To diagnose 10 cases of clinically suspected cases of sparganosis mansoni by pathogen identification. In the period from August 2009 to August 2011, 10 biopsy specimens were obtained from 10 patients of four hospitals to identify the pathogen. Among the 10 cases, 4 cases showed abdominal subcutaneous mass, 3 showed eyelid swelling, 1 displayed brain lesions, 1 showed pulmonary mass, and 1 showed pleural effusion. There was one parasite each from three patients with eyelid swelling, and one patient with abdominal subcutaneous mass, which were observed by naked eye and microscope morphologically and histologically. Specimens from other six cases were examined by microscope after paraffin embedding, sectioning, and HE staining. For further identification, the parasite biopsy tissue specimens were detected by immunohistochemistry with Sparganum mansoni-immunized rabbit serum as the primary antibody. Three intact worms, from three patients with eyelid swelling, showed typical S. mansoni morphological characteristics. One residue parasite from the abdominal subcutaneous mass showed network structures and full of calcareous corpuscles in the body under microscope same as that of S. mansoni. The histological structure in three of the six sections showed typically the body wall with folds, which was dense, thick and deeply eosine stained, part of the tegument outside was covered by micro-hairs. In the worm body there was net-like loose structure and calcareous corpuscles without cavity. The structure of the other three worm sections was atypical. The six worm sections were positive by immunohistochemical detection. The 10 clinically suspected cases are diagnosed as sparganosis mansoni.

Evidence for Shared Predisposition in the Relationship between Cannabis Use and Subcortical Brain Structure

PubMed Central

Pagliaccio, David; Barch, Deanna M.; Bogdan, Ryan; Wood, Phillip K.; Lynskey, Michael T.; Heath, Andrew C.; Agrawal, Arpana

2015-01-01

Importance Prior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use. Objective To determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations. Design Cross-sectional diagnostic interview, behavioral, and neuroimaging data. Setting Community sampling and established family registries. Participants Data from 483 participants (22-35 years old), enrolled in the on-going Human Connectome Project; 262 participants reported cannabis exposure, i.e. ever using cannabis in their lifetime. Main Outcome Measures Whole brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever use, age of onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed-models were used to examine volume differences in sex-matched, concordant unexposed (Npairs=71), exposed (Npairs=81), or exposure discordant (Npairs=89) sibling pairs. Results Cannabis exposure was related to smaller left amygdala (~2.3%) and right ventral striatum volumes (~3.5%). These volumetric differences were within the range of normal variation. The relationship between left amygdala volume and cannabis use was largely due to shared genetic factors (ρg=−0.43, p=0.004), while the origin of the association with right ventral striatum volumes was unclear. Importantly, brain volumes did not differ between sex-matched siblings discordant for use. Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs. Conclusions and Relevance Differences in amygdala volume in cannabis users are attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences. Causal influences, in isolation or in conjunction with predispositional factors, may exist for other brain regions (e.g. ventral striatum) or at more severe levels of cannabis involvement and deserve further study. PMID:26308883

Utilization of real time PCR for the assessment of egg burden in the organs of Schistosoma japonicum experimentally infected mice.

PubMed

Dang-Trinh, Minh-Anh; Angeles, Jose Ma M; Moendeg, Kharleezelle J; Macalanda, Adrian Miki C; Higuchi, Luna; Oto, Chiho; Kirinoki, Masashi; Chigusa, Yuichi; Kawazu, Shin-Ichiro

2018-06-01

Schistosoma japonicum, causing zoonotic intestinal schistosomiasis, is found in China, the Philippines and parts of Indonesia. Severe disease manifestations are basically due to the deposition of eggs in some vital organs such as the liver, spleen and brain. Traditionally, histopathological microscopic examination of the egg burden was used to evaluate the intensity of infection in the affected organs. However, this technique is laborious, time-consuming and requires trained personnel. In this study, real time PCR targeting the mitochondrial NADH dehydrogenase I gene was used to compare with microscopic examination of tissue sections in evaluating the egg burdens in different affected organs. Livers, spleens and brains of the S. japonicum infected mice after 8 and 18 weeks post-infection (p.i) were harvested and examined. Results showed that there were statistically significant correlations between the egg burden evaluated by tissue section examination, and the Ct values of the real time PCR of livers with heavy egg burden at 8 (r = -0.81) and 18 (r = -0.80) weeks p.i. Furthermore, a correlation (r = -0.56) between the egg burden assessed by the microscopic examination and Ct value of the real time PCR of spleens with moderate egg burden after 18 weeks p.i and not 8 weeks p.i was also observed. Brains with low egg burden showed no schistosome eggs in the microscopic examination, however one sample tested positive by real time PCR. These results suggested that real time PCR is useful in evaluating schistosome egg burden in the organs of the experimentally infected mice model that will give further insights into the pathology of schistosomiasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Beta-galactosidase deficiency in a Korat cat: a new form of feline GM1-gangliosidosis.

PubMed

De Maria, R; Divari, S; Bo, S; Sonnio, S; Lotti, D; Capucchio, M T; Castagnaro, M

1998-09-01

A 7-month-old Korat cat was referred for a slowly progressive neurological disease. Circulating monocytes and lymphocytes showed the presence of single or multiple empty vacuoles and blood leukocytes enzyme assay revealed a very low beta-galactosidase activity level (4.7 nmol/mg per h) as compared to unaffected parents and relatives. Histologically, the cat, euthanized at the owner request at 21 months of age, presented diffuse vacuolization and enlargement of neurons throughout the brain, spinal cord and peripheral ganglia, severe cerebellar neuronal cell loss, and moderate astrocytosis. Stored material was stained with periodic acid-Schiff on frozen sections and with the lectins Ricinus conmmunis agglutinin-I, concanavalin A and wheat germ agglutinin on paraffin-embedded sections. Ultrastructurally, neuronal vacuoles were filled with concentrically whorled lamellae and small membrane-bound vesicles. In the affected cat, beta-galactosidase activity was markedly reduced in brain (18.9%) and liver (33.25%), while total beta-hexosaminidase activity showed a remarkable increase. Quantitation of total gangliosides revealed a 3-fold increase in brain and 1.7-fold in liver of affected cat. High-performance thin layer chromatography (HPTLC) detected a striking increase of GM1-ganglioside. On densitometric analysis of HPTLC bands, the absorption of GM1-ganglioside band was 98.52% of all stained bands (GD1a, GD1b, GT1b). Based on clinical onset, morphological and histochemical features, and biochemical findings, the Korat cat GM1-gangliosidosis is comparable with the human type II (juvenile) form. However, clinical progression, survival time and level of beta-galactosidase deficiency do not completely fit with those of human type II GM1-gangliosidosis. The disease in the Korat cat is also different from other reported forms of feline GM1-gangliosidosis.

‘Miracle baby’: an outcome of multidisciplinary approach to neurotrauma in pregnancy

PubMed Central

Neville, Grace; Kaliaperumal, Chandrasekaran; Kaar, George

2012-01-01

Traumatic brain injury (TBI) warranting neurosurgical intervention in the pregnant population is a rarity. We describe a case of a 27-year-old woman who at 13 weeks of gestation presented with multiple traumas having been involved in a near fatal road traffic accident. Glasgow Coma Scale was 6/15. CT brain showed extensive haemorrhagic contusions, diffuse brain swelling and multiple skull and facial fractures. Decompressive craniectomy was performed to control her intracranial pressure during her management in the intensive care. A viable intrauterine pregnancy was confirmed and progressed as maternal stabilisation and rehabilitation continued. At 35+3 weeks a 2770 g male child was delivered via emergency caesarean section after spontaneous onset of labour. The child had no detectable abnormalities and is clinically well. Eight months post-TBI the patient continues to make gradual improvements but is left with severe cognitive impairment and currently undergoing rehabilitation. A multidisciplinary approach was adopted in the management of this patient. PMID:22805738

Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions.

PubMed

Naderi, Fariba; Eslami, Samira Rajabi; Mirak, Sohrab Afshari; Khak, Mohammad; Amiri, Jalaladin; Beyrami, Bahram; Shekarchi, Babak; Poureisa, Masoud

2015-01-01

Growth hormone deficiency (GHD) is a major problem among children with short stature. In this study, the role of brain magnetic resonance imaging (MRI) in defining the underlying defects among short children with GHD is evaluated. In a cross-sectional study, data of 158 children were evaluated. Growth hormone (GH) levels were measured using stimulating tests and brain MRI with gadolinium contrast was applied, as well. Some 25.3% of patients had GHD with a mean age of 8.01±3.40 years. MRI results showed 35 as normal, four with pituitary hypoplasia, and one with microadenoma. The MRI results were significantly associated with GH levels and presence of other endocrine disorders. There was a significant association between prenatal disorders and patients' bone age delay. In patients with severe GHD and patients with multiple pituitary hormone deficiencies, MRI is more likely to be abnormal, and bone age is much delayed in patients with history of prenatal disorders.

Generating Textures for Arbitrary Surfaces Using Reaction-Diffusion

DTIC Science & Technology

1990-01-01

Review and Classification," Computer Aided Design, Vol. 20, No. 1, pp. 27-38 (January/February 1988). [ Hubel and Wiesel 79] Hubel , David H. and...columns found in mammals [ Hubel and Wiesel 791. Complex Patterns This section shows how we can generate more complex patterns using reaction-diffusion by... Torsten N. Wiesel , "Brain Mechanisms of Vision," Scientific American, Vol. 241, No. 3, pp. 150-162 (September 1979). [Hunding 90] Hunding, Axel, Stuart A

Effects of Microwave Irradiation on Embryonic Brain Tissue.

DTIC Science & Technology

1979-03-01

less than 1 hour) post partum in the experiment described in Section III, page 13. Table 2 The significance of the difference in weight of the irradiated...appeared normal. Two of the control and two of the exposed rats showed small depressions of the external surface of the hemisphere unilaterally with...some thinning of the underlying cortex. The depressions occurred, one just dorsal to the rhinal fissure and the other lateral to the longitudinal sulcus

Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with γ-secretase and regulates neuronal amyloid β-peptide levels.

PubMed

Schedin-Weiss, Sophia; Inoue, Mitsuhiro; Hromadkova, Lenka; Teranishi, Yasuhiro; Yamamoto, Natsuko Goto; Wiehager, Birgitta; Bogdanovic, Nenad; Winblad, Bengt; Sandebring-Matton, Anna; Frykman, Susanne; Tjernberg, Lars O

2017-08-01

Increased levels of the pathogenic amyloid β-peptide (Aβ), released from its precursor by the transmembrane protease γ-secretase, are found in Alzheimer disease (AD) brains. Interestingly, monoamine oxidase B (MAO-B) activity is also increased in AD brain, but its role in AD pathogenesis is not known. Recent neuroimaging studies have shown that the increased MAO-B expression in AD brain starts several years before the onset of the disease. Here, we show a potential connection between MAO-B, γ-secretase and Aβ in neurons. MAO-B immunohistochemistry was performed on postmortem human brain. Affinity purification of γ-secretase followed by mass spectrometry was used for unbiased identification of γ-secretase-associated proteins. The association of MAO-B with γ-secretase was studied by coimmunoprecipitation from brain homogenate, and by in-situ proximity ligation assay (PLA) in neurons as well as mouse and human brain sections. The effect of MAO-B on Aβ production and Notch processing in cell cultures was analyzed by siRNA silencing or overexpression experiments followed by ELISA, western blot or FRET analysis. Methodology for measuring relative intraneuronal MAO-B and Aβ42 levels in single cells was developed by combining immunocytochemistry and confocal microscopy with quantitative image analysis. Immunohistochemistry revealed MAO-B staining in neurons in the frontal cortex, hippocampus CA1 and entorhinal cortex in postmortem human brain. Interestingly, the neuronal staining intensity was higher in AD brain than in control brain in these regions. Mass spectrometric data from affinity purified γ-secretase suggested that MAO-B is a γ-secretase-associated protein, which was confirmed by immunoprecipitation and PLA, and a neuronal location of the interaction was shown. Strikingly, intraneuronal Aβ42 levels correlated with MAO-B levels, and siRNA silencing of MAO-B resulted in significantly reduced levels of intraneuronal Aβ42. Furthermore, overexpression of MAO-B enhanced Aβ production. This study shows that MAO-B levels are increased not only in astrocytes but also in pyramidal neurons in AD brain. The study also suggests that MAO-B regulates Aβ production in neurons via γ-secretase and thereby provides a key to understanding the relationship between MAO-B and AD pathogenesis. Potentially, the γ-secretase/MAO-B association may be a target for reducing Aβ levels using protein-protein interaction breakers.

Students with Acquired Brain Injury. The School's Response.

ERIC Educational Resources Information Center

Glang, Ann, Ed.; Singer, George H. S., Ed.; Todis, Bonnie, Ed.

Designed for educators, this book focuses on educational issues relating to students with acquired brain injury (ABI), and describes approaches that have been effective in improving the school experiences of students with brain injury. Section 1 provides an introduction to issues related to ABI in children and youth and includes: "An Overview of…

A Novel Application for the Cavalieri Principle: A Stereological and Methodological Study

PubMed Central

Altunkaynak, Berrin Zuhal; Altunkaynak, Eyup; Unal, Deniz; Unal, Bunyamin

2009-01-01

Objective The Cavalieri principle was applied to consecutive pathology sections that were photographed at the same magnification and used to estimate tissue volumes via superimposing a point counting grid on these images. The goal of this study was to perform the Cavalieri method quickly and practically. Materials and Methods In this study, 10 adult female Sprague Dawley rats were used. Brain tissue was removed and sampled both systematically and randomly. Brain volumes were estimated using two different methods. First, all brain slices were scanned with an HP ScanJet 3400C scanner, and their images were shown on a PC monitor. Brain volume was then calculated based on these images. Second, all brain slices were photographed in 10× magnification with a microscope camera, and brain volumes were estimated based on these micrographs. Results There was no statistically significant difference between the volume measurements of the two techniques (P>0.05; Paired Samples t Test). Conclusion This study demonstrates that personal computer scanning of serial tissue sections allows for easy and reliable volume determination based on the Cavalieri method. PMID:25610077

A novel application for the cavalieri principle: a stereological and methodological study.

PubMed

Altunkaynak, Berrin Zuhal; Altunkaynak, Eyup; Unal, Deniz; Unal, Bunyamin

2009-08-01

The Cavalieri principle was applied to consecutive pathology sections that were photographed at the same magnification and used to estimate tissue volumes via superimposing a point counting grid on these images. The goal of this study was to perform the Cavalieri method quickly and practically. In this study, 10 adult female Sprague Dawley rats were used. Brain tissue was removed and sampled both systematically and randomly. Brain volumes were estimated using two different methods. First, all brain slices were scanned with an HP ScanJet 3400C scanner, and their images were shown on a PC monitor. Brain volume was then calculated based on these images. Second, all brain slices were photographed in 10× magnification with a microscope camera, and brain volumes were estimated based on these micrographs. There was no statistically significant difference between the volume measurements of the two techniques (P>0.05; Paired Samples t Test). This study demonstrates that personal computer scanning of serial tissue sections allows for easy and reliable volume determination based on the Cavalieri method.

Balamuthia mandrillaris meningoencephalitis: the first case in southeast Asia.

PubMed

Intalapaporn, Poj; Suankratay, Chusana; Shuangshoti, Shanop; Phantumchinda, Kammant; Keelawat, Somboon; Wilde, Henry

2004-06-01

We present a case of 23-year-old man with acute meningoencephalitis, accompanied by inflammation of a nasal ulcer. He had been healthy until six months prior to admission to the hospital when he had a motorcycle accident. A star-shaped wound at his nose was incurred after falling into a swamp. A computed tomogram of the brain showed two nonenhancing hypodense lesions at the left caudate nucleus and the right parietal lobe, ependymitis and leptomeningeal enhancement. A skin biopsy showed chronic noncaseous granulomatous inflammation without demonstrated microorganisms. The patient did not respond to the empirical treatment with cloxacillin, ceftriaxone, and amphotericin B, and eventually died on the thirteenth day of hospitalization. At autopsy, hematoxylin and eosin-stained brain sections showed a chronic necrotizing inflammation with numerous amebic trophozoites and rare cysts. Definitive identification of Balamuthia mandrillaris was made by fluorescent immunohistochemical analysis. There were 10 Naegleria fowleri primary amebic meningoencephalitis, eight Acanthamoeba granulomatous amebic encephalitis, and three Acanthamoeba meningitis in Thailand. To our knowledge, this case is the first reported case of B. mandrillaris in Southeast Asia.

Venlafaxine inhibits apoptosis of hippocampal neurons by up-regulating brain-derived neurotrophic factor in a rat depression model

PubMed Central

Huang, Xiao; Mao, Yue-Shi; Li, Chao; Wang, Hao; Ji, Jian-Lin

2014-01-01

Objective: To study the effect of venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) in rat hippocampal neurons, as well as its inhibitory effect on apoptosis of hippocampal neurons. Methods: Differences in behavioral ability between the depression model group and the Venlafaxine treatment group were observed using behavioral, sucrose-water and open field tests. The rat hippocampal tissue was sliced, stained and observed for BDNF distribution by immunohistochemistry. Apoptosis of hippocampal neurons was detected by TUNEL. BDNF expression in the hippocampal tissue was detected by Western blot. Injury and apoptosis of the hippocampal tissue were observed by electron microscopy. Results: Behavioral test showed that venlafaxine effectively improved the behavioral abilities of depressed rats. Immunohistochemistry showed that venlafaxine markedly increased the BDNF expression in the rat hippocampus. TUNEL showed that venlafaxine markedly inhibited apoptosis of hippocampal neurons, which was also confirmed by electron microscopic observation of the pathologic sections. Conclusion: Venlafaxine improved the expression of BDNF through working on PI3k/PKB/eNOS pathway and repressed the apoptosis of hippocampal neurons. PMID:25197330

Bioimaging of metals in brain tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and metallomics.

PubMed

Becker, J Sabine; Matusch, Andreas; Palm, Christoph; Salber, Dagmar; Morton, Kathryn A; Becker, J Susanne

2010-02-01

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson's disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section.

Down syndrome's brain dynamics: analysis of fractality in resting state.

PubMed

Hemmati, Sahel; Ahmadlou, Mehran; Gharib, Masoud; Vameghi, Roshanak; Sajedi, Firoozeh

2013-08-01

To the best knowledge of the authors there is no study on nonlinear brain dynamics of down syndrome (DS) patients, whereas brain is a highly complex and nonlinear system. In this study, fractal dimension of EEG, as a key characteristic of brain dynamics, showing irregularity and complexity of brain dynamics, was used for evaluation of the dynamical changes in the DS brain. The results showed higher fractality of the DS brain in almost all regions compared to the normal brain, which indicates less centrality and higher irregular or random functioning of the DS brain regions. Also, laterality analysis of the frontal lobe showed that the normal brain had a right frontal laterality of complexity whereas the DS brain had an inverse pattern (left frontal laterality). Furthermore, the high accuracy of 95.8 % obtained by enhanced probabilistic neural network classifier showed the potential of nonlinear dynamic analysis of the brain for diagnosis of DS patients. Moreover, the results showed that the higher EEG fractality in DS is associated with the higher fractality in the low frequencies (delta and theta), in broad regions of the brain, and the high frequencies (beta and gamma), majorly in the frontal regions.

Magnetic resonance imaging for white matter degradation in fornix following mild traumatic brain injury

NASA Astrophysics Data System (ADS)

Zhan, Wang; Boreta, Lauren; Gauger, Grant

2010-03-01

The alterations of the fornix in mild traumatic brain injury (mTBI) were investigated using diffusion tensor imaging (DTI) and T1-weighetd anatomical imaging. The primary goal of this study was to test that hypothesis that the fornix might play a major role in the memory and learning dysfunctions in the post-concussion syndrome, which may related to the white matter (WM) degradations following mild traumatic brain injury. N=24 mTBI patients were longitudinally studied in two time points with 6-month intervals using a 4-Tesla MRI scanner to measure the WM integrity of fornix and the fornix-to-brain ratio (FBR), and compared with matched healthy controls. Our data show that the WM degradation in fornix onset in the acute stage after mild TBI when the post-injury time was less than 6 weeks, and that this WM degradation continued during the following 6-month period of recovery. In summary, using DTI and structural MRI together can effectively detect the fornix changes in both cross-sectional and longitudinal investigations. Further studies are warranted to exam the association between the fornix alterations and neurocognitive performance of TBI patients.

Maternal obesity increases inflammation and exacerbates damage following neonatal hypoxic-ischaemic brain injury in rats.

PubMed

Teo, Jonathan D; Morris, Margaret J; Jones, Nicole M

2017-07-01

In humans, maternal obesity is associated with an increase in the incidence of birth related difficulties. However, the impact of maternal obesity on the severity of brain injury in offspring is not known. Recent studies have found evidence of increased glial response and inflammatory mediators in the brains as a result of obesity in humans and rodents. We hypothesised that hypoxic-ischaemic (HI) brain injury is greater in neonatal offspring from obese rat mothers compared to lean controls. Female Sprague Dawley rats were randomly allocated to high fat (HFD, n=8) or chow (n=4) diet and mated with lean male rats. On postnatal day 7 (P7), male and female pups were randomly assigned to HI injury or control (C) groups. HI injury was induced by occlusion of the right carotid artery followed by 3h exposure to 8% oxygen, at 37°C. Control pups were removed from the mother for the same duration under ambient conditions. Righting behaviour was measured on day 1 and 7 following HI. The extent of brain injury was quantified in brain sections from P14 pups using cresyl violet staining and the difference in volume between brain hemispheres was measured. Before mating, HFD mothers were 11% heavier than Chow mothers (p<0.05, t-test). Righting reflex was delayed in offspring from HFD-fed mothers compared to the Chow mothers. The Chow-HI pups showed a loss in ipsilateral brain tissue, while the HFD-HI group had significantly greater loss. No significant difference was detected in brain volume between the HFD-C and Chow-C pups. When analysed on a per litter basis, the size of the injury was significantly correlated with maternal weight. Similar observations were made with neuronal staining showing a greater loss of neurons in the brain of offspring from HFD-mothers following HI compared to Chow. Astrocytes appeared to more hypertrophic and a greater number of microglia were present in the injured hemisphere in offspring from mothers on HFD. HI caused an increase in the proportion of amoeboid microglia and exposure to maternal HFD exacerbated this response. In the contralateral hemisphere, offspring exposed to maternal HFD displayed a reduced proportion of ramified microglia. Our data clearly demonstrate that maternal obesity can exacerbate the severity of brain damage caused by HI in neonatal offspring. Given that previous studies have shown enhanced inflammatory responses in offspring of obese mothers, these factors including gliosis and microglial infiltration are likely to contribute to enhanced brain injury. Copyright © 2016 Elsevier Inc. All rights reserved.

75 FR 51081 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-18

...- 0684, [email protected] . Name of Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group, Brain Injury and Neurovascular Pathologies Study Section. Date: September 27-28, 2010. Time...

Tracking Brain Development and Dimensional Psychiatric Symptoms in Children: A Longitudinal Population-Based Neuroimaging Study.

PubMed

Muetzel, Ryan L; Blanken, Laura M E; van der Ende, Jan; El Marroun, Hanan; Shaw, Philip; Sudre, Gustavo; van der Lugt, Aad; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning; White, Tonya

2018-01-01

Psychiatric symptomatology during childhood predicts persistent mental illness later in life. While neuroimaging methodologies are routinely applied cross-sectionally to the study of child and adolescent psychopathology, the nature of the relationship between childhood symptoms and the underlying neurodevelopmental processes remains unclear. The authors used a prospective population-based cohort to delineate the longitudinal relationship between childhood psychiatric problems and brain development. A total of 845 children participated in the study. Psychiatric symptoms were measured with the parent-rated Child Behavior Checklist at ages 6 and 10. MRI data were collected at ages 8 and 10. Cross-lagged panel models and linear mixed-effects models were used to determine the associations between psychiatric symptom ratings and quantitative anatomic and white matter microstructural measures over time. Higher ratings for externalizing and internalizing symptoms at baseline predicted smaller increases in both subcortical gray matter volume and global fractional anisotropy over time. The reverse relationship did not hold; thus, baseline measures of gray matter and white matter were not significantly related to changes in symptom ratings over time. Children presenting with behavioral problems at an early age show differential subcortical and white matter development. Most neuroimaging models tend to explain brain differences observed in psychopathology as an underlying (causal) neurobiological substrate. However, the present work suggests that future neuroimaging studies showing effects that are pathogenic in nature should additionally explore the possibility of the downstream effects of psychopathology on the brain.

A longitudinal study of brain atrophy over two years in community-dwelling older individuals.

PubMed

Jiang, Jiyang; Sachdev, Perminder; Lipnicki, Darren M; Zhang, Haobo; Liu, Tao; Zhu, Wanlin; Suo, Chao; Zhuang, Lin; Crawford, John; Reppermund, Simone; Trollor, Julian; Brodaty, Henry; Wen, Wei

2014-02-01

Most previous neuroimaging studies of age-related brain structural changes in older individuals have been cross-sectional and/or restricted to clinical samples. The present study of 345 community-dwelling non-demented individuals aged 70-90years aimed to examine age-related brain volumetric changes over two years. T1-weighted magnetic resonance imaging scans were obtained at baseline and at 2-year follow-up and analyzed using the FMRIB Software Library and FreeSurfer to investigate cortical thickness and shape and volumetric changes of subcortical structures. The results showed significant atrophy across much of the cerebral cortex with bilateral transverse temporal regions shrinking the fastest. Atrophy was also found in a number of subcortical structures, including the CA1 and subiculum subfields of the hippocampus. In some regions, such as left and right entorhinal cortices, right hippocampus and right precentral area, the rate of atrophy increased with age. Our analysis also showed that rostral middle frontal regions were thicker bilaterally in older participants, which may indicate its ability to compensate for medial temporal lobe atrophy. Compared to men, women had thicker cortical regions but greater rates of cortical atrophy. Women also had smaller subcortical structures. A longer period of education was associated with greater thickness in a number of cortical regions. Our results suggest a pattern of brain atrophy with non-demented people that resembles a less extreme form of the changes associated with Alzheimer's disease (AD). © 2013 Elsevier Inc. All rights reserved.

Identification of minimum carbohydrate moiety in N-glycosylation sites of brain endothelial cell glycoprotein 96 for interaction with Escherichia coli K1 outer membrane protein A

PubMed Central

Krishnan, Subramanian; Prasadarao, Nemani V.

2014-01-01

Bacterial meningitis is a serious central nervous system infection and Escherichia coli K1 (E. coli K1) is one of the leading etiological agents that cause meningitis in neonates. Outer membrane protein A (OmpA) of E. coli K1 is a major virulence factor in the pathogenesis of meningitis, and interacts with human brain microvascular endothelial cells (HBMEC) to cross the blood-brain barrier. Using site-directed mutagenesis, we demonstrate that two N-glycosylation sites (NG1 and NG2) in the extracellular domain of OmpA receptor, Ecgp96 are critical for bacterial binding to HBMEC. E. coli invasion assays using CHO-Lec1 cells that express truncated N-glycans, and sequential digestion of HBMEC surface N-glycans using specific glycosidases showed that GlcNAc1-4GlcNAc epitopes are sufficient for OmpA interaction with HBMEC. Lack of NG1 and NG2 sites in Ecgp96 inhibits E. coli OmpA induced F-actin polymerization, phosphorylation of protein kinase C-α, and disruption of transendothelial electrical resistance required for efficient invasion of E. coli in HBMEC. Furthermore, the microvessels of cortex and hippocampus of the brain sections of E. coli K1 infected mice showed increased expression of glycosylated Ecgp96. Therefore, the interface of OmpA and GlcNAc1-4GlcNAc epitope interaction would be a target for preventative strategies against E. coli K1 meningitis. PMID:24932957

Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults.

PubMed

Berti, Valentina; Walters, Michelle; Sterling, Joanna; Quinn, Crystal G; Logue, Michelle; Andrews, Randolph; Matthews, Dawn C; Osorio, Ricardo S; Pupi, Alberto; Vallabhajosula, Shankar; Isaacson, Richard S; de Leon, Mony J; Mosconi, Lisa

2018-05-15

To examine in a 3-year brain imaging study the effects of higher vs lower adherence to a Mediterranean-style diet (MeDi) on Alzheimer disease (AD) biomarker changes (brain β-amyloid load via 11 C-Pittsburgh compound B [PiB] PET and neurodegeneration via 18 F-fluorodeoxyglucose [FDG] PET and structural MRI) in midlife. Seventy 30- to 60-year-old cognitively normal participants with clinical, neuropsychological, and dietary examinations and imaging biomarkers at least 2 years apart were examined. These included 34 participants with higher (MeDi+) and 36 with lower (MeDi-) MeDi adherence. Statistical parametric mapping and volumes of interest were used to compare AD biomarkers between groups at cross section and longitudinally. MeDi groups were comparable for clinical and neuropsychological measures. At baseline, compared to the MeDi+ group, the MeDi- group showed reduced FDG-PET glucose metabolism (CMRglc) and higher PiB-PET deposition in AD-affected regions ( p < 0.001). Longitudinally, the MeDi--group showed CMRglc declines and PiB increases in these regions, which were greater than those in the MeDi+ group ( p interaction < 0.001). No effects were observed on MRI. Higher MeDi adherence was estimated to provide 1.5 to 3.5 years of protection against AD. Lower MeDi adherence was associated with progressive AD biomarker abnormalities in middle-aged adults. These data support further investigation of dietary interventions for protection against brain aging and AD. © 2018 American Academy of Neurology.

Back to the future: estimating pre-injury brain volume in patients with traumatic brain injury.

PubMed

Ross, David E; Ochs, Alfred L; D Zannoni, Megan; Seabaugh, Jan M

2014-11-15

A recent meta-analysis by Hedman et al. allows for accurate estimation of brain volume changes throughout the life span. Additionally, Tate et al. showed that intracranial volume at a later point in life can be used to estimate reliably brain volume at an earlier point in life. These advancements were combined to create a model which allowed the estimation of brain volume just prior to injury in a group of patients with mild or moderate traumatic brain injury (TBI). This volume estimation model was used in combination with actual measurements of brain volume to test hypotheses about progressive brain volume changes in the patients. Twenty six patients with mild or moderate TBI were compared to 20 normal control subjects. NeuroQuant® was used to measure brain MRI volume. Brain volume after the injury (from MRI scans performed at t1 and t2) was compared to brain volume just before the injury (volume estimation at t0) using longitudinal designs. Groups were compared with respect to volume changes in whole brain parenchyma (WBP) and its 3 major subdivisions: cortical gray matter (GM), cerebral white matter (CWM) and subcortical nuclei+infratentorial regions (SCN+IFT). Using the normal control data, the volume estimation model was tested by comparing measured brain volume to estimated brain volume; reliability ranged from good to excellent. During the initial phase after injury (t0-t1), the TBI patients had abnormally rapid atrophy of WBP and CWM, and abnormally rapid enlargement of SCN+IFT. Rates of volume change during t0-t1 correlated with cross-sectional measures of volume change at t1, supporting the internal reliability of the volume estimation model. A logistic regression analysis using the volume change data produced a function which perfectly predicted group membership (TBI patients vs. normal control subjects). During the first few months after injury, patients with mild or moderate TBI have rapid atrophy of WBP and CWM, and rapid enlargement of SCN+IFT. The magnitude and pattern of the changes in volume may allow for the eventual development of diagnostic tools based on the volume estimation approach. Copyright © 2014 Elsevier Inc. All rights reserved.

Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody

PubMed Central

Luo, Wenjie; Liu, Wencheng; Hu, Xiaoyan; Hanna, Mary; Caravaca, April; Paul, Steven M.

2015-01-01

Microglia have been shown to contribute to the clearance of brain amyloid β peptides (Aβ), the major component of amyloid plaques, in Alzheimer’s disease (AD). However, it is not known whether microglia play a similar role in the clearance of tau, the major component of neurofibrillary tangles (NFTs). We now report that murine microglia rapidly internalize and degrade hyperphosphorylated pathological tau isolated from AD brain tissue in a time-dependent manner in vitro. We further demonstrate that microglia readily degrade human tau species released from AD brain sections and eliminate NFTs from brain sections of P301S tauopathy mice. The anti-tau monoclonal antibody MC1 enhances microglia-mediated tau degradation in an Fc-dependent manner. Our data identify a potential role for microglia in the degradation and clearance of pathological tau species in brain and provide a mechanism explaining the potential therapeutic actions of passively administered anti-tau monoclonal antibodies. PMID:26057852

High-resolution digital brain atlases: a Hubble telescope for the brain.

PubMed

Jones, Edward G; Stone, James M; Karten, Harvey J

2011-05-01

We describe implementation of a method for digitizing at microscopic resolution brain tissue sections containing normal and experimental data and for making the content readily accessible online. Web-accessible brain atlases and virtual microscopes for online examination can be developed using existing computer and internet technologies. Resulting databases, made up of hierarchically organized, multiresolution images, enable rapid, seamless navigation through the vast image datasets generated by high-resolution scanning. Tools for visualization and annotation of virtual microscope slides enable remote and universal data sharing. Interactive visualization of a complete series of brain sections digitized at subneuronal levels of resolution offers fine grain and large-scale localization and quantification of many aspects of neural organization and structure. The method is straightforward and replicable; it can increase accessibility and facilitate sharing of neuroanatomical data. It provides an opportunity for capturing and preserving irreplaceable, archival neurohistological collections and making them available to all scientists in perpetuity, if resources could be obtained from hitherto uninterested agencies of scientific support. © 2011 New York Academy of Sciences.

Multi-modal imaging of long-term recovery post-stroke by positron emission tomography and matrix-assisted laser desorption/ionisation mass spectrometry.

PubMed

Henderson, Fiona; Hart, Philippa J; Pradillo, Jesus M; Kassiou, Michael; Christie, Lidan; Williams, Kaye J; Boutin, Herve; McMahon, Adam

2018-05-15

Stroke is a leading cause of disability worldwide. Understanding the recovery process post-stroke is essential; however, longer-term recovery studies are lacking. In vivo positron emission tomography (PET) can image biological recovery processes, but is limited by spatial resolution and its targeted nature. Untargeted mass spectrometry imaging offers high spatial resolution, providing an ideal ex vivo tool for brain recovery imaging. Magnetic resonance imaging (MRI) was used to image a rat brain 48 h after ischaemic stroke to locate the infarcted regions of the brain. PET was carried out 3 months post-stroke using the tracers [ 18 F]DPA-714 for TSPO and [ 18 F]IAM6067 for sigma-1 receptors to image neuroinflammation and neurodegeneration, respectively. The rat brain was flash-frozen immediately after PET scanning, and sectioned for matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) imaging. Three months post-stroke, PET imaging shows minimal detection of neurodegeneration and neuroinflammation, indicating that the brain has stabilised. However, MALDI-MS images reveal distinct differences in lipid distributions (e.g. phosphatidylcholine and sphingomyelin) between the scar and the healthy brain, suggesting that recovery processes are still in play. It is currently not known if the altered lipids in the scar will change on a longer time scale, or if they are stabilised products of the brain post-stroke. The data demonstrates the ability to combine MALD-MS with in vivo PET to image different aspects of stroke recovery. Copyright © 2018 John Wiley & Sons, Ltd.

Brain development during the preschool years

PubMed Central

Brown, Timothy T.; Jernigan, Terry L.

2012-01-01

The preschool years represent a time of expansive psychological growth, with the initial expression of many psychological abilities that will continue to be refined into young adulthood. Likewise, brain development during this age is characterized by its “blossoming” nature, showing some of its most dynamic and elaborative anatomical and physiological changes. In this article, we review human brain development during the preschool years, sampling scientific evidence from a variety of sources. First, we cover neurobiological foundations of early postnatal development, explaining some of the primary mechanisms seen at a larger scale within neuroimaging studies. Next, we review evidence from both structural and functional imaging studies, which now accounts for a large portion of our current understanding of typical brain development. Within anatomical imaging, we focus on studies of developing brain morphology and tissue properties, including diffusivity of white matter fiber tracts. We also present new data on changes during the preschool years in cortical area, thickness, and volume. Physiological brain development is then reviewed, touching on influential results from several different functional imaging and recording modalities in the preschool and early school-age years, including positron emission tomography (PET), electroencephalography (EEG) and event-related potentials (ERP), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and near-infrared spectroscopy (NIRS). Here, more space is devoted to explaining some of the key methodological factors that are required for interpretation. We end with a section on multimodal and multidimensional imaging approaches, which we believe will be critical for increasing our understanding of brain development and its relationship to cognitive and behavioral growth in the preschool years and beyond. PMID:23007644

Determination of intra-axial brain tumors cellularity through the analysis of T2 Relaxation time of brain tumors before surgery using MATLAB software.

PubMed

Abdolmohammadi, Jamil; Shafiee, Mohsen; Faeghi, Fariborz; Arefan, Douman; Zali, Alireza; Motiei-Langroudi, Rouzbeh; Farshidfar, Zahra; Nazarlou, Ali Kiani; Tavakkoli, Ali; Yarham, Mohammad

2016-08-01

Timely diagnosis of brain tumors could considerably affect the process of patient treatment. To do so, para-clinical methods, particularly MRI, cannot be ignored. MRI has so far answered significant questions regarding tumor characteristics, as well as helping neurosurgeons. In order to detect the tumor cellularity, neuro-surgeons currently have to sample specimens by biopsy and then send them to the pathology unit. The aim of this study is to determine the tumor cellularity in the brain. In this cross-sectional study, 32 patients (18 males and 14 females from 18-77 y/o) were admitted to the neurosurgery department of Shohada-E Tajrish Hospital in Tehran, Iran from April 2012 to February 2014. In addition to routine pulse sequences, T2W Multi echo pulse sequences were taken and the images were analyzed using the MATLAB software to determine the brain tumor cellularity, compared with the biopsy. These findings illustrate the need for more T2 relaxation time decreases, the higher classes of tumors will stand out in the designed table. In this study, the results show T2 relaxation time with a 85% diagnostic weight, compared with the biopsy, to determine the brain tumor cellularity (p<0.05). Our results indicate that the T2 relaxation time feature is the best method to distinguish and present the degree of intra-axial brain tumors cellularity (85% accuracy compared to biopsy). The use of more data is recommended in order to increase the percent accuracy of this techniques.

Dopamine precursor depletion impairs structure and efficiency of resting state brain functional networks.

PubMed

Carbonell, Felix; Nagano-Saito, Atsuko; Leyton, Marco; Cisek, Paul; Benkelfat, Chawki; He, Yong; Dagher, Alain

2014-09-01

Spatial patterns of functional connectivity derived from resting brain activity may be used to elucidate the topological properties of brain networks. Such networks are amenable to study using graph theory, which shows that they possess small world properties and can be used to differentiate healthy subjects and patient populations. Of particular interest is the possibility that some of these differences are related to alterations in the dopamine system. To investigate the role of dopamine in the topological organization of brain networks at rest, we tested the effects of reducing dopamine synthesis in 13 healthy subjects undergoing functional magnetic resonance imaging. All subjects were scanned twice, in a resting state, following ingestion of one of two amino acid drinks in a randomized, double-blind manner. One drink was a nutritionally balanced amino acid mixture, and the other was tyrosine and phenylalanine deficient. Functional connectivity between 90 cortical and subcortical regions was estimated for each individual subject under each dopaminergic condition. The lowered dopamine state caused the following network changes: reduced global and local efficiency of the whole brain network, reduced regional efficiency in limbic areas, reduced modularity of brain networks, and greater connection between the normally anti-correlated task-positive and default-mode networks. We conclude that dopamine plays a role in maintaining the efficient small-world properties and high modularity of functional brain networks, and in segregating the task-positive and default-mode networks. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Alcohol-related hospitalisations of trauma patients in Southern Taiwan: a cross-sectional study based on a trauma registry system

PubMed Central

Rau, Cheng-Shyuan; Liu, Hang-Tsung; Hsu, Shiun-Yuan; Cho, Tzu-Yu; Hsieh, Ching-Hua

2014-01-01

Objectives To provide an overview of the demographic characteristics of patients with positive blood alcohol concentration (BAC) and to investigate the performance of brain CT scans in these patients. Design Cross-sectional study. Setting Taiwan. Participants 2192 patients who had undergone a test for blood alcohol of 13 233 patients registered in the Trauma Registry System between 1 January 2009 and 31 December 2012. A BAC level of 50 mg/dL was defined as the cut-off value. Detailed information was retrieved from the patients with positive BAC (n=793) and was compared with information from those with a negative BAC (n=1399). Main outcome measures Glasgow Coma Scale (GCS) and Injury Severity Score (ISS) as well as the performance and findings of obtained brain CT scans. Results Patients with positive BAC had a higher rate of face injury, but a lower GCS score, a lower rate of head and neck injury, a lower ISS and New Injury Severity Score. Alcohol use was associated with a shorter length of hospital stay (8.6 vs 11.4 days, p=0.000) in patients with an ISS of <16. Of 496 patients with positive BAC who underwent brain CT, 164 (33.1%) showed positive findings on CT scan. In contrast, of 891 patients with negative BAC who underwent brain CT, 389 (43.7%) had positive findings on CT scan. The lower percentage of positive CT scan findings in patients with positive BAC was particularly evident in patients with an ISS <16 (18.0% vs 28.8%, p=0.001). Conclusions Patients who consumed alcohol tended to have a low GCS score and injuries that were less severe. However, given the significantly low percentage of positive findings, brain CT might be overused in these patients with less severe injuries. PMID:25361838

Limbic grey matter changes in early Parkinson's disease.

PubMed

Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

2017-05-02

The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Neuropathology and functional deficits in a model of birth asphyxia in the precocial spiny mouse (Acomys cahirinus).

PubMed

Hutton, Lisa C; Ratnayake, Udani; Shields, Amy; Walker, David W

2009-01-01

Birth asphyxia can result in sensory impairment, learning and memory deficits without gross brain injury and severe motor deficits. We developed a model of birth asphyxia resulting in mild neurological injury and cognitive impairment using a long-gestation species with precocial fetal development. Spiny mice (Acomys cahirinus) underwent caesarean-section delivery or 7.5 min of asphyxia at 37 days gestational age (term is 39 days). Brain histology was examined at 1 and 7 days of age, and behaviour was evaluated to 28 days of age. Asphyxiated offspring showed significant impairment in non-spatial memory and learning tasks, accompanied by central nervous system inflammation and increased apoptotic cell death but without the presence of large necrotic or cystic lesions. Copyright 2009 S. Karger AG, Basel.

Micromirror structured illumination microscope for high-speed in vivo drosophila brain imaging.

PubMed

Masson, A; Pedrazzani, M; Benrezzak, S; Tchenio, P; Preat, T; Nutarelli, D

2014-01-27

Genetic tools and especially genetically encoded fluorescent reporters have given a special place to optical microscopy in drosophila neurobiology research. In order to monitor neural networks activity, high speed and sensitive techniques, with high spatial resolution are required. Structured illumination microscopies are wide-field approaches with optical sectioning ability. Despite the large progress made with the introduction of the HiLo principle, they did not meet the criteria of speed and/or spatial resolution for drosophila brain imaging. We report on a new implementation that took advantage of micromirror matrix technology to structure the illumination. Thus, we showed that the developed instrument exhibits a spatial resolution close to that of confocal microscopy but it can record physiological responses with a speed improved by more than an order a magnitude.

The cerebral cortex of Albert Einstein: a description and preliminary analysis of unpublished photographs.

PubMed

Falk, Dean; Lepore, Frederick E; Noe, Adrianne

2013-04-01

Upon his death in 1955, Albert Einstein's brain was removed, fixed and photographed from multiple angles. It was then sectioned into 240 blocks, and histological slides were prepared. At the time, a roadmap was drawn that illustrates the location within the brain of each block and its associated slides. Here we describe the external gross neuroanatomy of Einstein's entire cerebral cortex from 14 recently discovered photographs, most of which were taken from unconventional angles. Two of the photographs reveal sulcal patterns of the medial surfaces of the hemispheres, and another shows the neuroanatomy of the right (exposed) insula. Most of Einstein's sulci are identified, and sulcal patterns in various parts of the brain are compared with those of 85 human brains that have been described in the literature. To the extent currently possible, unusual features of Einstein's brain are tentatively interpreted in light of what is known about the evolution of higher cognitive processes in humans. As an aid to future investigators, these (and other) features are correlated with blocks on the roadmap (and therefore histological slides). Einstein's brain has an extraordinary prefrontal cortex, which may have contributed to the neurological substrates for some of his remarkable cognitive abilities. The primary somatosensory and motor cortices near the regions that typically represent face and tongue are greatly expanded in the left hemisphere. Einstein's parietal lobes are also unusual and may have provided some of the neurological underpinnings for his visuospatial and mathematical skills, as others have hypothesized. Einstein's brain has typical frontal and occipital shape asymmetries (petalias) and grossly asymmetrical inferior and superior parietal lobules. Contrary to the literature, Einstein's brain is not spherical, does not lack parietal opercula and has non-confluent Sylvian and inferior postcentral sulci.

The cerebral cortex of Albert Einstein: a description and preliminary analysis of unpublished photographs

PubMed Central

Lepore, Frederick E.; Noe, Adrianne

2013-01-01

Upon his death in 1955, Albert Einstein’s brain was removed, fixed and photographed from multiple angles. It was then sectioned into 240 blocks, and histological slides were prepared. At the time, a roadmap was drawn that illustrates the location within the brain of each block and its associated slides. Here we describe the external gross neuroanatomy of Einstein’s entire cerebral cortex from 14 recently discovered photographs, most of which were taken from unconventional angles. Two of the photographs reveal sulcal patterns of the medial surfaces of the hemispheres, and another shows the neuroanatomy of the right (exposed) insula. Most of Einstein’s sulci are identified, and sulcal patterns in various parts of the brain are compared with those of 85 human brains that have been described in the literature. To the extent currently possible, unusual features of Einstein’s brain are tentatively interpreted in light of what is known about the evolution of higher cognitive processes in humans. As an aid to future investigators, these (and other) features are correlated with blocks on the roadmap (and therefore histological slides). Einstein’s brain has an extraordinary prefrontal cortex, which may have contributed to the neurological substrates for some of his remarkable cognitive abilities. The primary somatosensory and motor cortices near the regions that typically represent face and tongue are greatly expanded in the left hemisphere. Einstein’s parietal lobes are also unusual and may have provided some of the neurological underpinnings for his visuospatial and mathematical skills, as others have hypothesized. Einstein’s brain has typical frontal and occipital shape asymmetries (petalias) and grossly asymmetrical inferior and superior parietal lobules. Contrary to the literature, Einstein’s brain is not spherical, does not lack parietal opercula and has non-confluent Sylvian and inferior postcentral sulci. PMID:23161163

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings.

PubMed

Bralten, Janita; Greven, Corina U; Franke, Barbara; Mennes, Maarten; Zwiers, Marcel P; Rommelse, Nanda N J; Hartman, Catharina; van der Meer, Dennis; O'Dwyer, Laurence; Oosterlaan, Jaap; Hoekstra, Pieter J; Heslenfeld, Dirk; Arias-Vasquez, Alejandro; Buitelaar, Jan K

2016-06-01

Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. We performed voxel-based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8-30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research.

Anomalous single-subject based morphological cortical networks in drug-naive, first-episode major depressive disorder.

PubMed

Chen, Taolin; Kendrick, Keith M; Wang, Jinhui; Wu, Min; Li, Kaiming; Huang, Xiaoqi; Luo, Yuejia; Lui, Su; Sweeney, John A; Gong, Qiyong

2017-05-01

Major depressive disorder (MDD) has been associated with disruptions in the topological organization of brain morphological networks in group-level data. Such disruptions have not yet been identified in single-patients, which is needed to show relations with symptom severity and to evaluate their potential as biomarkers for illness. To address this issue, we conducted a cross-sectional structural brain network study of 33 treatment-naive, first-episode MDD patients and 33 age-, gender-, and education-matched healthy controls (HCs). Weighted graph-theory based network models were used to characterize the topological organization of brain networks between the two groups. Compared with HCs, MDD patients exhibited lower normalized global efficiency and higher modularity in their whole-brain morphological networks, suggesting impaired integration and increased segregation of morphological brain networks in the patients. Locally, MDD patients exhibited lower efficiency in anatomic organization for transferring information predominantly in default-mode regions including the hippocampus, parahippocampal gyrus, precuneus and superior parietal lobule, and higher efficiency in the insula, calcarine and posterior cingulate cortex, and in the cerebellum. Morphological connectivity comparisons revealed two subnetworks that exhibited higher connectivity strength in MDD mainly involving neocortex-striatum-thalamus-cerebellum and thalamo-hippocampal circuitry. MDD-related alterations correlated with symptom severity and differentiated individuals with MDD from HCs with a sensitivity of 87.9% and specificity of 81.8%. Our findings indicate that single subject grey matter morphological networks are often disrupted in clinically relevant ways in treatment-naive, first episode MDD patients. Circuit-specific changes in brain anatomic network organization suggest alterations in the efficiency of information transfer within particular brain networks in MDD. Hum Brain Mapp 38:2482-2494, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings

PubMed Central

Bralten, Janita; Greven, Corina U.; Franke, Barbara; Mennes, Maarten; Zwiers, Marcel P.; Rommelse, Nanda N.J.; Hartman, Catharina; van der Meer, Dennis; O’Dwyer, Laurence; Oosterlaan, Jaap; Hoekstra, Pieter J.; Heslenfeld, Dirk; Arias-Vasquez, Alejandro; Buitelaar, Jan K.

2016-01-01

Background Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. Methods We performed voxel-based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Results Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8–30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Limitations Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Conclusion Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research. PMID:26679925

Different partial volume correction methods lead to different conclusions: An (18)F-FDG-PET study of aging.

PubMed

Greve, Douglas N; Salat, David H; Bowen, Spencer L; Izquierdo-Garcia, David; Schultz, Aaron P; Catana, Ciprian; Becker, J Alex; Svarer, Claus; Knudsen, Gitte M; Sperling, Reisa A; Johnson, Keith A

2016-05-15

A cross-sectional group study of the effects of aging on brain metabolism as measured with (18)F-FDG-PET was performed using several different partial volume correction (PVC) methods: no correction (NoPVC), Meltzer (MZ), Müller-Gärtner (MG), and the symmetric geometric transfer matrix (SGTM) using 99 subjects aged 65-87years from the Harvard Aging Brain study. Sensitivity to parameter selection was tested for MZ and MG. The various methods and parameter settings resulted in an extremely wide range of conclusions as to the effects of age on metabolism, from almost no changes to virtually all of cortical regions showing a decrease with age. Simulations showed that NoPVC had significant bias that made the age effect on metabolism appear to be much larger and more significant than it is. MZ was found to be the same as NoPVC for liberal brain masks; for conservative brain masks, MZ showed few areas correlated with age. MG and SGTM were found to be similar; however, MG was sensitive to a thresholding parameter that can result in data loss. CSF uptake was surprisingly high at about 15% of that in gray matter. The exclusion of CSF from SGTM and MG models, which is almost universally done, caused a substantial loss in the power to detect age-related changes. This diversity of results reflects the literature on the metabolism of aging and suggests that extreme care should be taken when applying PVC or interpreting results that have been corrected for partial volume effects. Using the SGTM, significant age-related changes of about 7% per decade were found in frontal and cingulate cortices as well as primary visual and insular cortices. Copyright © 2016 Elsevier Inc. All rights reserved.

Different Partial Volume Correction Methods Lead to Different Conclusions: an 18F-FDG PET Study of Aging

PubMed Central

Greve, Douglas N.; Salat, David H.; Bowen, Spencer L.; Izquierdo-Garcia, David; Schultz, Aaron P.; Catana, Ciprian; Becker, J. Alex; Svarer, Claus; Knudsen, Gitte; Sperling, Reisa A.; Johnson, Keith A.

2016-01-01

A cross-sectional group study of the effects of aging on brain metabolism as measured with 18F-FDG PET was performed using several different partial volume correction (PVC) methods: no correction (NoPVC), Meltzer (MZ), Müller-Gärtner (MG), and the symmetric geometric transfer matrix (SGTM) using 99 subjects aged 65-87 from the Harvard Aging Brain study. Sensitivity to parameter selection was tested for MZ and MG. The various methods and parameter settings resulted in an extremely wide range of conclusions as to the effects of age on metabolism, from almost no changes to virtually all of cortical regions showing a decrease with age. Simulations showed that NoPVC had significant bias that made the age effect on metabolism appear to be much larger and more significant than it is. MZ was found to be the same as NoPVC for liberal brain masks; for conservative brain masks, MZ showed few areas correlated with age. MG and SGTM were found to be similar; however, MG was sensitive to a thresholding parameter that can result in data loss. CSF uptake was surprisingly high at about 15% of that in gray matter. Exclusion of CSF from SGTM and MG models, which is almost universally done, caused a substantial loss in the power to detect age-related changes. This diversity of results reflects the literature on the metabolism of aging and suggests that extreme care should be taken when applying PVC or interpreting results that have been corrected for partial volume effects. Using the SGTM, significant age-related changes of about 7% per decade were found in frontal and cingulate cortices as well as primary visual and insular cortices. PMID:26915497

Cognition and brain development in children with benign epilepsy with centrotemporal spikes.

PubMed

Garcia-Ramos, Camille; Jackson, Daren C; Lin, Jack J; Dabbs, Kevin; Jones, Jana E; Hsu, David A; Stafstrom, Carl E; Zawadzki, Lucy; Seidenberg, Michael; Prabhakaran, Vivek; Hermann, Bruce P

2015-10-01

Benign epilepsy with centrotemporal spikes (BECTS), the most common focal childhood epilepsy, is associated with subtle abnormalities in cognition and possible developmental alterations in brain structure when compared to healthy participants, as indicated by previous cross-sectional studies. To examine the natural history of BECTS, we investigated cognition, cortical thickness, and subcortical volumes in children with new/recent onset BECTS and healthy controls (HC). Participants were 8-15 years of age, including 24 children with new-onset BECTS and 41 age- and gender-matched HC. At baseline and 2 years later, all participants completed a cognitive assessment, and a subset (13 BECTS, 24 HC) underwent T1 volumetric magnetic resonance imaging (MRI) scans focusing on cortical thickness and subcortical volumes. Baseline cognitive abnormalities associated with BECTS (object naming, verbal learning, arithmetic computation, and psychomotor speed/dexterity) persisted over 2 years, with the rate of cognitive development paralleling that of HC. Baseline neuroimaging revealed thinner cortex in BECTS compared to controls in frontal, temporal, and occipital regions. Longitudinally, HC showed widespread cortical thinning in both hemispheres, whereas BECTS participants showed sparse regions of both cortical thinning and thickening. Analyses of subcortical volumes showed larger left and right putamens persisting over 2 years in BECTS compared to HC. Cognitive and structural brain abnormalities associated with BECTS are present at onset and persist (cognition) and/or evolve (brain structure) over time. Atypical maturation of cortical thickness antecedent to BECTS onset results in early identified abnormalities that continue to develop abnormally over time. However, compared to anatomic development, cognition appears more resistant to further change over time. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Penetration of immunoreagents in Vibratome-sectioned brain: a light and electron microscopic study.

PubMed

Piekut, D T; Casey, S M

1983-05-01

Immunocytochemical studies on the localization of peptides at the ultrastructural level have most frequently involved the application of the peroxidase--antiperoxidase (PAP) method of immunocytochemistry and the use of the preembedding or postembedding staining procedures. The present study was designed to determine the depth of penetration of Vibratome tissue sections by immunoreagents used in the preembedding method in which immunostaining of unembedded fixed tissue sections is accomplished prior to tissue dehydration and embedment. Our data indicate that penetration of immunoreagents is restricted to the superficial 8-9 micrometers of a 80-micrometers thick Vibratome tissue section of hypothalamus of brain using antisera generated against arginine vasopressin. The final immunoreaction product visualized in a Vibratome tissue section may reflect only a fraction of the amount of hormone contained within the thickness of the tissue section.

Effects of an imprinting procedure on cell proliferation in the chick brain.

PubMed

Komissarova, N V; Anokhin, K V

2008-03-01

We report here studies on the effects of an imprinting procedure on cell proliferation in neonatal chicks in brain structures known to undergo plastic changes in imprinting. Proliferating cells were detected immunohistochemically on brain sections by incorporation of pre-training doses of 5-bromodeoxyuridine (BrdU) into DNA; numbers of new cells were counted in the intermediate medial mesopallium, the intermediate arcopallium, the medial part of the mesopallium and the nidopallium, the dorsocaudal nidopallium, the hippocampus, and the parahippocampal region 24 h and seven days after training. The intermediate medial mesopallium showed an increase in the number of BrdU-positive cells 24 h after training. However, at seven days post-training, the number of BrdU-containing cells decreased in the medial nidopallium and mesopallium, in the dorsocaudal nidopallium, and the right intermediate medial mesopallium. Thus, the imprinting procedure had differently directed transient and long-term influences on the genesis of new cells in the chick brain, inducing the appearance of a large number of cells in the parenchyma of the brain one day after training and decreases in the numbers of cells at later time points. This double effect may be associated with the fact that the imprinting procedure simultaneously initiates two brain processes involving the control of cell proliferation - one related to maturation of a species-specific functional system for tracking individuals of the same species and one related to remembering the characteristics of the actual parent.

RB4CD12 epitope expression and heparan sulfate disaccharide composition in brain vasculature.

PubMed

Hosono-Fukao, Tomomi; Ohtake-Niimi, Shiori; Nishitsuji, Kazuchika; Hossain, Md Motarab; van Kuppevelt, Toin H; Michikawa, Makoto; Uchimura, Kenji

2011-11-01

RB4CD12 is a phage display antibody that recognizes a heparan sulfate (HS) glycosaminoglycan epitope. The epitope structure is proposed to contain a trisulfated disaccharide, [-IdoA(2-OSO(3))-GlcNSO(3) (6-OSO(3))-], which supports HS binding to various macromolecules such as growth factors and cytokines in central nervous tissues. Chemically modified heparins that lack the trisulfated disaccharides failed to inhibit the RB4CD12 recognition of HS chains. To determine the localization of the RB4CD12 anti-HS epitope in the brain, we performed an immunohistochemical analysis for cryocut sections of mouse brain. The RB4CD12 staining signals were colocalized with laminin and were detected abundantly in the vascular basement membrane. Bacterial heparinases eliminated the RB4CD12 staining signals. The RB4CD12 epitope localization was confirmed by immunoelectron microscopy. Western blotting analysis revealed that the size of a major RB4CD12-positive molecule is ∼460 kDa in a vessel-enriched fraction of the mouse brain. Disaccharide analysis with reversed-phase ion-pair HPLC showed that [-IdoA(2-OSO(3))-GlcNSO(3) (6-OSO(3))-] trisulfated disaccharide residues are present in HS purified from the vessel-enriched brain fraction. These results indicated that the RB4CD12 anti-HS epitope exists in large quantities in the brain vascular basement membrane. Copyright © 2011 Wiley-Liss, Inc.

Custom fit 3D-printed brain holders for comparison of histology with MRI in marmosets.

PubMed

Guy, Joseph R; Sati, Pascal; Leibovitch, Emily; Jacobson, Steven; Silva, Afonso C; Reich, Daniel S

2016-01-15

MRI has the advantage of sampling large areas of tissue and locating areas of interest in 3D space in both living and ex vivo systems, whereas histology has the ability to examine thin slices of ex vivo tissue with high detail and specificity. Although both are valuable tools, it is currently difficult to make high-precision comparisons between MRI and histology due to large differences inherent to the techniques. A method combining the advantages would be an asset to understanding the pathological correlates of MRI. 3D-printed brain holders were used to maintain marmoset brains in the same orientation during acquisition of ex vivo MRI and pathologic cutting of the tissue. The results of maintaining this same orientation show that sub-millimeter, discrete neuropathological features in marmoset brain consistently share size, shape, and location between histology and ex vivo MRI, which facilitates comparison with serial imaging acquired in vivo. Existing methods use computational approaches sensitive to data input in order to warp histologic images to match large-scale features on MRI, but the new method requires no warping of images, due to a preregistration accomplished in the technique, and is insensitive to data formatting and artifacts in both MRI and histology. The simple method of using 3D-printed brain holders to match brain orientation during pathologic sectioning and MRI acquisition enables rapid and precise comparison of small features seen on MRI to their underlying histology. Published by Elsevier B.V.

Interaction between LSD and dopamine D2/3 binding sites in pig brain.

PubMed

Minuzzi, Luciano; Nomikos, George G; Wade, Mark R; Jensen, Svend B; Olsen, Aage K; Cumming, Paul

2005-06-15

The psychoactive properties of the hallucinogen LSD have frequently been attributed to high affinity interactions with serotonin 5HT2 receptors in brain. Possible effects of LSD on dopamine D2/3 receptor availability have not previously been investigated in living brain. Therefore, we used PET to map the binding potential (pB) of [11C]raclopride in brain of three pigs, first in a baseline condition, and again at 1 and 4 h after administration of LSD (2.5 microg/kg, i.v.). There was a progressive treatment effect in striatum, where the pB was significantly reduced by 19% at 4 h after LSD administration. Concomitant maps of cerebral blood flow did not reveal significant changes in perfusion during this interval. Subsequent in vitro studies showed that LSD displaced [3H]raclopride (2 nM) from pig brain cryostat sections with an IC50 of 275 nM according to a one-site model. Fitting of a two-site model to the data suggested the presence of a component of the displacement curves with a subnanomolar IC50, comprising 20% of the total [3H]raclopride binding. In microdialysis experiments, LSD at similar and higher doses did not evoke changes in the interstitial concentration of dopamine or its acidic metabolites in rat striatum. Together, these results are consistent with a direct interaction between LSD and a portion of dopamine D2/3 receptors in pig brain, possibly contributing to the psychopharmacology of LSD. (c) 2005 Wiley-Liss, Inc.

Brain anatomy in Diplura (Hexapoda)

PubMed Central

2012-01-01

Background In the past decade neuroanatomy has proved to be a valuable source of character systems that provide insights into arthropod relationships. Since the most detailed description of dipluran brain anatomy dates back to Hanström (1940) we re-investigated the brains of Campodea augens and Catajapyx aquilonaris with modern neuroanatomical techniques. The analyses are based on antibody staining and 3D reconstruction of the major neuropils and tracts from semi-thin section series. Results Remarkable features of the investigated dipluran brains are a large central body, which is organized in nine columns and three layers, and well developed mushroom bodies with calyces receiving input from spheroidal olfactory glomeruli in the deutocerebrum. Antibody staining against a catalytic subunit of protein kinase A (DC0) was used to further characterize the mushroom bodies. The japygid Catajapyx aquilonaris possesses mushroom bodies which are connected across the midline, a unique condition within hexapods. Conclusions Mushroom body and central body structure shows a high correspondence between japygids and campodeids. Some unique features indicate that neuroanatomy further supports the monophyly of Diplura. In a broader phylogenetic context, however, the polarization of brain characters becomes ambiguous. The mushroom bodies and the central body of Diplura in several aspects resemble those of Dicondylia, suggesting homology. In contrast, Archaeognatha completely lack mushroom bodies and exhibit a central body organization reminiscent of certain malacostracan crustaceans. Several hypotheses of brain evolution at the base of the hexapod tree are discussed. PMID:23050723

Brain glutathione reductase induction increases early survival and decreases lipofuscin accumulation in aging frogs.

PubMed

López-Torres, M; Pérez-Campo, R; Fernandez, A; Barba, C; Barja de Quiroga, G

1993-02-01

Brain catalase was continuously depleted throughout the life span starting with a large population of initially young and old frogs. Free radical-related parameters were measured in the brain tissue once per year after 2.5, 14.5, and 26.5 months of experimentation. Brain lipofuscin accumulation was observed after 14.5 and 26.5 months, and survival was continuously followed during 33 months. The age of the animal did not decrease endogenous antioxidants nor increase tissue peroxidation either in cross-sectional or longitudinal comparisons. Continuous catalase depletion similarly affected young and old animals, inducing glutathione reductase, tending to decrease oxidized glutathione/reduced glutathione (GSSG/GSH) ratio, decreasing lipofuscin accumulation in the brain, and increasing survival from 46% to 91% after 14.5 months. At 26.5 months of experimentation the loss of the glutathione reductase induction in catalase-depleted animals was accompanied by the presence of higher lipofuscin deposits than in controls and was followed by a great increase in mortality rate. Even though the maximal life span (7 years) was the same in the control and treated animals which were already old (4.2 years) at the beginning of the experiment, the treated animals showed a strong reduction in the rates of early death. It is proposed that the maintenance of a high antioxidant/prooxidant balance in the vertebrate brain greatly increases the probability of the individual to reach the final segments of its species-specific life span.

MALDI imaging mass spectrometry analysis-A new approach for protein mapping in multiple sclerosis brain lesions.

PubMed

Maccarrone, Giuseppina; Nischwitz, Sandra; Deininger, Sören-Oliver; Hornung, Joachim; König, Fatima Barbara; Stadelmann, Christine; Turck, Christoph W; Weber, Frank

2017-03-15

Multiple sclerosis is a disease of the central nervous system characterized by recurrent inflammatory demyelinating lesions in the early disease stage. Lesion formation and mechanisms leading to lesion remyelination are not fully understood. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-IMS) is a technology which analyses proteins and peptides in tissue, preserves their spatial localization, and generates molecular maps within the tissue section. In a pilot study we employed MALDI imaging mass spectrometry to profile and identify peptides and proteins expressed in normal-appearing white matter, grey matter and multiple sclerosis brain lesions with different extents of remyelination. The unsupervised clustering analysis of the mass spectra generated images which reflected the tissue section morphology in luxol fast blue stain and in myelin basic protein immunohistochemistry. Lesions with low remyelination extent were defined by compounds with molecular weight smaller than 5300Da, while more completely remyelinated lesions showed compounds with molecular weights greater than 15,200Da. An in-depth analysis of the mass spectra enabled the detection of cortical lesions which were not seen by routine luxol fast blue histology. An ion mass, mainly distributed at the rim of multiple sclerosis lesions, was identified by liquid chromatography and tandem mass spectrometry as thymosin beta-4, a protein known to be involved in cell migration and in restorative processes. The ion mass of thymosin beta-4 was profiled by MALDI imaging mass spectrometry in brain slides of 12 multiple sclerosis patients and validated by immunohistochemical analysis. In summary, our results demonstrate the ability of the MALDI-IMS technology to map proteins within the brain parenchyma and multiple sclerosis lesions and to identify potential markers involved in multiple sclerosis pathogenesis and/or remyelination. Copyright © 2016 Elsevier B.V. All rights reserved.

[Regularities of fixation of brain serum antibodies from patients with lateral amyotrophic sclerosis in rabbit CNS].

PubMed

Musaeva, L S; Gannyshkina, I V; Zavalishin, I A; Markova, E D; Ivanova-Smolenskaia, I A

2002-01-01

Kuhns' indirect immunofluorescent test was used to study fixation of serum brain antibodies (Ab) of patients with bulbar, cervicothoracic, lumbosacral lateral amyotropic sclerosis (LAS) on brain sections of rabbits. The disease is characterized by formation of brain Ab complementary to various structures of nervous and glial cells, myelin of fibers from different conducting systems, vessels which exhibit both common and individual antigenic properties. It was found that fixation of antineuronal, antimyelin brain Ab of patients with bulbar, cervicothoracic and lumbosacral LAS in different CNS structures varies.

Automated brain volumetrics in multiple sclerosis: a step closer to clinical application.

PubMed

Wang, C; Beadnall, H N; Hatton, S N; Bader, G; Tomic, D; Silva, D G; Barnett, M H

2016-07-01

Whole brain volume (WBV) estimates in patients with multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. Numerous algorithms to measure WBV have been developed over the past two decades. We compare Structural Image Evaluation using Normalisation of Atrophy-Cross-sectional (SIENAX) to NeuroQuant and MSmetrix, for assessment of cross-sectional WBV in patients with MS. MRIs from 61 patients with relapsing-remitting MS and 2 patients with clinically isolated syndrome were analysed. WBV measurements were calculated using SIENAX, NeuroQuant and MSmetrix. Statistical agreement between the methods was evaluated using linear regression and Bland-Altman plots. Precision and accuracy of WBV measurement was calculated for (1) NeuroQuant versus SIENAX and (2) MSmetrix versus SIENAX. Precision (Pearson's r) of WBV estimation for NeuroQuant and MSmetrix versus SIENAX was 0.983 and 0.992, respectively. Accuracy (Cb) was 0.871 and 0.994, respectively. NeuroQuant and MSmetrix showed a 5.5% and 1.0% volume difference compared with SIENAX, respectively, that was consistent across low and high values. In the analysed population, NeuroQuant and MSmetrix both quantified cross-sectional WBV with comparable statistical agreement to SIENAX, a well-validated cross-sectional tool that has been used extensively in MS clinical studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The PRP Effect Following Callosotomy: Residual Interference Despite Uncoupling of Lateralized Response Codes

NASA Technical Reports Server (NTRS)

Ivry, Richard B.; Franz, Elizabeth A.; Kingstone, Alan; Johnston, James C.; Null, Cynthia H. (Technical Monitor)

1995-01-01

A callosotomy patient was tested in two dual-task experiments requiring successive speeded responses to lateralized stimuli. In accord with the recent findings of Pashler, O'Brien, Luck, Hillyard, Mangun, and Gazzaniga (in press), the patient showed a robust psychological refractory period effect (PRP) responses on Task 2 were inversely related to the stimulus-onset asynchrony (SOA). However, three aspects of our data indicated that the processing limitations for the patient were different than those observed with control subjects. First, the split-brain patient did not show an increase in reaction time when the two tasks required responses from a common output system (i.e., both manual responses) in comparison to when different output systems were used (i.e., manual-vocal). Second, inconsistent stimulus-response mappings for the two tasks greatly inflated response latencies for the control subjects, but had minimal effect on the performance of the split-brain patient. Third, the consistency manipulation was underadditive with SOA for only the patient, suggesting a later bottleneck in processing following callosotomy than was observed for the control subjects. It is proposed that sectioning the corpus callosum eliminates interference resulting from competing stimulus response codes. Nonetheless, dual-task interference persists for the split-brain subject because a subcortical gate constrains when selected responses can be implemented.

Cocaine, Appetitive Memory and Neural Connectivity

PubMed Central

Ray, Suchismita

2013-01-01

This review examines existing cognitive experimental and brain imaging research related to cocaine addiction. In section 1, previous studies that have examined cognitive processes, such as implicit and explicit memory processes in cocaine users are reported. Next, in section 2, brain imaging studies are reported that have used chronic users of cocaine as study participants. In section 3, several conclusions are drawn. They are: (a) in cognitive experimental literature, no study has examined both implicit and explicit memory processes involving cocaine related visual information in the same cocaine user, (b) neural mechanisms underlying implicit and explicit memory processes for cocaine-related visual cues have not been directly investigated in cocaine users in the imaging literature, and (c) none of the previous imaging studies has examined connectivity between the memory system and craving system in the brain of chronic users of cocaine. Finally, future directions in the field of cocaine addiction are suggested. PMID:25009766

Extraction efficiency and implications for absolute quantitation of propranolol in mouse brain, liver and kidney thin tissue sections using droplet-based liquid microjunction surface sampling-HPLC ESI-MS/MS

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

Kertesz, Vilmos; Weiskittel, Taylor M.; Vavek, Marissa

Currently, absolute quantitation aspects of droplet-based surface sampling for thin tissue analysis using a fully automated autosampler/HPLC-ESI-MS/MS system are not fully evaluated. Knowledge of extraction efficiency and its reproducibility is required to judge the potential of the method for absolute quantitation of analytes from thin tissue sections. Methods: Adjacent thin tissue sections of propranolol dosed mouse brain (10- μm-thick), kidney (10- μm-thick) and liver (8-, 10-, 16- and 24- μm-thick) were obtained. Absolute concentration of propranolol was determined in tissue punches from serial sections using standard bulk tissue extraction protocols and subsequent HPLC separations and tandem mass spectrometric analysis. Thesemore » values were used to determine propranolol extraction efficiency from the tissues with the droplet-based surface sampling approach. Results: Extraction efficiency of propranolol using 10- μm-thick brain, kidney and liver thin tissues using droplet-based surface sampling varied between ~45-63%. Extraction efficiency decreased from ~65% to ~36% with liver thickness increasing from 8 μm to 24 μm. Randomly selecting half of the samples as standards, precision and accuracy of propranolol concentrations obtained for the other half of samples as quality control metrics were determined. Resulting precision ( ±15%) and accuracy ( ±3%) values, respectively, were within acceptable limits. In conclusion, comparative quantitation of adjacent mouse thin tissue sections of different organs and of various thicknesses by droplet-based surface sampling and by bulk extraction of tissue punches showed that extraction efficiency was incomplete using the former method, and that it depended on the organ and tissue thickness. However, once extraction efficiency was determined and applied, the droplet-based approach provided the required quantitation accuracy and precision for assay validations. Furthermore, this means that once the extraction efficiency was calibrated for a given tissue type and drug, the droplet-based approach provides a non-labor intensive and high-throughput means to acquire spatially resolved quantitative analysis of multiple samples of the same type.« less

Extraction efficiency and implications for absolute quantitation of propranolol in mouse brain, liver and kidney thin tissue sections using droplet-based liquid microjunction surface sampling-HPLC ESI-MS/MS

DOE PAGES

Kertesz, Vilmos; Weiskittel, Taylor M.; Vavek, Marissa; ...

2016-06-22

Currently, absolute quantitation aspects of droplet-based surface sampling for thin tissue analysis using a fully automated autosampler/HPLC-ESI-MS/MS system are not fully evaluated. Knowledge of extraction efficiency and its reproducibility is required to judge the potential of the method for absolute quantitation of analytes from thin tissue sections. Methods: Adjacent thin tissue sections of propranolol dosed mouse brain (10- μm-thick), kidney (10- μm-thick) and liver (8-, 10-, 16- and 24- μm-thick) were obtained. Absolute concentration of propranolol was determined in tissue punches from serial sections using standard bulk tissue extraction protocols and subsequent HPLC separations and tandem mass spectrometric analysis. Thesemore » values were used to determine propranolol extraction efficiency from the tissues with the droplet-based surface sampling approach. Results: Extraction efficiency of propranolol using 10- μm-thick brain, kidney and liver thin tissues using droplet-based surface sampling varied between ~45-63%. Extraction efficiency decreased from ~65% to ~36% with liver thickness increasing from 8 μm to 24 μm. Randomly selecting half of the samples as standards, precision and accuracy of propranolol concentrations obtained for the other half of samples as quality control metrics were determined. Resulting precision ( ±15%) and accuracy ( ±3%) values, respectively, were within acceptable limits. In conclusion, comparative quantitation of adjacent mouse thin tissue sections of different organs and of various thicknesses by droplet-based surface sampling and by bulk extraction of tissue punches showed that extraction efficiency was incomplete using the former method, and that it depended on the organ and tissue thickness. However, once extraction efficiency was determined and applied, the droplet-based approach provided the required quantitation accuracy and precision for assay validations. Furthermore, this means that once the extraction efficiency was calibrated for a given tissue type and drug, the droplet-based approach provides a non-labor intensive and high-throughput means to acquire spatially resolved quantitative analysis of multiple samples of the same type.« less

Structural, Functional, and Metabolic Brain Markers Differentiate Collision versus Contact and Non-Contact Athletes

PubMed Central

Churchill, Nathan W.; Hutchison, Michael G.; Di Battista, Alex P.; Graham, Simon J.; Schweizer, Tom A.

2017-01-01

There is growing concern about how participation in contact sports affects the brain. Retrospective evidence suggests that contact sports are associated with long-term negative health outcomes. However, much of the research to date has focused on former athletes with significant health problems. Less is known about the health of current athletes in contact and collision sports who have not reported significant medical issues. In this cross-sectional study, advanced magnetic resonance imaging (MRI) was used to evaluate multiple aspects of brain physiology in three groups of athletes participating in non-contact sports (N = 20), contact sports (N = 22), and collision sports (N = 23). Diffusion tensor imaging was used to assess white matter microstructure based on measures of fractional anisotropy (FA) and mean diffusivity (MD); resting-state functional MRI was used to evaluate global functional connectivity; single-voxel spectroscopy was used to compare ratios of neural metabolites, including N-acetyl aspartate (NAA), creatine (Cr), choline, and myo-inositol. Multivariate analysis revealed structural, functional, and metabolic measures that reliably differentiated between sport groups. The collision group had significantly elevated FA and reduced MD in white matter, compared to both contact and non-contact groups. In contrast, the collision group showed significant reductions in functional connectivity and the NAA/Cr metabolite ratio, relative to only the non-contact group, while the contact group overlapped with both non-contact and collision groups. For brain regions associated with contact sport participation, athletes with a history of concussion also showed greater alterations in FA and functional connectivity, indicating a potential cumulative effect of both contact exposure and concussion history on brain physiology. These findings indicate persistent differences in brain physiology for athletes participating in contact and collision sports, which should be considered in future studies of concussion and subconcussive impacts. PMID:28878729

Employment status and termination among survivors of pediatric brain tumors: a cross-sectional survey.

PubMed

Sato, Iori; Higuchi, Akiko; Yanagisawa, Takaaki; Murayama, Shiho; Kumabe, Toshihiro; Sugiyama, Kazuhiko; Mukasa, Akitake; Saito, Nobuhito; Sawamura, Yutaka; Terasaki, Mizuhiko; Shibui, Soichiro; Takahashi, Jun; Nishikawa, Ryo; Ishida, Yasushi; Kamibeppu, Kiyoko

2018-04-30

Some childhood cancer survivors experience employment difficulties. This study aimed to describe pediatric brain-tumor survivors' employment status. A cross-sectional, observational study was conducted, with questionnaires distributed to 101 pediatric brain-tumor survivors (aged 15 years or older) and their attending physicians from nine institutions in Japan. We compared category and time-series histories for participants' first-time employment using national census information. Factors related to delayed employment or early employment termination were examined using survival-time analyses. Excluding students and homemakers, 38 brain-tumor survivors (median age 27 years, with 15 years since diagnosis) were of working age. Of these, 12 (32%) were unemployed and 9 (24%) had never been employed. First-time employment occurred later for brain-tumor survivors than the general population, particularly in those with lower educational levels. The number of brain-tumor survivors whose first job was terminated within the first year was higher than that for the general population, particularly in male survivors and germ cell-tumor survivors. Brain-tumor survivors described their working patterns (irregular), job types (specialist or professional), reasons for early termination (unsuitable job), and thoughts about working (they wished to serve their communities but lacked confidence). Brain-tumor survivors are associated with high unemployment rates and multiple unemployment-related factors. Education and welfare systems should identify individual methods of social participation for this group.

A novel application of the fluorescent dye bis-ANS for labeling neurons in acute brain slices.

PubMed

Mozes, Emese; Hunya, Akos; Toth, Aniko; Ayaydin, Ferhan; Penke, Botond; Datki, Zsolt L

2011-10-10

The cell-impermeant oligomer-(e.g. beta-amyloid-, or tubulin-) specific fluorescent dye, bis-ANS (4,4'-bis-1-anilinonaphtalene-8-sulfonate), was successfully used for labeling mechanically damaged but still viable neuron bodies, neurites and neurite cross sections in acute brain slices. Acute hippocampal brain slices of rats were co-stained with bis-ANS and the cell-impermeant, DNA-specific dye propidium iodide (PI) and were then analyzed using fluorescence and confocal microscopes. Both the neuron bodies and the neurites were found to exhibit increased fluorescence intensities, suggesting that using this method they can be detected more easily. In addition, bis-ANS showed good region - but not cell specific co-localization with the neuron-specific fluorescent dye Dil (1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate). These two dyes label different neuronal structures: Dil binds specifically to intact cell membranes while bis-ANS can enter cells with compromised cell membranes and then stain the microtubules in the cytoplasm. For a quick (10min) staining of acute brain slices with bis-ANS both HEPES and NaHCO(3) were needed in order to achieve high signal intensity. Labeling with bis-ANS fluorescent dye is an easy method for imaging the neuronal structures on the surface of acute brain slices. Copyright © 2011 Elsevier Inc. All rights reserved.

[An automatic system for anatomophysiological correlation in three planes simultaneously during functional neurosurgery].

PubMed

Teijeiro, E J; Macías, R J; Morales, J M; Guerra, E; López, G; Alvarez, L M; Fernández, F; Maragoto, C; Seijo, F; Alvarez, E

The Neurosurgical Deep Recording System (NDRS) using a personal computer takes the place of complex electronic equipment for recording and processing deep cerebral electrical activity, as a guide in stereotaxic functional neurosurgery. It also permits increased possibilities of presenting information in direct graphic form with automatic management and sufficient flexibility to implement different analyses. This paper describes the possibilities of automatic simultaneous graphic representation in three almost orthogonal planes, available with the new 5.1 version of NDRS so as to facilitate the analysis of anatomophysiological correlation in the localization of deep structures of the brain during minimal access surgery. This new version can automatically show the spatial behaviour of signals registered throughout the path of the electrode inside the brain, superimposed simultaneously on sagittal, coronal and axial sections of an anatomical atlas of the brain, after adjusting the scale automatically according to the dimensions of the brain of each individual patient. This may also be shown in a tridimensional representation of the different planes themselves intercepting. The NDRS system has been successfully used in Spain and Cuba in over 300 functional neurosurgery operations. The new version further facilitates analysis of spatial anatomophysiological correlation for the localization of brain structures. This system has contributed to increase the precision and safety in selecting surgical targets in the control of Parkinson s disease and other disorders of movement.

Cell-penetrating anti-GFAP VHH and corresponding fluorescent fusion protein VHH-GFP spontaneously cross the blood-brain barrier and specifically recognize astrocytes: application to brain imaging.

PubMed

Li, Tengfei; Bourgeois, Jean-Pierre; Celli, Susanna; Glacial, Fabienne; Le Sourd, Anne-Marie; Mecheri, Salah; Weksler, Babette; Romero, Ignacio; Couraud, Pierre-Olivier; Rougeon, François; Lafaye, Pierre

2012-10-01

Antibodies normally do not cross the blood-brain barrier (BBB) and cannot bind an intracellular cerebral antigen. We demonstrate here for the first time that a new class of antibodies can cross the BBB without treatment. Camelids produce native homodimeric heavy-chain antibodies, the paratope being composed of a single-variable domain called VHH. Here, we used recombinant VHH directed against human glial fibrillary acidic protein (GFAP), a specific marker of astrocytes. Only basic VHHs (e.g., pI=9.4) were able to cross the BBB in vitro (7.8 vs. 0% for VHH with pI=7.7). By intracarotid and intravenous injections into live mice, we showed that these basic VHHs are able to cross the BBB in vivo, diffuse into the brain tissue, penetrate into astrocytes, and specifically label GFAP. To analyze their ability to be used as a specific transporter, we then expressed a recombinant fusion protein VHH-green fluorescent protein (GFP). These "fluobodies" specifically labeled GFAP on murine brain sections, and a basic variant (pI=9.3) of the fusion protein VHH-GFP was able to cross the BBB and to label astrocytes in vivo. The potential of VHHs as diagnostic or therapeutic agents in the central nervous system now deserves attention.

[Value of computer tomography in the managment of brain injuries].

PubMed

Keita, A D; Toure, M; Sissako, A; Doumbia, S; Coulibaly, Y; Doumbia, D; Kane, M; Diallo, A K; Toure, A A; Traore, I

2005-11-01

The purpose of this prospective study conducted from January 2001 to December 2001 was to ascertain the value of computer tomography for evaluation of brain injuries. Computer tomography was performed using a Toshiba X VID system with contiguous 5 mm axial sections through the posterior fossa and 10 mm contiguous axial sections through the subtentorial region without contrast injection. A total of 107 patients with brain injuries were enrolled over the one-year study period. These patients accounted for 0.8% of all admissions to surgical emergency unit of Gabriel Toure Hospital in Bamako, Mali. The predominant age group for brain injuries was the 20- to 29-year-old group (35 cases). The male-to-female sex ratio was 5:1. Vehicular accident was the most frequent cause of brain injury (76 cases). Trauma was severe in 48 patients with a Glasgow score less than 8. Coma occurred immediately after injury in 90 cases. Ventricular hemorrhage led to coma in 100% of cases whereas brain hemorrhage and hematoma led to coma in 93.3% and 83.3% of cases respectively. Treatment was medical in 99 cases and neurosurgical in 8. The mortality rate was 34% and the morbidity rate (permanent sequels) was 36%. Computer tomography is a valuable tool for therapeutic decision-making in medico-surgical emergencies involving brain injuries.

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.

Autoradiographic evidence for two classes of mu opioid binding sites in rat brain using (/sup 125/I)FK33824

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

Rothman, R.B.; Jacobson, A.E.; Rice, K.C.

1987-11-01

Previous studies demonstrated that pretreatment of brain membranes with the irreversible mu antagonist, beta-funaltrexamine (beta-FNA), partially eliminated mu binding sites (25,35), consistent with the existence of two mu binding sites distinguished by beta-FNA. This paper tests the hypothesis that the FNA-sensitive and FNA-insensitive mu binding sites have different anatomical distributions in rat brain. Prior to autoradiographic visualization of mu binding sites, (/sup 3/H)oxymorphone, (/sup 3/H)D-ala2-MePhe4, Gly-ol5-enkephalin (DAGO), and (/sup 125/I)D-ala2-Me-Phe4-met(o)-ol)enkephalin (FK33824) were shown to selectively label mu binding sites using slide mounted sections of molded minced rat brain. As found using membranes, beta-FNA eliminated only a portion of mu bindingmore » sites. Autoradiographic visualization of mu binding sites using the mu-selective ligand (/sup 125/I)FK33824 in control and FNA-treated sections of rat brain demonstrated that the proportion of mu binding sites sensitive to beta-FNA varied across regions of the brain, particularly the dorsal thalamus, ventrobasal complex and the hypothalamus, providing anatomical data supporting the existence of two classes of mu binding sites in rat brain.« less

A robust, efficient and flexible method for staining myelinated axons in blocks of brain tissue.

PubMed

Wahlsten, Douglas; Colbourne, Frederick; Pleus, Richard

2003-03-15

Previous studies have demonstrated the utility of the gold chloride method for en bloc staining of a bisected brain in mice and rats. The present study explores several variations in the method, assesses its reliability, and extends the limits of its application. We conclude that the method is very efficient, highly robust, sufficiently accurate for most purposes, and adaptable to many morphometric measures. We obtained acceptable staining of commissures in every brain, despite a wide variety of fixation methods. One-half could be stained 24 h after the brain was extracted and the other half could be stained months later. When staining failed because of an exhausted solution, the brain could be stained successfully in fresh solution. Relatively small changes were found in the sizes of commissures several weeks after initial fixation or staining. A half brain stained to reveal the mid-sagittal section could then be sectioned coronally and stained again in either gold chloride for myelin or cresyl violet for Nissl substance. Uncertainty, arising from pixelation of digitized images was far less than errors arising from human judgments about the histological limits of major commissures. Useful data for morphometric analysis were obtained by scanning the surface of a gold chloride stained block of brain with an inexpensive flatbed scanner.

MRI-Based Measurement of Brain Stem Cross-Sectional Area in Relapsing-Remitting Multiple Sclerosis.

PubMed

Chivers, Tomos R; Constantinescu, Cris S; Tench, Christopher R

2015-01-01

To determine if patients with relapsing-remitting multiple sclerosis (RRMS) have a reduced brain stem cross-sectional area (CSA) compared to age- and sex-matched controls. The brain stem is a common site of involvement in MS. However, relatively few imaging studies have investigated brain stem atrophy. Brain magnetic resonance imaging (MRI) was performed on patients and controls using a 1.5T MRI scanner with a quadrature head coil. Three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) images with 128 contiguous slices, covering the whole brain and brain stem and a T2-weighted image with 3 mm transverse contiguous images were acquired. We measured the brain stem CSA at three sites, the midbrain, the pons, and the medulla oblongata in 35 RRMS patients and 35 controls using a semiautomated algorithm. CSA readings were normalized using the total external cranial volume to reduce normal population variance and increase statistical power. A significant CSA reduction was found in the midbrain (P ≤ .001), pons (P ≤ .001), and the medulla oblongata (P = .047) postnormalization. A CSA reduction of 9.3% was found in the midbrain, 8.7% in the pons, and 6.5% in the medulla oblongata. A significantly reduced, normalized brain stem CSA was detected in all areas of the brain stem of the RRMS patients, when compared to age- and gender-matched controls. Lack of detectable upper cervical cord atrophy in the same patients suggests some independence of the MS pathology in these regions. Copyright © 2015 by the American Society of Neuroimaging.

Mapping Cortical Laminar Structure in the 3D BigBrain.

PubMed

Wagstyl, Konrad; Lepage, Claude; Bludau, Sebastian; Zilles, Karl; Fletcher, Paul C; Amunts, Katrin; Evans, Alan C

2018-07-01

Histological sections offer high spatial resolution to examine laminar architecture of the human cerebral cortex; however, they are restricted by being 2D, hence only regions with sufficiently optimal cutting planes can be analyzed. Conversely, noninvasive neuroimaging approaches are whole brain but have relatively low resolution. Consequently, correct 3D cross-cortical patterns of laminar architecture have never been mapped in histological sections. We developed an automated technique to identify and analyze laminar structure within the high-resolution 3D histological BigBrain. We extracted white matter and pial surfaces, from which we derived histologically verified surfaces at the layer I/II boundary and within layer IV. Layer IV depth was strongly predicted by cortical curvature but varied between areas. This fully automated 3D laminar analysis is an important requirement for bridging high-resolution 2D cytoarchitecture and in vivo 3D neuroimaging. It lays the foundation for in-depth, whole-brain analyses of cortical layering.

Detecting Mental States by Machine Learning Techniques: The Berlin Brain-Computer Interface

NASA Astrophysics Data System (ADS)

Blankertz, Benjamin; Tangermann, Michael; Vidaurre, Carmen; Dickhaus, Thorsten; Sannelli, Claudia; Popescu, Florin; Fazli, Siamac; Danóczy, Márton; Curio, Gabriel; Müller, Klaus-Robert

The Berlin Brain-Computer Interface Brain-Computer Interface (BBCI) uses a machine learning approach to extract user-specific patterns from high-dimensional EEG-features optimized for revealing the user's mental state. Classical BCI applications are brain actuated tools for patients such as prostheses (see Section 4.1) or mental text entry systems ([1] and see [2-5] for an overview on BCI). In these applications, the BBCI uses natural motor skills of the users and specifically tailored pattern recognition algorithms for detecting the user's intent. But beyond rehabilitation, there is a wide range of possible applications in which BCI technology is used to monitor other mental states, often even covert ones (see also [6] in the fMRI realm). While this field is still largely unexplored, two examples from our studies are exemplified in Sections 4.3 and 4.4.

Computer-Based Learning: Graphical Integration of Whole and Sectional Neuroanatomy Improves Long-Term Retention

PubMed Central

Naaz, Farah; Chariker, Julia H.; Pani, John R.

2013-01-01

A study was conducted to test the hypothesis that instruction with graphically integrated representations of whole and sectional neuroanatomy is especially effective for learning to recognize neural structures in sectional imagery (such as MRI images). Neuroanatomy was taught to two groups of participants using computer graphical models of the human brain. Both groups learned whole anatomy first with a three-dimensional model of the brain. One group then learned sectional anatomy using two-dimensional sectional representations, with the expectation that there would be transfer of learning from whole to sectional anatomy. The second group learned sectional anatomy by moving a virtual cutting plane through the three-dimensional model. In tests of long-term retention of sectional neuroanatomy, the group with graphically integrated representation recognized more neural structures that were known to be challenging to learn. This study demonstrates the use of graphical representation to facilitate a more elaborated (deeper) understanding of complex spatial relations. PMID:24563579

Analysis of acute brain slices by electron microscopy: a correlative light-electron microscopy workflow based on Tokuyasu cryo-sectioning.

PubMed

Loussert Fonta, Celine; Leis, Andrew; Mathisen, Cliff; Bouvier, David S; Blanchard, Willy; Volterra, Andrea; Lich, Ben; Humbel, Bruno M

2015-01-01

Acute brain slices are slices of brain tissue that are kept vital in vitro for further recordings and analyses. This tool is of major importance in neurobiology and allows the study of brain cells such as microglia, astrocytes, neurons and their inter/intracellular communications via ion channels or transporters. In combination with light/fluorescence microscopies, acute brain slices enable the ex vivo analysis of specific cells or groups of cells inside the slice, e.g. astrocytes. To bridge ex vivo knowledge of a cell with its ultrastructure, we developed a correlative microscopy approach for acute brain slices. The workflow begins with sampling of the tissue and precise trimming of a region of interest, which contains GFP-tagged astrocytes that can be visualised by fluorescence microscopy of ultrathin sections. The astrocytes and their surroundings are then analysed by high resolution scanning transmission electron microscopy (STEM). An important aspect of this workflow is the modification of a commercial cryo-ultramicrotome to observe the fluorescent GFP signal during the trimming process. It ensured that sections contained at least one GFP astrocyte. After cryo-sectioning, a map of the GFP-expressing astrocytes is established and transferred to correlation software installed on a focused ion beam scanning electron microscope equipped with a STEM detector. Next, the areas displaying fluorescence are selected for high resolution STEM imaging. An overview area (e.g. a whole mesh of the grid) is imaged with an automated tiling and stitching process. In the final stitched image, the local organisation of the brain tissue can be surveyed or areas of interest can be magnified to observe fine details, e.g. vesicles or gold labels on specific proteins. The robustness of this workflow is contingent on the quality of sample preparation, based on Tokuyasu's protocol. This method results in a reasonable compromise between preservation of morphology and maintenance of antigenicity. Finally, an important feature of this approach is that the fluorescence of the GFP signal is preserved throughout the entire preparation process until the last step before electron microscopy. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Direct visualization of anatomic subfields within the superior aspect of the human lateral thalamus by MRI at 7T.

PubMed

Kanowski, M; Voges, J; Buentjen, L; Stadler, J; Heinze, H-J; Tempelmann, C

2014-09-01

The morphology of the human thalamus shows high interindividual variability. Therefore, direct visualization of landmarks within the thalamus is essential for an improved definition of electrode positions for deep brain stimulation. The aim of this study was to provide anatomic detail in the thalamus by using inversion recovery TSE imaging at 7T. The MR imaging protocol was optimized on 1 healthy subject to segment thalamic nuclei from one another. Final images, acquired with 0.5(2)-mm2 in-plane resolution and 3-mm section thickness, were compared with stereotactic brain atlases to assign visualized details to known anatomy. The robustness of the visualization of thalamic nuclei was assessed with 4 healthy subjects at lower image resolution. Thalamic subfields were successfully delineated in the dorsal aspect of the lateral thalamus. T1-weighting was essential. MR images had an appearance very similar to that of myelin-stained sections seen in brain atlases. Visualized intrathalamic structures were, among others, the lamella medialis, the external medullary lamina, the reticulatum thalami, the nucleus centre médian, the boundary between the nuclei dorso-oralis internus and externus, and the boundary between the nuclei dorso-oralis internus and zentrolateralis intermedius internus. Inversion recovery-prepared TSE imaging at 7T has a high potential to reveal fine anatomic detail in the thalamus, which may be helpful in enhancing the planning of stereotactic neurosurgery in the future. © 2014 by American Journal of Neuroradiology.

A novel, modernized Golgi-Cox stain optimized for CLARITY cleared tissue.

PubMed

Kassem, Mustafa S; Fok, Sandra Y Y; Smith, Kristie L; Kuligowski, Michael; Balleine, Bernard W

2018-01-15

High resolution neuronal information is extraordinarily useful in understanding the brain's functionality. The development of the Golgi-Cox stain allowed observation of the neuron in its entirety with unrivalled detail. Tissue clearing techniques, e.g., CLARITY and CUBIC, provide the potential to observe entire neuronal circuits intact within tissue and without previous restrictions with regard to section thickness. Here we describe an improved Golgi-Cox stain method, optimised for use with CLARITY and CUBIC that can be used in both fresh and fixed tissue. Using this method, we were able to observe neurons in their entirety within a fraction of the time traditionally taken to clear tissue (48h). We were also able to show for the first-time that Golgi stained tissue is fluorescent when visualized using a multi-photon microscope, allowing us to image synaptic spines with a detail previously unachievable. These novel methods provide cheap and easy to use techniques to investigate the morphology of cellular processes in the brain at a new-found depth, speed, utility and detail, without previous restrictions of time, tissue type and section thickness. This is the first application of a Golgi-Cox stain to cleared brain tissue, it is investigated and discussed in detail, describing different methodologies that may be used, a comparison between the different clearing techniques and lastly the novel interaction of these techniques with this ultra-rapid stain. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

Raji, Cyrus A; Henderson, Theodore A

2018-02-01

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

Antitumor efficacy and intratumoral distribution of SN-38 from polymeric depots in brain tumor model

PubMed Central

Vejjasilpa, Ketpat; Manaspon, Chawan; Larbcharoensub, Noppadol; Boongird, Atthaporn; Hongeng, Suradej; Israsena, Nipan

2015-01-01

We investigate antitumor efficacy and 2D and 3D intratumoral distribution of 7-ethyl-10-hydroxycamptothecin (SN-38) from polymeric depots inside U-87MG xenograft tumor model in nude mice. Results showed that polymeric depots could be used to administer and controlled release of a large amount of SN-38 directly to the brain tumor model. SN-38 released from depots suppressed tumor growth, where the extent of suppression greatly depended on doses and the number of depot injections. Tumor suppression of SN-38 from depots was three-fold higher in animals which received double injections of depots at high dose (9.7 mg of SN-38) compared to single injection (2.2 mg). H&E staining of tumor sections showed that the area of tumor cell death/survival of the former group was two-fold higher than those of the latter group. Fluorescence imaging based on self-fluorescent property of SN-38 was used to evaluate the intratumoral distribution of this drug compared to histological results. The linear correlation between fluorescence intensity and the amount of SN-38 allowed quantitative determination of SN-38 in tumor tissues. Results clearly showed direct correlation between the amount of SN-38 in tumor sections and cancer cell death. Moreover, 3D reconstruction representing the distribution of SN-38 in tumors was obtained. Results from this study suggest the rationale for intratumoral drug administration and release of drugs inside tumor, which is necessary to design drug delivery systems with efficient antitumor activity. PMID:26080460

[Immunocytochemical demonstration of astrocytes in brain sections combined with Nissl staining].

PubMed

Korzhevskiĭ, D E; Otellin, V A

2004-01-01

The aim of the present study was to develop an easy and reliable protocol of combined preparation staining, which would unite the advantages of immunocytochemical demonstration of astrocytes with the availability to evaluate functional state of neurons provided by Nissl technique. The presented protocol of paraffin sections processing allows to retain high quality of tissue structure and provides for selective demonstration of astrocytes using the monoclonal antibodies against glial fibrillary acidic protein and contrast Nissl staining of cells. The protocol can be used without any changes for processing of brain sections obtained from the humans and other mammals with the exception of mice and rabbits.

Combined glutamate and glutamine levels in pain-processing brain regions are associated with individual pain sensitivity.

PubMed

Zunhammer, Matthias; Schweizer, Lauren M; Witte, Vanessa; Harris, Richard E; Bingel, Ulrike; Schmidt-Wilcke, Tobias

2016-10-01

The relationship between glutamate and γ-aminobutyric acid (GABA) levels in the living human brain and pain sensitivity is unknown. Combined glutamine/glutamate (Glx), as well as GABA levels can be measured in vivo with single-voxel proton magnetic resonance spectroscopy. In this cross-sectional study, we aimed at determining whether Glx and/or GABA levels in pain-related brain regions are associated with individual differences in pain sensitivity. Experimental heat, cold, and mechanical pain thresholds were obtained from 39 healthy, drug-free individuals (25 men) according to the quantitative sensory testing protocol and summarized into 1 composite measure of pain sensitivity. The Glx levels were measured using point-resolved spectroscopy at 3 T, within a network of pain-associated brain regions comprising the insula, the anterior cingulate cortex, the mid-cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus. GABA levels were measured using GABA-edited spectroscopy (Mescher-Garwood point-resolved spectroscopy) within the insula, the anterior cingulate cortex, and the mid-cingulate cortex. Glx and/or GABA levels correlated positively across all brain regions. Gender, weekly alcohol consumption, and depressive symptoms were significantly associated with Glx and/or GABA levels. A linear regression analysis including all these factors indicated that Glx levels pooled across pain-related brain regions were positively associated with pain sensitivity, whereas no appreciable relationship with GABA was found. In sum, we show that the levels of the excitatory neurotransmitter glutamate and its precursor glutamine across pain-related brain regions are positively correlated with individual pain sensitivity. Future studies will have to determine whether our findings also apply to clinical populations.

Intrauterine proximity to male fetuses affects the morphology of the sexually dimorphic nucleus of the preoptic area in the adult rat brain.

PubMed

Pei, Minjuan; Matsuda, Ken-Ichi; Sakamoto, Hirotaka; Kawata, Mitsuhiro

2006-03-01

Previous studies on polytocous rodents have revealed that the fetal intrauterine position influences its later anatomy, physiology, reproductive performance and behavior. To investigate whether the position of a fetus in the uterus modifies the development of the brain, we examined whether the structure of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of rat brains accorded to their intrauterine positions. Brain sections of adult rats gestated between two male fetuses (2M) and between two female fetuses (2F) in the uterus were analysed for their immunoreactivity to calbindin-D28k, which is a marker of the SDN-POA. The SDN-POA volume of the 2M adult males was greater than that of the 2F adult males, whereas the SDN-POA volume of the 2M and 2F adult females showed no significant difference. This result indicated that contiguous male fetuses have a masculinizing effect on the SDN-POA volume of the male. To further examine whether the increment of SDN-POA volume in adulthood was due to exposure to elevated steroid hormones during fetal life, concentrations of testosterone and 17beta-estradiol in the brain were measured with 2M and 2F fetuses during gestation, respectively. On gestation day 21, the concentrations of testosterone and 17beta-estradiol in the brain were significantly higher in the 2M male rats as compared with the 2F male rats. The results suggested that there was a relationship between the fetal intrauterine position, hormone transfer from adjacent fetuses and the SDN-POA volume in adult rat brains.

Subcortical brain volume differences of participants with ADHD across the lifespan: an ENIGMA collaboration

PubMed Central

Hoogman, Martine; Bralten, Janita; Hibar, Derrek P.; Mennes, Maarten; Zwiers, Marcel P.; Schweren, Lizanne; van Hulzen, Kimm J.E.; Medland, Sarah E.; Shumskaya, Elena; Jahanshad, Neda; de Zeeuw, Patrick; Szekely, Eszter; Sudre, Gustavo; Wolfers, Thomas; Onnink, Alberdingk M.H.; Dammers, Janneke T.; Mostert, Jeanette C.; Vives-Gilabert, Yolanda; Kohls, Gregor; Oberwelland, Eileen; Seitz, Jochen; Schulte-Rüther, Martin; di Bruttopilo, Sara Ambrosino; Doyle, Alysa E.; Høvik, Marie F.; Dramsdahl, Margaretha; Tamm, Leanne; van Erp, Theo G.M.; Dale, Anders; Schork, Andrew; Conzelmann, Annette; Zierhut, Kathrin; Baur, Ramona; McCarthy, Hazel; Yoncheva, Yuliya N.; Cubillo, Ana; Chantiluke, Kaylita; Mehta, Mitul A.; Paloyelis, Yannis; Hohmann, Sarah; Baumeister, Sarah; Bramati, Ivanei; Mattos, Paulo; Tovar-Moll, Fernanda; Douglas, Pamela; Banaschewski, Tobias; Brandeis, Daniel; Kuntsi, Jonna; Asherson, Phil; Rubia, Katya; Kelly, Clare; Di Martino, Adriana; Milham, Michael P.; Castellanos, Francisco X.; Frodl, Thomas; Zentis, Mariam; Lesch, Klaus-Peter; Reif, Andreas; Pauli, Paul; Jernigan, Terry; Haavik, Jan; Plessen, Kerstin J.; Lundervold, Astri J.; Hugdahl, Kenneth; Seidman, Larry J.; Biederman, Joseph; Rommelse, Nanda; Heslenfeld, Dirk J.; Hartman, Catharina; Hoekstra, Pieter J.; Oosterlaan, Jaap; von Polier, Georg; Konrad, Kerstin; Vilarroya, Oscar; Ramos-Quiroga, Josep-Antoni; Soliva, Joan Carles; Durston, Sarah; Buitelaar, Jan K.; Faraone, Stephen V.; Shaw, Philip; Thompson, Paul; Franke, Barbara

2017-01-01

BACKGROUND Neuroimaging studies show structural alterations in several brain regions in children and adults with attention-deficit/hyperactivity disorder (ADHD). Through the formation of the worldwide ENIGMA ADHD Working Group, we addressed weaknesses of prior imaging studies and meta-analyses in sample size and methodological heterogeneity. METHODS Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites (age range: 4–63 years; 66% males). Individual sites analyzed magnetic resonance imaging brain scans with harmonized protocols. Case-control differences in subcortical structures and intracranial volume (ICV) were assessed through mega-and meta-analysis. FINDINGS The volumes of the accumbens (Cohen’s d=−0.15), amygdala (d=−0.19), caudate (d=−0.11), hippocampus (d=−0.11), putamen (d=−0.14), and ICV (d=−0.10) were found to be smaller in cases relative to controls. Effect sizes were highest in children, case-control differences were not present in adults. Explorative lifespan modeling suggested a delay of maturation and a delay of degeneration. Psychostimulant medication use or presence of comorbid psychiatric disorders did not influence results, nor did symptom scores correlate with brain volume. INTERPRETATION Using the largest data set to date, we extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. We add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD, and provide unprecedented precision in effect size estimates. Lifespan analyses suggest that, in the absence of well-powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of life provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING National Institutes of Health PMID:28219628

Subjective cognitive complaints, personality and brain amyloid-beta in cognitively normal older adults

PubMed Central

Snitz, Beth E.; Weissfeld, Lisa A.; Cohen, Ann D.; Lopez, Oscar L.; Nebes, Robert D.; Aizenstein, Howard J.; McDade, Eric; Price, Julie C.; Mathis, Chester A.; Klunk, William E.

2015-01-01

Objectives Subjective cognitive complaints in otherwise normal aging are common but may be associated with preclinical Alzheimer Disease in some individuals. Little is known about who is mostly likely to show associations between cognitive complaints and preclinical Alzheimer pathology. We sought to 1) demonstrate associations between subjective complaints and brain amyloid-β in cognitively normal older adults; 2) to explore personality factors as potential moderators of this association. Design Cross-sectional observational study. Setting Clinical neuroimaging research center. Participants Community volunteer sample of 92 healthy older adults, screened for normal cognition with comprehensive neuropsychological evaluation. Measurements Subjective cognitive self-report measures included the Memory Functioning Questionnaire, Cognitive Failures Questionnaire, and the Subjective Cognitive Complaint Scale. Personality was measured with the NEO Five Factor Inventory. Brain amyloid-β deposition was assessed with Pittsburgh compound B (PiB)-PET imaging. Results One of three cognitive complaint measures, the Memory Functioning Questionnaire, was associated with global PiB retention (standardized beta =−.230, p=.046, adjusting for age, sex and depressive symptoms). Neuroticism moderated this association such that only high neuroticism individuals showed the predicted pattern of high complaint – high amyloid-β association. Conclusions Evidence for association between subjective cognition and brain amyloid-β deposition in healthy older adults is demonstrable but measure-specific. Neuroticism may moderate the MFQ – amyloid-β association such that it is observed in the context of higher trait neuroticism. Subjective cognitive complaints and neuroticism may reflect a common susceptibility toward psychological distress and negative affect, which are in turn risk factors for cognitive decline in aging and incident Alzheimer Disease. PMID:25746485

Preliminary report on macroscopic age changes in the human prosencephalon. A stereologic investigation.

PubMed

Eggers, R; Haug, H; Fischer, D

1984-01-01

The studies here reported were performed on the prosencephalons of 12 human brains between 37 and 86 years of age having no signs of neuropathological alteration. The evaluation was carried out on serial frontal sections with a mean thickness of 5 mm with stereological point counting procedures for volume and surface area. The results were mainly given in relative values since the range of variation is very high and the sample small. The aging process was evaluated with the aid of a linear regression function. The stereological investigation regarding the absolute values of volume and surface area (border face) of the macroscopical brain parts show a high interindividual variability. However, the relative volume of brain parts shows only small variations. Changes during aging could consequently only be revealed with the help of the relative values. The relative volumes and surface areas of the frontal lobe and the prosencephalic ganglia decrease with aging, while the parieto-occipital lobe and the striate cortex increase. However, if we refer these relative increases to the absolute decrease of brain volume, corresponding changes cannot be found in the parieto-occipital lobe until old age. The shrinkage of the frontal lobe, of the centrum semiovale and of the prosencephalic ganglia exceeds 10%. In the grays it is probably accompanied by a loss of neurons. The relative sizes of the surface area do not change significantly during aging with exception of the frontal cortex. The thickness of the cortex remains probably constant. The size of lateral ventricles increases with aging.

Bioluminescent Study of the Distribution of High-Molecular-Weight Protein Fraction of Cellex Daily Preparation in the Brain after Intranasal Administation.

PubMed

Baklaushev, V P; Yusubalieva, G M; Burenkov, M S; Mel'nikov, P A; Bozhko, E A; Mentyukov, G A; Lavrent'eva, L S; Sokolov, M A; Chekhonin, V P

2017-12-01

Permeability of the blood-brain barrier for protein fractions 50-100 kDa (PF 50-100 ) of Cellex Daily preparation labeled with fluorescent tracer FITC and non-conjugated FITC were compared after intranasal administration of the preparations to healthy rats. Fluorimetrical analysis of the serum and cerebrospinal fluid samples showed that Cellex Daily PF 50-100 -FITC administered intranasally penetrated into the blood and cerebrospinal fluid with maximum accumulation in 2 h after administration and persists in the circulation for 24 h probably due to binding with plasma proteins. The differences in the kinetic profile of PF 50-100 -FITC and free FITC indirectly suggest that the major part of the preparation is not degraded within 24 h and FITC is probably not cleaved from the protein components of the preparation. In vivo fluorescence analysis showed significant fluorescent signal in the olfactory bulbs in 6 h after intranasal administration; hence, the preparation administered via this route can bypass the blood-brain barrier. Scanning laser confocal microscopy of rat brain sections confirmed penetration of the high-molecular weight protein fraction PF 50-100 -FITC into CNS structures. The most pronounced accumulation of the labeled drug was observed in the olfactory bulb in 6 and 12 h after administration. In contrast to free FITC administered in the control group, significant accumulation of PF 50-100 -FITC in the olfactory cortex and frontal cortex neurons with functionally active nuclei was observed in 6, 12 and 24 h after intranasal administration.

Relationship between grey matter integrity and executive abilities in aging.

PubMed

Manard, Marine; Bahri, Mohamed Ali; Salmon, Eric; Collette, Fabienne

2016-07-01

This cross-sectional study was designed to investigate grey matter changes that occur in healthy aging and the relationship between grey matter characteristics and executive functioning. Thirty-six young adults (18-30 years old) and 43 seniors (60-75 years old) were included. A general executive score was derived from a large battery of neuropsychological tests assessing three major aspects of executive functioning (inhibition, updating and shifting). Age-related grey matter changes were investigated by comparing young and older adults using voxel-based morphometry and voxel-based cortical thickness methods. A widespread difference in grey matter volume was found across many brain regions, whereas cortical thinning was mainly restricted to central areas. Multivariate analyses showed age-related changes in relatively similar brain regions to the respective univariate analyses but appeared more limited. Finally, in the older adult sample, a significant relationship between global executive performance and decreased grey matter volume in anterior (i.e. frontal, insular and cingulate cortex) but also some posterior brain areas (i.e. temporal and parietal cortices) as well as subcortical structures was observed. Results of this study highlight the distribution of age-related effects on grey matter volume and show that cortical atrophy does not appear primarily in "frontal" brain regions. From a cognitive viewpoint, age-related executive functioning seems to be related to grey matter volume but not to cortical thickness. Therefore, our results also highlight the influence of methodological aspects (from preprocessing to statistical analysis) on the pattern of results, which could explain the lack of consensus in literature. Copyright © 2016 Elsevier B.V. All rights reserved.

Medial prefrontal brain activation to anticipated reward and loss in obsessive–compulsive disorder☆

PubMed Central

Kaufmann, C.; Beucke, J.C.; Preuße, F.; Endrass, T.; Schlagenhauf, F.; Heinz, A.; Juckel, G.; Kathmann, N.

2013-01-01

Obsessive–compulsive disorder (OCD) is associated with dysfunctional brain activity in several regions which are also involved in the processing of motivational stimuli. Processing of reward and punishment appears to be of special importance to understand clinical symptoms. There is evidence for higher sensitivity to punishment in patients with OCD which raises the question how avoidance of punishment relates to activity within the brain's reward circuitry. We employed the monetary incentive delay task paradigm optimized for modeling the anticipation phase of immediate reward and punishment, in the context of a cross-sectional event-related FMRI study comparing OCD patients and healthy control participants (n = 19 in each group). While overall behavioral performance was similar in both groups, patients showed increased activation upon anticipated losses in a medial and superior frontal cortex region extending into the cingulate cortex, and decreased activation upon anticipated rewards. No evidence was found for altered activation of dorsal or ventral striatal regions. Patients also showed more delayed responses for anticipated rewards than for anticipated losses whereas the reverse was true in healthy participants. The medial prefrontal cortex has been shown to implement a domain-general process comprising negative affect, pain and cognitive control. This process uses information about punishment to control aversively motivated actions by integrating signals arriving from subcortical regions. Our results support the notion that OCD is associated with altered sensitivity to anticipated rewards and losses in a medial prefrontal region whereas there is no significant aberrant activation in ventral or dorsal striatal brain regions during processing of reinforcement anticipation. PMID:24179774

Medial prefrontal brain activation to anticipated reward and loss in obsessive-compulsive disorder.

PubMed

Kaufmann, C; Beucke, J C; Preuße, F; Endrass, T; Schlagenhauf, F; Heinz, A; Juckel, G; Kathmann, N

2013-01-01

Obsessive-compulsive disorder (OCD) is associated with dysfunctional brain activity in several regions which are also involved in the processing of motivational stimuli. Processing of reward and punishment appears to be of special importance to understand clinical symptoms. There is evidence for higher sensitivity to punishment in patients with OCD which raises the question how avoidance of punishment relates to activity within the brain's reward circuitry. We employed the monetary incentive delay task paradigm optimized for modeling the anticipation phase of immediate reward and punishment, in the context of a cross-sectional event-related FMRI study comparing OCD patients and healthy control participants (n = 19 in each group). While overall behavioral performance was similar in both groups, patients showed increased activation upon anticipated losses in a medial and superior frontal cortex region extending into the cingulate cortex, and decreased activation upon anticipated rewards. No evidence was found for altered activation of dorsal or ventral striatal regions. Patients also showed more delayed responses for anticipated rewards than for anticipated losses whereas the reverse was true in healthy participants. The medial prefrontal cortex has been shown to implement a domain-general process comprising negative affect, pain and cognitive control. This process uses information about punishment to control aversively motivated actions by integrating signals arriving from subcortical regions. Our results support the notion that OCD is associated with altered sensitivity to anticipated rewards and losses in a medial prefrontal region whereas there is no significant aberrant activation in ventral or dorsal striatal brain regions during processing of reinforcement anticipation.

Characterization and classification of zebrafish brain morphology mutants

PubMed Central

Lowery, Laura Anne; De Rienzo, Gianluca; Gutzman, Jennifer H.; Sive, Hazel

2010-01-01

The mechanisms by which the vertebrate brain achieves its three-dimensional structure are clearly complex, requiring the functions of many genes. Using the zebrafish as a model, we have begun to define genes required for brain morphogenesis, including brain ventricle formation, by studying 16 mutants previously identified as having embryonic brain morphology defects. We report the phenotypic characterization of these mutants at several time-points, using brain ventricle dye injection, imaging, and immunohistochemistry with neuronal markers. Most of these mutants display early phenotypes, affecting initial brain shaping, while others show later phenotypes, affecting brain ventricle expansion. In the early phenotype group, we further define four phenotypic classes and corresponding functions required for brain morphogenesis. Although we did not use known genotypes for this classification, basing it solely on phenotypes, many mutants with defects in functionally related genes clustered in a single class. In particular, class 1 mutants show midline separation defects, corresponding to epithelial junction defects; class 2 mutants show reduced brain ventricle size; class 3 mutants show midbrain-hindbrain abnormalities, corresponding to basement membrane defects; and class 4 mutants show absence of ventricle lumen inflation, corresponding to defective ion pumping. Later brain ventricle expansion requires the extracellular matrix, cardiovascular circulation, and transcription/splicing-dependent events. We suggest that these mutants define processes likely to be used during brain morphogenesis throughout the vertebrates. PMID:19051268

Evaluation of 64Cu-Based Radiopharmaceuticals that Target Aβ Peptide Aggregates as Diagnostic Tools for Alzheimer's Disease.

PubMed

Bandara, Nilantha; Sharma, Anuj K; Krieger, Stephanie; Schultz, Jason W; Han, Byung Hee; Rogers, Buck E; Mirica, Liviu M

2017-09-13

Positron emission tomography (PET) imaging agents that detect amyloid plaques containing amyloid beta (Aβ) peptide aggregates in the brain of Alzheimer's disease (AD) patients have been successfully developed and recently approved by the FDA for clinical use. However, the short half-lives of the currently used radionuclides 11 C (20.4 min) and 18 F (109.8 min) may limit the widespread use of these imaging agents. Therefore, we have begun to evaluate novel AD diagnostic agents that can be radiolabeled with 64 Cu, a radionuclide with a half-life of 12.7 h, ideal for PET imaging. Described herein are a series of bifunctional chelators (BFCs), L 1 -L 5 , that were designed to tightly bind 64 Cu and shown to interact with Aβ aggregates both in vitro and in transgenic AD mouse brain sections. Importantly, biodistribution studies show that these compounds exhibit promising brain uptake and rapid clearance in wild-type mice, and initial microPET imaging studies of transgenic AD mice suggest that these compounds could serve as lead compounds for the development of improved diagnostic agents for AD.

Numerical modeling of an experimental shock tube for traumatic brain injury studies

NASA Astrophysics Data System (ADS)

Phillips, Michael; Regele, Jonathan D.

2015-11-01

Unfortunately, Improvised Explosive Devices (IEDs) are encountered commonly by both civilians and military soldiers throughout the world. Over a decade of medical history suggests that traumatic brain injury (TBI) may result from exposure to the blast waves created by these explosions, even if the person does not experience any immediate injury or lose consciousness. Medical researchers study the exposure of mice and rats to blast waves created in specially designed shock tubes to understand the effect on brain tissue. A newly developed table-top shock tube with a short driver section has been developed for mice experiments to reduce the time necessary to administer the blast radiation and increase the amount of statistical information available. In this study, numerical simulations of this shock tube are performed to assess how the blast wave takes its shape. The pressure profiles obtained from the numerical results are compared with the pressure histories from the experimental pressure transducers. The results show differences in behavior from what was expected, but the blast wave may still be an effective means of studying TBI.

Multimodal detection of GM2 and GM3 lipid species in the brain of mucopolysaccharidosis type II mouse by serial imaging mass spectrometry and immunohistochemistry.

PubMed

Dufresne, Martin; Guneysu, Daniel; Patterson, Nathan Heath; Marcinkiewicz, Mieczyslaw Martin; Regina, Anthony; Demeule, Michel; Chaurand, Pierre

2017-02-01

Mucopolysaccharidosis type II (Hunter's disease) mouse model (IdS-KO) was investigated by both imaging mass spectrometry (IMS) and immunohistochemistry (IHC) performed on the same tissue sections. For this purpose, IdS-KO mice brain sections were coated with sublimated 1,5-diaminonaphtalene and analyzed by high spatial resolution IMS (5 μm) and anti-GM3 IHC on the same tissue sections to characterize the ganglioside monosialated ganglioside (GM) deposits found in Hunter's disease. IMS analysis have found that two species of GM3 and GM2 that are only different due to the length of their fatty acid residue (stearic or arachidic residue) were overexpressed in the IdS-KO mice compared to a control mouse. GM3 and GM2 were characterized by on-tissue exact mass and MS/MS compared to a GM3 standard. Realignment of both IMS and IHC data sets further confirmed the observed regioselective signal previously detected by providing direct correlation of the IMS image for the two GM3 overly expressed MS signals with the anti-GM3 IHC image. Furthermore, these regioselective GM MS signals were also found to have highly heterogeneous distributions within the GM3-IHC staining. Some deposits showed high content in GM3 and GM2 stearic species (r = 0.74) and others had more abundant GM3 and GM2 arachidic species (r = 0.76). Same-section analysis of Hunter's disease mouse model by both high spatial resolution IMS and IHC provides a more in-depth analysis of the composition of the GM aggregates while providing spatial distribution of the observed molecular species. Graphical Abstract Ganglioside imaging mass spectrometry followed by immunohistochemistry performed on the same tissue section.

Effect of 12-Day Spaceflight on Brain of Thick-Toed Geckos

NASA Astrophysics Data System (ADS)

Proshchina, A. E.; Karlamova, A. S.; Barabanovet, V. M.; Godovalova, O. S.; Guilimova, V. I.; Krivova, Y. S.; Makarov, A. N.; Nikitin, V. B.; Savelieva, E. S.; Saveliev, S. V.

2008-06-01

In the frames of Russian-American joint space experiment onboard Foton-M3 satellite there was undertaken a study of spaceflight influence on brain of the thick-toed gecko (Pachydactylus turneri Gray, 1864). Serial brain sections were stained according to Nissl and also the immunohistochemical method with antibodies to NGF-receptor (p75NGFR), CD95 (also known as Fas and APO-1), glial fibrillary acidic protein (GFAP) and transferrin-receptor (CD71). Detailed examination of the sections of rhombencephalon revealed cytological changes in the neuron bodies of vestibular nuclei inside the flight group. Immunohistochemicaly we found the increase density of CD95 and p75NGFR and decrease of GFAP expression in medial cortex and epithalamus in flight group compared both control.

Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

PubMed Central

Wang, Jian-Qin; Yin, Jie; Song, Yan-Feng; Zhang, Lang; Ren, Ying-Xiang; Wang, De-Gui; Gao, Li-Ping; Jing, Yu-Hong

2014-01-01

Objective. Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies. PMID:25197672

Synthesis of three novel fluorine-18 labeled analogues of L-deprenyl for positron emission tomography (PET) studies of monoamine oxidase B (MAO-B).

PubMed

Nag, Sangram; Lehmann, Lutz; Heinrich, Tobias; Thiele, Andrea; Kettschau, Georg; Nakao, Ryuji; Gulyás, Balázs; Halldin, Christer

2011-10-27

The aim in this project was to synthesize and to study fluorine-18 labeled analogues of l-deprenyl which bind selectively to the enzyme monoamine oxidase B (MAO-B). Three fluorinated l-deprenyl analogues have been generated in multistep organic syntheses. The most promising fluorine-18 compound N-[(2S)-1-[(18)F]fluoro-3-phenylpropan-2-yl]-N-methylprop-2-yn-1-amine (4c) was synthesized by a one-step fluorine-18 nucleophilic substitution reaction. Autoradiography on human brain tissue sections demonstrated specific binding for compound 4c to brain regions known to have a high content of MAO-B. In addition, the corresponding nonradioactive fluorine-19 compound (13) inhibited recombinant human MAO-B with an IC(50) of 170.5 ± 29 nM but did not inhibit recombinant human MAO-A (IC(50) > 2000 nM), demonstrating its specificity. Biodistribution of 4c in mice showed high initial brain uptake leveling at 5.2 ± 0.04%ID/g after 2 min post injection. In conclusion, compound 4c is a specific inhibitor of MAO-B with high initial brain uptake in mice and is, therefore, a candidate for further investigation in PET.

Live imaging of mitosis in the developing mouse embryonic cortex.

PubMed

Pilaz, Louis-Jan; Silver, Debra L

2014-06-04

Although of short duration, mitosis is a complex and dynamic multi-step process fundamental for development of organs including the brain. In the developing cerebral cortex, abnormal mitosis of neural progenitors can cause defects in brain size and function. Hence, there is a critical need for tools to understand the mechanisms of neural progenitor mitosis. Cortical development in rodents is an outstanding model for studying this process. Neural progenitor mitosis is commonly examined in fixed brain sections. This protocol will describe in detail an approach for live imaging of mitosis in ex vivo embryonic brain slices. We will describe the critical steps for this procedure, which include: brain extraction, brain embedding, vibratome sectioning of brain slices, staining and culturing of slices, and time-lapse imaging. We will then demonstrate and describe in detail how to perform post-acquisition analysis of mitosis. We include representative results from this assay using the vital dye Syto11, transgenic mice (histone H2B-EGFP and centrin-EGFP), and in utero electroporation (mCherry-α-tubulin). We will discuss how this procedure can be best optimized and how it can be modified for study of genetic regulation of mitosis. Live imaging of mitosis in brain slices is a flexible approach to assess the impact of age, anatomy, and genetic perturbation in a controlled environment, and to generate a large amount of data with high temporal and spatial resolution. Hence this protocol will complement existing tools for analysis of neural progenitor mitosis.

Hippocampal Sclerosis of Aging Can Be Segmental: Two Cases and Review of the Literature.

PubMed

Ighodaro, Eseosa T; Jicha, Gregory A; Schmitt, Frederick A; Neltner, Janna H; Abner, Erin L; Kryscio, Richard J; Smith, Charles D; Duplessis, Taylor; Anderson, Sonya; Patel, Ela; Bachstetter, Adam; Van Eldik, Linda J; Nelson, Peter T

2015-07-01

Hippocampal sclerosis of aging (HS-Aging) is a neurodegenerative disease that mimics Alzheimer disease (AD) clinically and has a prevalence rivaling AD in advanced age. Whereas clinical biomarkers are not yet optimized, HS-Aging has distinctive pathological features that distinguish it from other diseases with "hippocampal sclerosis" pathology, such as epilepsy, cerebrovascular perturbations, and frontotemporal lobar degeneration. By definition, HS-Aging brains show neuronal cell loss and gliosis in the hippocampal formation out of proportion to AD-type pathology; it is strongly associated with aberrant TDP-43 pathology and arteriolosclerosis. Here, we describe 2 cases of "segmental" HS-Aging in which "sclerosis" in the hippocampus was evident only in a subset of brain sections by hematoxylin and eosin (H&E) stain. In these cases, TDP-43 pathology was more widespread on immunostained sections than the neuronal cell loss and gliosis seen in H&E stains. The 2 patients were cognitively intact at baseline and were tracked longitudinally over a decade using cognitive studies with at least 1 neuroimaging scan. We discuss the relevant HS-Aging literature, which indicates the need for a clearer consensus-based delineation of "hippocampal sclerosis" and TDP-43 pathologies in aged subjects.

Brain stem sites mediating specific and non-specific temperature effects on thermoregulation in the pekin duck.

PubMed Central

Martin, R; Simon, E; Simon-Oppermann, C

1981-01-01

1. Thermodes were chronically implanted into various levels of the brain stem of sixteen Pekin ducks. The effects of local thermal stimulation on metabolic heat production, core temperature, peripheral skin temperature and respiratory frequency were investigated. 2. Four areas of thermode positions were determined according to the responses observed and were histologically identified at the end of the investigation. 3. Thermal stimulation of the lower mid-brain/upper pontine brain stem (Pos. III) elicited an increase in metabolic heat production, cutaneous vasoconstriction and rises in core temperature in response to cooling at thermoneutral and cold ambient conditions and, further, inhibition of panting by cooling and activation of panting by heating at warm ambient conditions. The metabolic response to cooling this brain stem section amounted to -0.1 W/kg. degrees C as compared with -7 W/kg. degrees C in response to total body cooling. 4. Cooling of the anterior and middle hypothalamus (Pos. II) caused vasodilatation in the skin and did not elicit shivering. The resulting drop in core temperature at a given degree of cooling was greater than the rise in core temperature in response to equivalent cooling of the lower mid-brain/upper pontine brain stem. 5. Cooling of the preoptic forebrain (Pos. I) and of the myelencephalon (Pos. IV) did not elicit thermoregulatory reactions. 6. It is concluded that the duck's brain stem contains thermoreceptive structures in the lower mid-brain/upper pontine section. However, the brain stem as a whole appears to contribute little to cold defence during general hypothermia because of the inhibitory effects originating in the anterior and middle hypothalamus. Cold defence in the duck, which is comparable in strength to that in mammals, has to rely on extracerebral thermosensory structures. PMID:7310688

76 FR 55400 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-07

...: Integrative, Functional and Cognitive Neuroscience Integrated Review Group; Auditory System Study Section... Neuroscience Integrated Review Group; Neurotoxicology and Alcohol Study Section. Date: October 13, 2011. Time... Disorders and Clinical Neuroscience Integrated Review Group; Developmental Brain Disorders Study Section...

Traumatic brain injury caused by laser-induced shock wave in rats: a novel laboratory model for studying blast-induced traumatic brain injury

NASA Astrophysics Data System (ADS)

Hatano, Ben; Matsumoto, Yoshihisa; Otani, Naoki; Saitoh, Daizoh; Tokuno, Shinichi; Satoh, Yasushi; Nawashiro, Hiroshi; Matsushita, Yoshitaro; Sato, Shunichi

2011-03-01

The detailed mechanism of blast-induced traumatic brain injury (bTBI) has not been revealed yet. Thus, reliable laboratory animal models for bTBI are needed to investigate the possible diagnosis and treatment for bTBI. In this study, we used laser-induced shock wave (LISW) to induce TBI in rats and investigated the histopathological similarities to actual bTBI. After craniotomy, the rat brain was exposed to a single shot of LISW with a diameter of 3 mm at various laser fluences. At 24 h after LISW exposure, perfusion fixation was performed and the extracted brain was sectioned; the sections were stained with hematoxylin-eosin. Evans blue (EB) staining was also used to evaluate disruption of the blood brain barrier. At certain laser fluence levels, neural cell injury and hemorrhagic lesions were observed in the cortex and subcortical region. However, injury was limited in the tissue region that interacted with the LISW. The severity of injury increased with increasing laser fluence and hence peak pressure of the LISW. Fluorescence originating from EB was diffusively observed in the injuries at high fluence levels. Due to the grade and spatial controllability of injuries and the histological observations similar to those in actual bTBI, brain injuries caused by LISWs would be useful models to study bTBI.

Imaging brain development: the adolescent brain.

PubMed

Blakemore, Sarah-Jayne

2012-06-01

The past 15 years have seen a rapid expansion in the number of studies using neuroimaging techniques to investigate maturational changes in the human brain. In this paper, I review MRI studies on structural changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence. Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental neuroimaging in the next twenty years. Future studies might focus on complex questions including the development of functional connectivity; how gender and puberty influence adolescent brain development; the effects of genes, environment and culture on the adolescent brain; development of the atypical adolescent brain; and implications for policy of the study of the adolescent brain. Copyright © 2011 Elsevier Inc. All rights reserved.

High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates.

PubMed

Seiriki, Kaoru; Kasai, Atsushi; Hashimoto, Takeshi; Schulze, Wiebke; Niu, Misaki; Yamaguchi, Shun; Nakazawa, Takanobu; Inoue, Ken-Ichi; Uezono, Shiori; Takada, Masahiko; Naka, Yuichiro; Igarashi, Hisato; Tanuma, Masato; Waschek, James A; Ago, Yukio; Tanaka, Kenji F; Hayata-Takano, Atsuko; Nagayasu, Kazuki; Shintani, Norihito; Hashimoto, Ryota; Kunii, Yasuto; Hino, Mizuki; Matsumoto, Junya; Yabe, Hirooki; Nagai, Takeharu; Fujita, Katsumasa; Matsuda, Toshio; Takuma, Kazuhiro; Baba, Akemichi; Hashimoto, Hitoshi

2017-06-21

Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures. FAST renders unbiased quantitative group comparisons of normal and disease model brain cells for the whole brain at a high spatial resolution. Furthermore, FAST is highly scalable to non-human primate brains and human postmortem brain tissues, and can visualize neuronal projections in a whole adult marmoset brain. Thus, FAST provides new opportunities for global approaches that will allow for a better understanding of brain systems in multiple animal models and in human diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Methods to uncover an antibody epitope in the KPI domain of Alzheimer's amyloid precursor protein for immunohistochemistry in human brain.

PubMed

Campbell, E; Pearson, R C; Parkinson, D

1999-11-15

A novel polyclonal antibody (Ab993), specific for a KPI domain epitope of APP, was characterised for use in immunoprecipitation, Western blotting and immunohistochemistry. Conditioned medium from NTera2/D1 cells was used for immunoprecipitation and Western blots. Paraffin-embedded human brain sections were used for immunohistochemistry. The antibody recognised KPI-containing APP on Western blots after standard solubilisation but immunoprecipitation of soluble APP required reduction with 2-mercaptoethanol followed by alkylation of reduced sulphydryl bonds with sodium iodoacetate. Immunohistochemical staining of human brain sections was significantly enhanced by this pre-treatment. Microwaving of sections also increased immunolabelling, by a mechanism that was additive to reduction and alkylation. Incubation in 80% formic acid did not confer any enhancement of immunoreactivity. Ab993, applied with the methods reported here, is expected to be valuable in investigations of the pathogenesis of Alzheimer's disease to determine the source of the beta-amyloid peptide.

Computer tomographic imaging and anatomic correlation of the human brain: A comparative atlas of thin CT-scan sections and correlated neuro-anatomic preparations

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

Plets, C.; Baert, A.L.; Nijs, G.L.

1986-01-01

It is of the greatest importance to the radiologist, the neurologist and the neurosurgeon to be able to localize topographically a pathological brain process on the CT scan as precisely as possible. For that purpose, the identification of as many anatomical structures as possible on the CT scan image are necessary and indispensable. In this atlas a great number of detailed anatomical data on frontal horizontal CT scan sections, each being only 2 mm thick, are indicated, e.g. the cortical gyri, the basal ganglia, details of the white matter, extracranial muscles and blood vessels, parts of the base and themore » vault of the skull, etc. The very precise topographical description of the numerous CT scan images was realized by the author by confrontation of these images with the corresponding anatomical sections of the same brain specimen, performed by an original technique.« less

Journey to the Center of the Fetal Brain: Environmental Exposures and Autophagy.

PubMed

Lei, Jun; Calvo, Pilar; Vigh, Richard; Burd, Irina

2018-01-01

Fetal brain development is known to be affected by adverse environmental exposures during pregnancy, including infection, inflammation, hypoxia, alcohol, starvation, and toxins. These exposures are thought to alter autophagy activity in the fetal brain, leading to adverse perinatal outcomes, such as cognitive and sensorimotor deficits. This review introduces the physiologic autophagy pathways in the fetal brain. Next, methods to detect and monitor fetal brain autophagy activity are outlined. An additional discussion explores possible mechanisms by which environmental exposures during pregnancy alter fetal brain autophagy activity. In the final section, a correlation of fetal autophagy activity with the observed postnatal phenotype is attempted. Our main purpose is to provide the current understanding or a lack thereof mechanisms on autophagy, underlying the fetal brain injury exposed to environmental insults.

Extracting the inclination angle of nerve fibers within the human brain with 3D-PLI independent of system properties

NASA Astrophysics Data System (ADS)

Reckfort, Julia; Wiese, Hendrik; Dohmen, Melanie; Grässel, David; Pietrzyk, Uwe; Zilles, Karl; Amunts, Katrin; Axer, Markus

2013-09-01

The neuroimaging technique 3D-polarized light imaging (3D-PLI) has opened up new avenues to study the complex nerve fiber architecture of the human brain at sub-millimeter spatial resolution. This polarimetry technique is applicable to histological sections of postmortem brains utilizing the birefringence of nerve fibers caused by the regular arrangement of lipids and proteins in the myelin sheaths surrounding axons. 3D-PLI provides a three-dimensional description of the anatomical wiring scheme defined by the in-section direction angle and the out-of-section inclination angle. To date, 3D-PLI is the only available method that allows bridging the microscopic and the macroscopic description of the fiber architecture of the human brain. Here we introduce a new approach to retrieve the inclination angle of the fibers independently of the properties of the used polarimeters. This is relevant because the image resolution and the signal transmission inuence the measured birefringent signal (retardation) significantly. The image resolution was determined using the USAF- 1951 testchart applying the Rayleigh criterion. The signal transmission was measured by elliptical polarizers applying the Michelson contrast and histological slices of the optic tract of a postmortem brain. Based on these results, a modified retardation-inclination transfer function was proposed to extract the fiber inclination. The comparison of the actual and the inclination angles calculated with the theoretically proposed and the modified transfer function revealed a significant improvement in the extraction of the fiber inclinations.

Diet, Environment and Children's Development.

ERIC Educational Resources Information Center

Senemaud, B.

1988-01-01

This report describes the relationship between maternal malnutrition and child development. The report is divided into three sections. The first section, which describes child development, focuses on brain, mental, and psychomotor development. The second section describes the methodological difficulties of measuring effects of malnutrition on the…

Revealing pathologies in the liquid crystalline structures of the brain by polarimetric studies (Presentation Recording)

NASA Astrophysics Data System (ADS)

Bakhshetyan, Karen; Melkonyan, Gurgen G.; Galstian, Tigran V.; Saghatelyan, Armen

2015-10-01

Natural or "self" alignment of molecular complexes in living tissue represents many similarities with liquid crystals (LC), which are anisotropic liquids. The orientational characteristics of those complexes may be related to many important functional parameters and their study may reveal important pathologies. The know-how, accumulated thanks to the study of LC materials, may thus be used to this end. One of the traditionally used methods, to characterize those materials, is the polarized light imaging (PLI) that allows for label-free analysis of anisotropic structures in the brain tissue and can be used, for example, for the analysis of myelinated fiber bundles. In the current work, we first attempted to apply the PLI on the mouse histological brain sections to create a map of anisotropic structures using cross-polarizer transmission light. Then we implemented the PLI for comparative study of histological sections of human postmortem brain samples under normal and pathological conditions, such as Parkinson's disease (PD). Imaging the coronal, sagittal and horizontal sections of mouse brain allowed us to create a false color-coded fiber orientation map under polarized light. In human brain datasets for both control and PD groups we measured the pixel intensities in myelin-rich subregions of internal capsule and normalized these to non-myelinated background signal from putamen and caudate nucleus. Quantification of intensities revealed a statistically significant reduction of fiber intensity of PD compared to control subjects (2.801 +/- 0.303 and 3.724 +/- 0.07 respectively; *p < 0.05). Our study confirms the validity of PLI method for visualizing myelinated axonal fibers. This relatively simple technique can become a promising tool for study of neurodegenerative diseases where labeling-free imaging is an important benefit.

An Integrated Micro- and Macroarchitectural Analysis of the Drosophila Brain by Computer-Assisted Serial Section Electron Microscopy

PubMed Central

Cardona, Albert; Saalfeld, Stephan; Preibisch, Stephan; Schmid, Benjamin; Cheng, Anchi; Pulokas, Jim; Tomancak, Pavel; Hartenstein, Volker

2010-01-01

The analysis of microcircuitry (the connectivity at the level of individual neuronal processes and synapses), which is indispensable for our understanding of brain function, is based on serial transmission electron microscopy (TEM) or one of its modern variants. Due to technical limitations, most previous studies that used serial TEM recorded relatively small stacks of individual neurons. As a result, our knowledge of microcircuitry in any nervous system is very limited. We applied the software package TrakEM2 to reconstruct neuronal microcircuitry from TEM sections of a small brain, the early larval brain of Drosophila melanogaster. TrakEM2 enables us to embed the analysis of the TEM image volumes at the microcircuit level into a light microscopically derived neuro-anatomical framework, by registering confocal stacks containing sparsely labeled neural structures with the TEM image volume. We imaged two sets of serial TEM sections of the Drosophila first instar larval brain neuropile and one ventral nerve cord segment, and here report our first results pertaining to Drosophila brain microcircuitry. Terminal neurites fall into a small number of generic classes termed globular, varicose, axiform, and dendritiform. Globular and varicose neurites have large diameter segments that carry almost exclusively presynaptic sites. Dendritiform neurites are thin, highly branched processes that are almost exclusively postsynaptic. Due to the high branching density of dendritiform fibers and the fact that synapses are polyadic, neurites are highly interconnected even within small neuropile volumes. We describe the network motifs most frequently encountered in the Drosophila neuropile. Our study introduces an approach towards a comprehensive anatomical reconstruction of neuronal microcircuitry and delivers microcircuitry comparisons between vertebrate and insect neuropile. PMID:20957184

Long-Term Experience of Chinese Calligraphic Handwriting Is Associated with Better Executive Functions and Stronger Resting-State Functional Connectivity in Related Brain Regions

PubMed Central

He, Yong; Gao, Yang; Zhang, Cuiping; Chen, Chuansheng; Bi, Suyu; Yang, Pin; Wang, Yiwen; Wang, Wenjing

2017-01-01

Chinese calligraphic handwriting (CCH) is a traditional art form that requires high levels of concentration and motor control. Previous research has linked short-term training in CCH to improvements in attention and memory. Little is known about the potential impacts of long-term CCH practice on a broader array of executive functions and their potential neural substrates. In this cross-sectional study, we recruited 36 practitioners with at least 5 years of CCH experience and 50 control subjects with no more than one month of CCH practice and investigated their differences in the three components of executive functions (i.e., shifting, updating, and inhibition). Valid resting-state fMRI data were collected from 31 CCH and 40 control participants. Compared with the controls, CCH individuals showed better updating (as measured by the Corsi Block Test) and inhibition (as measured by the Stroop Word-Color Test), but the two groups did not differ in shifting (as measured by a cue-target task). The CCH group showed stronger resting-state functional connectivity (RSFC) than the control group in brain areas involved in updating and inhibition. These results suggested that long-term CCH training may be associated with improvements in specific aspects of executive functions and strengthened neural networks in related brain regions. PMID:28129407

Is balance performance reduced after mild traumatic brain injury?: Interim analysis from chronic effects of neurotrauma consortium (CENC) multi-centre study.

PubMed

Walker, William C; Nowak, Kayla J; Kenney, Kimbra; Franke, Laura Manning; Eapen, Blessen C; Skop, Karen; Levin, Harvey; Agyemang, Amma A; Tate, David F; Wilde, Elisabeth A; Hinds, Sidney; Nolen, Tracy L

2018-06-12

Determine if mild traumatic brain injury (mTBI) history is associated with balance disturbances. Chronic Effects of Neurotrauma Consortium (CENC) centres. The CENC multi-centre study enrols post-9/11 era Service Members and Veterans with combat exposure. This sample (n = 322) consisted of enrolees completing initial evaluation by September 2016 at the three sites conducting computerized dynamic post-urography (CDP) testing. Observational study with cross-sectional analyses using structural equation modelling. Comprehensive structured interviews were used to diagnose all lifetime mild traumatic brain injuries (mTBIs). The outcome, Sensory Organization Test (SOT), was measured on CDP dual-plate force platform. Other studied variables were measured by structured interviews, record review and questionnaires. The overall positive/negative mTBI classification did not have a significant effect on the composite equilibrium score. However, the repetitive mTBI classification showed lower scores for participants with ≥ 3 mTBI versus 1-2 lifetime mTBIs. For repetitive mTBI, pain interference acted as a mediator for the indirect effect, and a direct effect was evident on some sensory condition equilibrium scores. These findings show that repeated mTBI, partially mediated by pain, may lead to later balance disturbances among military combatants. Further study of CDP outcomes within this accruing cohort is warranted.

Long-Term Experience of Chinese Calligraphic Handwriting Is Associated with Better Executive Functions and Stronger Resting-State Functional Connectivity in Related Brain Regions.

PubMed

Chen, Wen; He, Yong; Gao, Yang; Zhang, Cuiping; Chen, Chuansheng; Bi, Suyu; Yang, Pin; Wang, Yiwen; Wang, Wenjing

2017-01-01

Chinese calligraphic handwriting (CCH) is a traditional art form that requires high levels of concentration and motor control. Previous research has linked short-term training in CCH to improvements in attention and memory. Little is known about the potential impacts of long-term CCH practice on a broader array of executive functions and their potential neural substrates. In this cross-sectional study, we recruited 36 practitioners with at least 5 years of CCH experience and 50 control subjects with no more than one month of CCH practice and investigated their differences in the three components of executive functions (i.e., shifting, updating, and inhibition). Valid resting-state fMRI data were collected from 31 CCH and 40 control participants. Compared with the controls, CCH individuals showed better updating (as measured by the Corsi Block Test) and inhibition (as measured by the Stroop Word-Color Test), but the two groups did not differ in shifting (as measured by a cue-target task). The CCH group showed stronger resting-state functional connectivity (RSFC) than the control group in brain areas involved in updating and inhibition. These results suggested that long-term CCH training may be associated with improvements in specific aspects of executive functions and strengthened neural networks in related brain regions.

Frontal Lobe Hemodynamic Responses to Painful Stimulation: A Potential Brain Marker of Nociception

PubMed Central

Steele, Sarah C.; Peng, Ke; Boas, David A.; Becerra, Lino; Borsook, David

2016-01-01

The purpose of this study was to use functional near-infrared spectroscopy (fNIRS) to examine patterns of both activation and deactivation that occur in the frontal lobe in response to noxious stimuli. The frontal lobe was selected because it has been shown to be activated by noxious stimuli in functional magnetic resonance imaging studies. The brain region is located behind the forehead which is devoid of hair, providing a relative ease of placement for fNIRS probes on this area of the head. Based on functional magnetic resonance imaging studies showing blood-oxygenation-level dependent changes in the frontal lobes, we evaluated functional near-infrared spectroscopy measures in response to two levels of electrical pain in awake, healthy human subjects (n = 10; male = 10). Each subject underwent two recording sessions separated by a 30-minute resting period. Data collected from 7 subjects were analyzed, containing a total of 38/36 low/high intensity pain stimuli for the first recording session and 27/31 pain stimuli for the second session. Our results show that there is a robust and significant deactivation in sections of the frontal cortices. Further development and definition of the specificity and sensitivity of the approach may provide an objective measure of nociceptive activity in the brain that can be easily applied in the surgical setting. PMID:27806119

Frontal Lobe Hemodynamic Responses to Painful Stimulation: A Potential Brain Marker of Nociception.

PubMed

Aasted, Christopher M; Yücel, Meryem A; Steele, Sarah C; Peng, Ke; Boas, David A; Becerra, Lino; Borsook, David

2016-01-01

The purpose of this study was to use functional near-infrared spectroscopy (fNIRS) to examine patterns of both activation and deactivation that occur in the frontal lobe in response to noxious stimuli. The frontal lobe was selected because it has been shown to be activated by noxious stimuli in functional magnetic resonance imaging studies. The brain region is located behind the forehead which is devoid of hair, providing a relative ease of placement for fNIRS probes on this area of the head. Based on functional magnetic resonance imaging studies showing blood-oxygenation-level dependent changes in the frontal lobes, we evaluated functional near-infrared spectroscopy measures in response to two levels of electrical pain in awake, healthy human subjects (n = 10; male = 10). Each subject underwent two recording sessions separated by a 30-minute resting period. Data collected from 7 subjects were analyzed, containing a total of 38/36 low/high intensity pain stimuli for the first recording session and 27/31 pain stimuli for the second session. Our results show that there is a robust and significant deactivation in sections of the frontal cortices. Further development and definition of the specificity and sensitivity of the approach may provide an objective measure of nociceptive activity in the brain that can be easily applied in the surgical setting.

Gyrification brain abnormalities associated with adolescence and early-adulthood cannabis use.

PubMed

Mata, Ignacio; Perez-Iglesias, Rocio; Roiz-Santiañez, Roberto; Tordesillas-Gutierrez, Diana; Pazos, Angel; Gutierrez, Agustin; Vazquez-Barquero, Jose Luis; Crespo-Facorro, Benedicto

2010-03-04

Although cannabis is the most widely used illicit drug in the world, the long-term effect of its use in the brain remains controversial. In order to determine whether adolescence and early-adulthood cannabis use is associated with gross volumetric and gyrification abnormalities in the brain, we set up a cross-sectional study using structural magnetic resonance imaging in a sample of general population subjects. Thirty cannabis-using subjects (mean age, 25.7 years; mean duration of regular use, 8.4 years, range: 3-21) with no history of polydrug use or neurologic/mental disorder and 44 non-using control subjects (mean age, 25.8 years) were included. Cannabis users showed bilaterally decreased concavity of the sulci and thinner sulci in the right frontal lobe. Among non-users, age was significantly correlated with decreased gyrification (i.e., less concave sulci and more convexe gyri) and decreased cortical thickness, supporting the notion of age-related gyrification changes. However, among cannabis users gyrification indices did not show significant dependency on age, age of regular cannabis use initiation, or cumulative exposure to cannabis. These results suggest that cannabis use in adolescence and early-adulthood might involve a premature alteration in cortical gyrification similar to what is normally observed at a later age, probably through disruption of normal neurodevelopment. 2009 Elsevier B.V. All rights reserved.

Estrogenic Effects of Several BPA Analogs in the Developing Zebrafish Brain

PubMed Central

Cano-Nicolau, Joel; Vaillant, Colette; Pellegrini, Elisabeth; Charlier, Thierry D.; Kah, Olivier; Coumailleau, Pascal

2016-01-01

Important set of studies have demonstrated the endocrine disrupting activity of Bisphenol A (BPA). The present work aimed at defining estrogenic-like activity of several BPA structural analogs, including BPS, BPF, BPAF, and BPAP, on 4- or 7-day post-fertilization (dpf) zebrafish larva as an in vivo model. We measured the induction level of the estrogen-sensitive marker cyp19a1b gene (Aromatase B), expressed in the brain, using three different in situ/in vivo strategies: (1) Quantification of cyp19a1b transcripts using RT-qPCR in wild type 7-dpf larva brains exposed to bisphenols; (2) Detection and distribution of cyp19a1b transcripts using in situ hybridization on 7-dpf brain sections (hypothalamus); and (3) Quantification of the cyp19a1b promoter activity in live cyp19a1b-GFP transgenic zebrafish (EASZY assay) at 4-dpf larval stage. These three different experimental approaches demonstrated that BPS, BPF, or BPAF exposure, similarly to BPA, significantly activates the expression of the estrogenic marker in the brain of developing zebrafish. In vitro experiments using both reporter gene assay in a glial cell context and competitive ligand binding assays strongly suggested that up-regulation of cyp19a1b is largely mediated by the zebrafish estrogen nuclear receptor alpha (zfERα). Importantly, and in contrast to other tested bisphenol A analogs, the bisphenol AP (BPAP) did not show estrogenic activity in our model. PMID:27047331

Pseudallescheria boydii brain abscess in a renal transplant recipient: first case report in Southeast Asia.

PubMed

Satirapoj, B; Ruangkanchanasetr, P; Treewatchareekorn, S; Supasyndh, O; Luesutthiviboon, L; Supaporn, T

2008-09-01

Pseudallescheria boydii and its asexual form, Scedosporium apiospermum, are ubiquitous filamentous fungi that rarely cause central nervous system (CNS) infection. Brain abscess caused by P. boydii is a highly lethal infection, usually seen in organ transplant recipients who receive a number of immunosuppressive agents. We have presented a case of a 48-year-old man 6 years after renal transplantation who received methylprednisolone followed by antithymocyte globulin for treatment of acute cellular rejection. Eight weeks later, he developed fever, headache, and left-sided hemiparesis. Further investigation with magnetic resonance imaging of the brain showed multiple ring-enhancing hypodense lesions with marked edema which were compatible with brain abscesses. Following surgical drainage, multiple fungal elements were initially described as Aspergillus species. The patient failed to improve and died from rapidly progressive infection despite treatment with amphotericin B. Later a diagnosis was finally made by the isolation of P. boydii in pus culture. The specific diagnosis is difficult to rapidly make, because P. boydii mimics other fungi morphologically in tissue sections and may produce infections clinically similar to other mycoses. Culture of the organism is required for definitive diagnosis. P. boydii infections are important complications of transplantation. They are difficult to treat due to resistance to amphotericin B. Physicians should consider P. boydii a possible cause of brain abscess in organ transplant recipients, especially with heavy immunosuppressive agents. This is the first case report of CNS infection due to P. boydii in a renal transplant patient in Southeast Asia.

Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery.

PubMed

Kumar, Manoj; Pandey, Ravi Shankar; Patra, Kartik Chandra; Jain, Sunil Kumar; Soni, Muarai Lal; Dangi, Jawahar Singh; Madan, Jitender

2013-10-01

Leucine-enkephalin (Leu-Enk) is a neurotransmitter or neuromodulator in pain transmission. Due to non-addictive opioid analgesic activity of this peptide, it might have great potential in pain management. Leu-Enk loaded N-trimethyl chitosan (TMC) nanoparticles were prepared and evaluated as a brain delivery vehicle via nasal route. TMC biopolymer was synthesized and analyzed by (1)H NMR spectroscopy. TMC nanoparticles were prepared by ionic gelation method. Mean peptide encapsulation efficiency and loading capacity were 78.28±3.8% and 14±1.3%, respectively. Mean particle size, polydispersity index and zeta potential were found to be 443±23 nm, 0.317±0.17 and +15±2 mV respectively for optimized formulations. Apparent permeability coefficient (Papp) of Leu-Enk released from nanoparticles across the porcine nasal mucosa was determined to be 7.45±0.30×10(-6) cm s(-1). Permeability of Leu-Enk released from nanoparticles was 35 fold improved from the nasal mucosa as compared to Leu-Enk solution. Fluorescent microscopy of brain sections of mice showed higher accumulation of fluorescent marker NBD-F labelled Leu-Enk, when administered nasally by TMC nanoparticles, while low brain uptake of marker solution was observed. Furthermore, enhancement in brain uptake resulted into significant improvement in the observed antinociceptive effect of Leu-Enk as evidenced by hot plate and acetic acid induced writhing assay. Copyright © 2013 Elsevier B.V. All rights reserved.

Neuroanatomy: The added value of the Klingler method.

PubMed

Silva, Susana M; Andrade, José Paulo

2016-11-01

Undergraduate neuroanatomy students are usually not able to achieve a clear comprehension of the spatial relationships existing between the white matter fiber tracts in spite of numerous neuroanatomy textbooks, atlases and multimedia tools. The objective of this paper is to show the educational value of the application of the Klingler fiber dissection technique and the use of these dissections in the understanding of the three-dimensional intrinsic anatomy of the brain white matter for medical students. Four formalin-fixed brains were dissected using the Klingler methodology in order to reveal the inner anatomical organization of the brain white matter. The most important fiber systems were dissected and their relationships to the cerebral and cerebellar gray matter structures visualized. These dissections were used as a learning tool in teaching the brain white matter structural and topographical connectivity. The white matter fiber systems were presented to undergraduate medical students during a neuroanatomy course. They observed and manipulated the dissected specimens leading to a thorough understanding of the configuration and location of the white matter fiber tracts, and their relationships to the ventricular system and gray matter structures. Subsequently, students were asked to answer a survey concerning the importance of the utilization of this material in their understanding of the three-dimensional intrinsic anatomy of the brain white matter. The knowledge acquired with this technique, complemented by conventional formalin-fixed sections may improve the neuroanatomical knowledge and future retention of medical students. Copyright © 2016 Elsevier GmbH. All rights reserved.

Alterations in L-Glutamate Binding in Alzheimer's and Huntington's Diseases

NASA Astrophysics Data System (ADS)

Greenamyre, J. Timothy; Penney, John B.; Young, Anne B.; D'Amato, Constance J.; Hicks, Samuel P.; Shoulson, Ira

1985-03-01

Brain sections from patients who had died with senile dementia of the Alzheimer's type (SDAT), Huntington's disease (HD), or no neurologic disease were studied by autoradiography to measure sodium-independent L-[3H]glutamate binding. In brain sections from SDAT patients, glutamate binding was normal in the caudate, putamen, and claustrum but was lower than normal in the cortex. The decreased cortical binding represented a reduction in numbers of binding sites, not a change in binding affinity, and appeared to be the result of a specific decrease in numbers of the low-affinity quisqualate binding site. No significant changes in cortical binding of other ligands were observed. In brains from Huntington's disease patients, glutamate binding was lower in the caudate and putamen than in the same regions of brains from control and SDAT patients but was normal in the cortex. It is possible that development of positron-emitting probes for glutamate receptors may permit diagnosis of SDAT in vivo by means of positron emission tomographic scanning.

Spatial ability and training in virtual neuroanatomy.

PubMed

Plumley, Leah; Armstrong, Ryan; De Ribaupierre, Sandrine; Eagleson, Roy

2013-01-01

Neuroanatomy is one of the most challenging sections of anatomy to learn, partially related to the intricate relation of multiple 3D structures. As part of the medical student curriculum, it is usually taught in 2D using illustrations and plastinated brain section, since the number of hours devoted to anatomy have dropped in the curriculum, making the dissection of brain too time-consuming to be done. In this study we are analyzing the role of innate spatial ability of novices in learning some basic structures and placing them back in a 3D volumetric brain. Two tasks are performed after a short training session: the first one is to localize the ventricular tip as would be required during a temporal lobectomy, and the second task requires that the subject 'reconstruct' 3D anatomical structures within the context of our 3D brain model. We report our findings on the performance scores obtained from a population of subjects of differing backgrounds and spatial abilities.

Methamphetamine users show greater than normal age-related cortical gray matter loss.

PubMed

Nakama, Helenna; Chang, Linda; Fein, George; Shimotsu, Ryan; Jiang, Caroline S; Ernst, Thomas

2011-08-01

Methamphetamine (Meth) abuse continues to be a major illicit drug of abuse. Neuroimaging findings suggest that Meth is neurotoxic and may alter various brain structures, but the effect of Meth on the aging brain has not been studied. The aim was to determine regional volumes of cortical gray matter in the brains of adult Meth users versus healthy control subjects, and their interaction with age and Meth-usage variables. Cross-sectional study Magnetic resonance imaging (MRI) Research Center located in a university-affiliated hospital. Thirty-four Meth-dependent subjects (21 men and 13 women; ages 33.1 ± 8.9 years), diagnosed according to DSM-IV criteria, and 31 healthy non-Meth user comparison subjects (23 men and 8 women ages 35.7 ± 8.4 years). Regional gray matter volumes were segmented automatically in all subjects and evaluated in relation to age, using high-resolution MRIs at 3.0 Tesla. After adjustment for the effects of cranium size, the Meth users showed enhanced cortical gray matter volume loss with age in the frontal (analysis of covariance interaction P = 0.02), occipital (interaction P = 0.01), temporal (interaction P < 0.001) and the insular lobes (interaction P = 0.01) compared to controls, independently of Meth-usage patterns. Additionally, Meth users showed smaller gray matter volumes than control subjects in several subregions (dorsolateral prefrontal: P = 0.02; orbitofrontal: P = 0.03; prefrontal: P = 0.047; superior temporal: P = 0.04). Methamphetamine users appear to show increased cortical gray matter loss with age which raises the possibility of accelerated decline in mental functioning. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Neuronal Deletion of Caspase 8 Protects against Brain Injury in Mouse Models of Controlled Cortical Impact and Kainic Acid-Induced Excitotoxicity

PubMed Central

Krajewska, Maryla; You, Zerong; Rong, Juan; Kress, Christina; Huang, Xianshu; Yang, Jinsheng; Kyoda, Tiffany; Leyva, Ricardo; Banares, Steven; Hu, Yue; Sze, Chia-Hung; Whalen, Michael J.; Salmena, Leonardo; Hakem, Razqallah; Head, Brian P.; Reed, John C.; Krajewski, Stan

2011-01-01

Background Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8 −/−), in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system. Methodology/Principal Findings Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal cultures and in whole brain organotypic coronal slice cultures prepared from 4 and 8 month old mice and cultivated up to 14 days in vitro. Treatments of cultures with recombinant murine TNFα (100 ng/ml) or TRAIL (250 ng/mL) plus cyclohexamide significantly protected neurons against cell death induced by these apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was also demonstrated using a controlled cortical impact (CCI) model of traumatic brain injury (TBI) and seizure-induced brain injury caused by kainic acid (KA). Morphometric analyses were performed using digital imaging in conjunction with image analysis algorithms. By employing virtual images of hundreds of brain sections, we were able to perform quantitative morphometry of histological and immunohistochemical staining data in an unbiased manner. In the TBI model, homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved post-injury motor performance, superior learning and memory retention, decreased apoptosis, diminished proteolytic processing of caspases and caspase substrates, and less neuronal degeneration, compared to wild type, homozygous cre, and caspase 8-floxed control mice. In the KA model, Ncasp8 −/− mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging. Conclusions Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this caspase in pathophysiology of acute brain trauma. PMID:21957448

Two-Photon Microscopy Imaging of thy1GFP-M Transgenic Mice: A Novel Animal Model to Investigate Brain Dendritic Cell Subsets In Vivo

PubMed Central

Laperchia, Claudia; Allegra Mascaro, Anna L.; Sacconi, Leonardo; Andrioli, Anna; Mattè, Alessandro; De Franceschi, Lucia; Grassi-Zucconi, Gigliola; Bentivoglio, Marina; Buffelli, Mario; Pavone, Francesco S.

2013-01-01

Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF) microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP) in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype. With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity) of dendritic cells (DCs), and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions. PMID:23409142

Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

PubMed Central

Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

2016-01-01

Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied, the changes in mechanical properties were modest. Moreover, the effect of ventricular enlargement is not limited to the CC+PVWM and ventral internal capsule, the extent of microstructural changes vary between brain regions, and there is regional and temporal variation in brain tissue stiffness during hydrocephalus development. PMID:26848844

Peripheral Precocious Puberty Caused by Human Chorionic Gonadotropin Producing Pineal Gland Tumor.

PubMed

Hammadur Rahaman, S K; Khandelwal, Deepak; Khadgawat, Rajesh; Kandasamy, Devasenathipathy; Bakhshi, Sameer

2018-03-15

Pineal gland lesions usually present with central precocious puberty. A 3½-yr-old boy presented with precocious puberty. Clinically and biochemically, it was gonadotropin releasing hormone (GnRH) independent. Serum and CSF beta-hCG levels were increased. Thin section magnetic resonance imaging of brain revealed a pineal gland tumor. He received chemotherapy followed by radiotherapy and responded well. CSF beta-hCG should be measured in all cases of peripheral precocity, and if CSF beta-hCG is elevated, thin section magnetic resonance imaging of brain should be considered.

Can brain scans prove criminals unaccountable?

PubMed Central

Roache, Rebecca

2014-01-01

Leonard Berlin reports that neuroscientific data play an increasing role in court. They have been used to argue that criminals are not morally responsible for their behaviour because their brains are ‘faulty’, and there is evidence that such data lead judges to pass more lenient sentences. I raise two concerns about the view that neuroscience can show criminals not to be morally responsible: That the brains of (say) violent criminals differ from most people’s brains does not straightforwardly show that violent criminals are less morally responsible. Behavioral states arise inter alia from brain states, and since violent criminals’ behavioral states differ from those of most people, it is unsurprising that violent criminals’ brains should differ from most people’s brains. This no more shows violent criminals to have diminished moral responsibility than differences between the brains of cheerful and uncheerful people show either group to have diminished moral responsibility.Those who view brain abnormalities as evidence of reduced moral responsibility rely on the assumptions that people with normal brains have free will and that we know what sorts of brain activity undermine free will. However, both of these assumptions are highly controversial. As a result, neuroscience is not a reliable source of information about moral responsibility. I conclude that, until we settle whether and under what circumstances brain activity is incompatible with free will, neuroscience cannot tell us anything useful about criminal accountability. PMID:25009758

Leishmania amastigotes in the central nervous system of a naturally infected dog.

PubMed

Márquez, Merce; Pedregosa, José Raúl; López, Jesús; Marco-Salazar, Paola; Fondevila, Dolors; Pumarola, Martí

2013-01-01

A 4-year-old male Labrador Retriever dog was presented with a 10-day history of tetraplegia, depression, and absent postural reflexes. The cerebrospinal fluid was positive for Leishmania spp. DNA. At necropsy, a 2-cm long mass was observed adhered to C(7) and C(8) left spinal nerves. Microscopically, nerve fiber destruction together with mixed inflammatory infiltration was observed in the spinal nerves. Cervical spinal cord sections showed multifocal, diffuse granulomatous inflammation in the white matter. In the brain, perivascular infiltrates were observed in some areas together with subtle pallor of the parenchyma. Immunohistochemistry for Leishmania infantum confirmed the presence of amastigotes in the spinal nerves, spinal cord, brain parenchyma, and choroid plexuses. The current study describes the presence of Leishmania amastigotes in nervous tissue inciting radiculoneuritis, myelitis, and mild meningoencephalitis, suggesting a likely route by which L. infantum amastigotes reach and affect the central nervous system parenchyma.

Color vision abnormality as the sole manifestation of posterior reversible encephalopathy due to post-partum HELLP syndrome.

PubMed

Takahashi, Hironori; Matsubara, Teppei; Makino, Shinji; Horie, Kenji; Matsubara, Shigeki

2017-03-01

Posterior reversible encephalopathy syndrome (PRES) is associated with several symptoms; of those, visual acuity loss, light oversensitivity (photophobia), and light flashes (photopsia) are known as PRES-related eye symptoms. We report a post-partum woman with PRES associated with hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP), in whom color vision abnormality (achromatopsia) was the sole manifestation. Cesarean section was performed at 28 weeks due to headache, epigastralgia, and severe hypertension. HELLP became evident after delivery. On post-partum day 1, she complained of achromatopsia, stating: "all things look brownish-gray". Ophthalmologic examination was normal, but brain magnetic resonance imaging showed occipital lobe lesions, indicative of PRES, and, interestingly, also color vision center (area V4) lesions, suggesting that the achromatopsia had been caused by brain damage. It may be prudent to question HELLP patients concerning achromatopsia. © 2017 Japan Society of Obstetrics and Gynecology.

Localization of brain-derived neurotrophic factor, neurotrophin-4, tropomyosin-related kinase b receptor, and p75 NTR receptor by high-resolution immunohistochemistry on the adult mouse neuromuscular junction.

PubMed

Garcia, Neus; Tomàs, Marta; Santafe, Manel M; Lanuza, M Angel; Besalduch, Nuria; Tomàs, Josep

2010-03-01

Neurotrophins and their receptors, the trk receptor tyrosine kinases (trks) and p75(NTR), are differentially expressed among the cell types that make up synapses. It is important to determine the precise location of these molecules involved in neurotransmission. Here we use immunostaining and Western blotting to study the localization and expression of neurotrophin brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) and the receptors tropomyosin-related kinase b (trkB) and p75(NTR) at the adult neuromuscular junction. Our confocal immunofluorescence results on the whole mounts of the mouse Levator auris longus muscle and on semithin cross-sections showed that BDNF, NT-4, trkB, and p75(NTR) were localized on the three cells in the neuromuscular synapse (motor axons, post-synaptic muscle and Schwann cells).

Lysosomal Accumulation of SCMAS (Subunit c of Mitochondrial ATP Synthase) in Neurons of the Mouse Model of Mucopolysaccharidosis III B

PubMed Central

Ryazantsev, Sergey; Yu, Wei-Hong; Zhao, Hui-Zhi; Neufeld, Elizabeth F.; Ohmi, Kazuhiro

2007-01-01

The neurodegenerative disease MPS III B (Sanfilippo syndrome type B) is caused by mutations in the gene encoding the lysosomal enzyme α-N-acetylglucosaminidase, with a resulting block in heparan sulfate degradation. A mouse model with disruption of the Naglu gene allows detailed study of brain pathology. In contrast to somatic cells, which accumulate primarily heparan sulfate, neurons accumulate a number of apparently unrelated metabolites, including subunit c of mitochondrial ATP synthase (SCMAS). SCMAS accumulated from 1 month of age, primarily in the medial entorhinal cortex and layer V of the somatosensory cortex. Its accumulation was not due to the absence of specific proteases. Light microscopy of brain sections of 6 months-old mice showed SCMAS to accumulate in the same areas as glycosaminoglycan and unesterified cholesterol, in the same cells as ubiquitin and GM3 ganglioside, and in the same organelles as Lamp 1 and Lamp 2. Cryo-immuno electron microscopy showed SCMAS to be present in Lamp positive vesicles bounded by a single membrane (lysosomes), in fingerprint-like layered arrays. GM3 ganglioside was found in the same lysosomes, but was not associated with the SCMAS arrays. GM3 ganglioside was also seen in lysosomes of microglia, suggesting phagocytosis of neuronal membranes. Samples used for cryo-EM and further processed by standard EM procedures (osmium tetroxide fixation and plastic embedding) showed the disappearance of the SCMAS fingerprint arrays and appearance in the same location of “zebra bodies”, well known but little understood inclusions in the brain of patients with mucopolysaccharidoses. PMID:17185018

Computer-assisted mapping of immunoreactive mammalian gonadotropin-releasing hormone in adult human basal forebrain and amygdala.

PubMed

Stopa, E G; Koh, E T; Svendsen, C N; Rogers, W T; Schwaber, J S; King, J C

1991-06-01

Immunocytochemistry performed on 80-microns unembedded tissue sections was used to study the localization of GnRH-containing neurons and fibers in the basal forebrain and amygdala of six adult (four male, two female) human brains. Sections from one of the female brains were subjected to computer-assisted microscopic mapping to generate a three-dimensional analysis of immunoreactive structures. In all six brains examined, cell bodies were concentrated in the preoptic area and basal hypothalamus, but were also evident in the septal region, anterior olfactory area, and cortical and medial amygdaloid nuclei. GnRH-containing fibers were observed within the hypothalamus (predominantly infundibular region and preoptic area), septum, stria terminalis, ventral pallidum, dorsomedial thalamus, olfactory stria, and anterior olfactory area. Many fibers could also be seen coursing along the base of the brain between the hypothalamus and cortical and medial amygdaloid nuclei. The localization of GnRH-containing cells and fibers in several of these areas represents new observations in the human brain and suggests a role for the amygdaloid complex in the regulation of gonadotropin secretion. The comprehensive view provided by these data may be useful in the clinical application of novel transplantation strategies.

Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection.

PubMed

Mertz, Jerome; Kim, Jinhyun

2010-01-01

It is well known that light-sheet illumination can enable optically sectioned wide-field imaging of macroscopic samples. However, the optical sectioning capacity of a light-sheet macroscope is undermined by sample-induced scattering or aberrations that broaden the thickness of the sheet illumination. We present a technique to enhance the optical sectioning capacity of a scanning light-sheet microscope by out-of-focus background rejection. The technique, called HiLo microscopy, makes use of two images sequentially acquired with uniform and structured sheet illumination. An optically sectioned image is then synthesized by fusing high and low spatial frequency information from both images. The benefits of combining light-sheet macroscopy and HiLo background rejection are demonstrated in optically cleared whole mouse brain samples, using both green fluorescent protein (GFP)-fluorescence and dark-field scattered light contrast.

Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection

NASA Astrophysics Data System (ADS)

Mertz, Jerome; Kim, Jinhyun

2010-01-01

It is well known that light-sheet illumination can enable optically sectioned wide-field imaging of macroscopic samples. However, the optical sectioning capacity of a light-sheet macroscope is undermined by sample-induced scattering or aberrations that broaden the thickness of the sheet illumination. We present a technique to enhance the optical sectioning capacity of a scanning light-sheet microscope by out-of-focus background rejection. The technique, called HiLo microscopy, makes use of two images sequentially acquired with uniform and structured sheet illumination. An optically sectioned image is then synthesized by fusing high and low spatial frequency information from both images. The benefits of combining light-sheet macroscopy and HiLo background rejection are demonstrated in optically cleared whole mouse brain samples, using both green fluorescent protein (GFP)-fluorescence and dark-field scattered light contrast.

Feasibility of in Vivo SAXS Imaging for Detection of Alzheiemer's Disease

NASA Astrophysics Data System (ADS)

Choi, Mina

Small-angle x-ray scattering (SAXS) imaging has been proposed as a technique to characterize and selectively image structures based on electron density structure which allows for discriminating materials based on their scatter cross sections. This dissertation explores the feasibility of SAXS imaging for the detection of Alzheimer's disease (AD) amyloid plaques. The inherent scatter cross sections of amyloid plaque serve as biomarkers in vivo without the need of injected molecular tags. SAXS imaging can also assist in a better understanding of how these biomarkers play a role in Alzheimer's disease which in turn can lead to the development of more effective disease-modifying therapies. I implement simulations of x-ray transport using Monte Carlo methods for SAXS imaging enabling accurate calculation of radiation dose and image quality in SAXS-computed tomography (CT). I describe SAXS imaging phantoms with tissue-mimicking material and embedded scatter targets as a way of demonstrating the characteristics of SAXS imaging. I also performed a comprehensive study of scattering cross sections of brain tissue from measurements of ex-vivo sections of a wild-type mouse brain and reported generalized cross sections of gray matter, white matter, and corpus callosum obtained and registered by planar SAXS imaging. Finally, I demonstrate the ability of SAXS imaging to locate an amyloid fibril pellet within a brain section. This work contributes to novel application of SAXS imaging for Alzheimer's disease detection and studies its feasibility as an imaging tool for AD biomarkers.

Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group.

PubMed

van Rooij, Daan; Anagnostou, Evdokia; Arango, Celso; Auzias, Guillaume; Behrmann, Marlene; Busatto, Geraldo F; Calderoni, Sara; Daly, Eileen; Deruelle, Christine; Di Martino, Adriana; Dinstein, Ilan; Duran, Fabio Luis Souza; Durston, Sarah; Ecker, Christine; Fair, Damien; Fedor, Jennifer; Fitzgerald, Jackie; Freitag, Christine M; Gallagher, Louise; Gori, Ilaria; Haar, Shlomi; Hoekstra, Liesbeth; Jahanshad, Neda; Jalbrzikowski, Maria; Janssen, Joost; Lerch, Jason; Luna, Beatriz; Martinho, Mauricio Moller; McGrath, Jane; Muratori, Filippo; Murphy, Clodagh M; Murphy, Declan G M; O'Hearn, Kirsten; Oranje, Bob; Parellada, Mara; Retico, Alessandra; Rosa, Pedro; Rubia, Katya; Shook, Devon; Taylor, Margot; Thompson, Paul M; Tosetti, Michela; Wallace, Gregory L; Zhou, Fengfeng; Buitelaar, Jan K

2018-04-01

Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.

Gray matter maturation and cognition in children with different APOE ε genotypes.

PubMed

Chang, Linda; Douet, Vanessa; Bloss, Cinnamon; Lee, Kristin; Pritchett, Alexandra; Jernigan, Terry L; Akshoomoff, Natacha; Murray, Sarah S; Frazier, Jean; Kennedy, David N; Amaral, David G; Gruen, Jeffrey; Kaufmann, Walter E; Casey, B J; Sowell, Elizabeth; Ernst, Thomas

2016-08-09

The aims of the current study were to determine whether children with the 6 different APOE ε genotypes show differences in gray matter maturation, particularly for those with ε4 and ε2 alleles, which are associated with poorer outcomes in many neurologic disorders. A total of 1,187 healthy children (aged 3-20 years, 52.1% boys, 47.9% girls) with acceptable data from the cross-sectional Pediatric Imaging Neurocognition and Genetics Study were evaluated for the effects of 6 APOE ε genotypes on macroscopic and microscopic cortical and subcortical gray matter structures (measured with 3-tesla MRI and FreeSurfer for automated morphometry) and on cognition (NIH Toolbox). Among APOE ε4 carriers, age-related changes in brain structures and cognition varied depending on genotype, with the smallest hippocampi in ε2ε4 children, the lowest hippocampal fractional anisotropy in younger ε4ε4 children, the largest medial orbitofrontal cortical areas in ε3ε4 children, and age-dependent thinning of the entorhinal cortex in ε4ε4 children. Younger ε4ε4 children had the lowest scores on executive function and working memory, while younger ε2ε4 children performed worse on attention tasks. Larger parietal gyri in the younger ε2ε4 children, and thinner temporal and cingulate isthmus cortices or smaller hippocampi in the younger ε4ε4 children, predicted poorer performance on attention or working memory. Our findings validated and extended prior smaller studies that showed altered brain development in APOE ε4-carrier children. The ε4ε4 and ε2ε4 genotypes may negatively influence brain development and brain aging at the extremes of age. Studying APOE ε polymorphisms in young children may provide the earliest indicators for individuals who might benefit from early interventions or preventive measures for future brain injuries and dementia. © 2016 American Academy of Neurology.

Brain Response to Working Memory Over Three Years of Adolescence: Influence of Initiating Heavy Drinking

PubMed Central

Squeglia, Lindsay M.; Pulido, Carmen; Wetherill, Reagan R.; Jacobus, Joanna; Brown, Gregory G.; Tapert, Susan F.

2012-01-01

Objective: Many adolescents engage in heavy alcohol use. The aim of this study was to disentangle whether brain abnormalities seen in adolescent heavy drinkers are a consequence of heavy drinking, a preexisting risk factor for initiation of alcohol use, or both. Method: Study 1 used cross-sectional functional magnetic resonance imaging (fMRI) visual working-memory (VWM) data from 15- to 19-year-olds (20 heavy drinkers, 20 controls) to identify brain regions affected by heavy adolescent alcohol use. Study 2 used longitudinal fMRI VWM data from 12- to 16-year-olds imaged before the onset of drinking and imaged again on the same scanner approximately 3 years later. Those who had transitioned into heavy drinking (n = 20) were matched to continuous nondrinkers (n = 20) on baseline alcohol risk and developmental factors (N = 40; 80 scans). Results: Study 1 found that heavy drinkers exhibited more frontal and parietal but less occipital activation than controls, defining the regions of interest for Study 2. In Study 2, adolescents who later transitioned into heavy drinking showed less fMRI response contrast at baseline than continuous nondrinkers, which increased after the onset of heavy drinking, in frontal (1,431 μL, p = .003; η2 = .19) and parietal (810 μL, p = .005; η2 = .23) regions, as in Study 1. Lower baseline activation in the frontal and parietal regions predicted subsequent substance use, more so than commonly observed predictors of youth drinking (p < .05). Conclusions: Adolescents who initiated heavy drinking showed different brain activation before the onset of drinking, then less efficient information processing after high-dose alcohol use started. This suggests neural response patterns that could be risk factors for future substance use and also supports prior neuropsychological reports indicating that initiating heavy episodic drinking in adolescence may be followed by subtle alterations in brain functioning. PMID:22846239

Brain activity changes in cognitive networks in relapsing-remitting multiple sclerosis - insights from a longitudinal FMRI study.

PubMed

Loitfelder, Marisa; Fazekas, Franz; Koschutnig, Karl; Fuchs, Siegrid; Petrovic, Katja; Ropele, Stefan; Pichler, Alexander; Jehna, Margit; Langkammer, Christian; Schmidt, Reinhold; Neuper, Christa; Enzinger, Christian

2014-01-01

Extrapolations from previous cross-sectional fMRI studies suggest cerebral functional changes with progression of Multiple Sclerosis (MS), but longitudinal studies are scarce. We assessed brain activation changes over time in MS patients using a cognitive fMRI paradigm and examined correlations with clinical and cognitive status and brain morphology. 13 MS patients and 15 healthy controls (HC) underwent MRI including fMRI (go/no-go task), neurological and neuropsychological exams at baseline (BL) and follow-up (FU; minimum 12, median 20 months). We assessed estimates of and changes in fMRI activation, total brain and subcortical grey matter volumes, cortical thickness, and T2-lesion load. Bland-Altman (BA) plots served to assess fMRI signal variability. Cognitive and disability levels remained largely stable in the patients. With the fMRI task, both at BL and FU, patients compared to HC showed increased activation in the insular cortex, precuneus, cerebellum, posterior cingulate cortex, and occipital cortex. At BL, patients vs. HC also had lower caudate nucleus, thalamus and putamen volumes. Over time, patients (but not HC) demonstrated fMRI activity increments in the left inferior parietal lobule. These correlated with worse single-digit-modality test (SDMT) performance. BA-plots attested to reproducibility of the fMRI task. In the patients, the right caudate nucleus decreased in volume which again correlated with worsening SDMT performance. Given preserved cognitive performance, the increased activation at BL in the patients may be viewed as largely adaptive. In contrast, the negative correlation with SDMT performance suggests increasing parietal activation over time to be maladaptive. Several areas with purported relevance for cognition showed decreased volumes at BL and right caudate nucleus volume decline correlated with decreasing SDMT performance. This highlights the dynamics of functional changes and the strategic importance of specific brain areas for cognitive processes in MS.

The effects of chronic alcohol self-administration in nonhuman primate brain networks.

PubMed

Telesford, Qawi K; Laurienti, Paul J; Davenport, April T; Friedman, David P; Kraft, Robert A; Daunais, James B

2015-04-01

Long-term alcohol abuse is associated with change in behavior, brain structure, and brain function. However, the nature of these changes is not well understood. In this study, we used network science to analyze a nonhuman primate model of ethanol self-administration to evaluate functional differences between animals with chronic alcohol use and animals with no exposure to alcohol. Of particular interest was how chronic alcohol exposure may affect the resting state network. Baseline resting state functional magnetic resonance imaging was acquired in a cohort of vervet monkeys. Animals underwent an induction period where they were exposed to an isocaloric maltose dextrin solution (control) or ethanol in escalating doses over three 30-day epochs. Following induction, animals were given ad libitum access to water and a maltose dextrin solution (control) or water and ethanol for 22 h/d over 12 months. Cross-sectional analyses examined region of interests in hubs and community structure across animals to determine differences between drinking and nondrinking animals after the 12-month free access period. Animals were classified as lighter (<2.0 g/kg/d) or heavier drinkers (≥2.0 g/kg/d) based on a median split of their intake pattern during the 12-month ethanol free access period. Statistical analysis of hub connectivity showed significant differences in heavier drinkers for hubs in the precuneus, posterior parietal cortices, superior temporal gyrus, subgenual cingulate, and sensorimotor cortex. Heavier drinkers were also shown to have less consistent communities across the brain compared to lighter drinkers. The different level of consumption between the lighter and heavier drinking monkeys suggests that differences in connectivity may be intake dependent. Animals that consume alcohol show topological differences in brain network organization, particularly in animals that drink heavily. Differences in the resting state network were linked to areas that are associated with spatial association, working memory, and visuomotor processing. Copyright © 2015 by the Research Society on Alcoholism.

Longitudinal and cross-sectional structural magnetic resonance imaging correlates of AV-1451 uptake.

PubMed

Das, Sandhitsu R; Xie, Long; Wisse, Laura E M; Ittyerah, Ranjit; Tustison, Nicholas J; Dickerson, Bradford C; Yushkevich, Paul A; Wolk, David A

2018-06-01

We examined the relationship between in vivo estimates of tau deposition as measured by 18 F-AV-1451 tau positron emission tomography imaging and cross-sectional cortical thickness, as well as rates of antecedent cortical thinning measured from magnetic resonance imaging in individuals with and without evidence of cerebral amyloid in 63 participants from the Alzheimer's Disease Neuroimaging Initiative study, including 32 cognitively normal individuals (mean age 74 years), 27 patients with mild cognitive impairment (mean age 76.8 years), and 4 patients diagnosed with Alzheimer's disease (mean age 80 years). We hypothesized that structural measures would correlate with 18 F-AV-1451 in a spatially local manner and that this correlation would be stronger for longitudinal compared to cross-sectional measures of cortical thickness and in those with cerebral amyloid versus those without. Cross-sectional and longitudinal estimates of voxelwise atrophy were made from whole brain maps of cortical thickness and rates of thickness change. In amyloid-β-positive individuals, the correlation of voxelwise atrophy across the whole brain with a summary measure of medial temporal lobe (MTL) 18 F-AV-1451 uptake demonstrated strong local correlations in the MTL with longitudinal atrophy that was weaker in cross-sectional analysis. Similar effects were seen in correlations between 31 bilateral cortical regions of interest. In addition, several nonlocal correlations between atrophy and 18 F-AV-1451 uptake were observed, including association between MTL atrophy and 18 F-AV-1451 uptake in parietal lobe regions of interest such as the precuneus. Amyloid-β-negative individuals only showed weaker correlations in data uncorrected for multiple comparisons. While these data replicate previous reports of associations between 18 F-AV-1451 uptake and cross-sectional structural measures, the current results demonstrate a strong relationship with longitudinal measures of atrophy. These data support the notion that in vivo measures of tau pathology are tightly linked to the rate of neurodegenerative change. Copyright © 2018 Elsevier Inc. All rights reserved.

Histochemical detection of GM1 ganglioside using cholera toxin-B subunit. Evaluation of critical factors optimal for in situ detection with special emphasis to acetone pre-extraction

PubMed Central

Petr, T.; Šmíd, V.; Šmídová, J.; Hůlková, H.; Jirkovská, M.; Elleder, M.; Muchová, L.; Vítek, L.; Šmíd, F.

2010-01-01

A comparison of histochemical detection of GM1 ganglioside in cryostat sections using cholera toxin B-subunit after fixation with 4% formaldehyde and dry acetone gave tissue-dependent results. In the liver no pre-treatment showed detectable differences related to GM1 reaction products, while studies in the brain showed the superiority of acetone pre-extraction (followed by formaldehyde), which yielded sharper images compared with the diffuse, blurred staining pattern associated with formaldehyde. Therefore, the aim of our study was to define the optimal conditions for the GM1 detection using cholera toxin B-subunit. Ganglioside extractability with acetone, the ever neglected topic, was tested comparing anhydrous acetone with acetone containing admixture of water. TLC analysis of acetone extractable GM1 ganglioside from liver sections did not exceed 2% of the total GM1 ganglioside content using anhydrous acetone at −20°C, and 4% at room temperature. The loss increased to 30.5% using 9:1 acetone/water. Similarly, photometric analysis of lipid sialic acid, extracted from dried liver homogenates with anhydrous acetone, showed the loss of gangliosides into acetone 3.0±0.3% only. The loss from dried brain homogenate was 9.5±1.1%. Thus, anhydrous conditions (dry tissue samples and anhydrous acetone) are crucial factors for optimal in situ ganglioside detection using acetone pre-treatment. This ensures effective physical fixation, especially in tissues rich in polar lipids (precipitation, prevention of in situ diffusion), and removal of cholesterol, which can act as a hydrophobic blocking barrier. PMID:20558344

Structural covariance of neostriatal and limbic regions in patients with obsessive-compulsive disorder.

PubMed

Subirà, Marta; Cano, Marta; de Wit, Stella J; Alonso, Pino; Cardoner, Narcís; Hoexter, Marcelo Q; Kwon, Jun Soo; Nakamae, Takashi; Lochner, Christine; Sato, João R; Jung, Wi Hoon; Narumoto, Jin; Stein, Dan J; Pujol, Jesus; Mataix-Cols, David; Veltman, Dick J; Menchón, José M; van den Heuvel, Odile A; Soriano-Mas, Carles

2016-03-01

Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored. We performed a mega-analysis pooling structural MRI scans from the Obsessive-compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mapping software. Our analyses involved 329 patients with OCD and 316 healthy controls. Patients showed increased structural covariance between the left ventral-rostral putamen and the left inferior frontal gyrus/frontal operculum region. This finding had a significant interaction with age; the association held only in the subgroup of older participants. Patients with OCD also showed increased structural covariance between the right centromedial-superficial amygdala and the ventromedial prefrontal cortex. This was a cross-sectional study. Because this is a multisite data set analysis, participant recruitment and image acquisition were performed in different centres. Most patients were taking medication, and treatment protocols differed across centres. Our results provide evidence for structural network-level alterations in patients with OCD involving 2 frontosubcortical circuits of relevance for the disorder and indicate that structural covariance contributes to fully characterizing brain alterations in patients with psychiatric disorders.

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

PubMed

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

2007-01-01

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

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

PubMed Central

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

2009-01-01

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

Identification of minimum carbohydrate moiety in N-glycosylation sites of brain endothelial cell glycoprotein 96 for interaction with Escherichia coli K1 outer membrane protein A.

PubMed

Krishnan, Subramanian; Prasadarao, Nemani V

2014-07-01

Bacterial meningitis is a serious central nervous system infection and Escherichia coli K1 (E. coli K1) is one of the leading etiological agents that cause meningitis in neonates. Outer membrane protein A (OmpA) of E. coli K1 is a major virulence factor in the pathogenesis of meningitis, and interacts with human brain microvascular endothelial cells (HBMEC) to cross the blood-brain barrier. Using site-directed mutagenesis, we demonstrate that two N-glycosylation sites (NG1 and NG2) in the extracellular domain of OmpA receptor, Ecgp96 are critical for bacterial binding to HBMEC. E. coli K1 invasion assays using CHO-Lec1 cells that express truncated N-glycans, and sequential digestion of HBMEC surface N-glycans using specific glycosidases showed that GlcNAc1-4GlcNAc epitopes are sufficient for OmpA interaction with HBMEC. Lack of NG1 and NG2 sites in Ecgp96 inhibits E. coli K1 OmpA induced F-actin polymerization, phosphorylation of protein kinase C-α, and disruption of transendothelial electrical resistance required for efficient invasion of E. coli K1 in HBMEC. Furthermore, the microvessels of cortex and hippocampus of the brain sections of E. coli K1 infected mice showed increased expression of glycosylated Ecgp96. Therefore, the interface of OmpA and GlcNAc1-4GlcNAc epitope interaction would be a target for preventative strategies against E. coli K1 meningitis. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Brain-derived neurotrophic factor transgenic mice exhibit passive avoidance deficits, increased seizure severity and in vitro hyperexcitability in the hippocampus and entorhinal cortex.

PubMed

Croll, S D; Suri, C; Compton, D L; Simmons, M V; Yancopoulos, G D; Lindsay, R M; Wiegand, S J; Rudge, J S; Scharfman, H E

1999-01-01

Transgenic mice overexpressing brain-derived neurotrophic factor from the beta-actin promoter were tested for behavioral, gross anatomical and physiological abnormalities. Brain-derived neurotrophic factor messenger RNA overexpression was widespread throughout brain. Overexpression declined with age, such that levels of overexpression decreased sharply by nine months. Brain-derived neurotrophic factor transgenic mice had no gross deformities or behavioral abnormalities. However, they showed a significant passive avoidance deficit. This deficit was dependent on continued overexpression, and resolved with age as brain-derived neurotrophic factor transcripts decreased. In addition, the brain-derived neurotrophic factor transgenic mice showed increased seizure severity in response to kainic acid. Hippocampal slices from brain-derived neurotrophic factor transgenic mice showed hyperexcitability in area CA3 and entorhinal cortex, but not in dentate gyrus. Finally, area CA1 long-term potentiation was disrupted, indicating abnormal plasticity. Our data suggest that overexpression of brain-derived neurotrophic factor in the brain can interfere with normal brain function by causing learning impairments and increased excitability. The results also support the hypothesis that excess brain-derived neurotrophic factor could be pro-convulsant in the limbic system.

[Research of anti-aging mechanism of ginsenoside Rg1 on brain].

PubMed

Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

2014-11-01

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in section of brain tissue decreased, the activity of antioxidant enzyme SOD and the contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in hippocampus decreased, the length contraction of telomere suppressed while the change of telomerase activity increased in hippocampus. Compared with that of normal group, the spatial learning and memory capacities were enhanced in Rg1 normal group, SA-beta-Gal positive granules in section of brain tissue decreased in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1 normal group. The results indicated that improvement of antioxidant ability, regulating the level of proinflammatory cytokines and regulation of telomerase system may be the underlying anti-aging mechanism of Ginsenoside Rg1.

Brain and Brown Adipose Tissue Metabolism in Transgenic Tg2576 Mice Models of Alzheimer Disease Assessed Using 18F-FDG PET Imaging

PubMed Central

Coleman, Robert A.; Liang, Christopher; Patel, Rima; Ali, Sarah

2017-01-01

Objective: Imaging animal models of Alzheimer disease (AD) is useful for the development of therapeutic drugs and understanding AD. Transgenic Swedish hAPPswe Tg2576 mice are a good model of β-amyloid plaques. We report 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) imaging of brain and intrascapular brown adipose tissue (IBAT) in transgenic mice 2576 (Tg2576) and wild-type (WT) mice. Methods: Transgenic Tg2576 mice and WT mice, >18 months were injected intraperitonally with ≈ 25 to 30 MBq 18F-FDG while awake. After 60 minutes, they were anesthetized with isoflurane (2.5%) and imaged with Inveon MicroPET. Select mice were killed, imaged ex vivo, and 20 µm sections cut for autoradiography. 18F-FDG uptake in brain and IBAT PET and brain autoradiographs were analyzed. Results: Fasting blood glucose levels averaged 120 mg/dL for WT and 100 mg/dL for Tg2576. Compared to WT, Tg2576 mice exhibited a decrease in SUVglc in the various brain regions. Average reductions in the cerebrum regions were as high as −20%, while changes in cerebellum were −3%. Uptake of 18F-FDG in IBAT decreased by −60% in Tg2576 mice and was found to be significant. Intrascapular brown adipose tissue findings in Tg2576 mice are new and not previously reported. Use of blood glucose for PET data analysis and corpus callosum as reference region for autoradiographic analysis were important to detect change in Tg2576 mice. Conclusion: Our results suggest that 18F-FDG uptake in the Tg2576 mice brain show 18F-FDG deficits only when blood glucose is taken into consideration. PMID:28654383

Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-2.

PubMed

Morihara, Ryuta; Yamashita, Toru; Kono, Syoichiro; Shang, Jingwei; Nakano, Yumiko; Sato, Kota; Hishikawa, Nozomi; Ohta, Yasuyuki; Heitmeier, Stefan; Perzborn, Elisabeth; Abe, Koji

2017-09-01

This study aimed to assess the risk of intracerebral hemorrhage (ICH) after tissue-type plasminogen activator (tPA) treatment in rivaroxaban compared with warfarin-pretreated male Wistar rat brain after ischemia in relation to activation profiles of protease-activated receptor-1, -2, -3, and -4 (PAR-1, -2, -3, and -4). After pretreatment with warfarin (0.2 mg/kg/day), low-dose rivaroxaban (60 mg/kg/day), high-dose rivaroxaban (120 mg/kg/day), or vehicle for 14 days, transient middle cerebral artery occlusion was induced for 90 min, followed by reperfusion with tPA (10 mg/kg/10 ml). Infarct volume, hemorrhagic volume, immunoglobulin G leakage, and blood parameters were examined. Twenty-four hours after reperfusion, immunohistochemistry for PARs was performed in brain sections. ICH volume was increased in the warfarin-pretreated group compared with the rivaroxaban-treated group. PAR-1, -2, -3, and -4 were widely expressed in the normal brain, and their levels were increased in the ischemic brain, especially in the peri-ischemic lesion. Warfarin pretreatment enhanced the expression of PAR-1 and PAR-2 in the peri-ischemic lesion, whereas rivaroxaban pretreatment did not. The present study shows a lower risk of brain hemorrhage in rivaroxaban-pretreated compared with warfarin-pretreated rats following tPA administration to the ischemic brain. It is suggested that the relative downregulation of PAR-1 and PAR-2 by rivaroxaban compared with warfarin pretreatment might be partly involved in the mechanism of reduced hemorrhagic complications in patients receiving rivaroxaban in clinical trials. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Use of Social Media Communications in Brain Aneurysms and Subarachnoid Hemorrhage: A Mixed-Method Analysis.

PubMed

Alotaibi, Naif M; Samuel, Nardin; Wang, Justin; Ahuja, Christopher S; Guha, Daipayan; Ibrahim, George M; Schweizer, Tom A; Saposnik, Gustavo; Macdonald, R Loch

2017-02-01

The diagnosis of a ruptured or unruptured brain aneurysm has a significant impact on patients' quality of life and their psychosocial well-being. As a result, patients and caregivers may resort to social media platforms for support and education. The aim of this report is to evaluate the use of social media and the online communications regarding brain aneurysms. Three social media platforms (Facebook, Twitter, and YouTube) were assessed for public content pertaining to brain aneurysms in March 2016. We conducted a mixed-method analysis that includes a descriptive examination of cross-sectional data and a qualitative evaluation of online communications for thematic analysis. We assessed categorized data using nonparametric tests for statistical significance. Our analyses showed that Facebook was the most highly used social media platform, with 11 relevant pages and 83 groups. Facebook accounts were all nonprofit foundations or patient support groups. Most users in Facebook groups were joining private support groups as opposed to public (P < 0.05). The most frequently viewed category of YouTube videos was on treatment procedures (P < 0.001). Six prominent themes emerged from the coded data of posts and comments: inspiration and motivation (27.7%), providing and sharing information (26.3%), requesting information (14.4%), seeking emotional support (12.1%), admiration (8.3%), and loss and grief (8.3%). This study is the first to provide insight into characteristics and patterns of social media communications regarding brain aneurysms. These findings should serve to inform the treating physicians of the needs and expectations of individuals affected by brain aneurysms. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced tumorigenicity of rat glioma cells in the brain when mediated by hygromycin phosphotransferase.

PubMed

Hormigo, A; Friedlander, D R; Brittis, P A; Zagzag, D; Grumet, M

2001-04-01

A variant of C6 glioma cells, C6R-G/H cells express hygromycin phosphotransferase (HPT) and appear to have reduced tumorigenicity in the embryonic brain. The goal of this study was to investigate their reduced capacity to generate tumors in the adult rat brain. Cell lines were implanted into rat brains and tumorigenesis was evaluated. After 3 weeks, all rats with C6 cells showed signs of neurological disease, whereas rats with C6R-G/H cells did not and were either killed then or allowed to survive until later. Histological studies were performed to analyze tumor size, malignancy, angiogenesis, and cell proliferation. Cells isolated from rat brain tumors were analyzed for mutation to HPT by testing their sensitivity to hygromycin. The results indicate that HPT suppresses tumor formation. Three weeks after implantation, only 44% of animals implanted with C6R-G/H cells developed tumors, whereas all animals that received C6 glioma cells developed high-grade gliomas. The C6R-G/H cells filled a 20-fold smaller maximal cross-sectional area than the C6 cells, and exhibited less malignant characteristics, including reduced angiogenesis, mitosis, and cell proliferation. Similar results were obtained in the brain of nude rats, indicating that the immune system did not play a significant role in suppressing tumor growth. The combination of green fluorescent protein (GFP) and HPT was more effective in suppressing tumorigenesis than either plasmid by itself, indicating that the GFP may protect against inactivation of the HPT. Interestingly. hygromycin resistance was lost in tumor cells that were recovered from a group of animals in which C6R-G/H cells formed tumors, confirming the correlation of HPT with reduced tumorigenicity.

Imaging-based biomarkers of cognitive performance in older adults constructed via high-dimensional pattern regression applied to MRI and PET.

PubMed

Wang, Ying; Goh, Joshua O; Resnick, Susan M; Davatzikos, Christos

2013-01-01

In this study, we used high-dimensional pattern regression methods based on structural (gray and white matter; GM and WM) and functional (positron emission tomography of regional cerebral blood flow; PET) brain data to identify cross-sectional imaging biomarkers of cognitive performance in cognitively normal older adults from the Baltimore Longitudinal Study of Aging (BLSA). We focused on specific components of executive and memory domains known to decline with aging, including manipulation, semantic retrieval, long-term memory (LTM), and short-term memory (STM). For each imaging modality, brain regions associated with each cognitive domain were generated by adaptive regional clustering. A relevance vector machine was adopted to model the nonlinear continuous relationship between brain regions and cognitive performance, with cross-validation to select the most informative brain regions (using recursive feature elimination) as imaging biomarkers and optimize model parameters. Predicted cognitive scores using our regression algorithm based on the resulting brain regions correlated well with actual performance. Also, regression models obtained using combined GM, WM, and PET imaging modalities outperformed models based on single modalities. Imaging biomarkers related to memory performance included the orbito-frontal and medial temporal cortical regions with LTM showing stronger correlation with the temporal lobe than STM. Brain regions predicting executive performance included orbito-frontal, and occipito-temporal areas. The PET modality had higher contribution to most cognitive domains except manipulation, which had higher WM contribution from the superior longitudinal fasciculus and the genu of the corpus callosum. These findings based on machine-learning methods demonstrate the importance of combining structural and functional imaging data in understanding complex cognitive mechanisms and also their potential usage as biomarkers that predict cognitive status.

Histopathological alterations in mice under sub-acute treatment with Hintonia latiflora methanolic stem bark extract.

PubMed

Flores-Jiménez, Nancy G; Rojas-Lemus, Marcela; Fortoul, Teresa I; Zepeda-Rodríguez, Armando; López-Camacho, Perla Y; Anacleto-Santos, Jhony; Gutiérrez, Filiberto Malagón; Basurto-Islas, Gustavo; Rivera-Fernández, Norma

2018-06-20

The indiscriminate use of herbal products is increasingly growing worldwide; nonetheless consumers are not warned about the potential health risks that these products may cause. Hintonia latiflora (Hl) is a tree native to the American continent belonging to the Rubiaceae family and its stem bark is empirically used mainly to treat diabetes and malaria; supplements containing Hl are sold in America and Europe without medical prescription, thus scientific information regarding its toxicity as a consequence of a regular consumption is needed. In the present study, the histopathological effect of 200 and 1000 mg/kg of Hintonia latiflora methanolic stem bark extract (HlMeOHe) was evaluated in the small bowel, liver, pancreas, kidneys and brain of CD-1 male mice after oral sub-acute treatment for 28 days. No histopathological alterations were observed in the brain and small bowel of the treated animals; however, mice presented diarrhea from day 2 of treatment with both doses. No histological changes were observed in the tissues collected from the animals treated with 200 mg /kg, except for the liver that depicted periportal hepatitis. Animals treated with the higher dose showed in the liver sections hydropic degeneration, hepatitis and necrosis, kidney sections depicted tubular necrosis and in pancreas sections, hydropic degeneration of the pancreatic islets was observed. In conclusion, HlMeOHe damaged the liver with an oral dose of 200 mg/kg, and at 1000 mg/kg injured the kidneys and pancreas of the CD-1 male mice.

Frequency and topography of small cerebrovascular lesions in vascular and in mixed dementia: a post-mortem 7-tesla magnetic resonance imaging study with neuropathological correlates.

PubMed

De Reuck, Jacques; Auger, Florent; Durieux, Nicolas; Deramecourt, Vincent; Maurage, Claude-Alain; Cordonnier, Charlotte; Pasquier, Florence; Leys, Didier; Bordet, Regis

2017-01-01

Introduction: Mixed dementia (MixD) refers to a combination of definite Alzheimer's disease (AD) and vascular encephalopathy. The existence of a "pure" type of vascular dementia (VaD) is controversial. There is a need to find magnetic resonance imaging (MRI) characteristics allowing the distinction between VaD and MixD. The present post-mortem 7.0-tesla MRI compares the frequency or severity and the topography of the small cerebrovascular lesions in brains of patients with VaD and with MixD. Material and methods: Based on neuropathological criteria, 14 brains were classified as VaD, 24 as MixD and 11 as controls. Three coronal sections of a cerebral hemisphere and a horizontal section of a cerebellar hemisphere underwent T2 and T2* 7.0-tesla MRI examination. The mean values and topographic distribution of white matter changes (WMCs), lacunar infarcts (LIs), cortical microbleeds (CoMBs) and cortical microinfarcts (CoMIs) were determined and compared between the different groups. Results: Compared to the controls, both VaD and MixD brains had significantly more severe WMCs and increased numbers of CoMBs and CoMIs. Lacunar infarcts predominated only in the VaD cases. On mutual comparison of VaD and MixD brains, CoMBs and CoMIs predominated in the frontal lobe and the cerebellum of VaD, while were mainly present in the occipital lobe of MixD. White matter changes predominated in the temporal lobe of MixD cases. Lacunar infarcts were significantly increased in the corona radiata and putamen of VaD patients. Conclusions: The present post-mortem MRI study shows clear differences in the distribution and the types of cerebrovascular lesions on high-field MRI, confirming that VaD and MixD are different diseases. .

Conductive carbon tape used for support and mounting of both whole animal and fragile heat-treated tissue sections for MALDI MS imaging and quantitation.

PubMed

Goodwin, Richard J A; Nilsson, Anna; Borg, Daniel; Langridge-Smith, Pat R R; Harrison, David J; Mackay, C Logan; Iverson, Suzanne L; Andrén, Per E

2012-08-30

Analysis of whole animal tissue sections by MALDI MS imaging (MSI) requires effective sample collection and transfer methods to allow the highest quality of in situ analysis of small or hard to dissect tissues. We report on the use of double-sided adhesive conductive carbon tape during whole adult rat tissue sectioning of carboxymethyl cellulose (CMC) embedded animals, with samples mounted onto large format conductive glass and conductive plastic MALDI targets, enabling MSI analysis to be performed on both TOF and FT-ICR MALDI mass spectrometers. We show that mounting does not unduly affect small molecule MSI detection by analyzing tiotropium abundance and distribution in rat lung tissues, with direct on-tissue quantitation achieved. Significantly, we use the adhesive tape to provide support to embedded delicate heat-stabilized tissues, enabling sectioning and mounting to be performed that maintained tissue integrity on samples that had previously been impossible to adequately prepare section for MSI analysis. The mapping of larger peptidomic molecules was not hindered by tape mounting samples and we demonstrate this by mapping the distribution of PEP-19 in both native and heat-stabilized rat brains. Furthermore, we show that without heat stabilization PEP-19 degradation fragments can detected and identified directly by MALDI MSI analysis. Copyright © 2012 Elsevier B.V. All rights reserved.

Pathology, immunohistochemistry, and ultrastructural findings associated with neurological sarcocystosis in cattle

USDA-ARS?s Scientific Manuscript database

The case of neurological sarcocystosis in a nine months old bull calf that died in 1982 was restudied. The bull was suspected to have rabies. Therefore, only brain was examined histologically. Thirty four years later, we restudied sections from paraffin-embedded blocks of brain. Numerous schizonts a...

Traumatic Brain Injury and Vocational Rehabilitation.

ERIC Educational Resources Information Center

Corthell, David W., Ed.

Intended to serve as a resource guide on traumatic brain injury for rehabilitation practitioners, the book's 10 chapters are grouped into sections which provide an introduction and examine aspects of evaluation, treatment and placement planning, and unresolved issues. Chapters have the following titles and authors: "Scope of the Problem" (Marilyn…

Combination of intracellular staining of retrogradely labeled neurons and anterograde fluorescent tracing: use of the confocal laser scanning microscope.

PubMed

Shi, C; Cassell, M D

1993-04-01

This report describes a combined retrograde tracing, intracellular injection and anterograde fluorescence labeling method using the application of confocal laser scanning microscopy. By simultaneously viewing the morphology of identified projection neurons and the distribution of anterogradely labeled fibers and terminals, this approach allows accurate characterization of the anatomical relationships between these two elements. To demonstrate this approach, the retrograde tracer Fast Blue was injected into the bed nucleus of stria terminalis (BNST) and the anterograde tracer tetramethylrhodamine-conjugated dextran was injected into the insular cortex in adult rats. After one week survival time, the brains were fixed and sectioned on a vibratome. Individual BNST projecting neurons identified in the amygdaloid complex on 120 microns thick sections were intracellularly injected with Lucifer Yellow under visual control and analyzed with confocal laser scanning microscopy. The results demonstrate that images from very thin optical sections can clearly show potential synaptic contacts between anterograde labeling and intracellularly labeled projecting neurons. Stacked images from optical sections show, in very great detail, the morphology of projection neurons in three-dimensions. Compared to other methodological combinations, the present method provides a more simple and efficient means to trace three successive components of a putative neuron chain.

Shared Predisposition in the Association Between Cannabis Use and Subcortical Brain Structure.

PubMed

Pagliaccio, David; Barch, Deanna M; Bogdan, Ryan; Wood, Phillip K; Lynskey, Michael T; Heath, Andrew C; Agrawal, Arpana

2015-10-01

Prior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use. To determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations. Cross-sectional diagnostic interview, behavioral, and neuroimaging data were collected from community sampling and established family registries from August 2012 to September 2014. This study included data from 483 participants (22-35 years old) enrolled in the ongoing Human Connectome Project, with 262 participants reporting cannabis exposure (ie, ever used cannabis in their lifetime). Cannabis exposure was measured with the Semi-Structured Assessment for the Genetics of Alcoholism. Whole-brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever used, age at onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed models were used to examine volume differences in sex-matched concordant unexposed (n = 71 pairs), exposed (n = 81 pairs), or exposure discordant (n = 89 pairs) sibling pairs. Among 483 study participants, cannabis exposure was related to smaller left amygdala (approximately 2.3%; P = .007) and right ventral striatum (approximately 3.5%; P < .005) volumes. These volumetric differences were within the range of normal variation. The association between left amygdala volume and cannabis use was largely owing to shared genetic factors (ρg = -0.43; P = .004), while the origin of the association with right ventral striatum volumes was unclear. Importantly, brain volumes did not differ between sex-matched siblings discordant for use (fixed effect = -7.43; t = -0.93, P = .35). Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs (fixed effect = 12.56; t = 2.97; P = .003). In this study, differences in amygdala volume in cannabis users were attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences. Causal influences, in isolation or in conjunction with predispositional factors, may exist for other brain regions (eg, ventral striatum) or at more severe levels of cannabis involvement and deserve further study.

[Intracerebral hemorrhage in a burn victim--burn hematoma, salvage injury or intra vitam origin?].

PubMed

Dirnhofer, R; Ranner, G

1982-01-01

Central sections of the brain of a severely charred, mortified cadaver showed extensive centers of hemorrhage which had partly ovular and partly slash forms. There was no doubt of the traumatic origin of the hemorrhage. Whether the origin occurred vitally or post-mortum, could only be established after reconstructing the case at the scene of the event and checking the testimonies of the firemen. The origin was traced back to the use of force during the recovery action made on the body.

Graph Analysis of Functional Brain Networks for Cognitive Control of Action in Traumatic Brain Injury

ERIC Educational Resources Information Center

Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H.; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P.

2012-01-01

Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly…

Optical Brain Imaging: A Powerful Tool for Neuroscience.

PubMed

Zhu, Xinpei; Xia, Yanfang; Wang, Xuecen; Si, Ke; Gong, Wei

2017-02-01

As the control center of organisms, the brain remains little understood due to its complexity. Taking advantage of imaging methods, scientists have found an accessible approach to unraveling the mystery of neuroscience. Among these methods, optical imaging techniques are widely used due to their high molecular specificity and single-molecule sensitivity. Here, we overview several optical imaging techniques in neuroscience of recent years, including brain clearing, the micro-optical sectioning tomography system, and deep tissue imaging.

Neuroanatomy-based matrix-guided trimming protocol for the rat brain.

PubMed

Defazio, Rossella; Criado, Ana; Zantedeschi, Valentina; Scanziani, Eugenio

2015-02-01

Brain trimming through defined neuroanatomical landmarks is recommended to obtain consistent sections in rat toxicity studies. In this article, we describe a matrix-guided trimming protocol that uses channels to reproduce coronal levels of anatomical landmarks. Both setup phase and validation study were performed on Han Wistar male rats (Crl:WI(Han)), 10-week-old, with bodyweight of 298 ± 29 (SD) g, using a matrix (ASI-Instruments(®), Houston, TX) fitted for brains of rats with 200 to 400 g bodyweight. In the setup phase, we identified eight channels, that is, 6, 8, 10, 12, 14, 16, 19, and 21, matching the recommended landmarks midway to the optic chiasm, frontal pole, optic chiasm, infundibulum, mamillary bodies, midbrain, middle cerebellum, and posterior cerebellum, respectively. In the validation study, we trimmed the immersion-fixed brains of 60 rats using the selected channels to determine how consistently the channels reproduced anatomical landmarks. Percentage of success (i.e., presence of expected targets for each level) ranged from 89 to 100%. Where 100% success was not achieved, it was noted that the shift in brain trimming was toward the caudal pole. In conclusion, we developed and validated a trimming protocol for the rat brain that allow comparable extensiveness, homology, and relevance of coronal sections as the landmark-guided trimming with the advantage of being quickly learned by technicians. © 2014 by The Author(s).

Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers.

PubMed

Cole, James H; Franke, Katja

2017-12-01

The brain changes as we age and these changes are associated with functional deterioration and neurodegenerative disease. It is vital that we better understand individual differences in the brain ageing process; hence, techniques for making individualised predictions of brain ageing have been developed. We present evidence supporting the use of neuroimaging-based 'brain age' as a biomarker of an individual's brain health. Increasingly, research is showing how brain disease or poor physical health negatively impacts brain age. Importantly, recent evidence shows that having an 'older'-appearing brain relates to advanced physiological and cognitive ageing and the risk of mortality. We discuss controversies surrounding brain age and highlight emerging trends such as the use of multimodality neuroimaging and the employment of 'deep learning' methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

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

Churchill, L.; Pazdernik, T.L.; Jackson, J.L.

1984-08-01

(3H)Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturationmore » curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.« less

[Telescience : Feasibility studies, definition and a fair answer to the scientific brain drain].

PubMed

Craemer, E M; Bassa, B; Jacobi, C; Becher, H; Meyding-Lamadé, U

2017-02-01

What is telescience? Is it feasible to transfer academic information with the help of telematics to educate and teach young scientists over large distances? The term telescience has so far not been defined but covers a variety of possibilities, which could be successfully implemented worldwide. This article gives examples and highlights the feasibility analysis of telescience. We have carried out feasibility analyses for neurological functional diagnostics, an epidemiological cross-sectional study as well as a laboratory study for detection of thrombocyte function during dengue fever with the help of telemedicine. The basis for all these projects was a telemedical transcontinental cooperation over a distance of 12,000 km. All performed studies demonstrated the feasibility. With the help of telematics the laboratory techniques, planning, conduction and interpretation of results as well as publication skills can be transferred. Telescience is feasible. Our studies showed that telescience is a very promising option to transfer knowledge, which will help to enable professional expertise to be transferred directly to the region/country without a brain drain. All too often young motivated scientists are enticed to move to well-known institutions, which involves the danger of a brain drain. Brain drain can be avoided in favor of local implementation of scientific projects. Our results illustrate that it is feasible to educate and guide scientists with the help of telematics infrastructures.

Long and short echo time proton magnetic resonance spectroscopic imaging of the healthy aging brain.

PubMed

McIntyre, Dominick J O; Charlton, Rebecca A; Markus, Hugh S; Howe, Franklyn A

2007-12-01

To investigate the relationship between subject age and white matter brain metabolite concentrations and R(2) relaxation rates in a cross-sectional study of human brain. Long- and short-echo proton spectroscopic imaging were used to investigate concentrations and R2 relaxation rates of N-acetyl aspartate (NAA) + N-acetyl aspartyl glutamate (NAAG), choline (Cho), creatine (Cr), and myoinositol (mI) in the white matter of the centrum semiovale of 106 healthy volunteers aged 50-90 years; usable data were obtained from 79 subjects. A major aim was to identify which parameters were most sensitive to changes with age. Spectra were analyzed using the LCModel method. The apparent R2 of NAA and the LCModel concentration of Cr at short echo time were significantly correlated with age after multiplicity correction. Large lipid resonances were observed in the brain midline of some subjects, the incidence increasing significantly with age. We believe this to result from lipid deposits in the falx cerebri. Since only short-echo spectroscopy showed a robust relationship between Cr and subject age, and detects more metabolites than long echo time, we conclude that short-echo is superior to long-echo for future aging studies. Future studies could usefully determine whether the Cr-age relationship is due to changes in concentration, T1, or both. (c) 2007 Wiley-Liss, Inc.

Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

PubMed

Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

2015-10-01

Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

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

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

Miyoshi, Ko, E-mail: miyoshi@cc.okayama-u.ac.jp; Kasahara, Kyosuke; Miyazaki, Ikuko

2009-10-30

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

Brain and sense organ anatomy and histology in hemoglobinless Antarctic icefishes (Perciformes: Notothenioidei: Channichthyidae).

PubMed

Eastman, Joseph T; Lannoo, Michael J

2004-04-01

The Channichthyidae, one of five Antarctic notothenioid families, includes 16 species and 11 genera. Most live at depths of 200-800 m and are a major component of fish biomass in many shelf areas. Channichthyids are unique among adult fishes in possessing pale white blood containing a few vestigal erythrocytes and no hemoglobin. Here we describe the brains of seven species and special sense organs of eight species of channichthyids. We emphasize Chionodraco hamatus and C. myersi, compare these species to other channichthyids, and relate our findings to what is known about brains and sense organs of red-blooded notothenioids living sympatrically on the Antarctic shelf. Brains of channichthyids generally resemble those of their bathydraconid sister group. Among channichthyids the telencephalon is slightly regressed, resulting in a stalked appearance, but the tectum, corpus cerebellum, and mechanoreceptive areas are well developed. Interspecific variation is present but slight. The most interesting features of channichthyid brains are not in the nervous tissue but in support structures: the vasculature and the subependymal expansions show considerable elaboration. Channichthyids have large accessory nasal sacs and olfactory lamellae are more numerous than in other notothenioids. The eyes are relatively large and laterally oriented with similar duplex (cone and rod) retinae in all eight species. Twin cones are the qualitatively dominant photoreceptor in histological sections and, unlike bathydraconids, there are no species with rod-dominated retinae. Eyes possess the most extensive system of hyaloid arteries known in teleosts. Unlike the radial pattern seen in red-blooded notothenioids and most other teleosts, channichthyid hyaloid arteries arise from four or five main branches and form a closely spaced anastomosing series of parallel channels. Cephalic lateral line canals are membranous and some exhibit extensions (canaliculi), but canals are more ossified than those of deeper-living bathydraconids. We conclude that, with respect to the anatomy and histology of the neural structures, the brain and sensory systems show little that is remarkable compared to other fishes, and exhibit little diversification within the family. Thus, the unusual habitat and a potentially deleterious mutation resulting in a hemoglobinless phenotype are reflected primarily in expansion of the vasculature in the brain and eye partially compensating for the absence of respiratory pigments. Neural morphology gives the impression that channichthyids are a homogeneous and little diversified group. Copyright 2004 Wiley-Liss, Inc.

Researchers Find Essential Brain Circuit in Visual Development

MedlinePlus

... Release Monday, August 26, 2013 Researchers find essential brain circuit in visual development NIH-funded study could ... shows the connections from the eyes to the brain in a mouse. The right image shows the ...

Medico-legal and ethical aspects in the management of wandering patients following brain injury: questionnaire survey.

PubMed

Gaber, Tarek A-Z K

2006-11-30

Different methods are often used to deter head injury patients, who have a tendency to wander, from leaving the rehabilitation wards. The extent to which these patients could be restrained is controversial. Despite the fact that the majority of these patients lack mental capacity, Mental Health Act sections are rarely invoked. Under common law, informal patients should have the right to refuse treatment and to leave the hospital whenever they like. To examine the current practice in the management of wandering patients following brain injury in rehabilitation units in the UK and to formulate practical guidelines based on this common practice. A postal survey in the form of a structured questionnaire was sent to 58 consultants in Rehabilitation Medicine and Neuropsychologists based at different neurological rehabilitation units in the UK. A total of 30 clinicians (52%) completed the questionnaire. One-to-one supervision was the method most commonly used to manage wandering patients (83%) followed by implementation of a structured daily routine (73%) and the use of different medications (70%). Only 17% would lock the door without giving the patient lock combination/key and another 17% would physically restrain the patient without invoking mental health act (MHA) section; 60% would consider MHA section with great variability in the mental health team response time and the place where patient is managed once under MHA section. The questionnaire showed great variations in the methods and the medico-legal framework used in the management of wandering patients. There was, however, a tendency to avoid physical restraint which may reflect the recognition of the unlawfulness of detaining informal patients.

Comparative Tissue Stainability of Lawsonia inermis (Henna) and Eosin as Counterstains to Hematoxylin in Brain Tissues.

PubMed

Alawa, Judith N; Gideon, Gbenga O; Adetiba, Bamidele; Alawa, Clement B

2015-04-01

We hyposthesized that henna staining could provide an alternative to eosin when used as a counterstain to hematoxylin for understanding basic neurohistological principles. Therefore, this study was aimed at investigating the suitability of henna as counterstain to hematoxylin for the demonstration of the layer stratification and cellular distribution in the brain tissue. Henna stained nervous tissue by reacting with the basic elements in proteins via its amino groups. It stained the neuropil and connective tissue membranes brown and effectively outlined the perikarya of neurons with no visible nuclei demonstrating that it is an acidic dye. Henna as a counterstain to hematoxylin demonstrated reliability as a new neurohistological stain. It facilitated identification of cortical layer stratification and cellular distribution in brain tissue sections from Wistar rats. This was comparable to standard hematoxylin and eosin staining as morphological and morphometrical analyses of stained cells did not show significant differences in size or number. This study presents a method for staining with henna and demonstrates that although henna and eosin belong to different dye groups (anthraquinone and xanthenes, respectively) based on their chromophores, they share similar staining techniques and thus could be used interchangeably in neurohistology.

A stereotaxic atlas of the forebrain of the bank vole (Clethrionomys glareolus).

PubMed

Vandebroek, I; Bouche, K; D'Herde, K; Caemaert, J; Roels, F; Odberg, F O

1999-04-01

In this article part of the forebrain of the bank vole (Clethrionomys glareolus) is presented in stereotaxic coordinates. The stereotaxic procedure was performed as follows. With the vole's head mounted in a stereotaxic adaptor, internal reference tracks were made with a 0.5-mm diameter microdialysis cannula and India ink, 2 mm in front and 2.6 mm behind the skull landmark bregma. Brains were fixed for 72 h in 4% commercial formaldehyde in sodiumcacodylate buffer containing 1% CaCl2. To determine shrinkage they were weighed before and after fixation. After embedding in paraffin they were sectioned at 25 microm and stained with Nissl. Photomicrographs were taken from the brain of one animal while its frontal (antero-posterior) coordinates of five neural structures were compared with those of 12 other voles. Variability was also checked in lateral and vertical directions at frontal level -1.0 mm (relative to bregma). The results show that the distance between the two skull landmarks bregma and lambda correlates significantly and negatively with the antero-posterior position of each of the brain areas. On the basis of these results an equation is proposed to improve accuracy in locating neural structures that deviate due to biological variability.

Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection

PubMed Central

Mertz, Jerome; Kim, Jinhyun

2010-01-01

It is well known that light-sheet illumination can enable optically sectioned wide-field imaging of macroscopic samples. However, the optical sectioning capacity of a light-sheet macroscope is undermined by sample-induced scattering or aberrations that broaden the thickness of the sheet illumination. We present a technique to enhance the optical sectioning capacity of a scanning light-sheet microscope by out-of-focus background rejection. The technique, called HiLo microscopy, makes use of two images sequentially acquired with uniform and structured sheet illumination. An optically sectioned image is then synthesized by fusing high and low spatial frequency information from both images. The benefits of combining light-sheet macroscopy and HiLo background rejection are demonstrated in optically cleared whole mouse brain samples, using both green fluorescent protein (GFP)-fluorescence and dark-field scattered light contrast. PMID:20210471

Prizes, lectures, and awards of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors.

PubMed

Barker, Fred G; McDermott, Michael W

2005-04-15

An important goal of the Section on Tumors of the American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) since its founding in 1985 has been to foster both education and research in the field of brain tumor treatment. As one means of achieving this, the Section awards a number of prizes, research grants, and named lectures at the annual meetings of the AANS and CNS. After a brief examination of similar honors that were given in recognition of pioneering work by Knapp, Cushing, and other early brain tumor researchers, the authors describe the various awards given by the AANS/CNS Section on Tumors since its founding, their philanthropic donors, and the recipients of the awards. The subsequent career of the recipients is briefly examined, in terms of the rate of full publication of award-winning abstracts and achievement of grant funding by awardees.

Infant Visual Attention and Object Recognition

PubMed Central

Reynolds, Greg D.

2015-01-01

This paper explores the role visual attention plays in the recognition of objects in infancy. Research and theory on the development of infant attention and recognition memory are reviewed in three major sections. The first section reviews some of the major findings and theory emerging from a rich tradition of behavioral research utilizing preferential looking tasks to examine visual attention and recognition memory in infancy. The second section examines research utilizing neural measures of attention and object recognition in infancy as well as research on brain-behavior relations in the early development of attention and recognition memory. The third section addresses potential areas of the brain involved in infant object recognition and visual attention. An integrated synthesis of some of the existing models of the development of visual attention is presented which may account for the observed changes in behavioral and neural measures of visual attention and object recognition that occur across infancy. PMID:25596333

Blood-brain barrier KCa3.1 channels: evidence for a role in brain Na uptake and edema in ischemic stroke.

PubMed

Chen, Yi-Je; Wallace, Breanna K; Yuen, Natalie; Jenkins, David P; Wulff, Heike; O'Donnell, Martha E

2015-01-01

KCa3.1, a calcium-activated potassium channel, regulates ion and fluid secretion in the lung and gastrointestinal tract. It is also expressed on vascular endothelium where it participates in blood pressure regulation. However, the expression and physiological role of KCa3.1 in blood-brain barrier (BBB) endothelium has not been investigated. BBB endothelial cells transport Na(+) and Cl(-) from the blood into the brain transcellularly through the co-operation of multiple cotransporters, exchangers, pumps, and channels. In the early stages of cerebral ischemia, when the BBB is intact, edema formation occurs by processes involving increased BBB transcellular Na(+) transport. This study evaluated whether KCa3.1 is expressed on and participates in BBB ion transport. The expression of KCa3.1 on cultured cerebral microvascular endothelial cells, isolated microvessels, and brain sections was evaluated by Western blot and immunohistochemistry. Activity of KCa3.1 on cerebral microvascular endothelial cells was examined by K(+) flux assays and patch-clamp. Magnetic resonance spectroscopy and MRI were used to measure brain Na(+) uptake and edema formation in rats with focal ischemic stroke after TRAM-34 treatment. KCa3.1 current and channel protein were identified on bovine cerebral microvascular endothelial cells and freshly isolated rat microvessels. In situ KCa3.1 expression on BBB endothelium was confirmed in rat and human brain sections. TRAM-34 treatment significantly reduced Na(+) uptake, and cytotoxic edema in the ischemic brain. BBB endothelial cells exhibit KCa3.1 protein and activity and pharmacological blockade of KCa3.1 seems to provide an effective therapeutic approach for reducing cerebral edema formation in the first 3 hours of ischemic stroke. © 2014 American Heart Association, Inc.

Short communication: Experimental toxocarosis in Chinese Kun Ming mice: Dose-dependent larval distribution and modulation of immune responses.

PubMed

Ma, Guangxu; Tan, Yancai; Hu, Ling; Luo, Yongfang; Zhu, Honghong; Zhou, Rongqiong

2015-12-01

Toxocarosis is an important parasitic zoonosis which is mainly caused by the infective larvae of Toxocara canis. To identify whether there are correlations among the infectious dose, the larval migrans and immune modulation in inbred Chinese Kun Ming (KM) mice, experimental infections were carried out with a range of dosages of 100, 500, 1000, 2000, and 3000 embryonated eggs (EE). Pathogenic reactions were observed in terms of physical and central nervous symptoms. Distributions of T. canis larvae in liver, lung, kidney, heart and brain organs were respectively detected by scanning tissue sections. Moreover, quantitative real-time PCR was employed to identify the variations of Th2 immune response. The results showed that high inocula resulted in advanced larval emergences and arrested migrations in liver, lung, kidney and brain. However, no larvae were found in any of the histological sections of heart tissues. Higher levels of interleukin (IL)-4, IL-5, and IL-10 were detected along with the increasing inoculation doses, but the heaviest inoculum (3000 EE in this study) resulted in the sharp reduction of these ILs. Although no neurological symptoms or mortalities were noticed, these results indicated dose-dependent distribution patterns and immune regulations of T. canis larvae infection in KM mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Miscarriage history and Toxoplasma gondii infection: A cross-sectional study in women in Durango City, Mexico.

PubMed

Alvarado-Esquivel, C; Pacheco-Vega, S J; Hernández-Tinoco, J; Centeno-Tinoco, M M; Beristain-García, I; Sánchez-Anguiano, L F; Liesenfeld, O; Rábago-Sánchez, E; Berumen-Segovia, L O

2014-06-01

Through a cross-sectional study design, 326 women with a history of miscarriage were examined for anti-Toxoplasma gondii IgG and IgM antibodies in Durango City, Mexico. Prevalence association with sociodemographic, clinical, and behavioral characteristics in women with miscarriage was also investigated. Twenty-two (6.7%) of the 326 women studied had anti-T. gondii IgG antibodies and two (0.6%) were also positive for anti-T. gondii IgM antibodies. Seroprevalence of T. gondii infection was not influenced by age, birth place, occupation, educational level, or socioeconomic status. In contrast, logistic regression showed that T. gondii exposure was associated with consumption of raw or undercooked meat (OR = 6.84; 95% CI: 1.04-44.95; P = 0.04) and consumption of chicken brains (OR = 18.48; 95% CI: 1.26-269.43; P = 0.03). This is the first study on the seroepidemiology of T. gondii infection in women with a history of miscarriage in Northern Mexico. Of interest, we also observed an association of T. gondii exposure with consumption of chicken brains. Contributing factors for T. gondii exposure found in the present study should be taken into consideration for public health measures to avoid infection with T. gondii and its sequelae.

Miscarriage history and Toxoplasma gondii infection: A cross-sectional study in women in Durango City, Mexico

PubMed Central

Pacheco-Vega, S. J.; Hernández-Tinoco, J.; Centeno-Tinoco, M. M.; Beristain-García, I.; Sánchez-Anguiano, L. F.; Liesenfeld, O.; Rábago-Sánchez, E.; Berumen-Segovia, L. O.

2014-01-01

Through a cross-sectional study design, 326 women with a history of miscarriage were examined for anti-Toxoplasma gondii IgG and IgM antibodies in Durango City, Mexico. Prevalence association with sociodemographic, clinical, and behavioral characteristics in women with miscarriage was also investigated. Twenty-two (6.7%) of the 326 women studied had anti-T. gondii IgG antibodies and two (0.6%) were also positive for anti-T. gondii IgM antibodies. Seroprevalence of T. gondii infection was not influenced by age, birth place, occupation, educational level, or socioeconomic status. In contrast, logistic regression showed that T. gondii exposure was associated with consumption of raw or undercooked meat (OR = 6.84; 95% CI: 1.04–44.95; P = 0.04) and consumption of chicken brains (OR = 18.48; 95% CI: 1.26–269.43; P = 0.03). This is the first study on the seroepidemiology of T. gondii infection in women with a history of miscarriage in Northern Mexico. Of interest, we also observed an association of T. gondii exposure with consumption of chicken brains. Contributing factors for T. gondii exposure found in the present study should be taken into consideration for public health measures to avoid infection with T. gondii and its sequelae. PMID:24883197

Spinal cord atrophy in anterior-posterior direction reflects impairment in multiple sclerosis.

PubMed

Lundell, H; Svolgaard, O; Dogonowski, A-M; Romme Christensen, J; Selleberg, F; Soelberg Sørensen, P; Blinkenberg, M; Siebner, H R; Garde, E

2017-10-01

To investigate how atrophy is distributed over the cross section of the upper cervical spinal cord and how this relates to functional impairment in multiple sclerosis (MS). We analysed the structural brain MRI scans of 54 patients with relapsing-remitting MS (n=22), primary progressive MS (n=9), secondary progressive MS (n=23) and 23 age- and sex-matched healthy controls. We measured the cross-sectional area (CSA), left-right width (LRW) and anterior-posterior width (APW) of the spinal cord at the segmental level C2. We tested for a nonparametric linear relationship between these atrophy measures and clinical impairments as reflected by the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impairment Scale (MSIS). In patients with MS, CSA and APW but not LRW were reduced compared to healthy controls (P<.02) and showed significant correlations with EDSS, MSIS and specific MSIS subscores. In patients with MS, atrophy of the upper cervical cord is most evident in the antero-posterior direction. As APW of the cervical cord can be readily derived from standard structural MRI of the brain, APW constitutes a clinically useful neuroimaging marker of disease-related neurodegeneration in MS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-resolution MRI of cranial nerves in posterior fossa at 3.0 T.

PubMed

Guo, Zi-Yi; Chen, Jing; Liang, Qi-Zhou; Liao, Hai-Yan; Cheng, Qiong-Yue; Fu, Shui-Xi; Chen, Cai-Xiang; Yu, Dan

2013-02-01

To evaluate the influence of high-resolution imaging obtainable with the higher field strength of 3.0 T on the visualization of the brain nerves in the posterior fossa. In total, 20 nerves were investigated on MRI of 12 volunteers each and selected for comparison, respectively, with the FSE sequences with 5 mm and 2 mm section thicknesses and gradient recalled echo (GRE) sequences acquired with a 3.0-T scanner. The MR images were evaluated by three independent readers who rated image quality according to depiction of anatomic detail and contrast with use of a rating scale. In general, decrease of the slice thickness showed a significant increase in the detection of nerves as well as in the image quality characteristics. Comparing FSE and GRE imaging, the course of brain nerves and brainstem vessels was visualized best with use of the three-dimensional (3D) pulse sequence. The comparison revealed the clear advantage of a thin section. The increased resolution enabled immediate identification of all brainstem nerves. GRE sequence most distinctly and confidently depicted pertinent structures and enables 3D reconstruction to illustrate complex relations of the brainstem. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Hippocampal Sclerosis of Aging Can Be Segmental: Two Cases and Review of the Literature

PubMed Central

Ighodaro, Eseosa T.; Jicha, Gregory A.; Schmitt, Frederick A.; Neltner, Janna H.; Abner, Erin L.; Kryscio, Richard J.; Smith, Charles D.; Duplessis, Taylor; Anderson, Sonya; Patel, Ela; Bachstetter, Adam; Van Eldik, Linda J.; Nelson, Peter T.

2015-01-01

Hippocampal sclerosis of aging (HS-Aging) is a neurodegenerative disease that mimics Alzheimer disease (AD) clinically and has a prevalence rivaling AD in advanced age. Whereas clinical biomarkers are not yet optimized, HS-Aging has distinctive pathological features that distinguish it from other diseases with “hippocampal sclerosis” pathology, such as epilepsy, cerebrovascular perturbations, and frontotemporal lobar degeneration. By definition, HS-Aging brains show neuronal cell loss and gliosis in the hippocampal formation out of proportion to AD-type pathology; it is strongly associated with aberrant TDP-43 pathology and arteriolosclerosis. Here, we describe 2 cases of “segmental” HS-Aging in which “sclerosis” in the hippocampus was evident only in a subset of brain sections by hematoxylin and eosin (H&E) stain. In these cases, TDP-43 pathology was more widespread on immunostained sections than the neuronal cell loss and gliosis seen in H&E stains. The 2 patients were cognitively intact at baseline and were tracked longitudinally over a decade using cognitive studies with at least 1 neuroimaging scan. We discuss the relevant HS-Aging literature, which indicates the need for a clearer consensus-based delineation of “hippocampal sclerosis” and TDP-43 pathologies in aged subjects. PMID:26083567

In Vivo Investigation of the Effectiveness of a Hyper-viscoelastic Model in Simulating Brain Retraction

NASA Astrophysics Data System (ADS)

Li, Ping; Wang, Weiwei; Zhang, Chenxi; An, Yong; Song, Zhijian

2016-07-01

Intraoperative brain retraction leads to a misalignment between the intraoperative positions of the brain structures and their previous positions, as determined from preoperative images. In vitro swine brain sample uniaxial tests showed that the mechanical response of brain tissue to compression and extension could be described by the hyper-viscoelasticity theory. The brain retraction caused by the mechanical process is a combination of brain tissue compression and extension. In this paper, we first constructed a hyper-viscoelastic framework based on the extended finite element method (XFEM) to simulate intraoperative brain retraction. To explore its effectiveness, we then applied this framework to an in vivo brain retraction simulation. The simulation strictly followed the clinical scenario, in which seven swine were subjected to brain retraction. Our experimental results showed that the hyper-viscoelastic XFEM framework is capable of simulating intraoperative brain retraction and improving the navigation accuracy of an image-guided neurosurgery system (IGNS).

Neural biomarkers for assessing different types of imagery in pictorial health warning labels for cigarette packaging: a cross-sectional study

PubMed Central

Newman-Norlund, Roger D; Thrasher, James F; Fridriksson, Johann; Brixius, William; Froeliger, Brett; Hammond, David; Cummings, Michael K

2014-01-01

Objective Countries around the world have increasingly adopted pictorial health warning labels (HWLs) for tobacco packages to warn consumers about smoking-related risks. Research on how pictorial HWLs work has primarily analysed self-reported responses to HWLs; studies at the neural level comparing the brain's response to different types of HWLs may provide an important complement to prior studies, especially if self-reported responses are systematically biased. In this study we characterise the brain's response to three types of pictorial HWLs for which prior self-report studies indicated different levels of efficacy. Methods Current smokers rated pictorial HWLs and then observed the same HWLs during functional MRI (fMRI) scanning. Fifty 18–50-year-old current adult smokers who were free from neurological disorders were recruited from the general population and participated in the study. Demographics, smoking-related behaviours and self-reported ratings of pictorial HWL stimuli were obtained prior to scanning. Brain responses to HWLs were assessed using fMRI, focusing on a priori regions of interest. Results Pictorial HWL stimuli elicited activation in a broad network of brain areas associated with visual processing and emotion. Participants who rated the stimuli as more emotionally arousing also showed greater neural responses at these sites. Conclusions Self-reported ratings of pictorial HWLs are correlated with neural responses in brain areas associated with visual and emotional processing. Study results cross-validate self-reported ratings of pictorial HWLs and provide insights into how pictorial HWLs are processed. PMID:25552613

Mass-related traumatic tissue displacement and behavior: a screen for treatments that reduce [corrected] harm to bystander cells and recovery of function.

PubMed

Yang, Hongyan; Preston, Marnie; Chopp, Michael; Jiang, Feng; Zhang, Xuepeng; Schallert, Timothy

2006-05-01

In this study, we focused on a preclinical model of brain compression injury that has relevance to pathological conditions such as tumor, hematoma, blood clot, and intracerebral bony fragment. We investigated behavioral impairment as a result of rapid-onset small mass, and the factors involved in lesion formation and neuroplasticity. An epidural bead implantation method was adopted. Two sizes (1.5 mm and 2.0 mm thick) of hemisphere-shaped beads were used. The beads were implanted into various locations over the sensorimotor cortex (SMC--anterior, middle and posterior). The effects of early versus delayed bead removal were examined to model clinical neurosurgical or other treatment procedures. Forelimb and hind-limb behavioral deficits and recovery were observed, and histological changes were quantified to determine brain reaction to focal compression. Our results showed that the behavioral deficits of compression were influenced by the location, timing of compression release, and magnitude of compression. Even persistent compression by the thicker bead (2.0 mm) caused only minor behavioral deficits, followed by fast recovery within a week in most animals, suggesting a mild lesion pattern for this model. Brain tissue was compressed into a deformed shape under pressure with slight tissue damage, evidenced by pathological evaluation on hematoxylin and eosin (H&E)- and TUNEL-stained sections. Detectable but not severe behavioral dysfunction exhibited by this model makes it particularly suitable for direct assessment of adverse effects of interventions on neuroplasticity after brain compression injury. This model may permit development of treatment strategies to alleviate brain mass effects, without disrupting neuroplasticity.

High-resolution synchrotron radiation-based phase tomography of the healthy and epileptic brain

NASA Astrophysics Data System (ADS)

Bikis, Christos; Janz, Philipp; Schulz, Georg; Schweighauser, Gabriel; Hench, Jürgen; Thalmann, Peter; Deyhle, Hans; Chicherova, Natalia; Rack, Alexander; Khimchenko, Anna; Hieber, Simone E.; Mariani, Luigi; Haas, Carola A.; Müller, Bert

2016-10-01

Phase-contrast micro-tomography using synchrotron radiation has yielded superior soft tissue visualization down to the sub-cellular level. The isotropic spatial resolution down to about one micron is comparable to the one of histology. The methods, however, provide different physical quantities and are thus complementary, also allowing for the extension of histology into the third dimension. To prepare for cross-sectional animal studies on epilepsy, we have standardized the specimen's preparation and scanning procedure for mouse brains, so that subsequent histology remains entirely unaffected and scanning of all samples (n = 28) is possible in a realistic time frame. For that, we have scanned five healthy and epileptic mouse brains at the ID19 beamline, ESRF, Grenoble, France, using grating- and propagation-based phase contrast micro-tomography. The resulting datasets clearly show the cortex, ventricular system, thalamus, hypothalamus, and hippocampus. Our focus is on the latter, having planned kainate-induced epilepsy experiments. The cell density and organization in the dentate gyrus and Ammon's horn region were clearly visualized in control animals. This proof of principle was required to initiate experiment. The resulting three-dimensional data have been correlated to histology. The goal is a brain-wide quantification of cell death or structural reorganization associated with epilepsy as opposed to histology alone that represents small volumes of the total brain only. Thus, the proposed technique bears the potential to correlate the gold standard in analysis with independently obtained data sets. Such an achievement also fuels interest for other groups in neuroscience research to closely collaborate with experts in phase micro-tomography.

Knowledge, Attitudes, and Beliefs Toward Organ Donation Among Social Media Users.

PubMed

Hajjar, W M; Bin Abdulqader, S A; Aldayel, S S; Alfardan, A W; Alzaidy, N I

2016-09-01

Organ transplantation is the optimal treatment for end-stage organ diseases. The demand for organs has exceeded the available supply, which becomes a major obstacle worldwide. Identifying the factors affecting this gap will help in overcoming this obstacle. The purpose of the work was to study the knowledge, attitudes, and beliefs of organ donation and to determine the knowledge of brain death among social media users. A cross-sectional study was conducted among social media users living in Saudi Arabia. A pre-designed self-administrated questionnaire was distributed online randomly on social media networks in 2015. Of the total 1368 participants, only 913 met the criteria. Most respondents were between 18 and 29 years of age (61.2%) and living in the central region of Saudi Arabia (64.5%). The majority of respondents received their information from television (57%) and social media (50%) networks; 46.4% of respondents knew that the religious fatwa allowed organ donation; 51% of respondents were willing to donate their organs; 46.5% considered the brain-dead to be deceased, whereas 37.7% considered it a coma; 33.3% did not know if someone who was brain-dead would ever wake up; on the other hand, 323 (35.4%) said yes. Our study showed that the vast majority of our sample had enough information about organ donation. On the contrary, they had minimal knowledge about brain death. Moreover, a fair percentage of the participants had positive attitudes toward organ donation. Also, the media had a significant effect on the information about organ donation and brain death. Copyright © 2016 Elsevier Inc. All rights reserved.

Postnatal brain development of the pulse type, weakly electric gymnotid fish Gymnotus omarorum.

PubMed

Iribarne, Leticia; Castelló, María E

2014-01-01

Teleosts are a numerous and diverse group of fish showing great variation in body shape, ecological niches and behaviors, and a correspondent diversity in brain morphology, usually associated with their functional specialization. Weakly electric fish are a paradigmatic example of functional specialization, as these teleosts use self-generated electric fields to sense the nearby environment and communicate with conspecifics, enabling fish to better exploit particular ecological niches. We analyzed the development of the brain of the pulse type gymnotid Gymnotus omarorum, focusing on the brain regions involved directly or indirectly in electrosensory information processing. A morphometric analysis has been made of the whole brain and of brain regions of interest, based on volumetric data obtained from 3-D reconstructions to study the growth of the whole brain and the relative growth of brain regions, from late larvae to adulthood. In the smallest studied larvae some components of the electrosensory pathway appeared to be already organized and functional, as evidenced by tract-tracing and in vivo field potential recordings of electrosensory-evoked activity. From late larval to adult stages, rombencephalic brain regions (cerebellum and electrosensory lateral line lobe) showed a positive allometric growth, mesencephalic brain regions showed a negative allometric growth, and the telencephalon showed an isometric growth. In a first step towards elucidating the role of cell proliferation in the relative growth of the analyzed brain regions, we also studied the spatial distribution of proliferation zones by means of pulse type BrdU labeling revealed by immunohistochemistry. The brain of G. omarorum late larvae showed a widespread distribution of proliferating zones, most of which were located at the ventricular-cisternal lining. Interestingly, we also found extra ventricular-cisternal proliferation zones at in the rombencephalic cerebellum and electrosensory lateral line lobe. We discuss the role of extraventricular-cisternal proliferation in the relative growth of the latter brain regions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain Damage in School Age Children.

ERIC Educational Resources Information Center

Haywood, H. Carl, Ed.

The product of a professional workshop, 10 papers discuss brain damage. An introduction to clinical neuropsychology is presented by H. Carl Haywood. A section on neurological foundations includes papers on the organization of the central nervous system by Jack T. Tapp and Lance L. Simpson, on epilepsy by Angela T. Folsom, and on organic language…

Cannabis Use and Memory Brain Function in Adolescent Boys: A Cross-Sectional Multicenter Functional Magnetic Resonance Imaging Study

ERIC Educational Resources Information Center

Jager, Gerry; Block, Robert I.; Luijten, Maartje; Ramsey, Nick F.

2010-01-01

Objective: Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and…

21 CFR 882.1935 - Near Infrared (NIR) Brain Hematoma Detector.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Near Infrared (NIR) Brain Hematoma Detector. 882.1935 Section 882.1935 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... and the clinical training needed for the safe use of this device; (3) Appropriate analysis/testing...

A digital interactive human brain atlas based on Chinese visible human datasets for anatomy teaching.

PubMed

Li, Qiyu; Ran, Xu; Zhang, Shaoxiang; Tan, Liwen; Qiu, Mingguo

2014-01-01

As we know, the human brain is one of the most complicated organs in the human body, which is the key and difficult point in neuroanatomy and sectional anatomy teaching. With the rapid development and extensive application of imaging technology in clinical diagnosis, doctors are facing higher and higher requirement on their anatomy knowledge. Thus, to cultivate medical students to meet the needs of medical development today and to improve their ability to read and understand radiographic images have become urgent challenges for the medical teachers. In this context, we developed a digital interactive human brain atlas based on the Chinese visible human datasets for anatomy teaching (available for free download from http://www.chinesevisiblehuman.com/down/DHBA.rar). The atlas simultaneously provides views in all 3 primary planes of section. The main structures of the human brain have been anatomically labeled in all 3 views. It is potentially useful for anatomy browsing, user self-testing, and automatic student assessment. In a word, it is interactive, 3D, user friendly, and free of charge, which can provide a new, intuitive means for anatomy teaching.

Control networks and hubs.

PubMed

Gratton, Caterina; Sun, Haoxin; Petersen, Steven E

2018-03-01

Executive control functions are associated with frontal, parietal, cingulate, and insular brain regions that interact through distributed large-scale networks. Here, we discuss how fMRI functional connectivity can shed light on the organization of control networks and how they interact with other parts of the brain. In the first section of our review, we present convergent evidence from fMRI functional connectivity, activation, and lesion studies that there are multiple dissociable control networks in the brain with distinct functional properties. In the second section, we discuss how graph theoretical concepts can help illuminate the mechanisms by which control networks interact with other brain regions to carry out goal-directed functions, focusing on the role of specialized hub regions for mediating cross-network interactions. Again, we use a combination of functional connectivity, lesion, and task activation studies to bolster this claim. We conclude that a large-scale network perspective provides important neurobiological constraints on the neural underpinnings of executive control, which will guide future basic and translational research into executive function and its disruption in disease. © 2017 Society for Psychophysiological Research.

A New Antigen Retrieval Technique for Human Brain Tissue

PubMed Central

Byne, William; Haroutunian, Vahram; García-Villanueva, Mercedes; Rábano, Alberto; García-Amado, María; Prensa, Lucía; Giménez-Amaya, José Manuel

2008-01-01

Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times. PMID:18852880

Neuroanatomy of the killer whale (Orcinus orca) from magnetic resonance images.

PubMed

Marino, Lori; Sherwood, Chet C; Delman, Bradley N; Tang, Cheuk Y; Naidich, Thomas P; Hof, Patrick R

2004-12-01

This article presents the first series of MRI-based anatomically labeled sectioned images of the brain of the killer whale (Orcinus orca). Magnetic resonance images of the brain of an adult killer whale were acquired in the coronal and axial planes. The gross morphology of the killer whale brain is comparable in some respects to that of other odontocete brains, including the unusual spatial arrangement of midbrain structures. There are also intriguing differences. Cerebral hemispheres appear extremely convoluted and, in contrast to smaller cetacean species, the killer whale brain possesses an exceptional degree of cortical elaboration in the insular cortex, temporal operculum, and the cortical limbic lobe. The functional and evolutionary implications of these features are discussed. (c) 2004 Wiley-Liss, Inc.

Voltage-sensitive rhodol with enhanced two-photon brightness.

PubMed

Kulkarni, Rishikesh U; Kramer, Daniel J; Pourmandi, Narges; Karbasi, Kaveh; Bateup, Helen S; Miller, Evan W

2017-03-14

We have designed, synthesized, and applied a rhodol-based chromophore to a molecular wire-based platform for voltage sensing to achieve fast, sensitive, and bright voltage sensing using two-photon (2P) illumination. Rhodol VoltageFluor-5 (RVF5) is a voltage-sensitive dye with improved 2P cross-section for use in thick tissue or brain samples. RVF5 features a dichlororhodol core with pyrrolidyl substitution at the nitrogen center. In mammalian cells under one-photon (1P) illumination, RVF5 demonstrates high voltage sensitivity (28% ΔF/F per 100 mV) and improved photostability relative to first-generation voltage sensors. This photostability enables multisite optical recordings from neurons lacking tuberous sclerosis complex 1, Tsc1, in a mouse model of genetic epilepsy. Using RVF5, we show that Tsc1 KO neurons exhibit increased activity relative to wild-type neurons and additionally show that the proportion of active neurons in the network increases with the loss of Tsc1. The high photostability and voltage sensitivity of RVF5 is recapitulated under 2P illumination. Finally, the ability to chemically tune the 2P absorption profile through the use of rhodol scaffolds affords the unique opportunity to image neuronal voltage changes in acutely prepared mouse brain slices using 2P illumination. Stimulation of the mouse hippocampus evoked spiking activity that was readily discerned with bath-applied RVF5, demonstrating the utility of RVF5 and molecular wire-based voltage sensors with 2P-optimized fluorophores for imaging voltage in intact brain tissue.

Two different phenomena in basic motor speech performance in premanifest Huntington disease.

PubMed

Skodda, Sabine; Grönheit, Wenke; Lukas, Carsten; Bellenberg, Barbara; von Hein, Sarah M; Hoffmann, Rainer; Saft, Carsten

2016-03-09

Dysarthria is a common feature in Huntington disease (HD). The aim of this cross-sectional pilot study was the description and objective analysis of different speech parameters with special emphasis on the aspect of speech timing of connected speech and nonspeech verbal utterances in premanifest HD (preHD). A total of 28 preHD mutation carriers and 28 age- and sex-matched healthy speakers had to perform a reading task and several syllable repetition tasks. Results of computerized acoustic analysis of different variables for the measurement of speech rate and regularity were correlated with clinical measures and MRI-based brain atrophy assessment by voxel-based morphometry. An impaired capacity to steadily repeat single syllables with higher variations in preHD compared to healthy controls was found (variance 1: Cohen d = 1.46). Notably, speech rate was increased compared to controls and showed correlations to the volume of certain brain areas known to be involved in the sensory-motor speech networks (net speech rate: Cohen d = 1.19). Furthermore, speech rate showed correlations to disease burden score, probability of disease onset, the estimated years to onset, and clinical measures like the cognitive score. Measurement of speech rate and regularity might be helpful additional tools for the monitoring of subclinical functional disability in preHD. As one of the possible causes for higher performance in preHD, we discuss huntingtin-dependent temporarily advantageous development processes of the brain. © 2016 American Academy of Neurology.

Brain growth trajectories in mouse strains with central and peripheral serotonin differences: relevance to autism models.

PubMed

Flood, Z C; Engel, D L J; Simon, C C; Negherbon, K R; Murphy, L J; Tamavimok, W; Anderson, G M; Janušonis, S

2012-05-17

The genetic heterogeneity of autism spectrum disorders (ASDs) suggests that their underlying neurobiology involves dysfunction at the neural network level. Understanding these neural networks will require a major collaborative effort and will depend on validated and widely accepted animal models. Many mouse models have been proposed in autism research, but the assessment of their validity often has been limited to measuring social interactions. However, two other well-replicated findings have been reported in ASDs: transient brain overgrowth in early postnatal life and elevated 5-HT (serotonin) levels in blood platelets (platelet hyperserotonemia). We examined two inbred mouse strains (C57BL/6 and BALB/c) with respect to these phenomena. The BALB/c strain is less social and exhibits some other autistic-like behaviors. In addition, it has a lower 5-HT synthesis rate in the central nervous system due to a single-nucleotide polymorphism in the tryptophan hydroxylase 2 (Tph2) gene. The postnatal growth of brain mass was analyzed with mixed-effects models that included litter effects. The volume of the hippocampal complex and the thickness of the somatosensory cortex were measured in 3D-brain reconstructions from serial sections. The postnatal whole-blood 5-HT levels were assessed with high-performance liquid chromatography. With respect to the BALB/c strain, the C57BL/6 strain showed transient brain overgrowth and persistent blood hyperserotonemia. The hippocampal volume was permanently enlarged in the C57BL/6 strain, with no change in the adult brain mass. These results indicate that, in mice, autistic-like shifts in the brain and periphery may be associated with less autistic-like behaviors. Importantly, they suggest that consistency among behavioral, anatomical, and physiological measures may expedite the validation of new and previously proposed mouse models of autism, and that the construct validity of models should be demonstrated when these measures are inconsistent. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

[Immunohistochemical studies on neuronal changes in brain stem nucleus of forensic autopsied cases. I. Various cases of asphyxia and respiratory disorder].

PubMed

Kubo, S; Orihara, Y; Gotohda, T; Tokunaga, I; Tsuda, R; Ikematsu, K; Kitamura, O; Yamamoto, A; Nakasono, I

1998-12-01

Several nuclei in brain stem are well known to play an important role in supporting human life. However, the connection between neural changes of brain stem and the cause of death is not yet fully understood. To investigate the correlation of brain stem damage with various cause of respiratory disorders, neural changes of the arcuate nucleus (ARC), the hypoglossal nucleus (HN) and the inferior olivary nucleus (IO) were examined using immunohistochemical technique. Based on the cause of death, the forensic autopsy cases were divided into 5 groups as follows. Group I: hanging, ligature strangulation and manual strangulation, Group II: smothering and choking, Group III: drowning, Group IV: respiratory failure, control group: heat stroke and sun stroke. Brain was fixed with phosphate-buffer formalin, and the brain stem was horizontally dissected at the level of apex, then embedded in paraffin. The sections were stained with the antibodies against microtubule-associated protein 2 (MAP2), muscalinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos) and 72 kD heat-shock protein (HSP70). Three nuclei showed no obvious morphological changes in all examined groups. However, in case of asphyxia (Group I to III), neurons in HN were positively stained with both HSP70 and c-Fos antibodies. This may indicate that the occlusion of upper airway results in the neuronal damage of HN without their morphological changes. Positive staining of HSP70 and c-Fos in IO was more frequently observed in Group III than other 4 groups. Since IO is involved in maintaining body balance which is often disturbed by drowning, it seems possible that neuronal damage in IO observed in drowning may be related to the disturbance of body balance. These observations indicate that immunohistochemical study on the damage to neurons in brain stem nuclei can provide useful information for determining the cause of death.

Global and Regional Brain Assessment with Quantitative MR Imaging in Patients with Prior Exposure to Linear Gadolinium-based Contrast Agents.

PubMed

Kuno, Hirofumi; Jara, Hernán; Buch, Karen; Qureshi, Muhammad Mustafa; Chapman, Margaret N; Sakai, Osamu

2017-04-01

Purpose To assess the association of global and regional brain relaxation times in patients with prior exposure to linear gadolinium-based contrast agents (GBCAs). Materials and Methods The institutional review board approved this cross-sectional study. Thirty-five patients (nine who had received GBCA gadopentetate dimeglumine injections previously [one to eight times] and 26 patients who did not) who underwent brain magnetic resonance (MR) imaging with a mixed fast spin-echo pulse sequence were assessed. The whole brain was segmented according to white and gray matter by using a dual-clustering algorithm. In addition, regions of interest were measured in the globus pallidus, dentate nucleus, thalamus, and pons. The Mann-Whitney U test was used to assess the difference between groups. Multiple regression analysis was performed to assess the association of T1 and T2 with prior GBCA exposure. Results T1 values of gray matter were significantly shorter for patients with than for patients without prior GBCA exposure (P = .022). T1 of the gray matter of the whole brain (P < .001), globus pallidus (P = .002), dentate nucleus (P = .046), and thalamus (P = .026) and T2 of the whole brain (P = .004), dentate nucleus (P = .023), and thalamus (P = .002) showed a significant correlation with the accumulated dose of previous GBCA administration. There was no significant correlation between T1 and the accumulated dose of previous GBCA injections in the white matter (P = .187). Conclusion Global and regional quantitative assessments of T1 and T2 demonstrated an association with prior GBCA exposure, especially for gray matter structures. The results of this study confirm previous research findings that there is gadolinium deposition in wider distribution throughout the brain. © RSNA, 2016 Online supplemental material is available for this article.

Human FGF1 promoter is active in ependymal cells and dopaminergic neurons in the brains of F1B-GFP transgenic mice.

PubMed

Chen, Mei-Shu; Lin, Hua-Kuo; Chiu, Hsun; Lee, Don-Ching; Chung, Yu-Fen; Chiu, Ing-Ming

2015-03-01

FGF1 is involved in multiple biological functions and exhibits the importance in neuroprotective effects. Our previous studies indicated that, in human brain and retina, the FGF1B promoter controlled the expression of FGF1. However, the exact function and regulation of FGF1 in brain is still unclear. Here, we generated F1B-GFP transgenic mice that expressed the GFP reporter gene under the control of human FGF1B promoter (-540 to +31). Using the fresh brain sections of F1B-GFP transgenic mice, we found that the F1B-GFP cells expressed strong fluorescent signals in the ventricular system throughout the brain. The results of immunohistochemistry further showed that two distinct populations of F1B-GFP(+) cells existed in the brains of F1B-GFP transgenic mice. We demonstrated that one population of F1B-GFP(+) cells was ependymal cells, which distributed along the entire ventricles, and the second population of F1B-GFP(+) cells was neuronal cells that projected their long processes into multiple directions in specific areas of the brain. The double labeling of F1B-GFP(+) cells and tyrosine hydroxylase indicated that a subpopulation of F1B-GFP(+) -neuronal cells was dopaminergic neurons. Importantly, these F1B-GFP(+) /TH(+) cells were distributed in the main dopaminergic neuronal groups including hypothalamus, ventral tegmental area, and raphe nuclei. These results suggested that human FGF1B promoter was active in ependymal cells, neurons, and a portion of dopaminergic neurons. Thus, the F1B-GFP transgenic mice provide an animal model not only for studying FGF1 gene expression in vivo but also for understanding the role of FGF1 contribution in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. © 2014 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc.

Gender and age effects in structural brain asymmetry as measured by MRI texture analysis.

PubMed

Kovalev, Vassili A; Kruggel, Frithjof; von Cramon, D Yves

2003-07-01

Effects of gender and age on structural brain asymmetry were studied by 3D texture analysis in 380 adults. Asymmetry is detected by comparing the complex 3D gray-scale image patterns in the left and right cerebral hemispheres as revealed by anatomical T1-weighted MRI datasets. The Talairach and Tournoux parcellation system was applied to study the asymmetry on five levels: the whole cerebrum, nine coronal sections, 12 axial sections, boxes resulting from both coronal and axial subdivisions, and by a sliding spherical window of 9 mm diameter. The analysis revealed that the brain asymmetry increases in the anterior-posterior direction starting from the central region onward. Male brains were found to be more asymmetric than female. This gender-related effect is noticeable in all brain areas but is most significant in the superior temporal gyrus, Heschl's gyrus, the adjacent white matter regions in the temporal stem and the knee of the optic radiation, the thalamus, and the posterior cingulate. The brain asymmetry increases significantly with age in the inferior frontal gyrus, anterior insula, anterior cingulate, parahippocampal gyrus, retrosplenial cortex, coronal radiata, and knee region of the internal capsule. Asymmetry decreases with age in the optic radiation, precentral gyrus, and angular gyrus. The texture-based method reported here is based on extended multisort cooccurrence matrices that employ intensity, gradient, and anisotropy features in a uniform way. It is sensitive, simple to reproduce, robust, and unbiased in the sense that segmentation of brain compartments and spatial transformations are not necessary. Thus, it should be considered as another tool for digital morphometry in neuroscience.

The effect of ovariectomy on learning and memory and relationship to changes in brain volume and neuronal density.

PubMed

Su, Jian; Sripanidkulchai, Kittisak; Hu, Ying; Wyss, J Michael; Sripanidkulchai, Bungorn

2012-10-01

The loss of sex hormones in postmenopausal women has been suggested to be involved in cognitive degenerative diseases, such as Alzheimer's disease. In the present study, ovariectomized (OVX) and control rats were tested for 4 months in a Morris water maze (MWM) task to track their memory status. Thereafter, postmortem frozen brain sections were analyzed to determine if changes in brain area volumes and neuronal density were related to changes in cognitive ability. A modified artificial-land-mark-based method was used to assure the fidelity of the three dimensions (3D) reconstructed structures. Volumetric areas of the hippocampus, cortex, caudate putamen (cpu), and cerebellum were estimated from the reconstructions, and neuron densities of CA1 and CA3 subregions of the hippocampus were measured in an adjacent second series of Nissl-stained sections. Compared to the control rats, OVX rats displayed memory impairments, beginning in the second month after the ovariectomy (p < .05). Assessments at the end of the study demonstrated that OVX (compared to control) rats displayed reduced brain volume in the hippocampus and neocortex and in the brain as a whole. In contrast, when compared to controls, the volumes of cpu and cerebellum of OVX rats increased slightly. CA3 neuron density of OVX (compared to controls) rats was significantly lower, but the CA1 neuron density was significantly higher. In conclusion, ovariectomy impaired spatial memory and led to morphological changes in cognitive centers of rat brain. The results demonstrate that the 3D reconstructed method is useful for the study of brain morphological abnormality in rats.

Tentative Evidence for Striatal Hyperactivity in Adolescent Cannabis Using Boys: A Cross-Sectional Multicenter fMRI Study

PubMed Central

Jager, Gerry; Block, Robert I.; Luijten, Maartje; Ramsey, Nick F.

2013-01-01

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward (“go”) and inhibitory-control (“stop”) related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences. PMID:23909003

Specimen preparation, imaging, and analysis protocols for knife-edge scanning microscopy.

PubMed

Choe, Yoonsuck; Mayerich, David; Kwon, Jaerock; Miller, Daniel E; Sung, Chul; Chung, Ji Ryang; Huffman, Todd; Keyser, John; Abbott, Louise C

2011-12-09

Major advances in high-throughput, high-resolution, 3D microscopy techniques have enabled the acquisition of large volumes of neuroanatomical data at submicrometer resolution. One of the first such instruments producing whole-brain-scale data is the Knife-Edge Scanning Microscope (KESM), developed and hosted in the authors' lab. KESM has been used to section and image whole mouse brains at submicrometer resolution, revealing the intricate details of the neuronal networks (Golgi), vascular networks (India ink), and cell body distribution (Nissl). The use of KESM is not restricted to the mouse nor the brain. We have successfully imaged the octopus brain, mouse lung, and rat brain. We are currently working on whole zebra fish embryos. Data like these can greatly contribute to connectomics research; to microcirculation and hemodynamic research; and to stereology research by providing an exact ground-truth. In this article, we will describe the pipeline, including specimen preparation (fixing, staining, and embedding), KESM configuration and setup, sectioning and imaging with the KESM, image processing, data preparation, and data visualization and analysis. The emphasis will be on specimen preparation and visualization/analysis of obtained KESM data. We expect the detailed protocol presented in this article to help broaden the access to KESM and increase its utilization.

Tentative evidence for striatal hyperactivity in adolescent cannabis-using boys: a cross-sectional multicenter fMRI study.

PubMed

Jager, Gerry; Block, Robert I; Luijten, Maartje; Ramsey, Nick F

2013-01-01

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward ("go") and inhibitory-control ("stop")-related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study, we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences.

Magnetic Enhancement of Stem Cell-Targeted Delivery into the Brain Following MR-Guided Focused Ultrasound for Opening the Blood-Brain Barrier.

PubMed

Shen, Wei-Bin; Anastasiadis, Pavlos; Nguyen, Ben; Yarnell, Deborah; Yarowsky, Paul J; Frenkel, Victor; Fishman, Paul S

2017-07-01

Focused ultrasound (FUS)-mediated blood-brain barrier disruption (BBBD) can enable even large therapeutics such as stem cells to enter the brain from the bloodstream. However, the efficiency is relatively low. Our previous study showed that human neural progenitor cells (hNPCs) loaded with superparamagnetic iron oxide nanoparticles (SPIONs) in culture were attracted by an external magnetic field. In vivo, enhanced brain retention was observed near a magnet mounted on the skull in a rat model of traumatic brain injury, where BBBD also occurs. The goal of the current study was to determine whether magnetic attraction of SPION-loaded hNPCs would also enhance their retention in the brain after FUS-mediated BBBD. A small animal magnetic resonance imaging (MRI)-guided FUS system operating at 1.5 MHz was used to treat rats (∼120 g) without tissue damage or hemorrhage. Evidence of successful BBBD was validated with both radiologic enhancement of gadolinium on postsonication TI MRI and whole brain section visualization of Evans blue dye. The procedure was then combined with the application of a powerful magnet to the head directly after intravenous injection of the hNPCs. Validation of cells within the brain was performed by staining with Perls' Prussian blue for iron and by immunohistochemistry with a human-specific antigen. By injecting equal numbers of iron oxide (SPIONs) and noniron oxide nanoparticles-loaded hNPCs, each labeled with a different fluorophore, we found significantly greater numbers of SPIONs-loaded cells retained in the brain at the site of BBBD as compared to noniron loaded cells. This result was most pronounced in regions of the brain closest to the skull (dorsal cortex) in proximity to the magnet surface. A more powerful magnet and a Halbach magnetic array resulted in more effective retention of SPION-labeled cells in even deeper brain regions such as the striatum and ventral cortex. There, up to 90% of hNPCs observed contained SPIONs compared to 60% to 70% with the less powerful magnet. Fewer cells were observed at 24 h posttreatment compared to 2 h (primarily in the dorsal cortex). These results demonstrate that magnetic attraction can substantially enhance the retention of stem cells after FUS-mediated BBBD. This procedure could provide a safer and less invasive approach for delivering stem cells to the brain, compared to direct intracranial injections, substantially reducing the risk of bleeding and infection.

Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors.

PubMed

Liu, Hesheng; Stufflebeam, Steven M; Sepulcre, Jorge; Hedden, Trey; Buckner, Randy L

2009-12-01

Cerebral lateralization is a fundamental property of the human brain and a marker of successful development. Here we provide evidence that multiple mechanisms control asymmetry for distinct brain systems. Using intrinsic activity to measure asymmetry in 300 adults, we mapped the most strongly lateralized brain regions. Both men and women showed strong asymmetries with a significant, but small, group difference. Factor analysis on the asymmetric regions revealed 4 separate factors that each accounted for significant variation across subjects. The factors were associated with brain systems involved in vision, internal thought (the default network), attention, and language. An independent sample of right- and left-handed individuals showed that hand dominance affects brain asymmetry but differentially across the 4 factors supporting their independence. These findings show the feasibility of measuring brain asymmetry using intrinsic activity fluctuations and suggest that multiple genetic or environmental mechanisms control cerebral lateralization.

Validation of In utero Tractography of Human Fetal Commissural and Internal Capsule Fibers with Histological Structure Tensor Analysis

PubMed Central

Mitter, Christian; Jakab, András; Brugger, Peter C.; Ricken, Gerda; Gruber, Gerlinde M.; Bettelheim, Dieter; Scharrer, Anke; Langs, Georg; Hainfellner, Johannes A.; Prayer, Daniela; Kasprian, Gregor

2015-01-01

Diffusion tensor imaging (DTI) and tractography offer the unique possibility to visualize the developing white matter macroanatomy of the human fetal brain in vivo and in utero and are currently under investigation for their potential use in the diagnosis of developmental pathologies of the human central nervous system. However, in order to establish in utero DTI as a clinical imaging tool, an independent comparison between macroscopic imaging and microscopic histology data in the same subject is needed. The present study aimed to cross-validate normal as well as abnormal in utero tractography results of commissural and internal capsule fibers in human fetal brains using postmortem histological structure tensor (ST) analysis. In utero tractography findings from two structurally unremarkable and five abnormal fetal brains were compared to the results of postmortem ST analysis applied to digitalized whole hemisphere sections of the same subjects. An approach to perform ST-based deterministic tractography in histological sections was implemented to overcome limitations in correlating in utero tractography to postmortem histology data. ST analysis and histology-based tractography of fetal brain sections enabled the direct assessment of the anisotropic organization and main fiber orientation of fetal telencephalic layers on a micro- and macroscopic scale, and validated in utero tractography results of corpus callosum and internal capsule fiber tracts. Cross-validation of abnormal in utero tractography results could be achieved in four subjects with agenesis of the corpus callosum (ACC) and in two cases with malformations of internal capsule fibers. In addition, potential limitations of current DTI-based in utero tractography could be demonstrated in several brain regions. Combining the three-dimensional nature of DTI-based in utero tractography with the microscopic resolution provided by histological ST analysis may ultimately facilitate a more complete morphologic characterization of axon guidance disorders at prenatal stages of human brain development. PMID:26732460

At least eighty percent of brain grey matter is modifiable by physical activity: A review study.

PubMed

Batouli, Seyed Amir Hossein; Saba, Valiallah

2017-08-14

The human brain is plastic, i.e. it can show structural changes in response to the altered environment. Physical activity (PA) is a lifestyle factor which has significant associations with the structural and functional aspects of the human brain, as well as with the mind and body health. Many studies have reported regional/global brain volume increments due to exercising; however, a map which shows the overall extent of the influences of PAs on brain structure is not available. In this study, we collected all the reports on brain structural alterations in association with PA in healthy humans, and next, a brain map of the extent of these effects is provided. The results of this study showed that a large network of brain areas, equal to 82% of the total grey matter volume, were associated with PA. This finding has important implications in utilizing PA as a mediator factor for educational purposes in children, rehabilitation applications in patients, improving the cognitive abilities of the human brain such as in learning or memory, and preventing age-related brain deteriorations. Copyright © 2017 Elsevier B.V. All rights reserved.

Transverse section radionuclide scanning system

DOEpatents

Kuhl, David E.; Edwards, Roy Q.

1976-01-01

This invention provides a transverse section radionuclide scanning system for high-sensitivity quantification of brain radioactivity in cross-section picture format in order to permit accurate assessment of regional brain function localized in three-dimensions. High sensitivity crucially depends on overcoming the heretofore known raster type scanning, which requires back and forth detector movement involving dead-time or partial enclosure of the scan field. Accordingly, this invention provides a detector array having no back and forth movement by interlaced detectors that enclose the scan field and rotate as an integral unit around one axis of rotation in a slip ring that continuously transmits the detector data by means of laser emitting diodes, with the advantages that increased amounts of data can be continuously collected, processed and displayed with increased sensitivity according to a suitable computer program.

Mapping pharmaceuticals in rat brain sections using MALDI imaging mass spectrometry.

PubMed

Hsieh, Yunsheng; Li, Fangbiao; Korfmacher, Walter A

2010-01-01

Matrix-assisted laser desorption/ionization-tandem mass spectrometric method (MALDI-MS/MS) has proven to be a reliable tool for direct measurement of the disposition of small molecules in animal tissue sections. As example, MALDI-MS/MS imaging system was employed for visualizing the spatial distribution of astemizole and its primary metabolite in rat brain tissues. Astemizole is a second-generation antihistamine, a block peripheral H1 receptor, which was introduced to provide comparable therapeutic benefit but was withdrawn in most countries due to toxicity risks. Astemizole was observed to be heterogeneously distributed to most parts of brain tissue slices including cortex, hippocampus, hypothalamic, thalamus, and ventricle regions while its major metabolite, desmethylastemizole, was only found around ventricle sites. We have shown that astemizole alone is likely to be responsible for the central nervous system (CNS) side effects when its exposures became elevated.

Introduction to the special section: Myelin and oligodendrocyte abnormalities in schizophrenia.

PubMed

Haroutunian, Vahram; Davis, Kenneth L

2007-08-01

A central tenet of modern views of the neurobiology of schizophrenia is that the symptoms of schizophrenia arise from a failure of adequate communication between different brain regions and disruption of the circuitry that underlies behaviour and perception. Historically this disconnectivity syndrome has been approached from a neurotransmitter-based perspective. However, efficient communication between brain circuits is also contingent on saltatory signal propagation and salubrious myelination of axons. The papers in this Special Section examine the neuroanatomical and molecular biological evidence for abnormal myelination and oligodendroglial function in schizophrenia through studies of post-mortem brain tissue and animal model systems. The picture that emerges from the studies described suggests that although schizophrenia is not characterized by gross abnormalities of white matter such as those evident in multiple sclerosis, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths.

Multi-Modal Glioblastoma Segmentation: Man versus Machine

PubMed Central

Pica, Alessia; Schucht, Philippe; Beck, Jürgen; Verma, Rajeev Kumar; Slotboom, Johannes; Reyes, Mauricio; Wiest, Roland

2014-01-01

Background and Purpose Reproducible segmentation of brain tumors on magnetic resonance images is an important clinical need. This study was designed to evaluate the reliability of a novel fully automated segmentation tool for brain tumor image analysis in comparison to manually defined tumor segmentations. Methods We prospectively evaluated preoperative MR Images from 25 glioblastoma patients. Two independent expert raters performed manual segmentations. Automatic segmentations were performed using the Brain Tumor Image Analysis software (BraTumIA). In order to study the different tumor compartments, the complete tumor volume TV (enhancing part plus non-enhancing part plus necrotic core of the tumor), the TV+ (TV plus edema) and the contrast enhancing tumor volume CETV were identified. We quantified the overlap between manual and automated segmentation by calculation of diameter measurements as well as the Dice coefficients, the positive predictive values, sensitivity, relative volume error and absolute volume error. Results Comparison of automated versus manual extraction of 2-dimensional diameter measurements showed no significant difference (p = 0.29). Comparison of automated versus manual segmentation of volumetric segmentations showed significant differences for TV+ and TV (p<0.05) but no significant differences for CETV (p>0.05) with regard to the Dice overlap coefficients. Spearman's rank correlation coefficients (ρ) of TV+, TV and CETV showed highly significant correlations between automatic and manual segmentations. Tumor localization did not influence the accuracy of segmentation. Conclusions In summary, we demonstrated that BraTumIA supports radiologists and clinicians by providing accurate measures of cross-sectional diameter-based tumor extensions. The automated volume measurements were comparable to manual tumor delineation for CETV tumor volumes, and outperformed inter-rater variability for overlap and sensitivity. PMID:24804720

Optically sectioned in vivo imaging with speckle illumination HiLo microscopy

PubMed Central

Lim, Daryl; Ford, Tim N.; Chu, Kengyeh K.; Mertz, Jerome

2011-01-01

We present a simple wide-field imaging technique, called HiLo microscopy, that is capable of producing optically sectioned images in real time, comparable in quality to confocal laser scanning microscopy. The technique is based on the fusion of two raw images, one acquired with speckle illumination and another with standard uniform illumination. The fusion can be numerically adjusted, using a single parameter, to produce optically sectioned images of varying thicknesses with the same raw data. Direct comparison between our HiLo microscope and a commercial confocal laser scanning microscope is made on the basis of sectioning strength and imaging performance. Specifically, we show that HiLo and confocal 3-D imaging of a GFP-labeled mouse brain hippocampus are comparable in quality. Moreover, HiLo microscopy is capable of faster, near video rate imaging over larger fields of view than attainable with standard confocal microscopes. The goal of this paper is to advertise the simplicity, robustness, and versatility of HiLo microscopy, which we highlight with in vivo imaging of common model organisms including planaria, C. elegans, and zebrafish. PMID:21280920

Optically sectioned in vivo imaging with speckle illumination HiLo microscopy.

PubMed

Lim, Daryl; Ford, Tim N; Chu, Kengyeh K; Mertz, Jerome

2011-01-01

We present a simple wide-field imaging technique, called HiLo microscopy, that is capable of producing optically sectioned images in real time, comparable in quality to confocal laser scanning microscopy. The technique is based on the fusion of two raw images, one acquired with speckle illumination and another with standard uniform illumination. The fusion can be numerically adjusted, using a single parameter, to produce optically sectioned images of varying thicknesses with the same raw data. Direct comparison between our HiLo microscope and a commercial confocal laser scanning microscope is made on the basis of sectioning strength and imaging performance. Specifically, we show that HiLo and confocal 3-D imaging of a GFP-labeled mouse brain hippocampus are comparable in quality. Moreover, HiLo microscopy is capable of faster, near video rate imaging over larger fields of view than attainable with standard confocal microscopes. The goal of this paper is to advertise the simplicity, robustness, and versatility of HiLo microscopy, which we highlight with in vivo imaging of common model organisms including planaria, C. elegans, and zebrafish.

Optically sectioned in vivo imaging with speckle illumination HiLo microscopy

NASA Astrophysics Data System (ADS)

Lim, Daryl; Ford, Tim N.; Chu, Kengyeh K.; Mertz, Jerome

2011-01-01

We present a simple wide-field imaging technique, called HiLo microscopy, that is capable of producing optically sectioned images in real time, comparable in quality to confocal laser scanning microscopy. The technique is based on the fusion of two raw images, one acquired with speckle illumination and another with standard uniform illumination. The fusion can be numerically adjusted, using a single parameter, to produce optically sectioned images of varying thicknesses with the same raw data. Direct comparison between our HiLo microscope and a commercial confocal laser scanning microscope is made on the basis of sectioning strength and imaging performance. Specifically, we show that HiLo and confocal 3-D imaging of a GFP-labeled mouse brain hippocampus are comparable in quality. Moreover, HiLo microscopy is capable of faster, near video rate imaging over larger fields of view than attainable with standard confocal microscopes. The goal of this paper is to advertise the simplicity, robustness, and versatility of HiLo microscopy, which we highlight with in vivo imaging of common model organisms including planaria, C. elegans, and zebrafish.

Alterations in Pericyte Subpopulations are Associated with Elevated Blood-Tumor Barrier Permeability in Experimental Brain Metastasis of Breast Cancer

PubMed Central

Lyle, L. Tiffany; Lockman, Paul R.; Adkins, Chris E.; Mohammad, Afroz Shareef; Sechrest, Emily; Hua, Emily; Palmieri, Diane; Liewehr, David J.; Steinberg, Seth M.; Kloc, Wojciech; Izycka-Swieszewska, Ewa; Duchnowska, Renata; Nayyar, Naema; Brastianos, Priscilla K.; Steeg, Patricia S.; Gril, Brunilde

2016-01-01

Purpose The blood-brain barrier (BBB) is modified to a blood-tumor barrier (BTB) as a brain metastasis develops from breast or other cancers. We (a) quantified the permeability of experimental brain metastases; (b) determined the composition of the BTB; (c) identified which elements of the BTB distinguished metastases of lower permeability from those with higher permeability. Experimental Design A SUM190-BR3 experimental inflammatory breast cancer brain metastasis subline was established. Experimental brain metastases from this model system and two previously reported models (triple-negative MDA-231-BR6, HER2+ JIMT-1-BR3) were serially sectioned; low and high permeability lesions were identified with systemic 3kDa Texas Red dextran dye. Adjoining sections were used for quantitative immunofluorescence to known BBB and neuroinflammatory components. One-sample comparisons against a hypothesized value of one were performed with the Wilcoxon signed-rank test. Results When uninvolved brain was compared to any brain metastasis, alterations in endothelial, pericytic, astrocytic, and microglial components were observed. When metastases with relatively low- and high permeability were compared, increased expression of a desmin+ subpopulation of pericytes was associated with higher permeability (231-BR6 p=0.0002; JIMT-1-BR3 p=0.004; SUM190-BR3 p=0.008); desmin+ pericytes were also identified in human craniotomy specimens. Trends of reduced CD13+ pericytes (231-BR6 p=0.014; JIMT-1-BR3 p=0.002, SUM190-BR3, NS) and laminin α2 (231-BR6 p=0.001; JIMT-1-BR3 p=0.049; SUM190-BR3 p=0.023) were also observed with increased permeability. Conclusions We provide the first account of the composition of the BTB in experimental brain metastasis. Desmin+ pericytes and laminin α2 are potential targets for the development of novel approaches to increase chemotherapeutic efficacy. PMID:27245829

Alterations in Pericyte Subpopulations Are Associated with Elevated Blood-Tumor Barrier Permeability in Experimental Brain Metastasis of Breast Cancer.

PubMed

Lyle, L Tiffany; Lockman, Paul R; Adkins, Chris E; Mohammad, Afroz Shareef; Sechrest, Emily; Hua, Emily; Palmieri, Diane; Liewehr, David J; Steinberg, Seth M; Kloc, Wojciech; Izycka-Swieszewska, Ewa; Duchnowska, Renata; Nayyar, Naema; Brastianos, Priscilla K; Steeg, Patricia S; Gril, Brunilde

2016-11-01

The blood-brain barrier (BBB) is modified to a blood-tumor barrier (BTB) as a brain metastasis develops from breast or other cancers. We (i) quantified the permeability of experimental brain metastases, (ii) determined the composition of the BTB, and (iii) identified which elements of the BTB distinguished metastases of lower permeability from those with higher permeability. A SUM190-BR3 experimental inflammatory breast cancer brain metastasis subline was established. Experimental brain metastases from this model system and two previously reported models (triple-negative MDA-231-BR6, HER2 + JIMT-1-BR3) were serially sectioned; low- and high-permeability lesions were identified with systemic 3-kDa Texas Red dextran dye. Adjoining sections were used for quantitative immunofluorescence to known BBB and neuroinflammatory components. One-sample comparisons against a hypothesized value of one were performed with the Wilcoxon signed-rank test. When uninvolved brain was compared with any brain metastasis, alterations in endothelial, pericytic, astrocytic, and microglial components were observed. When metastases with relatively low and high permeability were compared, increased expression of a desmin + subpopulation of pericytes was associated with higher permeability (231-BR6 P = 0.0002; JIMT-1-BR3 P = 0.004; SUM190-BR3 P = 0.008); desmin + pericytes were also identified in human craniotomy specimens. Trends of reduced CD13 + pericytes (231-BR6 P = 0.014; JIMT-1-BR3 P = 0.002, SUM190-BR3, NS) and laminin α2 (231-BR6 P = 0.001; JIMT-1-BR3 P = 0.049; SUM190-BR3 P = 0.023) were also observed with increased permeability. We provide the first account of the composition of the BTB in experimental brain metastasis. Desmin + pericytes and laminin α2 are potential targets for the development of novel approaches to increase chemotherapeutic efficacy. Clin Cancer Res; 22(21); 5287-99. ©2016 AACR. ©2016 American Association for Cancer Research.

Confocal laser endomicroscopy for brain tumor surgery: a milestone journey from microscopy to cellular surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Charalampaki, Cleopatra

2017-02-01

The aim in brain tumor surgery is maximal tumor resection with minimal damage of normal neuronal tissue. Today diagnosis of tumor and definition of tumor borders intraoperatively is based on various visualization methods as well as on the histopathologic examination of a limited number of biopsy specimens via frozen sections. Unfortunately, intraoperative histopathology bears several shortcomings, and many biopsies are inconclusive. Therefore, the desirable treatment could be to have the ability to identify intraoperative cellular structures, and differentiate tumor from normal functional brain tissue on a cellular level. To achieve this goal new technological equipment integrated with new surgical concepts is needed.Confocal Laser Endomicroscopy (CLE) is an imaging technique which provides microscopic information of tissue in real-time. We are able to use these technique to perform intraoperative "optical biopsies" in bringing the microscope inside to the patients brain through miniaturized fiber-optic probes, and allow real-time histopathology. In our knowledge we are worldwide the only one neurosurgical group using CLE intraoperative for brain tumor surgery. We can detect and characterize intraoperative tumor cells, providing immediate online diagnosis without the need for frozen sections. It also provides delineation of borders between tumor and normal tissue on a cellular level, making surgical margins more accurate than ever before. The applications of CLE-assisted neurosurgery help to accurate the therapy by extending the resection borders and protecting the functionality of normal brain tissue in critical eloquent areas.

Graph analysis of functional brain networks for cognitive control of action in traumatic brain injury.

PubMed

Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P

2012-04-01

Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly dispersed frontal and parietal activity during performance of cognitive control tasks. We constructed binary and weighted functional networks and calculated their topological properties using a graph theoretical approach. Twenty-three adults with traumatic brain injury and 26 age-matched controls were instructed to switch between coordination modes while making spatially and temporally coupled circular motions with joysticks during event-related functional magnetic resonance imaging. Results demonstrated that switching performance was significantly lower in patients with traumatic brain injury compared with control subjects. Furthermore, although brain networks of both groups exhibited economical small-world topology, altered functional connectivity was demonstrated in patients with traumatic brain injury. In particular, compared with controls, patients with traumatic brain injury showed increased connectivity degree and strength, and higher values of local efficiency, suggesting adaptive mechanisms in this group. Finally, the degree of increased connectivity was significantly correlated with poorer switching task performance and more severe brain injury. We conclude that analysing the functional brain network connectivity provides new insights into understanding cognitive control changes following brain injury.

Effect of Lapatinib on the Outgrowth of Metastatic Breast Cancer Cells to the Brain

PubMed Central

Gril, Brunilde; Palmieri, Diane; Bronder, Julie L.; Herring, Jeanne M.; Vega-Valle, Eleazar; Feigenbaum, Lionel; Liewehr, David J.; Steinberg, Seth M.; Merino, Maria J.; Rubin, Stephen D.

2008-01-01

Background The brain is increasingly being recognized as a sanctuary site for metastatic tumor cells in women with HER2-overexpressing breast cancer who receive trastuzumab therapy. There are no approved or widely accepted treatments for brain metastases other than steroids, cranial radiotherapy, and surgical resection. We examined the efficacy of lapatinib, an inhibitor of the epidermal growth factor receptor (EGFR) and HER2 kinases, for preventing the outgrowth of breast cancer cells in the brain in a mouse xenograft model of brain metastasis. Methods EGFR-overexpressing MDA-MB-231-BR (231-BR) brain-seeking breast cancer cells were transfected with an expression vector that contained or lacked the HER2 cDNA and used to examine the effect of lapatinib on the activation (ie, phosphorylation) of cell signaling proteins by immunoblotting, on cell growth by the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and on cell migration using a Boyden chamber assay. The outgrowth of large (ie, >50 μm2) and micrometastases was counted in brain sections from nude mice that had been injected into the left cardiac ventricle with 231-BR cells and, beginning 5 days later, treated by oral gavage with lapatinib or vehicle (n = 22–26 mice per treatment group). All statistical tests were two-sided. Results In vitro, lapatinib inhibited the phosphorylation of EGFR, HER2, and downstream signaling proteins; cell proliferation; and migration in 231-BR cells (both with and without HER2). Among mice injected with 231-BR-vector cells, those treated with 100 mg lapatinib/kg body weight had 54% fewer large metastases 24 days after starting treatment than those treated with vehicle (mean number of large metastases per brain section: 1.56 vs 3.36, difference = 1.80, 95% confidence interval [CI] = 0.92 to 2.68, P < .001), whereas treatment with 30 mg lapatinib/kg body weight had no effect. Among mice injected with 231-BR-HER2 cells, those treated with either dose of lapatinib had 50%–53% fewer large metastases than those treated with vehicle (mean number of large metastases per brain section, 30 mg/kg vs vehicle: 3.21 vs 6.83, difference = 3.62, 95% CI = 2.30 to 4.94, P < .001; 100 mg/kg vs vehicle: 3.44 vs 6.83, difference = 3.39, 95% CI = 2.08 to 4.70, P < .001). Immunohistochemical analysis revealed reduced phosphorylation of HER2 in 231-BR-HER2 cell–derived brain metastases from mice treated with the higher dose of lapatinib compared with 231-BR-HER2 cell–derived brain metastases from vehicle-treated mice (P < .001). Conclusions Lapatinib is the first HER2-directed drug to be validated in a preclinical model for activity against brain metastases of breast cancer. PMID:18664652

Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain.

PubMed

Gril, Brunilde; Palmieri, Diane; Bronder, Julie L; Herring, Jeanne M; Vega-Valle, Eleazar; Feigenbaum, Lionel; Liewehr, David J; Steinberg, Seth M; Merino, Maria J; Rubin, Stephen D; Steeg, Patricia S

2008-08-06

The brain is increasingly being recognized as a sanctuary site for metastatic tumor cells in women with HER2-overexpressing breast cancer who receive trastuzumab therapy. There are no approved or widely accepted treatments for brain metastases other than steroids, cranial radiotherapy, and surgical resection. We examined the efficacy of lapatinib, an inhibitor of the epidermal growth factor receptor (EGFR) and HER2 kinases, for preventing the outgrowth of breast cancer cells in the brain in a mouse xenograft model of brain metastasis. EGFR-overexpressing MDA-MB-231-BR (231-BR) brain-seeking breast cancer cells were transfected with an expression vector that contained or lacked the HER2 cDNA and used to examine the effect of lapatinib on the activation (ie, phosphorylation) of cell signaling proteins by immunoblotting, on cell growth by the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and on cell migration using a Boyden chamber assay. The outgrowth of large (ie, >50 microm(2)) and micrometastases was counted in brain sections from nude mice that had been injected into the left cardiac ventricle with 231-BR cells and, beginning 5 days later, treated by oral gavage with lapatinib or vehicle (n = 22-26 mice per treatment group). All statistical tests were two-sided. In vitro, lapatinib inhibited the phosphorylation of EGFR, HER2, and downstream signaling proteins; cell proliferation; and migration in 231-BR cells (both with and without HER2). Among mice injected with 231-BR-vector cells, those treated with 100 mg lapatinib/kg body weight had 54% fewer large metastases 24 days after starting treatment than those treated with vehicle (mean number of large metastases per brain section: 1.56 vs 3.36, difference = 1.80, 95% confidence interval [CI] = 0.92 to 2.68, P < .001), whereas treatment with 30 mg lapatinib/kg body weight had no effect. Among mice injected with 231-BR-HER2 cells, those treated with either dose of lapatinib had 50%-53% fewer large metastases than those treated with vehicle (mean number of large metastases per brain section, 30 mg/kg vs vehicle: 3.21 vs 6.83, difference = 3.62, 95% CI = 2.30 to 4.94, P < .001; 100 mg/kg vs vehicle: 3.44 vs 6.83, difference = 3.39, 95% CI = 2.08 to 4.70, P < .001). Immunohistochemical analysis revealed reduced phosphorylation of HER2 in 231-BR-HER2 cell-derived brain metastases from mice treated with the higher dose of lapatinib compared with 231-BR-HER2 cell-derived brain metastases from vehicle-treated mice (P < .001). Lapatinib is the first HER2-directed drug to be validated in a preclinical model for activity against brain metastases of breast cancer.

Regional brain hematocrit in stroke by single photon emission computed tomography imaging

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

Loutfi, I.; Frackowiak, R.S.; Myers, M.J.

1987-01-01

Nineteen studies on 18 subjects were performed by single photon emission computed tomography (SPECT) of the head after the successive intravenous administration of a plasma label (/sup 99m/Tc-human serum albumin (HSA)) and /sup 99m/Tc-labeled autologous red blood cells (RBC). Two sets of cerebral tomographic sections were generated: for cerebral /sup 99m/Tc-HSA alone and for combined /sup 99m/Tc-HSA and /sup 99m/Tc-RBC. By relating counts in regions of interest from the cerebral tomograms to counts from blood samples obtained during each tomographic acquisition, regional cerebral haematocrit (Hct) was calculated by the application of a simple formula. Results show 1) lower cerebral Hctmore » than venous Hct (ratio of HCT brain/Hct venous 0.65-0.90) in all subjects, and 2) comparison between right and left hemisphere Hct in 3/3 normal subjects, 6/6 patients with transient ischaemic attacks and 3/8 patients with stroke showed no significant difference. However, in 3/8 patients with stroke (most recent strokes) significant differences were found, the higher Hct value corresponding to the affected side.« less

Promises of formal and informal musical activities in advancing neurocognitive development throughout childhood.

PubMed

Putkinen, Vesa; Tervaniemi, Mari; Saarikivi, Katri; Huotilainen, Minna

2015-03-01

Adult musicians show superior neural sound discrimination when compared to nonmusicians. However, it is unclear whether these group differences reflect the effects of experience or preexisting neural enhancement in individuals who seek out musical training. Tracking how brain function matures over time in musically trained and nontrained children can shed light on this issue. Here, we review our recent longitudinal event-related potential (ERP) studies that examine how formal musical training and less formal musical activities influence the maturation of brain responses related to sound discrimination and auditory attention. These studies found that musically trained school-aged children and preschool-aged children attending a musical playschool show more rapid maturation of neural sound discrimination than their control peers. Importantly, we found no evidence for pretraining group differences. In a related cross-sectional study, we found ERP and behavioral evidence for improved executive functions and control over auditory novelty processing in musically trained school-aged children and adolescents. Taken together, these studies provide evidence for the causal role of formal musical training and less formal musical activities in shaping the development of important neural auditory skills and suggest transfer effects with domain-general implications. © 2015 New York Academy of Sciences.

Serum brain-derived neurotrophic factor levels and personality traits in patients with major depression.

PubMed

Nomoto, Hiroshi; Baba, Hajime; Satomura, Emi; Maeshima, Hitoshi; Takebayashi, Naoko; Namekawa, Yuki; Suzuki, Toshihito; Arai, Heii

2015-03-04

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. Previous studies have demonstrated lower serum BDNF levels in patients with major depressive disorder (MDD) and reported an association between BDNF levels and depression-related personality traits in healthy subjects. The aim of the present study was to explore for a possible association between peripheral BDNF levels and personality traits in patients with MDD. In this cross-sectional study, a total of 123 inpatients with MDD (Diagnostic and Statistical Manual for Mental Disorders, 4th edition) at the Juntendo University Koshigaya Hospital were recruited. Serum levels of BDNF were measured. Personality traits were assessed using the 125-item short version of the Temperament and Character Inventory (TCI). Multiple regression analysis adjusted for age, sex, body mass index, dose of antidepressant, and depression severity showed that TCI Self-Directedness (SD) scores were negatively associated with serum BDNF levels (β = -0.23, p = 0.026). MDD patients who have low SD did not show the reduction in serum BDNF levels that is normally associated with depressive state. Our findings suggest that depression-related biological changes may not occur in these individuals.

Needs and Concerns of Male Combat Veterans with Mild Traumatic Brain Injury

DTIC Science & Technology

2013-01-01

is bothering me . . . . I bought an old house and I’ve been remodeling it. And I found some old dressers from an old house, I’ve been refin- ishing...EW, Tong EC, Yip SC, Lui WF, Lam CS. Health services needs and quality of life assessment of individuals with brain injuries: a pilot cross -sectional

Learn with the Classics: Using Music To Study Smart at Any Age.

ERIC Educational Resources Information Center

Andersen, Ole; Marsh, Marcy; Harvey, Arthur

This book, accompanied by a musical CD-ROM, provides information on how to enhance learning through music at any age. Sections include: (1) "Let Music Prime Your Brain For Learning," which teaches how important it is to prime the brain for learning through music; (2) "Study Smart," which demonstrates highly effective studying techniques devised by…

Restrained eaters show altered brain response to food odor.

PubMed

Kemmotsu, Nobuko; Murphy, Claire

2006-02-28

Do restrained and unrestrained eaters differ in their brain response to food odor? We addressed this question by examining restrained eaters' brain response to food (chocolate) and non-food (geraniol, floral) odors, both when odor was attended to and when ignored. Using olfactory event-related potentials (OERPs), we found that restrained eaters and controls responded similarly to the non-food odor; however, unlike controls, restrained eaters showed no increase in brain response to the food odor when they focused attention on it. Rather, restrained eaters showed attenuated OERP amplitudes to the food odor in both attended and ignored conditions, suggesting that the brain's response to attended food odor was abnormally suppressed.

In Vivo Investigation of the Effectiveness of a Hyper-viscoelastic Model in Simulating Brain Retraction

PubMed Central

Li, Ping; Wang, Weiwei; Zhang, Chenxi; An, Yong; Song, Zhijian

2016-01-01

Intraoperative brain retraction leads to a misalignment between the intraoperative positions of the brain structures and their previous positions, as determined from preoperative images. In vitro swine brain sample uniaxial tests showed that the mechanical response of brain tissue to compression and extension could be described by the hyper-viscoelasticity theory. The brain retraction caused by the mechanical process is a combination of brain tissue compression and extension. In this paper, we first constructed a hyper-viscoelastic framework based on the extended finite element method (XFEM) to simulate intraoperative brain retraction. To explore its effectiveness, we then applied this framework to an in vivo brain retraction simulation. The simulation strictly followed the clinical scenario, in which seven swine were subjected to brain retraction. Our experimental results showed that the hyper-viscoelastic XFEM framework is capable of simulating intraoperative brain retraction and improving the navigation accuracy of an image-guided neurosurgery system (IGNS). PMID:27387301

Clinical utility of third-trimester uterine artery Doppler in the prediction of brain hemodynamic deterioration and adverse perinatal outcome in small-for-gestational-age fetuses.

PubMed

Cruz-Martinez, R; Savchev, S; Cruz-Lemini, M; Mendez, A; Gratacos, E; Figueras, F

2015-03-01

To assess the clinical value of third-trimester uterine artery (UtA) Doppler ultrasound in the prediction of hemodynamic deterioration and adverse perinatal outcome in term small-for-gestational-age (SGA) fetuses. UtA Doppler parameters, cerebroplacental ratio (CPR) and fetal middle cerebral artery (MCA) pulsatility index (PI) were evaluated weekly, starting from the time of SGA diagnosis until 24 h before induction of labor, in a cohort of 327 SGA fetuses with normal umbilical artery PI (< 95th centile), delivered at > 37 weeks' gestation. Differences in the sequence of CPR and MCA-PI changes < 5th centile, between the group with normal UtA Doppler indices at diagnosis and those with abnormal UtA indices, were analyzed by survival analysis. In addition, the use of UtA Doppler value, alone or in combination with a brain Doppler scan before delivery, to predict the risk of Cesarean section, Cesarean section for non-reassuring fetal status (NRFS), neonatal acidosis and neonatal hospitalization was evaluated by logistic regression analysis, adjusted for gestational age at birth and birth-weight percentile. Abnormal UtA Doppler at diagnosis of SGA was associated with a higher risk of developing abnormal brain Doppler indices before induction of labor than in those with a normal UtA at diagnosis (62.7% vs 34.6%, respectively; P < 0.01). Compared to those with normal UtA Doppler indices, those with abnormal UtA Doppler findings were associated with a higher risk of intrapartum Cesarean section (52.2% vs 37.3%, respectively; P = 0.03), Cesarean section for NRFS (35.8% vs 23.1%, respectively; P = 0.03), neonatal acidosis (10.4% vs 7.7%, respectively; P = 0.47) and neonatal hospitalization (23.9% vs 16.5%, respectively; P = 0.16). Logistic regression analysis indicated that UtA Doppler findings were not significantly associated with adverse perinatal outcome independent of brain Doppler findings. UtA Doppler indices predict adverse perinatal outcome, but do not help to improve the predictive value of brain Doppler indices. However, at the time of SGA diagnosis they identify the subgroup of fetuses at highest risk of progression to abnormal brain Doppler findings. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Brain segmentation and forebrain development in amniotes.

PubMed

Puelles, L

2001-08-01

This essay contains a general introduction to the segmental paradigm postulated for interpreting morphologically cellular and molecular data on the developing forebrain of vertebrates. The introduction examines the nature of the problem, indicating the role of topological analysis in conjunction with analysis of various developmental cell processes in the developing brain. Another section explains how morphological analysis in essence depends on assumptions (paradigms), which should be reasonable and well founded in other research, but must remain tentative until time reveals their necessary status as facts for evolving theories (or leads to their substitution by alternative assumptions). The chosen paradigm affects many aspects of the analysis, including the sectioning planes one wants to use and the meaning of what one sees in brain sections. Dorsoventral patterning is presented as the fundament for defining what is longitudinal, whereas less well-understood anteroposterior patterning results from transversal regionalization. The concept of neural segmentation is covered, first historically, and then step by step, explaining the prosomeric model in basic detail, stopping at the diencephalon, the extratelencephalic secondary prosencephalon, and the telencephalon. A new pallial model for telencephalic development and evolution is presented as well, updating the proposed homologies between the sauropsidian and mammalian telencephalon.

ToF-SIMS cluster ion imaging of hippocampal CA1 pyramidal rat neurons

NASA Astrophysics Data System (ADS)

Francis, J. T.; Nie, H.-Y.; Taylor, A. R.; Walzak, M. J.; Chang, W. H.; MacFabe, D. F.; Lau, W. M.

2008-12-01

Recent studies have demonstrated the power of time-of-flight secondary ion mass spectrometry (ToF-SIMS) cluster ion imaging to characterize biological structures, such as that of the rat central nervous system. A large number of the studies to date have been carried out on the "structural scale" imaging several mm 2 using mounted thin sections. In this work, we present our ToF-SIMS cluster ion imaging results on hippocampal rat brain neurons, at the cellular and sub-cellular levels. As a part of an ongoing investigation to examine gut linked metabolic factors in autism spectrum disorders using a novel rat model, we have observed a possible variation in hippocampal Cornu ammonis 1 (CA1) pyramidal neuron geometry in thin, paraformaldehyde fixed brain sections. However, the fixation process alters the tissue matrix such that much biochemical information appears to be lost. In an effort to preserve as much as possible this original information, we have established a protocol using unfixed thin brain sections, along with low dose, 500 eV Cs + pre-sputtering that allows imaging down to the sub-cellular scale with minimal sample preparation.

Reorganization of brain function after a short-term behavioral intervention for stuttering.

PubMed

Lu, Chunming; Zheng, Lifen; Long, Yuhang; Yan, Qian; Ding, Guosheng; Liu, Li; Peng, Danling; Howell, Peter

2017-05-01

This study investigated changes in brain function that occurred over a 7-day behavioral intervention for adults who stutter (AWS). Thirteen AWS received the intervention (AWS+), and 13 AWS did not receive the intervention (AWS-). There were 13 fluent controls (FC-). All participants were scanned before and after the intervention. Whole-brain analysis pre-intervention showed significant differences in task-related brain activation between AWS and FC- in the right inferior frontal cortex (IFC) and left middle temporal cortex, but there were no differences between the two AWS groups. Across the 7-day period of the intervention, AWS+ alone showed a significant increase of brain activation in the left ventral IFC/insula. There were no changes in brain function for the other two groups. Further analysis revealed that the change did not correlate with resting-state functional connectivity (RSFC) that AWS showed in the cerebellum (Lu et al., 2012). However, both changes in task-related brain function and RSFC correlated with changes in speech fluency level. Together, these findings suggest that functional reorganization in a brain region close to the left IFC that shows anomalous function in AWS, occurs after a short-term behavioral intervention for stuttering. Copyright © 2017 Elsevier Inc. All rights reserved.

Agomelatine Increases BDNF Serum Levels in Depressed Patients in Correlation with the Improvement of Depressive Symptoms

PubMed Central

Pettorruso, Mauro; De Berardis, Domenico; Varasano, Paola Annunziata; Lucidi Pressanti, Gabriella; De Remigis, Valeria; Valchera, Alessandro; Ricci, Valerio; Di Nicola, Marco; Janiri, Luigi; Biggio, Giovanni; Di Giannantonio, Massimo

2016-01-01

Background: Agomelatine modulates brain-derived neurotrophic factor expression via its interaction with melatonergic and serotonergic receptors and has shown promising results in terms of brain-derived neurotrophic factor increase in animal models. Methods: Twenty-seven patients were started on agomelatine (25mg/d). Venous blood was collected and brain-derived neurotrophic factor serum levels were measured at baseline and after 2 and 8 weeks along with a clinical assessment, including Hamilton Depression Rating Scale and Snaith-Hamilton Pleasure Scale. Results: Brain-derived neurotrophic factor serum concentration increased after agomelatine treatment. Responders showed a significant increase in brain-derived neurotrophic factor levels after 2 weeks of agomelatine treatment; no difference was observed in nonresponders. Linear regression analysis showed that more prominent brain-derived neurotrophic factor level variation was associated with lower baseline BDNF levels and greater anhedonic features at baseline. Conclusions: Patients affected by depressive disorders showed an increase of brain-derived neurotrophic factor serum concentration after a 2-week treatment with agomelatine. The increase of brain-derived neurotrophic factor levels was found to be greater in patients with lower brain-derived neurotrophic factor levels and marked anhedonia at baseline. PMID:26775293

Abnormal Brain Iron Metabolism in Irp2 Deficient Mice Is Associated with Mild Neurological and Behavioral Impairments

PubMed Central

Zumbrennen-Bullough, Kimberly B.; Becker, Lore; Garrett, Lillian; Hölter, Sabine M.; Calzada-Wack, Julia; Mossbrugger, Ilona; Quintanilla-Fend, Leticia; Racz, Ildiko; Rathkolb, Birgit; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Romney, Steven J.; Leibold, Elizabeth A.

2014-01-01

Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2−/− mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2−/− mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments. PMID:24896637

Changes in brain anatomy during the course of PTSD

PubMed Central

Cardenas, Valerie A.; Samuelson, Kristin; Lenoci, Maryann; Studholme, Colin; Neylan, Thomas C.; Marmar, Charles R.; Schuff, Norbert; Weiner, Michael W.

2011-01-01

The goal of this study was to determine whether PTSD was associated with an increase in time-related decline in macrostructural brain volume and whether these changes were associated with accelerated cognitive decline. To quantify brain structure, 3 dimensional T1-weighted MRI scans were performed at baseline and again after a minimum of 24 months in 25 patients with PTSD and 22 controls. Longitudinal changes in brain volume were measured using deformation morphometry. For the group as a whole PTSD+ patients did not show significant ongoing brain atrophy compared to PTSD-. PTSD+ patients were then subgrouped into those with decreasing or increasing symptoms. We found little evidence for brain markers of accelerated atrophy in PTSD+ veterans whose symptoms improved over time, with only a small left parietal region showing greater ongoing tissue loss than PTSD-. PTSD patients whose symptoms increased over time showed accelerated atrophy throughout the brain, particularly brainstem and frontal and temporal lobes. Lastly, for the sample as a whole greater rates of brain atrophy were associated with greater rates of decline in verbal memory and delayed facial recognition. PMID:21683556

A Right Brain/Left Brain Model of Acting.

ERIC Educational Resources Information Center

Bowlen, Clark

Using current right brain/left brain research, this paper develops a model that explains acting's underlying quality--the actor is both himself and the character. Part 1 presents (1) the background of the right brain/left brain theory, (2) studies showing that propositional communication is a left hemisphere function while affective communication…

Non-destructive optical clearing technique enhances optical coherence tomography (OCT) for real-time, 3D histomorphometry of brain tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Paul, Akshay; Chang, Theodore H.; Chou, Li-Dek; Ramalingam, Tirunelveli S.

2016-03-01

Evaluation of neurodegenerative disease often requires examination of brain morphology. Volumetric analysis of brain regions and structures can be used to track developmental changes, progression of disease, and the presence of transgenic phenotypes. Current standards for microscopic investigation of brain morphology are limited to detection of superficial structures at a maximum depth of 300μm. While histological techniques can provide detailed cross-sections of brain structures, they require complicated tissue preparation and the ultimate destruction of the sample. A non-invasive, label-free imaging modality known as Optical Coherence Tomography (OCT) can produce 3-dimensional reconstructions through high-speed, cross-sectional scans of biological tissue. Although OCT allows for the preservation of intact samples, the highly scattering and absorbing properties of biological tissue limit imaging depth to 1-2mm. Optical clearing agents have been utilized to increase imaging depth by index matching and lipid digestion, however, these contemporary techniques are expensive and harsh on tissues, often irreversibly denaturing proteins. Here we present an ideal optical clearing agent that offers ease-of-use and reversibility. Similar to how SeeDB has been effective for microscopy, our fructose-based, reversible optical clearing technique provides improved OCT imaging and functional immunohistochemical mapping of disease. Fructose is a natural, non-toxic sugar with excellent water solubility, capable of increasing tissue transparency and reducing light scattering. We will demonstrate the improved depth-resolving performance of OCT for enhanced whole-brain imaging of normal and diseased murine brains following a fructose clearing treatment. This technique potentially enables rapid, 3-dimensional evaluation of biological tissues at axial and lateral resolutions comparable to histopathology.

A cross-sectional and longitudinal study evaluating brain volumes, RNFL, and cognitive functions in MS patients and healthy controls.

PubMed

Frau, Jessica; Fenu, Giuseppe; Signori, Alessio; Coghe, Giancarlo; Lorefice, Lorena; Barracciu, Maria Antonietta; Sechi, Vincenzo; Cabras, Federico; Badas, Mauro; Marrosu, Maria Giovanna; Cocco, Eleonora

2018-05-11

The principal biomarker of neurodegeneration in multiple sclerosis (MS) is believed to be brain volume, which is associated with cognitive functions and retinal nerve fibre layer (RNFL). A cross-sectional and longitudinal assessment of the relationship between RNFL, cognitive functions and brain volume. At baseline, relapsing patients and healthy controls underwent 1.5 T MRI to estimate the normalized volume of brain (NBV), grey (NGV), white (NWV) and peripheral grey (pNGV) matter. Cognitive functions were evaluated by BICAMS, RNFL by Spectral-Domain OCT. Patients were re-evaluated after 12 months. Cognitive functions, brain volume, and RNFL differed between the group of 66 patients and that of 16 healthy controls. In the MS group, at baseline, an association was found between: p-NGV and symbol-digit (SDMT) (p = 0.022); temporal-RNFL and NBV (p = 0.007), NWV (p = 0.012), NGV (p = 0.048), and p-NGV (p = 0.021); papillo-macular bundle-RNFL and NBV (p = 0.013), NWV (p = 0.02), NGV (p = 0.049), and p-NGV (p = 0.032). Over the observational period, we found a reduction of brain volume (p < 0.001), average-RNFL (p = 0.001), temporal-RNFL (p = 0.006), and papillo-macular bundle-RNFL (p = 0.009). No association was found between OCT, MRI, and cognitive changes. Brain volume, cognitive functions, and RNFL are continuous measures of different neurodegenerative aspects. BICAMS and OCT have low costs and can be easily used in clinical practice to monitor neurodegeneration.

Conditional N-WASP knockout in mouse brain implicates actin cytoskeleton regulation in hydrocephalus pathology.

PubMed

Jain, Neeraj; Lim, Lee Wei; Tan, Wei Ting; George, Bhawana; Makeyev, Eugene; Thanabalu, Thirumaran

2014-04-01

Cerebrospinal fluid (CSF) is produced by the choroid plexus and moved by multi-ciliated ependymal cells through the ventricular system of the vertebrate brain. Defects in the ependymal layer functionality are a common cause of hydrocephalus. N-WASP (Neural-Wiskott Aldrich Syndrome Protein) is a brain-enriched regulator of actin cytoskeleton and N-WASP knockout caused embryonic lethality in mice with neural tube and cardiac abnormalities. To shed light on the role of N-WASP in mouse brain development, we generated N-WASP conditional knockout mouse model N-WASP(fl/fl); Nestin-Cre (NKO-Nes). NKO-Nes mice were born with Mendelian ratios but exhibited reduced growth characteristics compared to their littermates containing functional N-WASP alleles. Importantly, all NKO-Nes mice developed cranial deformities due to excessive CSF accumulation and did not survive past weaning. Coronal brain sections of these animals revealed dilated lateral ventricles, defects in ciliogenesis, loss of ependymal layer integrity, reduced thickness of cerebral cortex and aqueductal stenosis. Immunostaining for N-cadherin suggests that ependymal integrity in NKO-Nes mice is lost as compared to normal morphology in the wild-type controls. Moreover, scanning electron microscopy and immunofluorescence analyses of coronal brain sections with anti-acetylated tubulin antibodies revealed the absence of cilia in ventricular walls of NKO-Nes mice indicative of ciliogenesis defects. N-WASP deficiency does not lead to altered expression of N-WASP regulatory proteins, Fyn and Cdc42, which have been previously implicated in hydrocephalus pathology. Taken together, our results suggest that N-WASP plays a critical role in normal brain development and implicate actin cytoskeleton regulation as a vulnerable axis frequently deregulated in hydrocephalus. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantitative autoradiography of the binding sites for ( sup 125 I) iodoglyburide, a novel high-affinity ligand for ATP-sensitive potassium channels in rat brain

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

Gehlert, D.R.; Gackenheimer, S.L.; Mais, D.E.

1991-05-01

We have developed a high specific activity ligand for localization of ATP-sensitive potassium channels in the brain. When brain sections were incubated with ({sup 125}I)iodoglyburide (N-(2-((((cyclohexylamino)carbonyl)amino)sulfonyl)ethyl)-5-{sup 125}I-2- methoxybenzamide), the ligand bound to a single site with a KD of 495 pM and a maximum binding site density of 176 fmol/mg of tissue. Glyburide was the most potent inhibitor of specific ({sup 125}I)iodoglyburide binding to rat forebrain sections whereas iodoglyburide and glipizide were slightly less potent. The binding was also sensitive to ATP which completely inhibited binding at concentrations of 10 mM. Autoradiographic localization of ({sup 125}I)iodoglyburide binding indicated a broadmore » distribution of the ATP-sensitive potassium channel in the brain. The highest levels of binding were seen in the globus pallidus and ventral pallidum followed by the septohippocampal nucleus, anterior pituitary, the CA2 and CA3 region of the hippocampus, ventral pallidum, the molecular layer of the cerebellum and substantia nigra zona reticulata. The hilus and dorsal subiculum of the hippocampus, molecular layer of the dentate gyrus, cerebral cortex, lateral olfactory tract nucleus, olfactory tubercle and the zona incerta contained relatively high levels of binding. A lower level of binding (approximately 3- to 4-fold) was found throughout the remainder of the brain. These results indicate that the ATP-sensitive potassium channel has a broad presence in the rat brain and that a few select brain regions are enriched in this subtype of neuronal potassium channels.« less

Supercomputer algorithms for efficient linear octree encoding of three-dimensional brain images.

PubMed

Berger, S B; Reis, D J

1995-02-01

We designed and implemented algorithms for three-dimensional (3-D) reconstruction of brain images from serial sections using two important supercomputer architectures, vector and parallel. These architectures were represented by the Cray YMP and Connection Machine CM-2, respectively. The programs operated on linear octree representations of the brain data sets, and achieved 500-800 times acceleration when compared with a conventional laboratory workstation. As the need for higher resolution data sets increases, supercomputer algorithms may offer a means of performing 3-D reconstruction well above current experimental limits.

HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

PubMed Central

Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

2010-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

Estrogen-2-hydroxylase in the brain of the male African catfish, Clarias gariepinus

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

Timmers, R.J.; Granneman, J.C.; Lambert, J.G.

1988-11-01

Estrogen-2-hydroxylase activity, involved in the biosynthesis of catecholestrogens, was localized in the brain of the male African catfish, Clarias gariepinus, by means of a radiometric assay using (2-TH)estradiol as substrate. Fore- and midbrain were divided in 18, 500-microns thick, transverse sections from which small defined areas were punched out and assayed. The estrogen-2-hydroxylase activity was calculated from the release of tritium during hydroxylation, and expressed in femtomole catecholestradiol.milligram-1 tissue.hour-1. The enzyme could be demonstrated throughout the brain. A high activity (greater than 350 fmol) was observed in the telencephalon, in particularly the rostral part and the area ventralis pars dorsalis;more » in the diencephalon in the preoptic region, including the magnocellular part of the preoptic nucleus and the rostral part of the anterior periventricular nucleus; and in the area tuberalis, including the nucleus lateralis tuberis, the rostral part of the nucleus anterior tuberis, the caudal part of the nucleus posterior periventricularis, and in the nucleus recessus posterioris. Also a high activity was detected in the mesencephalic tectum opticum and the dorsolateral part of the torus semicircularis. The ventral mesencephalon showed a moderate (200-350 fmol) to low (less than 200 fmol) activity, whereas the lowest activity was found in the hindbrain (118 fmol). The significance of the biosynthesis of catecholestrogens in the brain is discussed in light of the negative feedback mechanism of gonadal steroids on gonadotropin release.« less

Expression of mRNAs encoding ARPP-16/19, ARPP-21, and DARPP-32 in human brain tissue.

PubMed

Brené, S; Lindefors, N; Ehrlich, M; Taubes, T; Horiuchi, A; Kopp, J; Hall, H; Sedvall, G; Greengard, P; Persson, H

1994-03-01

In this study we have isolated and sequenced human cDNAs for the phosphoproteins DARPP-32, ARPP-21, and ARPP-16/19, and have compared these sequences to previously characterized bovine and rat cDNAs. In situ hybridization and Northern blot analysis with the human cDNA probes were used to study the expression of mRNAs encoding ARPP-16/19, ARPP-21, and DARPP-32 in human postmortem brain tissue. In situ hybridization was performed using horizontal whole hemisphere sections. Five representative levels of the brain ranging from 71 mm to 104 mm ventral to vertex were examined. All three probes showed distinct hybridization patterns in the caudate nucleus, putamen, nucleus accumbens, and the amygdaloid complex. For ARPP-16/19 mRNA, a hybridization signal comparable to the signal in caudate nucleus, putamen, and nucleus accumbens was also detected in the neocortex. ARPP-21 and DARPP-32 mRNA, on the other hand, were present in lower levels in neocortical regions. DARPP-32 mRNA was abundant in the cerebellar cortex at the level of the Purkinje cell layer. High levels of ARPP-16/19 and ARPP-21 mRNA were also found in the cerebellar cortex, where they were confined to deeper layers. The present result demonstrate that mRNAs for the three phosphoproteins are expressed in overlapping, but also distinct, areas of the human brain that in many cases coincide with previously described distribution of the dopamine D1 receptor.

The relationship between white matter brain metabolites and cognition in normal aging: the GENIE study.

PubMed

Charlton, R A; McIntyre, D J O; Howe, F A; Morris, R G; Markus, H S

2007-08-20

Magnetic resonance spectroscopy (MRS) has demonstrated age-related changes in brain metabolites that may underlie micro-structural brain changes, but few studies have examined their relationship with cognitive decline. We performed a cross-sectional study of brain metabolism and cognitive function in 82 healthy adults (aged 50-90) participating in the GENIE (St GEorge's Neuropsychology and Imaging in the Elderly) study. Absolute metabolite concentrations were measured by proton chemical shift imaging within voxels placed in the centrum semiovale white matter. Cognitive abilities assessed were executive function, working memory, information processing speed, long-term memory and fluid intelligence. Correlations showed that all cognitive domains declined with age. Total creatine (tCr) concentration increased with age (r=0.495, p<0.001). Regression analyses were performed for each cognitive variable, including estimated intelligence and the metabolites, with age then added as a final step. A significant relationship was observed between tCr and executive function, long-term memory, and fluid intelligence, although these relationships did not remain significant after age was added as a final step in the regression. The regression analysis also demonstrated a significant relationship between N-acetylaspartate (NAA) and executive function. As there was no age-related decline in NAA, this argues against axonal loss with age; however the relationship between NAA and executive function independent of age and estimated intelligence is consistent with white matter axonal integrity having an important role in executive function in normal individuals.

Alterations in regional homogeneity of resting-state brain activity in fatigue of Parkinson's disease.

PubMed

Li, Junyi; Yuan, Yongsheng; Wang, Min; Zhang, Jiejin; Zhang, Li; Jiang, Siming; Ding, Jian; Zhang, Kezhong

2017-10-01

Fatigue is a common complaint in patients with Parkinson's disease (PD). However, the neural bases of fatigue in PD remain uncertain. In this cross-sectional study, our aim was to study the change of the local brain function in PD patients with fatigue. Among 49 patients with PD, 17 of them had fatigue and the remaining 32 patients without fatigue, and 25 age- and gender-matched healthy controls were enrolled. All subjects were evaluated with Fatigue Severity Scale (FSS) and had a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The fMRI images were analyzed using regional homogeneity (ReHo) to study the change of the local brain function. ReHo analysis controlling for gray matter volume, age, gender, and education showed decreased ReHo in the left anterior cingulate cortex (ACC) and the right superior frontal gyrus (dorsolateral part), and increased ReHo in the left postcentral gyrus and the right inferior frontal gyrus (orbital and triangular part), compared PD-F with PD-NF; In PD patients, the regional activity in the left ACC and the right superior frontal gyrus (dorsolateral part) was negatively correlated with the FSS scores, while that in the left postcentral gyrus, the right inferior frontal gyrus (orbital and triangular part) was positively correlated with the FSS scores. This study demonstrates that brain areas including frontal, postcentral and ACC regions indicative of sensory, motor, and cognitive systems are involved in fatigue in PD patients.

Diattenuation of brain tissue and its impact on 3D polarized light imaging

PubMed Central

Menzel, Miriam; Reckfort, Julia; Weigand, Daniel; Köse, Hasan; Amunts, Katrin; Axer, Markus

2017-01-01

3D-polarized light imaging (3D-PLI) reconstructs nerve fibers in histological brain sections by measuring their birefringence. This study investigates another effect caused by the optical anisotropy of brain tissue – diattenuation. Based on numerical and experimental studies and a complete analytical description of the optical system, the diattenuation was determined to be below 4 % in rat brain tissue. It was demonstrated that the diattenuation effect has negligible impact on the fiber orientations derived by 3D-PLI. The diattenuation signal, however, was found to highlight different anatomical structures that cannot be distinguished with current imaging techniques, which makes Diattenuation Imaging a promising extension to 3D-PLI. PMID:28717561

Dynamics of myelin content decrease in the rat stroke model

NASA Astrophysics Data System (ADS)

Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

2017-08-01

The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

Preprotachykinin A mRNA expression in the rat brain during development.

PubMed

Brené, S; Lindefors, N; Friedman, W J; Persson, H

1990-12-15

Expression of preprotachykinin A (PPT-A) mRNA was analyzed by northern blots using mRNA prepared from rat brain at 12 different developmental stages ranging from embryonic day 15 (E15) to adult. A single PPT-A mRNA of 1.3 kb was detected throughout development. PPT-A mRNA was detected as early as E15 and an approximately 3-fold increase occurred at birth. This amount remained until 3 weeks of age when the level increased, reaching a peak at 5 weeks of age. Adult amounts were approximately 3-fold higher than the levels at birth. The distribution of PPT-A mRNA-expressing cells in rat brain was studied by in situ hybridization on sections from embryonic day 20, postnatal days 4 and 7 as well as adult. Cells expressing PPT-A mRNA were detected in the forebrain at all 4 ages analyzed. However, the hybridization pattern and the labeling intensity varied in different brain regions during development. In cingulate cortex, intense labeling was seen in numerous cells at embryonic day 20 and postnatal days 4 and 7, whereas in the adult cingulate cortex only a few scattered labeled cells were observed. In frontoparietal cortex labeled cells were found from postnatal day 4 to adult, with the highest density of labeled cells at P7. Developmental differences in both the distribution of PPT-A mRNA-expressing cells and the level of PPT-A mRNA expression were also found in caudate-putamen, lateral hypothalamus and amygdala. Thus, our results show several changes in PPT-A mRNA expression during ontogeny, indicating a region and time-specific regulation of PPT-A mRNA expression during brain maturation.

Coadministration of the Human Umbilical Cord Matrix-Derived Mesenchymal Cells and Aspirin Alters Postischemic Brain Injury in Rats.

PubMed

Shams ara, Ali; Sheibani, Vahid; Esmaeilpour, Khadije; Eslaminejad, Touba; Nematollahi-Mahani, Seyed N

2015-09-01

Ischemic stroke is an acute brain insult that induces dramatic changes in the neurons. Treatment of brain stroke is one of the main therapeutic targets of neuroprotective therapies. The aim of this study was to evaluate the protective potential of implanted human umbilical cord mesenchymal stem (hUCMs) cells with/without aspirin (ASA) against focal cerebral ischemia. We assessed the migration and distribution of PKH26-labeled cells after transplantation. After day 10 of transient occlusion, we evaluated the effect of ASA and hUCMs on the recovery of learning and memory in rats by Morris water maze. Afterward, animals were sacrificed, and the infarct area in the brain was evaluated using 2, 3, 5-triphenyltetrazolium chloride staining and also by hematoxylin and eosin. The recovery of learning and memory in ischemic animals that received ASA and hUCM cells improved significantly compared with the untreated ischemic animals. Coadministration of ASA and hUCM cells did not improve the outcome at a comparable rate with ASA and hUCM cells alone. PKH26-labeled cells were detectable in the ischemic area of the brain tissue sections. 2,3,5-Triphenyltetrazolium chloride staining and histologic examinations showed that treatment with ASA and hUCM cells could significantly alter the ischemic area. The results of the present study suggest that ASA and hUCM cells can withstand degenerative changes induced by artificial stroke in the rat. Also the learning and memory disturbance in the ASA and cell-treated animals is less pronounced than ischemic animals. Coadministration of ASA and hUCM cells did not raise the outcome higher than administration of ASA and hUCM cells alone. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Neurofeedback: One of today's techniques in psychiatry?

PubMed

Arns, M; Batail, J-M; Bioulac, S; Congedo, M; Daudet, C; Drapier, D; Fovet, T; Jardri, R; Le-Van-Quyen, M; Lotte, F; Mehler, D; Micoulaud-Franchi, J-A; Purper-Ouakil, D; Vialatte, F

2017-04-01

Neurofeedback is a technique that aims to teach a subject to regulate a brain parameter measured by a technical interface to modulate his/her related brain and cognitive activities. However, the use of neurofeedback as a therapeutic tool for psychiatric disorders remains controversial. The aim of this review is to summarize and to comment the level of evidence of electroencephalogram (EEG) neurofeedback and real-time functional magnetic resonance imaging (fMRI) neurofeedback for therapeutic application in psychiatry. Literature on neurofeedback and mental disorders but also on brain computer interfaces (BCI) used in the field of neurocognitive science has been considered by the group of expert of the Neurofeedback evaluation & training (NExT) section of the French Association of biological psychiatry and neuropsychopharmacology (AFPBN). Results show a potential efficacy of EEG-neurofeedback in the treatment of attentional-deficit/hyperactivity disorder (ADHD) in children, even if this is still debated. For other mental disorders, there is too limited research to warrant the use of EEG-neurofeedback in clinical practice. Regarding fMRI neurofeedback, the level of evidence remains too weak, for now, to justify clinical use. The literature review highlights various unclear points, such as indications (psychiatric disorders, pathophysiologic rationale), protocols (brain signals targeted, learning characteristics) and techniques (EEG, fMRI, signal processing). The field of neurofeedback involves psychiatrists, neurophysiologists and researchers in the field of brain computer interfaces. Future studies should determine the criteria for optimizing neurofeedback sessions. A better understanding of the learning processes underpinning neurofeedback could be a key element to develop the use of this technique in clinical practice. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Abnormal brain activation during emotion processing of euthymic bipolar patients taking different mood stabilizers.

PubMed

Li, Linling; Ji, Erni; Tang, Fei; Qiu, Yunhai; Han, Xue; Zhang, Shengli; Zhang, Zhiguo; Yang, Haichen

2018-06-16

Numerous functional magnetic resonance imaging studies have been conducted to elucidate emotion processing of patients with bipolar disorder (BD), but due to different inclusion criteria used, especially for the history of medication use, the results for euthymic BD patients are inconsistent. For this reason, brain functional effects of psychopharmacological treatments on BD patients have been investigated by numerous fMRI studies, but there is no existing report for brain functional effects of different mood stabilizers. In this study, we compared the emotion processing in BD patients treated by two popularly used mood stabilizer, lithium (N = 13; 30 ± 9 years) and valproate (N = 16; 33 ± 8 years), as well as healthy controls (HC; N = 16; 29 ± 7 years). Two emotional tasks were applied in this study: one used emotional pictures of everyday objects and scenes, and another used emotional facial expression pictures. The main findings were that BD on lithium showed increased fMRI activation in the right dorsal anterior cingulate cortex and bilateral lingual gyrus in response to the positive pictures relative to neutral pictures compared with BD on valproate and HC. Besides, no abnormal activation was observed in the amygdala. Limitations of this study comprise the small sample size and the cross-sectional design. Therefore, the results were suggestive of a different effect of lithium and valproate on brain activities during emotion processing but no causal role can be proposed. The enduring impairments in euthymic state could provide clues to the brain regions involved in the primary pathology of BD.

38 CFR 17.148 - Service dogs.

Code of Federal Regulations, 2014 CFR

2014-07-01

... that substantially limits mobility includes but is not limited to a traumatic brain injury that... section. (3) For the purposes of this section, substantial mobility impairment means a spinal cord injury... pay for items such as license tags, nonprescription food, grooming, insurance for personal injury, non...

38 CFR 17.148 - Service dogs.

Code of Federal Regulations, 2013 CFR

2013-07-01

... that substantially limits mobility includes but is not limited to a traumatic brain injury that... section. (3) For the purposes of this section, substantial mobility impairment means a spinal cord injury... pay for items such as license tags, nonprescription food, grooming, insurance for personal injury, non...

Accelerated recruitment of new brain development genes into the human genome.

PubMed

Zhang, Yong E; Landback, Patrick; Vibranovski, Maria D; Long, Manyuan

2011-10-01

How the human brain evolved has attracted tremendous interests for decades. Motivated by case studies of primate-specific genes implicated in brain function, we examined whether or not the young genes, those emerging genome-wide in the lineages specific to the primates or rodents, showed distinct spatial and temporal patterns of transcription compared to old genes, which had existed before primate and rodent split. We found consistent patterns across different sources of expression data: there is a significantly larger proportion of young genes expressed in the fetal or infant brain of humans than in mouse, and more young genes in humans have expression biased toward early developing brains than old genes. Most of these young genes are expressed in the evolutionarily newest part of human brain, the neocortex. Remarkably, we also identified a number of human-specific genes which are expressed in the prefrontal cortex, which is implicated in complex cognitive behaviors. The young genes upregulated in the early developing human brain play diverse functional roles, with a significant enrichment of transcription factors. Genes originating from different mechanisms show a similar expression bias in the developing brain. Moreover, we found that the young genes upregulated in early brain development showed rapid protein evolution compared to old genes also expressed in the fetal brain. Strikingly, genes expressed in the neocortex arose soon after its morphological origin. These four lines of evidence suggest that positive selection for brain function may have contributed to the origination of young genes expressed in the developing brain. These data demonstrate a striking recruitment of new genes into the early development of the human brain.

Site of anticonvulsant action on sodium channels: autoradiographic and electrophysiological studies in rat brain

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

Worley, P.F.; Baraban, J.M.

1987-05-01

The anticonvulsants phenytoin and carbamazepine interact allosterically with the batrachotoxin binding site of sodium channels. In the present study, we demonstrate an autoradiographic technique to localize the batrachotoxin binding site on sodium channels in rat brain using (/sup 3/H)batrachotoxinin-A 20-alpha-benzoate (BTX-B). Binding of (/sup 3/H)BTX-B to brain sections is dependent on potentiating allosteric interactions with scorpion venom and is displaced by BTX-B (Kd approximately 200 nM), aconitine, veratridine, and phenytoin with the same rank order of potencies as described in brain synaptosomes. The maximum number of (/sup 3/H)BTX-B binding sites in forebrain sections also agrees with biochemical determinations. Autoradiographic localizationsmore » indicate that (/sup 3/H)BTX-B binding sites are not restricted to cell bodies and axons but are present in synaptic zones throughout the brain. For example, a particularly dense concentration of these sites in the substantia nigra is associated with afferent terminals of the striatonigral projection. By contrast, myelinated structures possess much lower densities of binding sites. In addition, we present electrophysiological evidence that synaptic transmission, as opposed to axonal conduction, is preferentially sensitive to the action of aconitine and veratridine. Finally, the synaptic block produced by these sodium channel activators is inhibited by phenytoin and carbamazepine at therapeutic anticonvulsant concentrations.« less

Whole-brain serial-section electron microscopy in larval zebrafish.

PubMed

Hildebrand, David Grant Colburn; Cicconet, Marcelo; Torres, Russel Miguel; Choi, Woohyuk; Quan, Tran Minh; Moon, Jungmin; Wetzel, Arthur Willis; Scott Champion, Andrew; Graham, Brett Jesse; Randlett, Owen; Plummer, George Scott; Portugues, Ruben; Bianco, Isaac Henry; Saalfeld, Stephan; Baden, Alexander David; Lillaney, Kunal; Burns, Randal; Vogelstein, Joshua Tzvi; Schier, Alexander Franz; Lee, Wei-Chung Allen; Jeong, Won-Ki; Lichtman, Jeff William; Engert, Florian

2017-05-18

High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits. These efforts were recently transformed by advances in computing, sample handling, and imaging techniques, but high-resolution examination of entire brains remains a challenge. Here, we present ssEM data for the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post-fertilization. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management requirements. The resulting dataset can be analysed to reconstruct neuronal processes, permitting us to survey all myelinated axons (the projectome). These reconstructions enable precise investigations of neuronal morphology, which reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axons. We further set the stage for whole-brain structure-function comparisons by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. All obtained images and reconstructions are provided as an open-access resource.

Whole-brain serial-section electron microscopy in larval zebrafish

NASA Astrophysics Data System (ADS)

Hildebrand, David Grant Colburn; Cicconet, Marcelo; Torres, Russel Miguel; Choi, Woohyuk; Quan, Tran Minh; Moon, Jungmin; Wetzel, Arthur Willis; Scott Champion, Andrew; Graham, Brett Jesse; Randlett, Owen; Plummer, George Scott; Portugues, Ruben; Bianco, Isaac Henry; Saalfeld, Stephan; Baden, Alexander David; Lillaney, Kunal; Burns, Randal; Vogelstein, Joshua Tzvi; Schier, Alexander Franz; Lee, Wei-Chung Allen; Jeong, Won-Ki; Lichtman, Jeff William; Engert, Florian

2017-05-01

High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits. These efforts were recently transformed by advances in computing, sample handling, and imaging techniques, but high-resolution examination of entire brains remains a challenge. Here, we present ssEM data for the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post-fertilization. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management requirements. The resulting dataset can be analysed to reconstruct neuronal processes, permitting us to survey all myelinated axons (the projectome). These reconstructions enable precise investigations of neuronal morphology, which reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axons. We further set the stage for whole-brain structure-function comparisons by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. All obtained images and reconstructions are provided as an open-access resource.

Infant visual attention and object recognition.

PubMed

Reynolds, Greg D

2015-05-15

This paper explores the role visual attention plays in the recognition of objects in infancy. Research and theory on the development of infant attention and recognition memory are reviewed in three major sections. The first section reviews some of the major findings and theory emerging from a rich tradition of behavioral research utilizing preferential looking tasks to examine visual attention and recognition memory in infancy. The second section examines research utilizing neural measures of attention and object recognition in infancy as well as research on brain-behavior relations in the early development of attention and recognition memory. The third section addresses potential areas of the brain involved in infant object recognition and visual attention. An integrated synthesis of some of the existing models of the development of visual attention is presented which may account for the observed changes in behavioral and neural measures of visual attention and object recognition that occur across infancy. Copyright © 2015 Elsevier B.V. All rights reserved.

Sisters and Brothers, Brothers and Sisters in the Family Affected by Traumatic Brain Injury.

ERIC Educational Resources Information Center

Pieper, Betty

This report is based on a qualitative research study which utilized a nominal group process to identify major life stressors for parents of children with traumatic brain injuries (TBI). It focuses first on effects of TBI on siblings and then on effective interventions. The first section uses quotes from participating parents to identify their…

Left-Brain Finance for Right-Brain People: A Money Guide for the Creatively Inclined.

ERIC Educational Resources Information Center

Monroe, Paula Ann

This basic money book takes a creative approach for visual learners by using icons, varied fonts, and highlighted text. The book's design will appeal to holistic thinkers by allowing them to jump from point to point without losing overall meaning. It is divided into five sections, each with a subset of related topics: (1) "The Big…

Life Satisfaction Questionnaire (Lisat-9): Reliability and Validity for Patients with Acquired Brain Injury

ERIC Educational Resources Information Center

Boonstra, Anne M.; Reneman, Michiel F.; Stewart, Roy E.; Balk, Gerlof A.

2012-01-01

The aim of this study was to determine the reliability and discriminant validity of the Dutch version of the life satisfaction questionnaire (Lisat-9 DV) to assess patients with an acquired brain injury. The reliability study used a test-retest design, and the validity study used a cross-sectional design. The setting was the general rehabilitation…

A Cross-Sectional and Follow-Up Functional MRI Study with a Working Memory Task in Adolescent Anorexia Nervosa

ERIC Educational Resources Information Center

Castro-Fornieles, Josefina; Caldu, Xavier; Andres-Perpina, Susana; Lazaro, Luisa; Bargallo, Nuria; Falcon, Carles; Plana, Maria Teresa; Junque, Carme

2010-01-01

Structural and functional brain abnormalities have been described in anorexia nervosa (AN). The objective of this study was to examine whether there is abnormal regional brain activation during a working memory task not associated with any emotional stimuli in adolescent patients with anorexia and to detect possible changes after weight recovery.…

Magnetic Transfer Contrast Accurately Localizes Substantia Nigra Confirmed by Histology

PubMed Central

Bolding, Mark S.; Reid, Meredith A.; Avsar, Kathy B.; Roberts, Rosalinda C.; Gamlin, Paul D.; Gawne, Timothy J.; White, David M.; den Hollander, Jan A.; Lahti, Adrienne C.

2012-01-01

Background Magnetic Resonance Imaging (MRI) has multiple contrast mechanisms. Like various staining techniques in histology, each contrast type reveals different information about the structure of the brain. However, it is not always clear how structures visible in MRI correspond to structures previously identified by histology. The purpose of this study was to determine if magnetic transfer contrast (MTC) or T2 contrast MRI was better at delineating the substantia nigra. Methods MRI scans were acquired in-vivo from two non-human primates (NHPs). The NHPs were subsequently euthanized, perfused, and their brains sectioned for histological analyses. Each slice was photographed prior to sectioning. Each brain was sectioned into approximately 500, 40-micron sections, encompassing most of the cortex, midbrain, and dorsal parts of the hindbrain. Levels corresponding to anatomical MRI images were selected. From these, adjacent sections were stained using Kluver Barrera (myelin and cell bodies) or tyrosine hydroxylase (TH) (dopaminergic neurons) immunohistochemistry. The resulting images were coregistered to the block-face images using a moving least squares algorithm with similarity transformations. MR images were similarly coregistered to the block-face images, allowing the structures in the MRI to be identified with structures in the histological images. Results We found that hyperintense (light) areas in MTC images were coextensive with the SN as delineated histologically. The hypointense (dark) areas in T2-weighted images were not coextensive with the SN, but extended partially into the SN and partially into the cerebral peduncles. Conclusions MTC is a more accurate contrast mechanism than T2-weighting for localizing the SN in vivo. PMID:22981657

Educational professionals' understanding of childhood traumatic brain injury.

PubMed

Linden, Mark A; Braiden, Hannah-Jane; Miller, Sarah

2013-01-01

To determine the understanding of educational professionals around the topic of childhood brain injury and explore the factor structure of the Common Misconceptions about Traumatic Brain Injury Questionnaire (CM-TBI). Cross-sectional postal survey. The CM-TBI was posted to all educational establishments in one region of the UK. One representative from each school was asked to complete and return the questionnaire (n = 388). Differences were demonstrated between those participants who knew someone with a brain injury and those who did not, with a similar pattern being shown for those educators who had taught a child with brain injury. Participants who had taught a child with brain injury demonstrated greater knowledge in areas such as seatbelts/prevention, brain damage, brain injury sequelae, amnesia, recovery and rehabilitation. Principal components analysis suggested the existence of four factors and the discarding of half the original items of the questionnaire. In the first European study to explore this issue, it is highlighted that teachers are ill-prepared to cope with children who have sustained a brain injury. Given the importance of a supportive school environment in return to life following hospitalization, the lack of understanding demonstrated by teachers in this research may significantly impact on a successful return to school.